Tag Archives: fluoroquinolones

Fluoroquinolone Toxicity News in South Africa – Carte Blanche

I encourage you all to watch, and share, the WONDERFUL news story from Carte Blanche, a South African investigative journalism television series, about the dangers of fluoroquinolones. It’s one of the best pieces of journalism I have seen regarding fluoroquinolone adverse-effects. You can view the story through the Carte Blanche web site, or through Youtube:

Carte Blanche Web Site, “Antibiotic Alert”

Video Link

Carte Blanche tells the stories of pain brought on by fluoroquinolones for three South African “floxies,” Tracy Witelson, Gerald Ludwinsky, and Debbi Kinrade. Their stories are powerful and poignant, and they thoroughly describe the horror of fluoroquinolone toxicity.

The Carte Blanche journalist that interviews the victims of fluoroquinolones, as well as Bayer representatives and representatives of the South African Health Products Regulatory Authority (SAHPRA), does a WONDERFUL job of compassionately framing the stories of the victims, and pushing the pharmaceutical and SAHPRA representatives by asking them tough questions, challenging them, and doing what he can to hold them accountable for the harm done by fluoroquinolones.

In an exchange that is simply wonderful, journalist Derek Watts goes over the newly (2016-2018) highlighted warnings included on the FDA warning labels for fluoroquinolones (including a warning that notes that fluoroquinolones can cause permanent disability, one that notes that the risks of fluoroquinolone use outweigh the benefits, one that notes that fluoroquinolones cause blood-sugar irregularities and mental health adverse-effects, and one that notes that fluoroquinolones increase the risk of aortic aneurysm and dissection) with Dr. Naren Jairam, the Bayer Pharmaceuticals representative. Dr. Jairam dismissively asserts that these warnings are nothing new. Watts responds by asking Jairam why Bayer hasn’t been communicating the dangers of fluoroquinolones with doctors (much less patients). Jairam claims that Bayer supports responsible use of antibiotics and that Bayer has advocated that fluoroquinolones not be used as first-line antibiotics. Watts CALLS HIM OUT and says, “That’s not true,” and notes that millions of prescriptions for non-life-threatening infections are being given all over the world. It is truly wonderful to see a quick-witted journalist asking tough questions of pharmaceutical company representatives, and calling them out when they lie and mislead.

In another exchange, Watts asks Jairam, “Is your intention to obfuscate or clarify?” VERY good question – thank you for having the chutzpah to ask, Mr. Watts!

Watts also confronts Eric Chauke, Bayer’s Head of Regulatory Affairs, by asking him to show that Bayer is communicating the risk of harm by fluoroquinolones with doctors. Chauke shows Watts some general pamphlets on antibiotic stewardship, and Watts pushes back – noting that there is nothing in what Chauke is showing him that adequately communicates that fluoroquinolones can have “dreadful side-effects” or that adequately communicates that fluoroquinolones should not be used as first-line antibiotics.

Watts also asks Professor Marc Blockman, a representative of the South African Health Products Regulatory Authority (SAHPRA), some tough questions. He asks whether or not the SAHPRA warnings are adequate, and why SAHPRA can’t send a communication to doctors stating, “don’t prescribe these drugs unless it’s life threatening and there is no alternative?” Patient advocates have been asking the same thing for years, and it’s nice to hear a journalist ask this question to a drug regulator.

I love how tough Watts is on the Bayer and SAHPRA representatives. He is doing a wonderful job at being a journalist that brings to light stories of victims, and holding those in-power responsible for their role in victimizing people.

Please watch and share the Carte Blanche piece on fluoroquinolones. It’s wonderful, and it would be great for it to be internationally “viral.”

*****

 

EMA Hearing on Fluoroquinolone Toxicity Part 3

In the first post about the EMA hearings (EMA Hearing on Fluoroquinolone Toxicity Part 1) I summarized the testimonials provided by Elizabeth Carmouche, Manex Bettan Arguinzoniz, Richard Cooknell, Markus Hamedinger, and Miriam Knight (who also spoke on behalf of Raymond Miller and Geoffrey Robinson), and in the second post about the EMA hearings (EMA Hearing on Fluoroquinolone Toxicity Part 2) I shared the written testimonies of Julie Le Normand, Elsa Leitão, Jarosław Linka, Andrea Noya, and Joshua Sutton. Again, in part 3, I will share the written testimonies submitted to the EMA by the people who testified. I encourage everyone to read the submissions in full, and to watch the video of the testimonies–they are moving and poignant:

Speaker 11. Miriam van Staveren, The Netherlands

Dear EMA,

I am a physician from the Netherlands. I am also badly affected by the side effects of levofloxacin.

In July 2014 I went for a holiday on the Canary Islands. I was prescribed a 6 day course of levofloxacin for an inner ear infection and a sinusitis. During the treatment I noticed my Achilles tendons started hurting. I thought it was due to the fact that I had exercised too much: I took tennis lessons, I hiked and swam a lot, played ping pong, engaged in water aerobics, and dancing.

Travelling home, I felt all right. But after a week, my Achilles tendons started to hurt again, so severely, that I suddenly could not walk anymore. After yet another week my ankles started hurting as well. Followed by my knees, my left shoulder and both my thumbs. During the next 6 months I also developed (amongst others): muscle cramps and trembling (fasciculation’s), neuropathy, joint pain and swelling, night sweats, severe itching, hair loss, intolerance against even the lightest exertion such as taking a shower, intolerance to light, profound insomnia and very painfull dry eyes.

I became depended on a wheelchair and crutches. I was in pain day to day. I recently even lost my license as a physician due to the fact that I could not work anymore.

An MRI showed knee cartilage damage and a large meniscus tear, with fluid in both knees. My Achilles tendons were thickened as if I had been a Marathon skater. I had visible skin damage to my ankles and lower legs. My orthopedic surgeon was reluctant to operate me. Which, as you know, is rather remarkable for a surgeon.

Yet my surgeon wanted to explore what was going on in my body before he dared to operate on my knees. This is why he referred me to a professor in an University hospital in Amsterdam. This to perform a medical evaluation by a team of specialists: a toxicologist, a geneticist and internist and so on.

Unfortunately, after this rather optimistic beginning of my medical condition being believed, I could not find one single doctor who was familiar with the symptoms of the delayed and long lasting side effects of the fluoroquinolone antibiotics. The above mentioned professor told me he couldn’t help me. Not even a clinical pharmacologist specialized in side effects of medication had heard of these severe and lasting side effects. I had to refer her to a professor from the university of California to convince her my symptoms were real and caused by levofloxacin.

In total I visited at least 7 specialist of 3 different top teaching hospitals in Amsterdam. None of them could help me, most could not believe my symptoms were due to taking levofloxacin. I remember once a GP asking me: “did you sprain your ankle?” This because my ankle was very swollen and painfull.

No matter how much peer reviewed literature I showed, my doctors could not believe my symptoms were caused by levofloxacin nor were they able to help me. Even if believed, there hasn’t been found a cure yet against the persistent and debilitating side effects of fluoroquinolones also called fluoroquinolone toxicity syndrome (FQT).

I have tried to warn various health care organizations in Holland involved in medication side effects. They all told me I was the first patient they ever met to have these persistent side effects. I tried to publish an article in a medical Dutch magazine. Sadly my article was refused because the editors deemed it not relevant for the Netherlands. As I agree, in the Netherlands antibiotics are prescribe quite reluctantly, however I got to know various other patients in my home country.

I performed a literature search and wrote a “Dear doctor” letter which I published online in august 2015. This letter was also sent to the FDA hearing about fluoroquinolones in November 5th 2015. My letter was meant for patients to show to their own doctors.

I learned there were many patients in various countries in the world desperately looking for knowledge, validation and help. They were gathered in Facebook groups. Some of those patients are also working in the medical field: medical doctors, nurses or pharmacists. They were all as astonished as I was that a few pills can cause such havoc. One medical doctor told me she thought the side effects of fluoroquinolones are much worse than the side effects of Chemo. On a certain moment she suffered so much she considered to go to a clinic in Switzerland to be euthanized.

Not being able to help other patients felt very frustrating for me. Up to this day I carry the stories of many of them with me in my heart. Some of those patients committed suicide in their despair. Almost all of them lost their previous active life and or jobs. I heard many of them were too ill to come to speak here today. Even too ill for a teleconference. I can understand this, as four years ago I would not have been able to be here myself, due to the side effects. I have been in contact with many patients. In Europe: Italy, Germany, Great Britain, Spain, Switzerland, Finland, the Netherlands, Sweden, Austria, Hungary and Belgium.

In the fall of 2017 I was approached by an author of Nature magazine. She was told I was a physician living in Europe who was knowledgeable about the side effects we are speaking about here today. She wrote an excellent article about the syndrome called fluoroquinolone associated disability (FQAD: name given by the FDA). Yet even after the article in Nature was published in the March 21th issue I was not able to get Dutch doctors interested. This detached attitude is no exception in the European medical field. I almost never heard of a patient being believed their symptoms are from taking the antibiotic this hearing is about.

This is why I am very grateful I was invited to speak at the EMA hearing. I know EMA is influential and I know you already put a lot of time in studying these side effects.

It is my strong belief that there is no safe use of fluoroquinolones. That is, until further in vivo human research can select those who will be harmed by taking them. It is very well possible that anyone can be affected, although some people are probably more vulnerable than others. Some patients are hit after having taken this antibiotics multiple times. Some are hit after just 2 pills. Obviously there is a personal threshold.

Further research should not only emphasize on safe use, – if at all possible -, but also on the exact mechanism of harm done. This to help those who are currently suffering from this complicated syndrome, which should get a diagnostic code. Firm upgraded warnings and full information about the debilitating side effects should be issued broadly in Europe as soon as possible. Possible mitochondrial toxicity should be included in the warnings.

Its use should be reserved for serious life threatening infections that do not respond to any other treatment. Any such infection should be cultured first. Patients should always be fully informed about the risk to become disabled after the use of a fluoroquinolone antibiotic.

Speaker 12. John Crowley, Luxembourg

My name is John Crowley, Im Irish but living in Luxembourg and the story Im about to tell you I would not have believed was possible if I had not experienced myself.

In 2009 I was in an accident which left me with a stricture of my urethra.

Over the next 9 years whenever I suffered from pain in penis my urologist put me on Ciprofloxacin as he told me it could be an infection and this would make my condition worse. He unfortunately never sent me for tests to verify if I had an infection.

In October 2014 (aged 38) while taking Ciprofloxacin I developed a sharp burning pain in my right Achilles tendon. The next day I felt the same in my left leg. At this point I was barely able to walk and went to the emergency room at my local hospital.

I was put on crutches and told this was a common side effect and would disappear in a few weeks.

Next up I developed pains in my arms and hands.

I went to an orthopaedic specialist and was diagnosed with Achilles tendonitis in both legs, golf and tennis elbow in both arms.

After months of physio I saw limited improvement and was sent for an MRI scan which confirmed the above diagnosis. 2 and a half years later the tendonitis is still visible via MRI.

Unfortunately the tendonitis remains and in the interim I also have developed tendonitis in both knees. I am no longer able to participate in sports and am in pain in my daily life constantly having to use ice to dull the pain. Even simple things like playing football with my children or bringing shopping bags into the house are no longer possible.

I work in an office and have had to change to a special ergonomic mouse as I can no longer use a standard mouse. I find it difficult but to date have been able to hold on the my job. If I was working in a manual profession such as a carpenter there is no doubt I would now be unemployed.

The next side effect I experienced was a pain in my arm which felt like an electric shock. This was followed by involuntary movement of my arm at night time which lasted for a period of several months and was very scary.

I went to see a Neurologist but by that time I got an appointment and took tests my symptoms had receded and my tests came back negative. The dr was unable to explain what might have happened.

Finally I have no evidence to link this to Ciprofloxacin but I have also developed the following over the past 3 years:

i. Chronic dry eyes (I need to put drops in my eyes throughout the day and a special cream at night) ii. Eyes not focussing correctly iii. Dry skin iv. Dry ears v. Damage to my hearing vi. Stomach and digestion issues leading to acid reflux for which Im now on PPI’s vii. Insomnia viii. Less control over my bladder which requires me to urinate 1-2 per night

There is no history of any of the above in my family and my dr’s are unable to explain the root cause. Perhaps just bad luck but I don’t believe a healthy man at my age who always ate and exercised well could have so much bad luck in such a short space of time.

I have no doubt quinolones are a useful tool and have their place in the dr armoury but I believe it is used too frequently without a proper understanding of the side effects.

While some dr’s have been very sympathetic to my plight the vast majority to be quite frank did not believe that it was possible that a quinolone could do this.

My recommendation would be for Dr’s to be formally made aware of the dangers by the regulatory body, to be issued with a very strong recommendation that this only be used where alternatives were not available and finally for much enhanced warnings on the packaging.

I read that this medication could cause tendonitis on the label – it didn’t say anywhere that this would last over 3 years (and at this point probably for the rest of my life). That’s just not right and needs to be addressed.

Answers to 3 PRAC questions:

I have no doubt quinolones are a useful tool and have their place in the dr armoury but I believe it is used too frequently without a proper understanding of how dangerous the side effects are One dr summed it up well when he said you dont use a bazooka to kill a mouse in your house. While you would no doubt get rid of the mouse the collateral damage would be too great and I believe a similar logic can be applied to quinilones.

While some dr’s have been very sympathetic to my plight the vast majority to be quite frank did not believe that it was possible that a quinolone could do this.

My recommendation would be for Dr’s to be formally made aware of the dangers by the regulatory body, to be issued with a very strong recommendation that this only be used where alternatives were not available (and if prescribed risks to be clearly explained to patients) and finally for much enhanced warnings on the packaging.

I read that this medication could cause tendonitis on the label – it didn’t say anywhere that this would last over 3 years (and at this point probably for the rest of my life). That’s just not right and the labelling needs to be addressed (for example in the US the packaging carries a black box warning).

Speaker 13. Enikő Pongrácz, Hungary

Dear PRAC,

I was prescribed in October, 2014, ciprofloxacin 500mg 1/day for UTI, and in March, 2015, Ciloxan ear drops for Otitis media. After 5 weeks in both cases extreme high blood pressure and debilitating headache appeared, which very hardly could get back in control.

And the rest came after each…Gained +30 kg in 3 month, hypovolemia, sudden hair greying in 3 weeks, my hair can not be dyed ever since- low cardiolipin, low autophagy. My ears and nose are clogged, dry- Sjorgen Syndrome, Tinnitus loud ever since, sensorineural hearing damage, Myoclonus Tympani-Stapedius-Eustachian tubes-Palate, sleep apnea and insomnia. Carotid damage, Lymph nodes inflamed to double. Eye floaters, foggy vision, dry eyes, uveitis, vision worsened, frequent morning cornea bleedings due to high blood pressure during sleep reaching 200/150 and very high pulse, supratentorial flairs = mini stroke, shrinking frontal lobe, constricted hypothalamus arteries =release hormones problems leading all hormone problems, cortisol, estrogen, ovarian cysts several times, uterus myoma, GERD, SIBO, hiatus hernia, gallbladder blocked, colon pain, diarrhea, colon/fecal incontinence, urinary incontinence, tendonitis-capsulitis, insulin resistance, EHS (electro hyper sensitivity, or microwave sickness is due to mitochondrial damage), detox blocked still, not sweating for 2 years. Mitral insufficiency, LBBB, peripheral neuropathy (one hand and one leg), changed blood count, shifts in over range and under range. Reactivated EBV and HHV ever since, became chronic. Frey syndrome, teeth dentin browned, can not be cleaned and about 12 cavities ever since and 1 extraction. Multiple chemical sensitivity- to foods, smells, dust mites and suffocation from detergents and cleaning products. Several ER visits due to high blood pressure and angina. Continuous brain fog, ears and head pressure.

Since than I am half deaf, half heart and half limbs functioning.

I can not work anymore, previously I was business consultant, traveling for business and for private as well, doing all kind of dog-sports.

My life after cipro poisoning in sum its a total wrack: health-wise, financially and socially as well. I am disabled, several unrecoverable damages, however in Hungary there is no BNO code for fluoroquinolone toxicity and neither for electro hyper sensitivity – moreover doctors and healthcare deny both. All other symptoms I have are not subject to disability one by one. Misdiagnosed in row.

Can eat only bio, GMO free, no processed foods and take only additives free supplements to avoid side effects and diarrhea, with the significant extra costs of these products.

Natural and phisio-therapy and American doctor consultations are also significant costs.

Due to Electro-Hyper-Sensitivity can not go anywhere public (workplace included) only in nature and if 5G will be installed soon, I will have to move to a farm, in total isolation.

One hour shopping, a doctor visit, MRI/CT/ultrasound or any administrative sorting (bank, municipally, etc) is reactivating any virus I ever had (from contamination or from vaccine) – latest was shingles which I struggle since mid April.

Due to electrosmog (wifi, cell towers) following are also forbidden: public transportation, motorways, hotels, vacation, restaurant, shopping, café, cinema, theater,…

Due to peripheral neuropathy I can fall, can not held properly, I mistype.

I get tired very quickly, I can not run at all, I am not able to held my dog even for walking, while previously had done defense activity with him. Housework is limited to max one hour with protection mask and googles.

I lost connection to my friends- since can not meet them anywhere in public as before.

I vegetate and hope only, that PRAC will ask fuoroquinolone producers to research and develop the way by which we can expel this poison from our body, to stop further continuous damage occurring and repair damaged mitochondria. According to a research, ciprofloxacin stays forever, moves with exosomes at cell apoptosis so damage continues for lifelong –

https://www.researchgate.net/publication/319129045_Antibioticinduced_release_of_small_extracellular_vesicles_exosomes_with_surface-associated_DNA

Another research shows MRSA decreasing while stopping FQ use in hospitals:

https://www.consumerreports.org/hospitals/surprising-remedy-deadly-hospital-infections/

Post PRACs review all doctors, veterinarians and pharmacists should be noticed, and a health insurance protocol should be developed in each country for treating FQT.

Mitochondrial diseases’ major cause are medications, patients are misdiagnosed and not too much is done for them in EU.

https://mitochondrialdiseasenews.com/2018/05/11/multiple-consultations-tests-and-misdiagnosismark-mitochondrial-disease-odyssey-surveyfinds/?utm_source=Mito+Disease&utm_campaign=ccfc61e1a8- RSS_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_fdcf314ce5-ccfc61e1a8-72144013

https://www.ncbi.nlm.nih.gov/pubmed/?term=Medicationinduced+mitochondrial+damage+and+disease

https://mitochondrialdiseasenews.com/2018/05/17/ecrd2018-eu-must-do-more-for-rare-diseasepatients-eurordis-leaders-say/?utm_source=Mito+Disease&utm_campaign=ccfc61e1a8- RSS_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_fdcf314ce5-ccfc61e1a8-72144013

All severe adverse reactions must be black-boxed. I am confident that no disabling, debilitating (unrecoverable damage causing) medications should be on the market, until a recovery method is not found. Fluroquinolones should be withdrawn from public use, kept under lockers for Antrax or similar severe cases only, as misdiagnoses is very frequent ending in catastrophic consequences.

In Hungary pre- and postoperatory always FQs are used. Since I’ve been affected, my mother was prescribed FQ in the ER, 2 days later by her doctor as well, and she had ‘only’ allergy, no conjunctivitis. My dog diagnosed with prostatitis was given FQ as first choice, which I denied, but soon turned out it was due to excess estrogen from chicken meat. These are ‘only’ 2 examples from my family, but could give many examples from my surroundings as well.

What do you think is compensating for all these suffering and ruined life?

Thanks a lot for this hearing opportunity ! 2018. June. 01.

Dear PRAC,

Please find below inserted my answers related to Fluoroquinolone and Quinolone EMA Public Hearing and please consider them. Within the scope of this review and based on your experience with quinolone and fluoroquinolone treatment:

1. What is your view on the role of quinolones and fluoroquinolones in the treatment of infections?

A chemotherapy drug should be the last choice given, not the first, therefore should be available only in hospital care. Should never ever be given as a pre or post -operatory medicine – now is the first choice. Should never-ever be given to kids or adults for simple otitis or conjunctivitis or any other usual disease – now its the first choice. Should be given only after a bactericidal test. Same valid for veterinary care as we do not want our pets dead, or do not want to eat FQ infested meat ( see the study with pray-birds dead in Spain, due to eating FQ infested animal corps).

2. What is your view of the risks associated with quinolone and fluoroquinolone use?

All side effects should be mentioned on the patient info label. Mitochondrial and DNA permanent grave damage and unknown elimination time should be mentioned as well, according to latest research available. ( in animal research after 520 days FQ was still present)

3. In your opinion, what further measures could be taken to optimize the safe use of quinolones and fluoroquinolones?

All countries should recognize and compensate the patients affected by FQ, FQAD should be recognized and compensated accordingly and all medical and pharmaceutical and veterinary staff should be retrained according to new restrictions ASAP in place. As a main unknown side effect, EHS/microwave sickness should be recognized as well by all countries.

Manufacturers must be made responsible to research remedies for counteracting the damages and finding ways for quick elimination from the cells.

Thanks for your consideration!

 

 

EMA Hearing on Fluoroquinolone Toxicity Part 2

In the first post about the EMA hearings (EMA Hearing on Fluoroquinolone Toxicity Part 1) I summarized the testimonials provided by Elizabeth Carmouche, Manex Bettan Arguinzoniz, Richard Cooknell, Markus Hamedinger, and Miriam Knight (who also spoke on behalf of Raymond Miller and Geoffrey Robinson). In Part 2, and all subsequent posts about the EMA hearings, rather than summarizing my take on the testimony given, I will quote people directly from the written submissions that they provided to the EMA. Please note that not everything said in the hearing is included in the written submissions, and significant valuable information and insight can be gleaned from listening to the hearing. You can view the entire hearing through the following video:

Speaker 6. Julie Le Normand, France

1. What is your view on the role of quinolones and fluoroquinolones in the treatment of infections?

2. What is your view of the risks associated with quinolone and fluoroquinolone use?

3. In your opinion, what further measures could be taken to optimise the safe use of quinolones and fluoroquinolones?

My name is Julie Le Normand, I’m 37, I’m a French citizen and I am not representing any organization.

Back in November 2017, I had a terrible experience with levofloxacin (TAVANIC 500 mg, to be exact, twice a day for 10 days). That was the first time I ever took fluoroquinolones in my life, and it will certainly be the last.

Quinolones and fluoroquinolones (hereinafter referred to as Q & FQ) are far too broadly prescribed for cases where much less intense medicine would more than suffice for an efficient treatment. Having spoken with numerous people from across the world suffering from their adverse effects, I have learned that Q & FQ have been prescribed for everything from non-complicated urinary tract infections and sinusitis all the way to… anthrax exposure and the plague. I, for example, was prescribed a course of Levofloxacin by my general practitioner for a case of bronchitis/sinusitis at the end of November 2017. I would like the committee to know that I was never warned about the possible severe, longlasting side-effects of this medication by the doctor, nor by any other medical staff. It only took me two days on Levofloxacin after which I had no choice but to stop the medication because of the sudden onset of its adverse effects.

The manufacturers’ notice of the risks associated with Q & FQ is listed merely as “rare.” My experience—and those numerous others who have suffered from them—can attest to the fact that the risks of use of Q & FQ are anything but rare, contrary to what all of us have been led to believe. Please allow me to kindly state to the Committee that I took merely 4 pills in total of levofloxacin over two days, 7 months ago. For some, the adverse effects affecting the musculoskeletal and/or nervous system occur weeks or even months afterwards, which makes it even more difficult to connect the delayed symptoms with a course of antibiotics taken several weeks/months before. For me, the onset was as immediate as it was intense. I started to feel an extreme weakness in my legs. It was so bad that I could neither stand up on my feet nor walk anymore. I cannot do justice to you in describing just how uncomfortable the sensations inside my legs were. It felt as if bugs were crawling on them. Both my ankles and my Achilles heels started to hurt and swell. I could hardly breathe. My blood pressure rose dramatically, and I was overcome with a feeling of confusion and agitation. The experience was so bad that afterwards, I was completely bedridden for more than 3 weeks and on sick leave from work for 6 weeks. I felt depressed. And 7 months out, I still feel weak emotionally. My face has aged suddenly though I’m 37. I did not used to be this way. I used to be a very healthy person. I loved hiking, skiing. I am still a mother to 2 children both under the age of 5. But now I am limited in my physical and emotional capacities, and this is extremely upsetting and unfair. I will say that there have been some concrete improvements since the episode, but a part of me still wonders whether I will ever be able to fully heal from this “toxicity syndrome.” I have seen several doctors, each of whom have been helpless with the various symptoms I experienced. Long-lasting symptoms simply after a few pills of levofloxacin.

Please allow me to state for the record that I’m convinced Q & FQ should be limited only to life or death situations as their adverse side-effects far exceed what they can otherwise treat! In fact, I fear there is no such thing as a “safe use” of Q & FQ as the side-effects seem to be very common, almost the norm. Please allow me to reiterate that in my view Q & FQ should ONLY be prescribed at the hospital in certain circumstances with very cautious care and a thorough monitoring of any possible side-effects. General practitioners should not be able to prescribe them anymore without identifying the bacteria to treat, and in any event, not as a secondary intention but rather as a last resort treatment.

If I may add a final remark, I believe that the topical Q/FQ (such as eyedrops, ear drops) should also be included in this safety review as they are known to cause adverse reactions as well, that can be as severe as those triggered by the oral or IV antibiotics.

I do hope that the outcome of this Public Hearing will lead to:

1. An acknowledgement of a so called FQ associated toxicity syndrome/disability within Europe. To my view, there is an urging need that the EMA acknowledges the existence of a so called FQ associated toxicity syndrome/disability (FQAD, like the US Food and Drug Administration did a couple of years ago).

2. If not a complete BAN of FQs, at least a STRONG restriction of their use within Europe This would be for sure a historic choice (much stronger that the current “black box warnings” used in USA) and would give Europe the leadership in FQ toxicity awareness.

Thank you for your time and consideration and for the opportunity to present my experience to the Committee.

Speaker 7. Elsa Leitão, Germany

My name is Elsa Leitao. I’m from Portugal and I’m currently living in Germany where I work as a scientist in the field of human epigenetics.

I’m 39 years-old and until three years ago I was fairly healthy. Then I was prescribed Ciprofloxacin to treat a regular urinary infection. I had no further warning from my physician about the special risks associated with this drug. After a few days I developed side effects: joint pain, muscle pain, difficulty in walking, lack of strength and general tiredness. It took me several months until I started feeling better but I never got back to my previous health state. I haven’t been able to run longer distances again due to the fragility I still feel in certain tendons. Even after three years, I have sporadic episodes of severe joint pain that I believe are related to the ingestion of certain types of food that I became unable to tolerate.

I think quinolones and fluoroquinolones should only be used in life threatening conditions such has extremely severe infections. These drugs should be avoided when other treatments are possible. I believe that patients prescribed with these antibiotics are in great risk of becoming sicker than before the treatment. Moreover, the side effects take much longer to subside than the initial illness would take to disappear with other treatment and may even become permanently debilitating.

There are a few measures I think should be taken to optimise the safe use of these drugs: 1) Physicians should be better instructed about the severe long lasting side effects the administration of these drugs might have; these instructions should be clearly passed to medical school teachers, medical students and working physicians, so all links in the chain can simultaneously acquire this knowledge. 2) Physicians should inform the patients about the potential toxicity, so the patients can be alert to the appearance of potentially alarming signs. 3) Packages should contain clear warning labels. 4) The products information should be changed with regard to the use of these drugs to the treatment of non-severe infections.

Although this public hearing is more focused in trying to improve the future use of these drugs, I think the past shouldn’t be forgotten nor the patients whose life was most severely and permanently affected. In this regard, efforts should also be taken in understanding how to treat these patients.

Speaker 8. Jarosław Linka, Poland

1) What is your view on the role of quinolones and fluoroquinolones in the treatment of infections?

Fluoroquinolone (FQs) antibiotics are currently one of the most frequently prescribed drugs in Europe and play a very important role in treatment for bacterial infections, such as pneumonia, sinusitis, bronchitis, urinary tract infections, as well as for prostatitis. However, FQs are extremely toxic, have high potentials for adverse effects (AE) and associated with potentially long-lasting, frequently permanent, serious sides effects. Adverse reactions (ADRs) are often delayed for some weeks or months after cessation of FQs drug therapy, which makes it extremely difficult to make a correct medical diagnosis and apply symptomatic treatment. They belong to the group of broad-spectrum antibiotics, effective for both gram-positive and gram-negative bacteria. FQs employ their antibacterial effect by preventing bacterial DNA from unwinding and duplicating through inhibition of their topoisomerase and gyrase, which differentiate them from other common antibacterial agents. This mechanism places them closer to chemotherapy drugs then other antibiotics, which mostly interfere with specific steps in homeostatic cell wall biosynthesis. As a result of this broad-spectrum and misunderstanding of their safety profile, doctors in Europe consider them as a safe treatment option and prescribe them even as an empirical first line antibiotics therapy. This is leading to an overuse of FQs, and in consequence tens of thousands of people suffer by them each year, yet nearly all those damages remain misdiagnose or undiagnosed. Patients after FQs ADRs frequently are diagnosed as having Lyme disease, multiple sclerosis, neuropathies of every kind, lupus, rheumatoid diseases and most often fibromyalgia. Only a handful of doctors are aware of a devastating effects of FQs. The rest are uninformed and often deny the existence of fluoroquinolone associated disability (FQAD).

2) What is your view of the risks associated with quinolone and fluoroquinolone use?

According to the latest research and available literature, FQs toxicity results from many causes, including the formation of reactive oxygen species, and generation of oxidative stress damage of the mitochondrial DNA, as well as from the chelation of metals and a change in gene expression. These mechanisms explain the reason why FQs are often reported, to cause permanent and serious sides effects to: tendon, muscles, joints, nerves and other organs. Other long-lasting problems involve the cardiovascular system (QT interval prolongation), musculoskeletal system disorders (arthropathy, muscle weakness, joint pain and swelling), chronic fatigue and diabetes mellitus. Moreover, FQs have recently been discovered to induce delayed adverse neuropsychiatric effects including dizziness, sleep disturbance, anxiety, suicidal thoughts, hallucinations, psychosis, depression and recurrent mania. All the side effects should be mentioned on the patient info label, especially including psychiatric and potential delayed mitochondrial toxicity (like mitochondrial DNA depletion and mutations.)

3) In your opinion, what further measures could be taken to optimise the safe use of quinolones and fluoroquinolones?

The overuse of FQs and the growing number of reports on ADRs often leading to the fluoroquinolone associated disability (FQAD) is the main reason to avoid FQs when other safer alternatives are available. FQs should only be used as the last resort, exclusively in a hospital, by a well trained specialist. Unfortunately routine blood and urine tests are generally non-contributory to diagnoses of FQ’s ADR or FQAD, so specific molecular and genetic tests should be provided as quickly as possible. Special studies are necessary to find genetic factors underling susceptibility and the genotypes predisposing to ADRs. Multicenter clinical trials on long-lasting FQAD in large groups of patients are also required. Immediately, the basic guidelines and standard treatment methods for ADR and FQAD should be developed. This can’t be left to desperate patients and only several aware doctors who try to help them, like it was in my case. After one year of visiting numerous clinics in Poland, Germany, China, and USA I have finally found doctors, who were willing to help me and are aware of the FQ toxicity syndrome. Based on published data analysis and subsequent empirical searching, an individualised treatment plan was developed, which significantly reduced or even reversed some of my damage caused by Levofloxacine. Although, after three years my quality of life is better, a lot of environmental factors can induce intermittent episodes of symptoms. I am still suffering from chronic fatigue, Achilles and other tendons tendinopathy, multilevel degenerative disc disease, peripheral and small fibre neuropathy, uncommon food sensitivities, muscle weakness and headaches. A Review of currently available knowledge of possible ways to treat of FQAD, inspired by my case, was published last year in the Oxidative Medicine and Cellular Longevity under the title: “Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochehemical Implications”

I hope that a PRAC meeting will set new restrictions for FQs and new procedures of their use only in hospitals, under long-term supervision and as a last resort treatment. Limited action from EMA such as just copying FDA’s warning from June 26, 2016 will probably keep the current status quo for their use and spreading of their devastating delayed side effects, what we can still observe with the growing number of cases of FQAD from the United States.

https://doi.org/10.1155/2017/8023935

Speaker 9. Andrea Noya, Italy

As someone who’s suffered and is still suffering serious side effects from a fluoroquinolone, prescribed to me more then a year ago, I’d like to share my experience, in the hope that more consciousness would be applied, when using these types of drugs and also in the hope of bringing these side effects to the attention of the many doctors, that still seem to ignore them.

Answering the questions:

1. I think quinolones and fluoroquinolones are powerful and effective drugs that should be only prescribed for serious or life threatening infections.

2. The risks, in my opinion, exceed the benefits. A patient shouldn’t suffer serious or disabling side effects from a drug prescribed to treat or even prevent a common infection.

3. In my opinion, more restricting laws should be applied to this class of drugs and it should be mandatory for doctors to be better informed and trained on the use of quinolones and fluoroquinolones.

(Please note that Andrea Noya goes into significantly more detail about his experience with fluoroquinolone toxicity in his testimony.)

Speaker 10. Joshua Sutton, UK

My name is Joshua Sutton and I am a business student at Sheffield Hallam University.

I would like to begin by saying that there is a place for Fluoroquinolones in modern medicine, and the use of them in a proper manner could be very effective. However, the current use of them is far too frivolous and exceptionally dangerous. These drugs have such strong capabilities of causing major damage, as two days after the treatment of Ciprofloxacin for an unconfirmed and nonurgent infection my neurological health greatly deteriorated. The impact that these drugs have had on my life is beyond belief.

My view on the risks of Fluoroquinolones is that they very often outweigh the benefits, especially for unconfirmed and non-urgent infections. I was prescribed Ciprofloxacin on the 5th June 2017 by my GP. It was the 17th June when I first realised something was wrong, where my vision became very slurry and I felt very disorientated. This was accompanied by a horrible brain fog sensation that has never gone away, extreme light sensitivity and then walls of black snakes down the walls which ended up being the development of eye floaters.

Starting on the next day, the 18th June, I developed a terrible tremor and loss of sensation in my hands and feet where I quickly lost the ability to do even the most basic of tasks; tying my shoe laces, holding a knife and fork or even dressing myself. I would have excruciating deep rooted pains and aches down my glutes and hamstrings down into my feet, and the same down my arms into my hands that would refine me to my bed. The tops of my hands and feet would also be extremely sore, where moving my toes or fingers or clenching a fist would be agony.

I have burning and tingling pains and sensations all over my peripherals and head and face, and my limbs would consistently go numb. I couldn’t hold my phone up to use it as my hands and arms would quickly go numb and I would awake every morning with both my arms hanging by my side completely dead. I would and still get burning sensations down my back and limbs that makes even the weight of a cotton t-shirt against my skin excruciating. In addition to this, I would also find it impossible to empty my bladder and would have to strain to do so even a little bit.

Onto the fatigue and weakness, I would be so weak to the point where I couldn’t turn over a chicken breast in a frying pan or pick my feet up as I was walking so I would simply trip up over my own feet regularly. I would find it impossible to complete daily tasks. I was very reliant on my Mum to look after me and care for me during this period and I have had to make some major lifestyle adjustments in result of all of this. I am still very fatigued to this day and have great difficulty concentrating on anything. My cognitive abilities have been greatly affected by all this.

Alongside this, I have also been seeing a Cognitive Behavioural Psychotherapist to help me handle the anxiety involved with these symptoms.

Moving on, my opinion on further measures to optimise the safety of Fluoroquinolones should be to discontinue the use of them for unconfirmed and non-urgent infections, only allow GP’s to use them as a last resort, perhaps if the patient has allergies or sensitivities to many other alternative antibiotics. Also, the use in hospitals should also be as a last resort, and any prescribing doctor should not only be fully aware of the adverse capabilities of Fluoroquinolones but also discuss any adverse reaction symptoms with the patient so they are well informed because if they begin to have adverse symptoms during their course and continue taking them they are going to be very unwell for a very long time.

Fundamentally, this is all an iatrogenic catastrophe and there needs to be immediate regulation to mitigate these risks involved.

Ciprofloxacin took away my health, my fitness and my sanity, and for that, its unforgivable.

*****

Dominick Cruz’s Cipro-Induced Tendon Rupture

Dominick Cruz, two-time UFC Bantamweight Champion, was floxed by Cipro. He describes his experience in episode #921 of Joe Rogan’s podcast, The Joe Rogan Experience.

Starting around minute 53 in the video above (and 1:02 in the downloaded podcast), Dominick Cruz states:

I did research later, I’m now basically a doctor to figure all this stuff out because of all the injuries I’ve been through. But 3 weeks before I fought Mizugaki I had a staph infection on my right thumb that popped up. So I took an antibiotic called Cipro. Now, me trusting the doctors and me not – it’s my own fault, not the doctors fault – I should have read the hazards of the antibiotic. But you kind of trust the doctors and assume, why would he give me something bad, right? Well, Cipro has an after-effect for six months after you ingest it that it weakens your tendons, so it makes them soft like real putty. And so I took it three weeks before the fight – that made it about 2 months after I ingested the Cipro – I was throwing a left high kick – I’d never had a problem with my right knee ever in my entire life, and it just popped throwing a high kick. I pivot on my right leg, throwing my left leg high, and it just popped and I knew right away, obviously, ’cause I’ve done it twice, that I’d blown it out. I remember literally, blowing it out, sitting on the floor, and the guy that I was drilling with was like, “What’s up?” and I was like, “I just blew my knee out.” He’s like, “What? Nothing happened!” It was crazy. It was a weird feeling. What was even weirder was the peace I had sitting there – not even caring. I literally was just – I remember blowing it out and sitting on the ring like, I told Eric, “Come here – You ready for another 9-month ACL reconstructive surgery?” and he’s like, “What? What are you talking about? Your knee’s fine.” I’m like, “No, I blew it out just now.” He’s like, “no you didn’t.” I said, “yes, I did.” And, that was it. So, I start again. I started the rehab again.

The good news for Dominick Cruz, and the hopeful take-away for all of us who have been hurt by fluoroquinolone antibiotics, is that after he went through surgery to reconstruct his blown-out ACL, and after 9 months of rest along with physical therapy, he returned to fighting and won the UFC Bantamweight Championship in January, 2016. Being able to fight in the UFC after experiencing a Cipro-induced tendon injury is huge, and we should all be inspired by Dominick Cruz’s comeback.

I have never talked to Dominick Cruz, nor have I heard anything about his story other than what he shared in episode 921 of The Joe Rogan Experience, so, what follows involves some conjecture. With that disclaimer noted, here are some thoughts about Dominick Cruz’s experience.

Why did Dominic Cruz’s doctor give a professional UFC fighter, an elite athlete, a fluoroquinolone prescription???? What is wrong with his doctor? Is his doctor not aware that tendon ruptures are a well-documented effect of fluoroquinolone antibiotics? He or she should be. It’s on the black box warning label for Cipro, and all other fluoroquinolones. The first sentence of the black-box warning for Cipro, in 2016, stated, “Fluoroquinolones, including CIPRO®, are associated with an increased risk of tendinitis and tendon rupture in all ages.” Did Dominick Cruz’s doctor think that healthy and strong tendons weren’t necessary for Dominick Cruz to do his job as a UFC fighter? Did Dominick Cruz’s doctor think that it was okay for him to experience tendinitis and tendon ruptures? Maybe Dominick Cruz’s doctor is under the impression that UFC fighters don’t need healthy, strong, flexible, and durable tendons. It absolutely blows my mind that an ignorant fool of a doctor could give a UFC fighter, an elite athlete, and a man with a history of tendon injuries, a drug that has the documented effect of destroying tendons. It is unacceptable for a doctor to prescribe Cipro, a drug that has been shown to cause disabling tendon injuries in thousands of people, and which permanently alter the structure of rat tendons and causes permanent lameness in beagle puppies, as well as permanent disability in humans, to a man whose entire livelihood depends on his ability to use his tendons. That doctor is a dangerous ignoramus, and he should be fired then sued for every penny he’s got.

Every doctor who works with athletes, especially professional athletes, should read the article “Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the
Athletic Population” where the first guideline for use  of fluoroquinolones in the athletic population is: “Athletes should avoid all use of fluoroquinolone antibiotics unless no alternative is available.” DON’T PRESCRIBE ATHLETES FLUOROQUINOLONES. It’s not that hard. In Dominick Cruz’s case, he was prescribed Cipro for a staph infection. There are a dozen other antibiotics that treat staph infections, and, according to this list, fluoroquinolones aren’t even the recommended treatment for staph infections. So why was Dominick Cruz given an antibiotic that has the effect of permanently weakening tendons and causing tendon ruptures? What an ignorant, foolish, awful doctor.

Even if the doctor who prescribed Cipro to Cruz wasn’t aware of the recommendations in “Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the
Athletic Population,” he or she should have at least been aware of the black-box warning on Cipro which states, in the first sentence, “Fluoroquinolones, including CIPRO®, are associated with an increased risk of tendinitis and tendon rupture in all ages.” It’s inexcusable for a doctor not to know about the black-box warnings on the drugs that they prescribe. And, assuming that he isn’t ignorant of the black-box warning, why is he prescribing a tendon-destroying drug to an athlete like Dominick Cruz??

In the podcast, it sounds like Dominick Cruz isn’t angry with the doctor who prescribed Cipro. He states, “it’s my own fault, not the doctors fault – I should have read the hazards of the antibiotic.” He’s obviously more generous than I am. Though generosity, even generosity toward those who hurt you, is a virtue, I don’t think he’s right. According to the Learned Intermediary Doctrine, pharmaceutical manufacturers have no obligation to inform the consumer/patient about the dangers of drugs. Dominick Cruz, as the consumer/patient, wasn’t even supposed to be told about the dangers of Cipro. However, his doctor, the “learned intermediary,” WAS supposed to know about the dangers of Cipro. His doctor should have known that it isn’t appropriate to prescribe a tendon-destroying drug to a UFC athlete, and he should have known that there are safer alternative antibiotics that treat staph infections. His doctor should have known better, and his doctor should be held responsible for making such a terrible prescribing decision.

As much as I respect how Dominick Cruz has come to terms with his injuries and found peace and surrender that helped him to recover (described throughout the video/podcast), fighting is what he does for a living, and I’m a little disappointed to hear that he’s not interested in fighting the system that poisoned him and destroyed his tendons. It is not his fault that his tendons were weakened by Cipro (and maybe other fluoroquinolones). It is the fault of the pharmaceutical companies that produce these dangerous drugs and the doctors that prescribe them inappropriately and flippantly. He shouldn’t have been prescribed Cipro for various reasons (staph should be treated with other antibiotics, he has a history of tendon injuries, and he’s an athlete) and the people who endangered him by giving him these drugs should be held accountable. Dominick Cruz probably has the clout to actually fight the people who poisoned him (unlike most of us, who struggle to gain justice for various reasons), and I hope that he does.

The tendon rupture that Dominick Cruz attributed to Cipro was his third tendon rupture, and earlier in the podcast you can listen to him describe his other tendon injuries (both of which he attributes to getting hurt while fighting, not weakened tendons from Cipro or any other fluoroquinolone). I wonder if he had taken Cipro, Levaquin, Avelox, Floxin, or one of the generic fluoroquinolones prior to his other tendon injuries. He thinks that the effects of fluoroquinolones on tendons only last six months, but, unfortunately, he’s wrong. Fluoroquinolone antibiotics can permanently alter the structure and strength of tendons. If he had taken a fluoroquinolone prior to his other tendon injuries, maybe they’re due to the drugs too, and he just hasn’t connected those injuries to the antibiotics. (Or, it’s entirely possible that those injuries were from fighting and training as he asserts.) A young, fit, well-conditioned, athlete like Cruz shouldn’t have weak, easily injured, tendons though. For his tendons to be so prone to injury, something is going on – maybe his tendons were weakened and changed by Cipro, Levaquin, Avelox, Floxin, or generic fluoroquinolones.

Since Dominick Cruz won back, and defended, his Bantamweight Champion title, it’s tempting to assert that he has fully recovered from his tendon injuries. However, if you listen to the whole podcast/video, Cruz goes on to describe how he now has debilitating plantar fasciitis. His tendons are messed up. His fascia is messed up. I certainly hope that he recovers from the plantar fasciitis, and I hope that he never has another tendon injury again. But I’m betting that he’ll battle tendon and fascia injuries for a while, and that the musculoskeletal destruction caused by fluoroquinolones will end his UFC fighting career. I hope I’m wrong about that.

Another thing that Dominick Cruz mentions in the podcast/video is that the UFC is in constant contact with injured fighters’ doctors. Why is the UFC allowing their fighters to be prescribed fluoroquinolone antibiotics???? Seriously, these drugs are dangerous, they can cause permanent disability, and there is a black box warning on them that notes that they can increase the risk of tendinitis and tendon ruptures. What is the UFC thinking allowing their fighters, the people who make them money, to be prescribed drugs that can injure, disable, and even kill them? There are hundreds of articles about the dangers of fluoroquinolones RIGHT HERE. They’re not difficult to access. It’s not difficult to see that fluoroquinolones are more dangerous than other antibiotics, especially to athletes who need to have properly-functioning tendons in order to do their job. Yet, the UFC is standing by, watching, while doctors prescribe tendon-destroying drugs to UFC stars–making them miss fights and costing both the athletes and the UFC massive amounts of money. It’s absurd. The UFC has the clout to stop this, and to tell their athletes, and the doctors that work with them, that fluoroquinolones shouldn’t be used on UFC athletes unless there are no viable alternatives. The adverse effects of fluoroquinolones are too severe, and the risk of injury after taking fluoroquinolones is too high, for UFC athletes to be taking these dangerous drugs.

I’m willing to bet that infections are rampant within the UFC, and that there are a lot of “floxed” UFC athletes. Open wounds occur often, mats and other equipment may be cleaned as well as possible, but they’re probably still swimming with nasty bacteria. It’s an environment with a lot of person-to-person contact, sweat, blood, and, inevitably, infections. If Dominick Cruz’s doctor threw Cipro at him to treat a staph infection, I bet the UFC doctors generally throw fluoroquinolones (Cipro, Levaquin, Avelox, Floxin, and their generic equivalents) at the UFC fighters whenever they get an infection. Fluoroquinolones are powerful, broad-spectrum, antibiotics. They’ll kill the bacteria. They’ll also ruin the tendons of the athlete, and cause disability in those who are unlucky.

Strong, athletic, young, capable, people can get hurt by fluoroquinolones. People like Dominick Cruz, who are at the peak of their fitness and athletic career, can experience weakened tendons, tanked testosterone, and worse, after taking fluoroquinolones. If the UFC thinks that their fighters are too strong to get hurt by these dangerous chemotherapeutic concoctions that destroy mitochondrial DNA, well, they’re wrong–and the athletes/fighters who are taking these drugs are being victimized by the willful ignorance of the doctors who prescribe these dangerous drugs.

I hope that all athletic organizations, coaches, sponsors, and athletes get together and put pressure on doctors to stop prescribing fluoroquinolone antibiotics to athletes. The dangerous and disabling effects of fluoroquinolones are well-documented, and there is no reason to prescribe them to athletes when there are other viable alternative antibiotics. Ruining an athlete’s career with a dangerous drug, when there are safer alternatives, is unacceptable. I hope that more people will wake up to the dangers of fluoroquinolones, and that fewer people generally, and specifically fewer athletes, are hurt by these drugs in the future.

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New Fluoroquinolones in the Pipeline

The most commonly prescribed fluoroquinolones are Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, and Floxin/ofloxacin. Almost every “floxie” that has been poisoned by fluoroquinolones in the last 15 years has taken Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, or Floxin/ofloxacin. However, there are many other quinolones and fluoroquinolones that have been developed. Here is a list:

First-generation:

Second-generation:

  • ciprofloxacin (Cipro) -Still on the market. Millions of prescriptions dispensed annually worldwide. 
  • enoxacin (Enroxil, Penetrex) – withdrawn from the market
  • fleroxacin (Megalone, Roquinol) – withdrawn from the market
  • lomefloxacin (Maxaquin)  – withdrawn from the market
  • nadifloxacin (Acuatim, Nadoxin, Nadixa)  – withdrawn from the market
  • norfloxacin (Lexinor, Noroxin, Quinabic, Janacin)  – withdrawn from the market
  • ofloxacin (Floxin, Oxaldin, Tarivid) – Still on the market. Millions of prescriptions dispensed annually worldwide. 
  • pefloxacin (Peflacine) – withdrawn from the market
  • rufloxacin (Uroflox) – withdrawn from the market

Third-generation:

  • balofloxacin (Baloxin) – withdrawn from the market
  • grepafloxacin (Raxar) – withdrawn from the market
  • levofloxacin (Leflox, Cravit, Levaquin, Tavanic) – Still on the market. Millions of prescriptions dispensed annually worldwide. 
  • pazufloxacin (Pasil, Pazucross) – withdrawn from the market
  • sparfloxacin (Zagam) – withdrawn from the market
  • temafloxacin (Omniflox) – withdrawn from the market
  • tosufloxacin (Ozex, Tosacin) – withdrawn from the market

Fourth-generation:

  • clinafloxacin – Not withdrawn from market, but not commonly available
  • gatifloxacin (Zigat, Tequin) – Tequin removed from the U.S. market, but other forms remain available.
  • gemifloxacin (Factive) – Currently available. More commonly prescribed outside of the U.S.
  • moxifloxacin (Acflox Woodward, Avelox,Vigamox) – Still on the market. Millions of prescriptions dispensed annually worldwide. 
  • sitafloxacin (Gracevit) – withdrawn from the market
  • trovafloxacin (Trovan) – withdrawn from the market
  • prulifloxacin (Quisnon) – withdrawn from the market

Despite the fact that 22 of the 29 quinolones listed above have been removed from the market, and the fact that there is an updated black box warning label (the most serious warning possible on a pharmaceutical), that notes that the fluoroquinolones remaining on the market can cause permanent disability, several pharmaceutical companies are busily developing new fluoroquinolones.

Some of the fluoroquinolones in development include:

  • Delafloxacin (Baxdela) – Delafloxacin/Baxdela is being developed by Melinta Therapeutics, and is currently undergoing Phase III trials. It is supposed to be more effective at treating MRSA and other bacterial infections that are currently resistant to other fluoroquinolones. Melinta says that delafloxacin/Baxdela has a “favorable safety profile,” but, frankly, I don’t believe them. Bayer says that Cipro has an excellent safety profile, but thousands of people have been injured, disabled, and killed by it. Delafloxacin/Baxdela will be effective against gram-positive, gram-negative, atypical and anaerobic bacteria–meaning that it will be a broad-spectrum antibiotic that will kill all microorganisms in its path. I understand that MRSA is a serious, and potentially deadly infection, and that it may be appropriate to use an extra-powerful fluoroquinolone in cases of life-or-death. However, as an extra-strong fluoroquinolone, with an increased scope of bacteria that it kills, it will be a dangerous, and deadly for some, drug. I hope that delafloxacin/Baxdela will be reserved for treating life-threatening MRSA infections, and that it will not be prescribed for treatment of simpler or less dangerous infections.
  • JNJ-2Q – JNJ-2Q is being developed by Furiex Pharmaceuticals, who have licensed JNJ-Q2 from Janssen Pharmaceuticals, a unit of Johnson & Johnson. Like delafloxacin/Baxdela, JNJ-2Q is being developed for the treatment of MRSA, and it is also a particularly strong and potent fluoroquinolone. Again, I hope that it is only used for deadly MRSA infections.
  • Nemonoxacin (Taigexyn) – Nemonoxacin/Taigexyn, developed by TaiGen Biotechnology Company, is currently undergoing phase III trials in the U.S. However, it has already reached the market in Taiwan, Russia, Commonwealth Independent States, Turkey, mainland China, and Latin America. It is also more effective against MRSA than the fluoroquinolones that are currently on the market, and it is more potent than ciprofloxacin, levofloxacin, and moxifloxacin. Not-so-fun-fact – Nemonoxacin has been fast-tracked for approval by the FDA.
  • Zabofloxacin – Zabofloxacin was discovered by Dong Wha Pharmaceuticals and licensed to Pacific Beach BioSciences for development. It is currently undergoing clinical trials. “The spectrum of activity of zabofloxacin includes bacterial strains that are responsible for most community-acquired respiratory infections. Phase III clinical studies are currently ongoing at Dong-Wha for the treatment of patients with acute bacterial exacerbation of chronic obstructive pulmonary disease.” (source)

Be aware that these new fluoroquinolones are in the pipeline. Know their names so that you can avoid them.

I’m not sure how anyone else’s medical record works, but when I asked my doctor to put that I am allergic to fluoroquinolones on my medical record, her computer system wouldn’t allow her to do so. Instead, I had to list all of the fluoroquinolones that I wanted to avoid individually. I suggest that you tell your doctors not only that you can’t have fluoroquinolones, but that you can’t have Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, and Floxin/ofloxacin specifically. And, when they reach the market, I suggest that you add Baxdela/delafloxacin, JNN-2Q, Taigexyn/nemonoxacin, and zabofloxacin to your list of drugs that you cannot tolerate.

I find the dissonance between the people who review drug safety, and the people that approve new drugs, both of whom are within the FDA, to be a bit mind-boggling. How could the Antimicrobial Drugs Advisory Committee decide that the current warnings on fluoroquinolones are inadequate and that they shouldn’t be prescribed for sinus infections, colitis or UTIs, or chronic bronchitis because they are too dangerous, while another part of the FDA fast-tracks the approval of Taigexyn/nemonoxacin, an even more powerful fluoroquinolone antibiotic? Do they not speak to each other? I can’t fathom that there is not at least some overlap between the Antimicrobial Drugs Advisory Committee and the people who approve new antimicrobial drugs. Are there people at the FDA who are screaming about these new fluoroquinolones that are about to enter the market, and noting that they are horribly unsafe? Or, did the Antimicrobial Drugs Advisory Committee just update the warning labels on existing fluoroquinolones to shut up patient advocates (you and me)? Is there massive cognitive dissonance at the FDA? Because it certainly appears that there is. The people at the FDA, and the Antimicrobial Drugs Advisory Committee specifically, pretend to acknowledge the dangers of fluoroquinolones, and pretend to do something about those dangers, while still thinking that it’s appropriate to approve new, stronger fluoroquinolones for public use. It’s mind-boggling.

There is constant repetition of some mantra along the lines of “fluoroquinolones have an excellent record of safety and efficacy” among drug-makers, drug-regulators, and drug prescribers – despite a massive amount of evidence to the contrary. The list of quinolones/fluoroquinolones above clearly shows that 22 of the 29 drugs have been removed from the market–many because of serious safety concerns. Yet, new, more powerful, fluoroquinolones are entering the market, in part because, for some odd reason, Cipro and Levaquin are seen as “safe.” They’re not safe though. They cause permanent disability and death. The upcoming fluoroquinolones will be worse.

I hope that the new fluoroquinolones that are coming to market are only used to treat life-threatening MRSA infections, but I have no faith that that will be the case. These new fluoroquinolones will be marketed as being bigger/better/faster/more powerful than safer alternatives, doctors will prescribe them, and patients will suffer because of them. Hopefully I’m being too pessimistic, and some prudence will be shown in the prescribing of these dangerous drugs–I doubt that though.

Just be aware of the dangers of fluoroquinolones–both old and new, and protect yourself and your loved ones. Share information about the dangers of fluoroquinolones with your friends and family, and let them know that fluoroquinolones should never be used unless there are no viable alternatives, and the infection is life-threatening. These new fluoroquinolones are more powerful, and more dangerous, than the fluoroquinolones that are currently on the market, and the ones that are on the market are pretty horrible. They should all be avoided like the plague.

 

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Children are Being Hurt By Fluoroquinolone Antibiotics

It breaks my heart when I hear about children getting “floxed.” It’s bad enough that fluoroquinolones inflict pain, tendon tears and ruptures, dysglycemia, insomnia, psychiatric problems, autonomic nervous system disturbances, hormonal issues, and more, on adults–it’s horrifying when those things happen to children. Our children, our babies, our innocent and precious kids, are getting hurt by fluoroquinolones too. We try to protect our children–it’s our job to protect them. We trust that when we go to the pediatrician, he or she won’t poison our babies, but, tragically, sometimes pediatricians do, indeed, poison children with fluoroquinolones. Sometimes they prescribe Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, and Floxin/ofloxacin to children, and sometimes those children suffer devastating consequences from taking those drugs.

It is so incredibly wrong to give children drugs that can cause permanent pain and disability that I’m furious that it happens at all. I’m also furious that there aren’t any consequences for the various parties that allow fluoroquinolones to be prescribed to children. In case it needs to be said, hurting children, and chemically causing pain and disability for young boys and girls, is wrong.

It is well-documented that fluoroquinolones cause permanent lameness in juvenile animals and that they are contraindicated for the pediatric population. A review in U.S. Pharmacist notes that:

“Fluoroquinolones have demonstrated adverse effects on cartilage development in juvenile animals through the inflammation and destruction of weight-bearing joints.  These arthropathies were often irreversible, and their potential occurrence in children limited the use of fluoroquinolones in this population.  In one pediatric study, ciprofloxacin had a 3.3% (9.3% vs. 6.0%) absolute risk increase in musculoskeletal events within 6 weeks of treatment compared with control agents used to treat complicated UTIs or pyelonephritis. Adefurin and colleagues found a 57% increased relative risk of arthropathy in children given ciprofloxacin (21% overall) versus those in a non-fluoroquinolone comparator arm. In contrast to animal models, neither dose nor duration had an effect on the rate or severity of arthropathy.  A 2007 study by Noel and colleagues determined the incidence of musculoskeletal events (primarily arthralgias) to be greater in children treated with levofloxacin compared with nonfluoroquinolone-treated children at 2 months (2.1% vs. 0.9%; P = .04) and 12 months (3.4% vs. 1.8%; P = .03).  These results and the severity of the effects should be weighed heavily when initiation of fluoroquinolones is being contemplated in pediatric patients.”

To summarize, fluoroquinolones can cause irreversible musculoskeletal harm and in doing so, they can put an end to a child’s days of running, jumping, playing soccer, skiing, dancing, etc. Think about that for a second–a drug, an antibiotic no less, can cause permanent damage to the musculoskeletal system of a child. Fluoroquinolones also have serious CNS effects, and can cause psychiatric disturbances as well as loss of memory and concentration. Children, with their developing bodies and minds, should not be subjected to dangerous, disabling drugs that can set back their development and their lives.

Given the documented adverse effects of fluoroquinolones on children, and the black box warning that notes that they can cause disability, the following examples of children being hurt by fluoroquinolones are both infuriating and heartbreaking. Still, I think they should be shared, so as to warn other parents of the dangers of these drugs, and hopefully fewer children will get floxed in the future.

I have paraphrased the stories that I’ve heard, but all of these are true:

  1. A 16 year old boy has Cipro 17 times over the last 7 years. He has various health issues, including a problem with the bones in his feet. The pain in his feet is so bad that he has had to stop school and homeschool on the computer.
  2. A 9 year old took fluoroquinolone ear drops twice as a toddler and suffers with chronic foot and knee pain.
  3. A young woman was floxed 4 1/2 years ago at 16 years old. After about 2 years, she got better, eventually reaching about 90-95% better, only to have a relapse for no apparent reason about a year later (which is where we are now)! She has had MANY devastating side effects, and still cannot work. When she got her first job is when the relapse took place.
  4. A 15 year old girl passed away 6 days after her 10 day Levaquin script.
  5. An 8 year old girl had to quit all sports swimming and gymnastics. She is now going to school but no P.E., and no Dr. Wants to take responsibility for how to help with her pain. It’s been only 2 weeks since taking 3 days worth and then being hospitalized because of the effects.
  6. A 10 year old girl who cannot stand or walk, and no doctors believe her. 
  7. A 16 year old girl took 2 pills of 500 mg of cipro and now has nerve twitching, leg pain, anxiety, and a whole bunch of other symptoms. 

These are kids! They are children and adolescents who are being hurt by fluoroquinolones. They are suffering and there is nothing that doctors can do to relieve their pain. It’s beyond heartbreaking–it’s infuriating–and it needs to stop. The FDA needs to put enforceable restrictions on pediatric fluoroquinolone use. The doctors who prescribe fluoroquinolones to children need to be held accountable when they hurt children with fluoroquinolones (either through Medical Board punishment, or lawsuits). The pharmaceutical companies that make these dangerous drugs need to be punished and they need to compensate their victims. Researchers need to be looking into a cure for fluoroquinolone toxicity. All parties involved need to help these kids to recover, because there really isn’t anything okay about hurting a child.

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Publicizing Fluoroquinolone Warnings

I have such mixed feelings about the FDA’s response to the November, 2015 Antimicrobial Drugs Advisory Committee meeting regarding fluoroquinolone safety. On one hand, I feel like they really did hear those who testified, and they not only listened, they responded in a way that showed that they listened. The FDA did what the Antimicrobial Drugs Advisory Committee recommended they do: they updated fluoroquinolone warnings to note that, “the serious side effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options.” They not only updated the warning labels, they updated the black-box warnings–the most severe warning a drug can have. I am truly grateful for the steps forward in acknowledging fluoroquinolone adverse-reactions, and I’m hopeful that the updated warning labels will lead physicians and patients to realize that fluoroquinolones are dangerous drugs with potentially devastating consequences.

I wonder though, what good is an updated warning label? In the post, Who Reads the Drug Warning Labels? I go over the problem of people not knowing what is on the warning labels. Are physicians going to read the updated warning labels? Are patients? Is anyone other than the “floxie” community going to realize that the warning labels have been changed?

I appreciate the action taken by the FDA–I really do–but are updated warning labels actually going to change anything? Will fewer people get injured and killed by fluoroquinolones? I certainly hope that a significant portion of doctors hear about the warning label changes, and stop prescribing fluoroquinolones, but, unfortunately, the FDA isn’t taking any major steps to make this happen.

The FDA has no plans to inform individual doctors about the recent warning label changes made to fluoroquinolone warning labels. Even though the black-box warnings, again–the most severe warning label a drug can receive, have been updated to note that fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions, the FDA is not going to tell doctors about the changes. No “dear doctor” letter will be issued by the FDA. They will not do a massive publicity campaign to let physicians or patients know that the warning labels have been updated. They know about the dangers of fluoroquinolones, and, in their own way, they acknowledge them, but they’re not proactively communicating what they know to patients or physicians.

Since the FDA isn’t going to issue a “dear doctor” letter, it will likely be helpful if we (the people in the fluoroquinolone toxicity community, and those who care about drug safety) give the information the FDA has released to our doctors, local hospitals, and media.

I encourage everyone reading this to please, please, please send this information (that is directly from the FDA) to your doctors, the media, your friends, your loved ones, and anyone else who you think may benefit from the information. People need to know how dangerous Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, and Factive/gemifloxacin are. In order for them to know how dangerous these drugs are, we need to tell them.

Please forward these FDA releases to those who need this information:

  1. 5/12/16 – Fluoroquinolone Antibacterial Drugs: Drug Safety Communication – FDA Advises Restricting Use for Certain Uncomplicated Infections
  2. 7/26/16 – FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects
  3. July, 2016 Drug Safety Labeling Changes

Since most people don’t actually click on links, I’m also going to copy and paste what the FDA notices said (feel free to share this post with anyone who needs the information too).

Fluoroquinolone Antibacterial Drugs: Drug Safety Communication – FDA Advises Restricting Use for Certain Uncomplicated Infections:

AUDIENCE: Internal Medicine, Family Practice, Pharmacy, Patient

ISSUE: FDA is advising that the serious side effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options. For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options.

An FDA safety review has shown that fluoroquinolones when used systemically (i.e. tablets, capsules, and injectable) are associated with disabling and potentially permanent serious side effects that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system.

As a result, FDA is requiring the drug labels and Medication Guides for all fluoroquinolone antibacterial drugs to be updated to reflect this new safety information. FDA is continuing to investigate safety issues with fluoroquinolones and will update the public with additional information if it becomes available.

See the FDA Drug Safety Communication for a list of currently available FDA approved fluoroquinolones for systemic use.

BACKGROUND: The safety issues described in the Drug Safety Communication were also discussed at an FDA Advisory Committee meeting in November 2015.

RECOMMENDATION: Patients should contact your health care professional immediately if you experience any serious side effects while taking your fluoroquinolone medicine. Some signs and symptoms of serious side effects include tendon, joint and muscle pain, a “pins and needles” tingling or pricking sensation, confusion, and hallucinations. Patients should talk with your health care professional if you have any questions or concerns.

Health care professionals should stop systemic fluoroquinolone treatment immediately if a patient reports serious side effects, and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • Complete and submit the report Online: www.fda.gov/MedWatch/report

  • Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects:

SAFETY ANNOUNCEMENT

The U.S. Food and Drug Administration (FDA) approved changes to the labels of fluoroquinolone antibacterial drugs for systemic use (i.e., taken by mouth or by injection). These medicines are associated with disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system that can occur together in the same patient. As a result, we revised the Boxed Warning, FDA’s strongest warning, to address these serious safety issues. We also added a new warning and updated other parts of the drug label, including the patient Medication Guide.

We have determined that fluoroquinolones should be reserved for use in patients who have no other treatment options for acute bacterial sinusitis, (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI) because the risk of these serious side effects generally outweighs the benefits in these patients. For some serious bacterial infections the benefits of fluoroquinolones outweigh the risks, and it is appropriate for them to remain available as a therapeutic option.

Patients must contact your health care professional immediately if you experience any serious side effects while taking your fluoroquinolone medicine. Some signs and symptoms of serious side effects include unusual joint or tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness in the arms or legs, confusion, and hallucinations. Talk with your health care professional if you have any questions or concerns (see List of Serious Side Effects from Fluoroquinolones).

Health care professionals should not prescribe systemic fluoroquinolones to patients who have other treatment options for acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI) because the risks outweigh the benefits in these patients. Stop fluoroquinolone treatment immediately if a patient reports serious side effects, and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course (see List of Currently Available FDA-approved Fluoroquinolones for Systemic Use).

Fluoroquinolones are antibiotic medicines that work by killing or stopping the growth of bacteria that can cause illness. They are FDA-approved to prevent or treat certain serious bacterial infections.

The labels of fluoroquinolone medicines already have a Boxed Warning for tendinitis, tendon rupture, and worsening of myasthenia gravis. The labels also include warnings about the risks of peripheral neuropathy and central nervous system effects. Other serious risks associated with fluoroquinolones are described in the labels, such as cardiac, dermatologic, and hypersensitivity reactions. After FDA’s 2013 review that led to the additional warning that peripheral neuropathy may be irreversible, FDA evaluated post-marketing reports* of apparently healthy patients who experienced disabling and potentially permanent side effects involving two or more body systems after being treated with a systemic fluoroquinolone (see Data Summary). We evaluated only reports submitted to FDA, so there are likely additional cases of which we are unaware. The side effects occurred within hours to weeks after starting the fluoroquinolone, and at the time we received the reports, the side effects had continued for an average of 14 months to as long as 9 years after stopping the medicines. Several cases reported that some side effects stopped or improved after discontinuation of the medicine; others reported the side effects worsened or continued.

We previously communicated about these safety issues associated with fluoroquinolones in May 2016. Additional communications about related safety issues associated with fluoroquinolones occurred in August 2013 (peripheral neuropathy) and July 2008 (tendinitis and tendon rupture). The safety issues described in this Drug Safety Communication were also discussed at an FDA Advisory Committee meeting in November 2015.

In addition to updating information in the Boxed Warning, we are also including information about these safety issues in the Warnings and Precautions section of the label. The Indications and Usage section contains new limitation-of-use statements to reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI). The patient Medication Guide that is required to be given to the patient with each fluoroquinolone prescription describes the safety issues associated with these medicines. We are continuing to assess safety issues with fluoroquinolones as part of FDA’s usual ongoing review of drugs and will update the public if additional actions are needed.

We urge health care professionals and patients to report side effects involving fluoroquinolone antibacterials and other drugs to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

ADDITIONAL INFORMATION FOR PATIENTS

  • Fluoroquinolone antibiotic medicines are associated with disabling and potentially permanent serious side effects that can occur together in the same patient and should not be used to treat certain uncomplicated infections. These uncomplicated infections include acute bacterial sinusitis (ABS), acute worsening of bacterial chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI).
  • These side effects can involve the tendons, muscles, joints, nerves, and central nervous system, and can occur within hours to weeks after starting a fluoroquinolone medicine.
  • FDA has updated the Boxed Warning in the labels, added new warnings, and has revised the patient Medication Guide of all fluoroquinolone antibiotics.
  • Contact your health care professional immediately if you experience any serious side effects while you are taking your fluoroquinolone medicine.
  • Before starting a new fluoroquinolone medicine, inform your health care professional if you have previously experienced any serious side effects with another antibiotic.
  • Serious side effects involving the tendons, muscles, joints and nerves include:
    • Swelling or inflammation of the tendons
    • Tendon rupture
    • Tingling or pricking sensation (“pins and needles”)
    • Numbness in arms or legs
    • Muscle pain
    • Joint pain
    • Joint swelling
  • Serious central nervous system side effects include:
    • Depression
    • Hallucinations
    • Suicidal thoughts
    • Confusion
    • Anxiety
  • Other side effects include:
    • Abnormally rapid or irregular heart beat
    • Ringing or buzzing in the ears
    • Vision problems
    • Skin rash
    • Sensitivity of skin to sunlight
    • Headache
    • Trouble falling asleep
    • Fatigue
  • Read the patient Medication Guide you receive with your fluoroquinolone antibiotic prescriptions, which explains the benefits and risks of the medicine.
  • Talk to your health care professional if you have questions or concerns about fluoroquinolone antibiotic medicines.
  • We communicated safety information associated with fluoroquinolones in May 2016, August 2013, andJuly 2008.
  • Report side effects from a fluoroquinolone or any drug to your health care professional and the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of this page.

ADDITIONAL INFORMATION FOR HEALTH CARE PROFESSIONALS

  • FDA has approved label changes that reserve the use of fluoroquinolone antibacterial medicines when treating acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI) for patients who do not have alternative treatment options.

  • FDA has also updated the Boxed Warning and the Warnings and Precautions sections of the labels and revised the patient Medication Guide of the fluoroquinolone drug class to describe the serious risk of multiple disabling and potentially irreversible adverse reactions that can occur together.

  • These adverse reactions primarily include tendinitis and tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects.

  • The adverse reactions can occur within hours to weeks after starting treatment with a fluoroquinolone medicine.

  • Discontinue the fluoroquinolone medicine immediately at the first signs or symptoms of any serious adverse reaction.

  • Avoid fluoroquinolones in patients who have previously experienced serious adverse reactions associated with fluoroquinolones.

  • Serious Adverse reactions of the musculoskeletal system and peripheral nervous system include:

    • Tendinitis/Tendon rupture

    • Muscle pain

    • Muscle weakness

    • Joint pain

    • Joint swelling

    • Peripheral Neuropathy

    • Serious Central nervous system effects include:

      • Psychosis
      • Anxiety
      •  Insomnia
      • Depression
      • Hallucinations
      • Suicidal thoughts
      • Confusion
    • Other adverse reactions include:

      • Exacerbation of myasthenia gravis
      • Prolongation of the QT interval
      • Hypersensitivity reactions/anaphylaxis
      • Photosensitivity/phototoxicity
      • Blood glucose disturbances
      • Clostridium difficile-associated diarrhea
    • Encourage patients to read the Medication Guide that they receive with their fluoroquinolone prescriptions.

    • FDA convened a public advisory committee meeting in November 2015 to discuss the risks and benefits of fluoroquinolone antibacterial medicines for the treatment of ABS, ABECB, and uncomplicated UTI. We also communicated safety information associated with fluoroquinolones in May 2016, August 2013, and July 2008.

    • Report adverse reactions involving a fluoroquinolone or any drug to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of this page.

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Levaquin/levofloxacin Warning Label Changes (Please see July, 2016 Drug Safety Labeling Changes for the other fluoroquinolone label changes:

BOX WARNING (revised)

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS AND EXACERBATION OF MYASTHENIA GRAVIS

  • Fluoroquinolones, including LEVAQUIN®, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together including:
    • Tendinitis and tendon rupture
    • Peripheral neuropathy
    • Central nervous system effects
  • Discontinue LEVAQUIN immediately and avoid the use of fluoroquinolones, including LEVAQUIN, in patients who experience any of these serious adverse reactions. Fluoroquinolones, including LEVAQUIN, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid LEVAQUIN in patients with known history of myasthenia gravis.
  • Because fluoroquinolones, including LEVAQUIN, have been associated with serious adverse reactions, reserve LEVAQUIN for use in patients who have no alternative treatment options for the following indications:
    • Acute exacerbation of chronic bronchitis
    • Acute uncomplicated cystitis
    • Acute sinusitis

WARNINGS AND PRECAUTIONS

Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects (addition)
  • Fluoroquinolones, including LEVAQUIN, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting LEVAQUIN. Patients of any age or without pre-existing risk factors have experienced these adverse reactions.
  • Discontinue LEVAQUIN immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including LEVAQUIN, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.
Tendinitis and Tendon Rupture replaces Tendinopathy
  • Fluoroquinolones, including LEVAQUIN, have been associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur, within hours or days of starting LEVAQUIN, or as long as several months after completion of fluoroquinolone therapy… Tendinitis and tendon rupture can occur bilaterally.
  • The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Discontinue LEVAQUIN immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon. Avoid fluoroquinolones, including LEVAQUIN, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.
Peripheral Neuropathy (new sentences added)
  • Fluoroquinolones, including LEVAQUIN, have been associated with an increased risk of peripheral neuropathy. Cases of sensory…
  • …minimize the development of an irreversible condition…Avoid fluoroquinolones, including LEVAQUIN, in patients who have previously experienced peripheral neuropathy.

ADVERSE REACTIONS

  • The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
    • Disabling and Potentially Irreversible Serious Adverse Reactions (addition)
    • Tendinitis and Tendon Rupture (replaces Tendon Effects)

PATIENT COUNSELING INFORMATION

Serious Adverse Reactions
  • Advise patients to stop taking LEVAQUIN if they experience an adverse reaction and to call their healthcare provider for advice on completing the full course of treatment with another antibacterial drug. Inform patients of the following serious adverse reactions that have been associated with LEVAQUIN or other fluoroquinolone use:
  • Disabling and potentially irreversible serious adverse reactions that may occur together: Inform patients that disabling and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathies, and central nervous system effects, have been associated with use of LEVAQUIN and may occur together in the same patient. Inform patients to stop taking LEVAQUIN immediately if they experience an adverse reaction and to call their healthcare provider. (addition)
  • Tendinitis and tendon rupture replaces Tendon Disorders

MEDICATION GUIDE

What is the most important information I should know about LEVAQUIN?

Tendon rupture or swelling of the tendon (tendinitis).

  • Stop taking LEVAQUIN immediately and get medical help right away…
  • Worsening of myasthenia gravis (a problem that causes muscle weakness). Tell your healthcare provider if you have a history of myasthenia gravis before you start taking LEVAQUIN. (addition)

What is LEVAQUIN?

  • LEVAQUIN should not be used in patients with acute exacerbation of chronic bronchitis, acute uncomplicated cystitis, and sinus infections, if there are other treatment options available.
  • LEVAQUIN should not be used as the first choice of antibacterial medicine to treat lower respiratory tract infections cause by a certain type of bacterial called Streptococcus pneumoniae.

Before you take LEVAQUIN, tell your healthcare provider if you:

  • have a disease that causes muscle weakness (myasthenia gravis); LEVAQUIN should not be used in patients who have a known history of myasthenia gravis.
  • have nerve problems; LEVAQUIN should not be used in patients who have a history of a nerve problem called peripheral neuropathy

How should I take LEVAQUIN?

Do not skip any doses of LEVAQUIN, or stop taking it, even if you begin to feel better, until you finish your prescribed treatment unless:

  • you have nerve problems. See “What is the most important information I should know about LEVAQUIN?”

  • you have central nervous system problems. See “What is the most important information I should know about LEVAQUIN?”

     

All help in spreading the word about these FDA warnings will be greatly appreciated!

 

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Fluoroquinolones Removed From the Market

Several fluoroquinolones have been removed from the market because they caused acute toxicity and death. The fluoroquinolones that have been removed from the market are not terribly different from the ones that remain on the market in terms of damage done or damage mechanisms.

Here are some of the fluoroquinolones that have been removed from the market:

Omniflox/temafloxacin

In 1992 the fluoroquinolone antibiotic Omniflox/temifloxacin was removed from the US market after causing three deaths.

To note the removal from the market, the FDA released the following statement:

            “The Food and Drug Administration today announced that Abbott Laboratories of Abbott Park, Ill., is voluntarily recalling the broad-spectrum anti-infective drug Omniflox (temafloxacin) tablets, and will halt all further distribution of the drug.

This action is being taken because of severe adverse events associated with the use of the drug that have been reported to the company and to FDA in the first three months of marketing.

Temafloxacin was approved in late January 1992 and marketed in mid-February.  Since that time there have been approximately 50 reports of serious adverse reactions, including three deaths.  There were several cases of severe low blood sugar, especially in very elderly patients with decreased kidney function.  Among the severe reactions there were a number of cases of an unusual complex of adverse reactions consisting of hemolitic anemia (destruction of red blood cells) and other blood cell abnormalities.”

The fluoroquinolones that remain on the market also impair kidney function. From the 2013 Science Daily article, Risk of kidney disease doubled with use of fluoroquinolone antibiotics, “The risk of acute kidney disease is doubled for people taking oral fluoroquinolone antibiotics, according to a new study.” The article pointed out that the risk of acute kidney disease was increased for patients taking cipro/ciprofloxacin, levaquin/levofloxacin, avelox/moxifloxacin and floxin/ofloxacin – fluoroquinolones that remain on the market today.

The fluoroquinolones that remain on the market also cause blood-sugar abnormalities, including severe low blood sugar. A large 2013 study out of Taiwan looked at more than 78,000 patient records and found that, “The researchers found that patients with diabetes who had taken fluoroquinolone antibiotics had higher rates of both hyperglycemia and hypoglycemia compared with those who had taken macrolide antibiotics.” (source) Additionally, in the article, Fluoroquinolone antibiotics and type 2 diabetes mellitus, it is noted that, “Exposure to fluoroquinolone antibiotics is postulated as a risk factor for subsequent development of type 2 diabetes. It is hypothesized that fluoroquinolones induce an intracellular magnesium deficit that can lead to insulin resistance.”

Raxar/grepafloxacin

Raxar/grepafloxacin was removed from the worldwide market in 1999. The FDA withdrawal notice stated:

RAXAR is a fluoroquinolone antibiotic indicated for the treatment of infections caused by strains of bacteria susceptible to grepafloxacin in the following diseases: community-acquired pneumonia; acute bacterial exacerbations of chronic bronchitis; uncomplicated gonorrhea (urethral in males and endocervical and rectal in females); non-gonococcal urethritis and cervicitis.

Glaxo Wellcome has recently concluded an extensive review of the safety of RAXAR and determined that due to an effect of RAXAR on cardiac repolarization, manifested as QT interval prolongation on the electrocardiogram (ECG), some patients may be at risk of a very rare but serious ventricular arrhythmia known as torsade de pointes when treated with the product.

The warning label for Levaquin/levofloxacin (and the other fluoroquinolones that remain on the market) notes that:

“Prolongation of the QT interval and isolated cases of torsade de pointes have been reported. Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval.”

Additionally, a study entitled “Azithromycin and Levofloxacin Use and Increased Risk of Cardiac Arrhythmia and Death” compared the risk of cardiac arrhythmia for U.S. Veterans taking amoxicillin, azithromycin and levofloxacin. The study concluded that:

“Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.”

Just like Raxar/grepafloxacin, the fluoroquinolones that are still on the market prolong the QT interval and cause torsade de pointes, which can lead to arrhythmia and death.

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Zagam/sparfloxacin

Zagam/Sparfloxacin was also removed from the market because it caused QT interval prolongation.

Zagam/Sparfloxacin also caused incidents of Stevens Johnson Syndrome:

“When a patient using  Zagam develops SJS or TEN after taking the fluoroquinolone antibiotic treatment, the individual’s topmost skin cells die and fall off. This leaves the deeper layers exposed and unprotected, making it likely for a patient to experience infection and scarring. The sensitive mucous membrane also becomes exposed when the upper layer of skin sloughs off, and may be prone to blistering.” (source)

Trovan/trovafloxacin

Trovan/Trovafloxacin was removed from the market because of its high potential for inducing serious, sometimes fatal liver damage (hepatotoxicity). The wiki entry for Trovafloxacin notes that:

In June 1999 the U.S. Food and Drug Administration advised doctors to limit the prescription of Trovan after it had been found “strongly associated” with 14 cases of acute liver failure and six deaths. The FDA had received over 100 reports of liver problems in people taking Trovan, which was at that time being prescribed at a rate of 300,000 patients per month in the United States. Two days later the Committee for Proprietary Medicinal Products recommended to the European Commission that marketing approval of Trovan be suspended for a year.

One of the best articles about the hepatotoxicity of Trovan/Trovofloxacin is Trovafloxacin, a fluoroquinolone antibiotic with hepatotoxic potential, causes mitochondrial peroxynitrite stress in a mouse model of underlying mitochondrial dysfunction. The article, Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria, by some of the same authors, is also enlightening. Liver damage, mitochondrial damage, and ROS overload/oxidative stress are all intricately connected. I highly recommend that you read the two articles linked to (but, man, they’re both really difficult articles). I suspect that both articles hold many of the keys to understanding all fluoroquinolone toxicity reactions. In the post, Article Breakdown – “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria,” I go over some of the implications Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria has for floxies.

Interestingly, Trovan/Trovafloxacin has another area of shady history. In Kano, Nigeria, it was used in an improperly conducted trial on children with meningitis. Per the wiki entry for Trovafloxacin:

In 1996, during a meningitis epidemic in Kano, Nigeria, the drug was administered to approximately 200 [3] infected children. Eleven children died in the trial: five after taking Trovan and six after taking an older antibiotic used for comparison in the clinical trial. Others suffered blindness, deafness and brain damage, common sequalae of meningitis that have not been seen in patients treated with trovafloxacin for other infection types.[4][5][6] An investigation by the Washington Post concluded that Pfizer had administered the drug as part of an illegal clinical trial without authorization from the Nigerian government or consent from the children’s parents.[7] The case came to light in December 2000 as the result of an investigation by The Washington Post, and sparked significant public outcry. The most serious error was the falsification and backdating of an ethics approval leader by the lead investigator of the trial, Dr. Abdulhamid Isa Dutse. Dr. Dutse is now the chief medical officer of Aminu Kano Teaching Hospital. The result of the trial was that children treated with oral trovafloxacin had a 5% (5/100) mortality rate compared to a 6% (6/100) mortality rate with intramuscular ceftriaxone.

Between 2002 and 2005 the victims of the Trovan tests in Nigeria filed a series of unsuccessful lawsuits in the United States. However, in January 2009, the United States Court of Appeals for the Second Circuit ruled that the Nigerian victims and their families were entitled to bring suit against Pfizer in the United States under the Alien Tort Statute. A US$75 million settlement with the State of Kano was reached July 30, 2009.[8] Additionally two lawsuits also remain pending in New York, United States.[8] According to Wikileaked US embassy cables, Pfizer’s country manager admitted that “Pfizer had hired investigators to uncover corruption links to federal attorney general Michael Aondoakaa to expose him and put pressure on him to drop the federal cases.”[9]

Additional information about the Kano trial can be found in The Guardian article, Pfizer pays out to Nigerian families of meningitis drug trial victims.

Tequin/gatifloxacin

Tequin/Gatifloxacin was pulled from the market because it caused severe blood sugar reactions such as hyperglycemia and hypoglycemia.

The New England Journal of Medicine article, Outpatient Gatifloxacin Therapy and Dysglycemia in Older Adults, noted that:

“Between April 2002 and March 2004, we identified 788 patients treated for hypoglycemia within 30 days after antibiotic therapy. As compared with macrolide antibiotics, gatifloxacin was associated with an increased risk of hypoglycemia (adjusted odds ratio, 4.3; 95 percent confidence interval, 2.9 to 6.3). Levofloxacin was also associated with a slightly increased risk (adjusted odds ratio, 1.5; 95 percent confidence interval, 1.2 to 2.0), but no such risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. We then identified 470 patients treated for hyperglycemia within 30 days after antibiotic therapy. As compared with macrolides, gatifloxacin was associated with a considerably increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 percent confidence interval, 10.4 to 26.8), but no risk was noted with the other antibiotics. Risks were similar in the two studies regardless of the presence or absence of diabetes.”

A more recent study, that looked at a larger population than the NEJM study, Risk of Severe Dysglycemia Among Diabetic Patients Receiving Levofloxacin, Ciprofloxacin, or Moxifloxacin in Taiwan, found that all of the fluoroquinolones on the market increased the likelihood of both hyper and hypo glycemia in diabetic patients:

“A total of 78 433 diabetic patients receiving the antibiotics of interest were included in the study. The absolute risk of hyperglycemia per 1000 persons was 6.9 for moxifloxacin and 1.6 for macrolides. In contrast, the risk of hypoglycemia was 10.0 for moxifloxacin and 3.7 for macrolides. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of levofloxacin, ciprofloxacin, and moxifloxacin compared with macrolides were 1.75 (1.12–2.73), 1.87 (1.20–2.93), and 2.48 (1.50–4.12), respectively, for hyperglycemia and 1.79 (1.33–2.42), 1.46 (1.07–2.00), and 2.13 (1.44–3.14), respectively, for hypoglycemia. Patients taking moxifloxacin faced a significantly higher risk of hypoglycemia than those receiving ciprofloxacin. A significant increase in the risk of hypoglycemia was also observed among patients receiving moxifloxacin concomitantly with insulin (AOR, 2.28; 95% CI, 1.22–4.24).”

As mentioned in the Temafloxacin section of this post, fluoroquinolone use has been linked to development of diabetes. Given that all fluoroquinolones cause blood-sugar dysregulation, and two fluoroquinolones have been removed from the market because they caused severe blood-sugar fluctuations, perhaps fluoroquinolones are behind the dramatic increase in both type 1 and type 2 diabetes over the last 30 years. It is a hypothesis that should certainly be looked into.

Conclusion

I struggle with whether or not I think all fluoroquinolones should be taken off the market. Even though I know that they are all dangerous, and sometimes even deadly, drugs, I also know that we are running out of antibiotics in our arsenal and that sometimes dangerous drugs are necessary in order to save a person’s life. I tend to think that Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, Floxin/ofloxacin, and the other fluoroquinolones, should be severely restricted, and that there should be strict procedures followed when they are prescribed so that it is ensured that they will only be used in life-or-death situations where informed consent is given.

When looking at the fluoroquinolones that have been removed from the market, it always strikes me that they were removed from the market quickly after just a few deaths or a few studies that showed that they are dangerous drugs. The fluoroquinolones that remain on the market (Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, Floxin/ofloxacin) have also killed people. According to an FDA review with the subject, “Pediatric Exclusivity Postmarketing Adverse Event Review,” between 12/20/1996 and 08/27/2008, 924 people were killed by Levaquin/levofloxacin, including three children. The figures for Cipro/ciprofloxacin, Avelox/moxifloxacin, and Floxin/ofloxacin are similar. So, why do Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, Floxin/ofloxacin have such staying power? Why are they still on the market when Temafloxacin/Omniflox, Raxar/grepafloxacin, Zagam /Sparfloxacin, Trovan/Trovafloxacin, and Tequin/Gatifloxacin have been removed from the market? I don’t know the answers to those questions–I wish I did. It seems to me that the FDA used to be a stronger, more independent, more effective organization than it is today, and that it used to actually pull dangerous drugs from the market.

Rather than removing dangerous fluoroquinolones from the market, or even imposing meaningful restrictions on the fluoroquinolones that remain on the market, the FDA has instead chosen to increase the size of the fluoroquinolone warning labels. As I have noted before, changed warning labels open the door for lawsuits and that’s a good thing, but it is overall a useless move that is devoid of real change. Not enough doctors or patients read warning labels, and they are a lousy way to communicate the real risks of pharmaceuticals.

The fluoroquinolones that remain on the market are not significantly different from the fluoroquinolones that have been removed from the market. Updating warning labels isn’t keeping people from getting hurt by these dangerous drugs. I understand hesitation to remove them from the market completely, but there should be significant restrictions put on their use. Right now they are not being used prudently or appropriately. That must change. Too many people are being hurt by these dangerous drugs.

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FQ Toxicity Featured in The Anxiety Summit

The following post was originally sent out in an email. If you would like to sign up for the Floxie Hope email list, you can do so through THIS LINK. You also get a free copy of the ebook Hacking Fluoroquinolones when you sign up for the email list. 🙂

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Fluoroquinolone-Induced Anxiety

Dear Friends,

As many of you know, fluoroquinolones can induce awful anxiety. There is information about fluoroquinolone-induced anxiety in the following posts:

Fluoroquinolone-induced anxiety can be so horrible, that it can have truly tragic consequences, as described in PSYCHIATRIC ADVERSE REACTIONS TO PHARMACEUTICALS IGNORED. Shea McCarthy lost his life because of his serious and severe psychiatric reaction to Levaquin. It’s horrible, and my heart aches for all of his loved ones.

Anxiety Help and Information

I had the pleasure and honor of being interviewed by my colleague and friend, Food Mood Expert Trudy Scott for “The Anxiety Summit.”  Trudy is the author of The Antianxiety Food Solution: How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood and End Cravings and is on a mission to share the amazing healing powers of food and nutrients for anxiety and mood issues.

Between June 6 and June 16, 2016, she will be interviewing world-class experts and opinion leaders on the topic of anxiety and food.

Here are just a few of the amazing speakers and topics:
– “Anxiety: The Stressed and Toxic Gut” – Dr. Josh Axe, DNM, DC, CNS, author of Eat Dirt
– “Multiple sclerosis and anxiety: The Wahls Protocol” – Dr. Terry Wahls, MD, author of The Wahls Protocol
– “Anxiety and digestion: the microbiome, stomach acid, bile and the vagus nerve” – Prof. Liz Lipski, PhD, CCN, CNS, author of Digestive Wellness
– “Marijuana and anxiety: Panacea or Pandora’s Box?” – Dr. Hyla Cass, M.D., board-certified in psychiatry and integrative medicine, author of The Addicted Brain and How to Break Free
– “Anxiety and heavy metals: chelation of mercury and lead” – John Dempster, ND, host of the Mental Wellness Summit
– “Nutrients that Fuel Brain Power and Reduce Anxiety” – Dr. Drew Ramsey, M.D., psychiatrist, farmer, author of Eat Complete

— “Antibiotic Induced Anxiety – How Fluoroquinolone Antibiotics Induce Psychiatric Illness Symptoms” –Lisa Bloomquist of http://www.floxiehope.com

Check out the complete speaker lineup here: THE ANXIETY SUMMIT

You’ll hear the science and learn practical transformational tools you can apply right away.

Once you sign up (at no cost to you!), you will also receive a link to the page where you can download amazing gifts from many of the speakers, and get access to questionnaires and research as they become available.

Here are just a few of the gifts (and more are being added each day):

Top of the World – a custom song co-created by Trudy Scott and Amma Jo
The King’s Medicine Cabinet eBook: A complete guide on essential oils and their history, uses, cures, and recipes that will transform your health forever! By Dr. Josh Axe, author of Eat Dirt
The Leptin Blueprint by Mike Mutzel, author of The Belly Fat Effect
Hacking Fluoroquinolones by Lisa Bloomquist, patient advocate, creator of Floxie Hope
SCD Quick Start Guide by Steve Wright, creator of SCDlifestyle
10 Ways to Balance Serotonin Naturally by Dr. Peter Bongiorno, author of Put Anxiety Behind You
Food for Thought – an audio presentation by Dr. Terry Wahls, MD, author of The Wahls Protocol

You will also have the option to purchase the MP3s and/or transcripts (digital or CD version) of all the interviews if you’d like to keep them for your learning library.
I hope you’ll join the summit!

 

THE ANXIETY SUMMIT is FREE from June 6 – 16, 2016.

 

Thanks to all who join!

 

The Anxiety Summit – Antibiotic Induced Anxiety – How Fluoroquinolone Antibiotics Induce Psychiatric Illness Symptoms

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Comments From Doctors About Fluoroquinolone Toxicity

With every article about fluoroquinolone toxicity that is published (there are hundreds HERE), more and more people come forward and say, “that happened to me too,” or, “those drugs hurt my family member,” or some variation/elaboration of those sentiments. As awareness grows, more and more doctors are coming forward to say that fluoroquinolones are dangerous drugs whose risks are under-recognized. Growing awareness and recognition, especially from doctors, nurses, and other medical professionals, is important in the fight to reduce the number of lives ruined by these dangerous drugs.

It recently came to my attention that there were many good comments from doctors and other medical professionals on an article in Medscape Medical News, “FDA Panel Says Fluoroquinolones Need Stronger Warnings.” (If the link leads you to a sign-in form instead of the article, just google “FDA Panel Says Fluoroquinolones Need Stronger Warnings” to skip the sign-in-wall.) It should be noted that Medscape Medical News is aimed at medical professionals, and that one needs to work in medicine in order to comment on stories on the site. The comments are, for the most part, a conversation between doctors. It is heartening to see that most of the comments are supportive of the notion that stronger warnings are needed on fluoroquinolones, and that the real risks of Cipro/ciprofloxacin, Levaquin/levofloxacin, Floxin/ofloxacin and Avelox/moxifloxacin are under-recognized and under-appreciated. Several of the commenting doctors also noted that these drugs should only be used as a last-resort, after all other options had been exhausted.

In this post, I’m going to highlight some of the comments that were published on “FDA Panel Says Fluoroquinolones Need Stronger Warnings.” It’s good for “floxies” to hear from doctors who recognize the pain caused by fluoroquinolones, who are also fighting for more prudent and appropriate use of these dangerous drugs. It’s nice to hear from doctors who recognize that fluoroquinolones can cause a multi-symptom chronic illness, and that fluoroquinolone toxicity is not a simple “side-effect.” A huge “THANK YOU” to all the doctors who left supportive comments on the article! Conversations between doctors about the dangers of fluoroquinolones are going to do a lot to change how fluoroquinolones are thought of and prescribed.

Here are just a few of the comments (I ended up copying/pasting most of them, but there are still some gems left behind in the comments section of the article):

“At the age of 39, I suffered horribly from the use of Cipro. It changed my ability to practice Anesthesiology. I had to go to barely part time work when this occurred and could barely move. I had no preexisting health issues prior to the use of this fluoride containing poison in my opinion. I still have evidence of its destruction 6 years later. I have met several other individuals who have also suffered among them a classical pianist, two other physicians and several other highly educated individuals whose lives were changed monumentally especially for the first one to two years post “poisoning” as I call it.

The toxicity of this class of drugs is predominantly musculoskeletal and neurologic and I can truly sympathesize with patients who have been “blown off”as hypochondriacs by their PCP s or others when they present with severe musculoskeletal pain and neuro and neuropsych issues. There are other SE as well in various organ systems however as noted most seems centered in the MS and neuro psych realm. Many have expansive work ups (as did I) to rule out ominous diagnoses all to no avail but suffer greatly nonetheless in terms of years not weeks or months!

Fluoroquinones are cytotoxic to chondrocytes and the vasa vasorum is also thought to be greatly affected at the microscopic level and may lead to the neuropathy. Some feel this propensity in patients to suffer what is called (By victims of these drugs)”FQ syndrome”may point to a mitochondrial source.

Just because there is no blood test to measure the damage these poisons wreak on previously well patients or because the wide range of symptoms patients experience has yet to be acknowledged and named a formal syndrome, doesn’t mean the horrible side effects aren’t real or don’t exist. To do so, is folly. I was finally diagnosed at a well known academic center by a neurologist in conjunction with rheumatologist. Also of interest is the flood of multiple significant musculoskeletal and neurologic complaints suffered by a large proportion of government workers who were given Cipro after the Anthrax scare several years ago. However, again, many people were dismissed then.

One thing is certain is that significant side effects of these medications exists and failure to acknowledge patients who present with what seems to be a “positive review of systems” after FQ use should be taken seriously. Especially true when as a physician you know your patient was previously healthy prior to FQ use and not a patient who routinely presents with multiple mundane complaints.

I feel and have read many patients who experienced nearly identical symptoms to the ones I suffered. Most all blown off as head cases. If more physicians would entertain the possibility a FQ may be responsible for their patients suffering, maybe then they would

Report to the FDA and we would have a true idea as to the incidence of life changing and sometimes permanent havoc these drugs wreak on our patients. In my case, I’ve lived it and I welcome the added safety warnings on these drugs. People have abused these drugs which are extremely broad spectrum and powerful for conditions that don’t require a hammer to kill an ant. Hoping these warnings will ease the indiscriminate use of these very potentially damaging drugs.”

“This does not even mention the risk of acute toxic psychosis. I have witnessed it in a 17 year-old on levofloxacin for h. pylori. Dramatic, acute onset of psychosis after two doses with no prodromal history. There are more cases out there I understand. I have learned to reserve these drugs for cultured bacteria for which there is no other reasonable alternative. It is not a reasonable choice for prophylaxis or starting treatment pending culture results in my opinion.”

“I, myself, have had major issues with this class of drugs.  Took Avelox in July 2013 for an upper respiratory infection without issue.  Was given Avelox again in November of 2013 and within 10 minutes of my first pill, I was in anaphylactic shock.  I was transported to the ER and nearly died!  Over previous years, I was given Levaquin and Cipro for other URI s.  Guess my body had enough.  My joints are shot and I will never be the same again.”

“I agree with need for stronger language even a black box warning and better education of prescribers.”

“I am a nurse, and i never knew about this until i took Levoquin and Cipro. Now i am a disabled person. I lost my life. The side effects are not being reported. Check the study UCSD (University of California, San Diego) is doing. Thanks for reading our notes and joining in.”

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“I am a BSN, RNC-NIC nurse.  I had been given Levoquin and Cipro both at different times.  I am now a “FQAD” person otherwise know as a “Floxie”.

The medication was given appropriately both times as second and third choice for sinusitis and possible bacteria meningitis (it ended up being viral).  I am prone to meningitis and needed to be treated. After two other abx didn’t work, i had to go on a Fluoroquinolone.  My life was saved.  However, it is also ruined.  I was walking up a short flight of stairs, slowly, nothing special, and my Gluteus minimums and my Gluteus medius tore almost completely off my femur.  I was allowed to do nothing and no physical therapy allowed for 7 months.  pain, when not on analgesics was 10/10.  ON FIRE!!  Finally off to the Physical Terrorist and she seemed to somehow cure me.  It is coming back through.

I have concentration difficulties, issues with eyes, i fall asleep sitting up at the dinner table, i cannot remember words, faces, people i know well, EEG shows something as does MRI and have to go through Neurophsych testing, pain head to toe, dx with Fibromyalgia too.  I have never, ever in my life been depressed (unless called for in the case of a loved one dying etc).  I now have depression and am slightly suicidal.  (NEVER EVER that way previously, this is from the Fluoroquinolone.)  I have a chronic fatigue type of issue. I could go on – so many problems.  I have to go have my heart checked now i have issues there  – not sure what.

Please, do a culture.  Insist on a culture.  There may be another drug. I lived, but my life is ruined.  I loved being a nurse.  I cannot even garden now and had to hire a housekeeper.

This is serious!  These Fluoroquinolones are poison.  I don’t really do anything anymore.  i am afraid of running into people who know me and i should know but do not.  That is embarrassing.  I have taken to telling them i am sorry, i have fluoroquinolone toxicity and it has affected my brain.  Will you tell me how i know  you?  Embarrassing as hell, but so far so good, everyone has been nice about it.  When i run into someone who is not, i will probably end up back in my house.

In retrospect, i would rather have risked not taking it and not living.  Yes, it is that bad.

Do not poison your patients.  Tell the docs, they do not know.  Look us up on Facebook by typing in “Fluoroquinolone” in the search bar.  Meet us and see what our lives are like.   One Cipro tablet, one Levoquin can cause this.”

“had reaction to fluoroquinolone but question how many reactions are actually reported to FDA. I know mine wasn’t. Suspect rate of side effects is way higher than reported. also suspect the generic I had releases at a different rate of delivery than the older brand name Levaquin possibly causing reaction as I never had it with brand name in past.”

“After one dose of ciprofloxacin, I developed Achilles tendinitis, first on the right, later on the left. These impaired my mobility for more than one year.”

“Quite a few postal workers presented with today those of us in the “know” call FQ syndrome after prophylaxis for anthrax scare!

There’s a lot out there! Physicians have failed these patients by and large by not reporting these side effects and hence nothing has been done with veracity till now as more and more patients are getting vocal and advocating and demanding answers. The Internet has allowed many suffering to see they are not “crazy” and others are suffering too!”

“Excellent article ,discussing a very important subject.FLUOROQUINOLONES are terrible drugs ! no one can imagine how harmful are they till he suffers one side effect and i refer to the SENSORY NEUROPATHY involing the whole body from face to feet including chest and abdomen.”

“Fluoroquinolones ought to be the absolute last antibiotic of choice in every case. Its’ highly unfavorable safety profile would make me think long and hard before using it.”

“Some doctors still hand these things out like aspirin. I knew they were dangerous, but not this much. This announcement needs very effective publicity – especially to physicians and pharmacists.”

“don’t forget the neurotoxicity ( potential that is ) is not limited to the periphery and that patients with epilepsy should probably be spared the ”quinolone risk” unless options are limited and the treated condition dangerous.”

“FQ’s were brought on the scene with a lot of hype. IMO they have not lived up to the hype that preceded its use. Whatever happened to using Tetracycline for sinusitis, Bactrim for UTI’s. Of course you could go outside the box and use colloidal silver for any and all infections without worry of resistance.”

“I am amazed at how often the quinolones are prescribed when there are safer alternatives. They should not be a first choice!”

“I suffered horribly from Cipro and relate to the fact that MOST physicians have no idea of the wide swath of side effects these drugs are responsible for and unfortunately some of them are so severe they leave the victim with permanent sequelae. So many patients “blown off” by their physicians who either fail or refuse to acknowledge the poison these drugs are. It kills Anthrax.”

“I don’t know why any physician would risk prescribing fluoroquinolones. Tequin almost killed me and I’m not exaggerating. I spent several days close to death in the hospital. Thankfully I’m alive but my hearing and eyesight and blood vessels are permanently damaged and I STILL have other autoimmune, neuropathy and soft tissue issues as well ( since 2003). I spent several days in and out of a ‘ diabetic’ coma and the doctors were no help. No one would listen to me when I told them it was the Tequin that was killing me. Given my sed rate, I was given a Lupus diagnosis. That was the final straw for me and I knew I would die if I didn’t get out of there. When I was coherent long enough to speak to my husband, I told him to unplug me, give me some soda and crackers so that I could gain enough strength to walk out of the hospital. I went home proceeded to do my own research and find the help I needed from friends/colleagues. I was in so much pain all over my body and had to sleep on a hard floor ( with my dogs 😀 ) for two months because the bed was too soft and the slightest strenuous movement was too painful. It took a good year before I was completely pain-free and the tinnitus became tolerable. G-d help anyone in a similar situation that doesn’t have the same level of education to help themselves. These meds should be banned!!!!!!!!!!”

“With the possible exception of darifenacin (Enablex), anticholinergics (antimuscarinics) used in treatment of overactive bladder also increase the risk of QT prolongation and torsade de pointes. Perhaps we should show particular caution in prescribing fluoroquinolones for patients using longterm anticholinergic medications.”

“Maybe physicians should consider side effects more and potential for developing resistance. Cheaper first generation drugs can still be used effectively without going to the big guns for minor infections.Patients don’t always understand potential consequences. Physicians should.”

“It has been more than ten years ago now when the medical director of one of the hospitals I was on staff at told me that flourquinolones was appropriate first-line therapy for a UTI. I vehemently arqued with him to no avail. There was no changing his mind.

Tell me, did he sell out or was the drug manufacturer’s campaign so high powered to convince everyone, except me, that this was appropriate care?”

“Nice article. Warning may also include their effect on sleep, causing insomnia.”

“My father got severe drug reaction with ciprofloxacin in the form of bone marrow failure. I have also been reported cases of bone marrow suppression and skin rashes with ciprofloxacin. It needs further careful observation.”

 

 

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NSAIDs and FQs Damage Mitochondria, Increase Oxidative Stress, and Cause Cell Death

As I noted in the post, Why NSAIDs Suck for Floxies (and Probably Everyone Else Too), NSAIDs often exacerbate fluoroquinolone toxicity symptoms, and there are several mechanisms through which NSAIDs can interact with fluoroquinolones. The results of a recent article published in the Journal of Molecular and Cellular Cardiology by researchers at UC Davis, Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells, help to further explain why NSAIDs trigger fluoroquinolone toxicity symptoms, and why they are a horrible combination.

NSAIDs and Fluoroquinolones Damage Mitochondria

The study showed that NSAIDs “Attack mitochondria, reducing the cardiac cell’s ability to produce energy” (source).

Likewise, fluoroquinolones have been shown to attack mitochondria. The studies, Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells and Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells show that fluoroquinolones damage mitochondria, deplete mitochondrial DNA, and cause oxidative stress.  Also, the FDA admits that mitochondrial damage is the likely mechanism through which fluoroquinolones cause peripheral neuropathy.

Healthy mitochondria are vital for cellular energy and health. Unhealthy mitochondria have been linked to many diseases, including M.S., fibromyalgia, M.E./C.F.S., P.O.T.S., diabetes, cancer, aging, and more. Do NSAIDs and fluoroquinolones increase one’s chances of getting those diseases that are related to mitochondrial dysfunction? It’s certainly reasonable to think so – via the mitochondrial damage link – but studies have not shown a direct connection (mainly because neither have been researched).

NSAIDs and Fluoroquinolones Increase Reactive Oxygen Species (ROS)

NSAIDs also “Cause the production of reactive oxygen species, which stresses heart cells and is associated with many diseases, including heart disease” (source).

Fluoroquinolones have also been shown to increase production of reactive oxygen species (ROS – aka oxidative stress). The article, Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients notes that, “Several in vitro and in vivo study using animals revealed that fluoroquinolones induced oxidative stress by producing reactive oxygen species (ROS)” and that in vivo human studies show that, “ciprofloxacin and levofloxacin induce more reactive oxygen species that lead to cell damage than gatifloxacin.

ROS are described as follows:

Without oxygen, we could not exist. However, in the process of generating energy by “burning” nutrients with oxygen, certain “rogue” oxygen molecules are created as inevitable byproducts. Known as free radicals and reactive oxygen species, these unstable, highly reactive molecules play a role in cell signaling and other beneficial processes when they exist in benign concentrations.  But when their numbers climb, as may occur as a result of aging and other conditions, they may wreak havoc with other molecules with which they come into contact, such as DNA, proteins, and lipids. As such, these “pro-oxidant” molecules become especially toxic.

In fact, a prevailing theory of disease and aging states that the gradual accumulation of pro-oxidant molecules, and the harm they incur, is responsible for many of the adverse changes that eventually cause various diseases. These include cancer (possibly triggered by free radical-induced damage to cellular DNA) and inflammatory and degenerative diseases such as Alzheimer’s, arthritis, atherosclerosis, and diabetes. While scientists have not yet reached consensus on the topic, accumulated evidence overwhelmingly identifies increased oxidative stress with age as a source of damage to cellular structure and function. (source)

To drastically over-simplify things, ROS are the opposite of antioxidants. If you’ve ever read about the benefits of antioxidants like vitamin C or glutathione, ROS have the opposite effects. In excess, ROS are harmful and damaging to cells.

NSAIDs and Fluoroquinolones Cause Cell Death

NSAIDs were found to “Impair the cardiac cell’s proteasome, the mechanism for degrading harmful proteins. This leads to toxic buildup and eventually to the death of cardiac cells” (source).

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Fluoroquinolones have also been found to cause cell death (apoptosis). This has been shown in many articles that note that fluoroquinolones are useful as chemotherapeutic agents specifically because they kill cells. Unfortunately, they don’t just kill cancer cells, they also kill healthy cells. The following articles note that fluoroquinolones are chemotherapeutic drugs that damage and kill cells:

  1. In an article published in the journal Urology, it was noted that, “Ciprofloxacin and ofloxacin exhibit significant time and dose-dependent cytotoxicity against transitional carcinoma cells.” That’s great – excellent, actually – if you happen to have carcinoma cells in your bladder. But if you just happen to have a bladder infection, chemo drugs that exhibit toxicity toward human cells – cancer or otherwise – are inappropriate for use (1).
  2. The mechanism for action for fluoroquinolones is that they are topoisomerase interrupters (2).Topoisomerases are enzymes that are necessary for DNA replication and reproduction. All of the other drugs that are topoisomerase interrupters are approved only for use as chemotherapeutic agents. It is only appropriate to use drugs that disrupt the process of DNA replication and reproduction when someone’s cells are already so messed up that they have cancer.
  3. Fluoroquinolones have been found to interfere with the DNA replication process for human mitochondria (3, 4, 5). Mitochondria are vital parts of our cells, (cellular energy is produced in our mitochondria), and disrupting the process through which mitochondrial DNA replicates causes cellular destruction, oxidative stress and disease.
  4. Fluoroquinolones have been shown to be genotoxic and to lead to chromosomal abnormalities in immune system cells (6).
  5. Fluoroquinolones disrupt cellular tubulin assembly (7). All of the other drugs that disrupt tubulin assembly are chemotherapeutic drugs.
  6. Fluoroquinolones disrupt enzymes, including CYP1A2 enzymes, which are necessary for detoxification.

Avoid NSAIDs and Fluoroquinolones

Dr. Aldrin V. Gomes, one of the authors of Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells, “advised caution when using NSAIDs either topically or orally” (source). Likewise, caution is warranted when using fluoroquinolones, as one can gather from reading any of the stories of pain and suffering caused by fluoroquinolones. Personally, I will do everything in my power to avoid both NSAIDs and fluoroquinolones for the rest of my life. Mitochondrial destruction, oxidative stress, and cell death aren’t things I want.

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Serious Psychiatric Reactions from Fluoroquinolones

Heather McCarthy News Story

Please read and share post, “Psychiatric Adverse Reactions to Pharmaceuticals Ignored” that was published on Hormones Matter. It highlights the tragic story of Shea McCarthy, a young man who lost his life after suffering from a severe psychiatric adverse reaction to Levaquin.

The severe psychiatric adverse reactions to fluoroquinolones need to be recognized and acknowledged. No one is choosing to have a severe psychiatric adverse reaction to a drug, yet people with psychiatric adverse reactions are often ignored and disregarded. As you can see from Shea’s tragic story, not listening to people who have psychiatric adverse reactions to drugs can have tragic consequences.

Here is the video of the news story, “CALL 6: Mother blames antibiotic for son’s death – Purdue University student took Levaquin:”

There are several possible mechanisms through which fluoroquinolones can cause anxiety, depression, insomnia, psychosis, and other severe psychiatric adverse-effects. Oxidative stress may be the mechanism through which fluoroquinolones cause severe psychiatric problems, as I described in “Can Antibiotics Induce Psychiatric Reactions?” Maybe gut microbiome destruction by fluoroquinolones leads to the psychiatric adverse effects. The Psychology Today article, “The Gut-Brain Connection, Mental Illness, and Disease” goes over evidence that our gut microbiome is intricately linked to our mental health. Obviously, fluoroquinolones are powerful antibiotics that destroy the gut microbiome. Another possibility, one that I have not previously explored, is that fluoroquinolones cause severe psychiatric reactions because they have a piperazine attachment to the quinolone core. In the picture below, the quinolone core is zone 4 and the piperazine attachment is zone 3.

Cipro Molecular Structure

Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid.

Piperazine blocks GABA activity. GABA is gamma-Aminobutyric acid, “the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone.” (wiki) When GABA is blocked, people feel edgy, agitated, excited (not in a good way), anxious, and can suffer from insomnia, muscle spasms, seizures, and more.

Piperazine is often used “for making fake ecstasy because of the similarity in taste, and at certain doses, a user may experience favorable side effects and feel ‘high.’” (source) It is also often mixed with MDMA in ecstasy.

Additionally, it is noted in “Acetylcholine (ACh) – Related Damage” on http://fluoroquinolonethyroid.com/ that:

“Piperazines (anti-parasiticals which kill parasites by paralyzing them) have neuromuscular effects which are thought to be caused by blocking acetylcholine at the myoneural junction. (Plenty of pets have been poisoned with over the counter piperazine toxicity from wormers – so no, it’s not just helminths they affect). Among the numerous properties of Piperazine derivatives, they are not only muscarinic antagonists, but also are the basis for recreational drugs with euphoria and stimulant properties, such as amphetamines, BZP, MDMA [rather, ecstasy, as noted above], and TFMPP, along with all the negative side effects of these drugs (no wonder I was hallucinating during my acute reaction). So now we have a toxic neuromuscular agent with amphetamine/ecstasy-like effects (piperazine), along with a toxic iodine displacer (fluorine), attached to a chemotherapeutic agent with an intracellular, intranuclear, and intra-mitochondrial genotoxic mechanism of action (quinolone) – a synthetic, fluoridated, neurotoxic, genotoxic chemotherapeutic poison masquerading as an antibiotic and being given en masse to the human and animal population.”

Fluoroquinolones “are known to non-competitively inhibit the activity of the neurotransmitter, GABA, thus decreasing the activation threshold needed for that neuron to generate an impulse.” (source, source, source) Fluoroquinolones have also been shown to have similar effects on GABA neurotransmitters as benzodiazepine withdrawal (source).

The inhibition of GABA by the piperazine part of fluoroquinolones is a plausible, even likely, mechanism for the many horrible psychiatric effects that people suffer from after taking fluoroquinolones.

In a survey of 94 people who experienced adverse reactions to Levaquin/levofloxacin, a fluoroquinolone antibiotic, 72% reported experiencing anxiety, 62% reported depression, 48% reported insomnia, 37% reported panic attacks, 33% reported brain fog and/or cognitive impairment, 29% reported depersonalization and/or derealization, 24% reported thoughts of suicide and 22% reported psychosis. (source, source)

More than 20 million prescriptions for fluoroquinolones are given out in the U.S. each year. If even only 1% of the people who take fluoroquinolones experience a psychiatric adverse-reaction, that’s still a lot of people whose minds aren’t their own, who are suffering from depression, anxiety, insomnia and worse, because of an antibiotic that is made with a chemical that has amphetamine/ecstasy-like effects.

These effects can have tragic consequences, as can be seen in the video and article mentioned above about Shea McCarthy.

Psychiatric adverse effects of prescription drugs are serious, and they should be taken seriously. They are not a choice. No one would choose to feel psychotic, or even anxious.

There are many plausible mechanisms through which fluoroquinolones can cause psychiatric problems. Perhaps it is time that the psychiatric effects of fluoroquinolones become more widely recognized.

 

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How to Stop Overprescribing Fluoroquinolone Antibiotics

Overprescription of Antibiotics

I found this New York Times article, How to Stop Overprescribing Antibiotics, to be really interesting. Doctors know that antibiotic resistance is a serious problem–the word has gotten out sufficiently, but that knowledge hasn’t done much to change antibiotic prescribing patterns. Doctors are still overprescribing antibiotics, despite knowing that antibiotic resistance poses a significant threat to both modern medicine and human health.

I’m not sure what the root of this overprescribing is. It may be from a lack of knowledge of what ailments antibiotics should be prescribed for (many cases of prostatitis, as well as many sinus infections, aren’t bacterial), tradition (it’s the way it has “always” been done), a notion that antibiotics “can’t hurt,” patient pressure on the physician to do something, or if there’s another root to the problem.

Antibiotic overprescription IS a problem though. It’s a problem not only because of bacterial resistance to antibiotics, but also because of the links between antibiotic use and many of the diseases of modernity, and because some popular antibiotics (FLUOROQUINOLONES in particular, but I’ve heard from people who have been devastated by other antibiotics too) are causing multi-symptom, chronic illnesses that are devastating people’s lives.

Overprescription of Fluoroquinolone Antibiotics

How can we get doctors to stop overprescribing fluoroquinolone antibiotics? The NYT article has some good insight and possible courses of action for floxie advocates.

“we asked a group of doctors to place a signed poster in their exam rooms pledging to follow standard guidelines on antibiotic prescription. This tactic, which pressured doctors to act consistently with their own publicly stated commitments, reduced inappropriate prescribing 20 percentage points relative to doctors in a control group who displayed a poster with generic information about antibiotic use.”

A 20% reduction in inappropriate prescribing is pretty good. At the very least, it’s a good place to start.

Guidelines for Prescribing Fluoroquinolones

What should the guidelines for fluoroquinolone (Cipro, Levaquin, Avelox, Floxin, and their generic equivalents) prescriptions be? My suggestions are:

  • Only prescribe fluoroquinolones for verified infections.
  • Only prescribe fluoroquinolones in life-or-death situations.
  • Only prescribe fluoroquinolones if there is no safer antibiotic that can be tried.
  • Review the warning label with the patient.
  • Review the black box warning with the patient. Notify the patient that black box warnings are the most severe warning possible before a drug is removed from the market.
  • Inform the patient that severe musculoskeletal problems have been experienced post-exposure to fluoroquinolones, including, but not limited to, tendon tears that occur months or years after exposure to the drug has stopped.
  • Note that, per the FDA, “A review of the FDA Adverse Event Reporting System (FAERS) was performed to characterize a constellation of symptoms leading to disability that had been observed during FDA monitoring of fluoroquinolone safety reports. This constellation of symptoms will be referred to in this review as ‘fluoroquinolone-associated disability’ (FQAD). While most of the individual AEs that exist within FQAD are currently described in fluoroquinolone labeling, the particular constellation of symptoms across organ systems is not. Individuals with FQAD were defined as U.S. patients who were reported to be previously healthy and prescribed an oral fluoroquinolone antibacterial drug for the treatment of uncomplicated sinusitis, bronchitis, or urinary tract infection (UTI). To qualify, individuals had to have AEs reported in two or more of the following body systems: peripheral nervous system, neuropsychiatric, musculoskeletal, senses, cardiovascular and skin. These body systems were chosen as they had been observed to be frequently involved with the fluoroquinolone reports describing disability. In addition, the AEs had to have been reported to last 30 days or longer after stopping the fluoroquinolone, and had to have a reported outcome of disability.”
  • Fluoroquinolones cause mitochondrial damage and dysfunction, and mitochondrial damage/dysfunction is linked to many diseases, including autoimmune diseases.
  • Fluoroquinolone effects include serious psychiatric problems.
  • Fluoroquinolones are a likely endocrine disruptor.

I suspect that if those guidelines were in every physician’s office, fluoroquinolone prescriptions would decrease significantly.

Present Alternatives to Antibiotics

The NYT article also notes:

“we showed that doctors tended to prescribe less aggressive medications when such options were presented more prominently (one by one, in a vertical column), with more aggressive options presented less prominently (grouped side by side, in a single category). Previous research suggested that listing alternatives individually made them appear more popular — and therefore more appropriate — than when they were grouped together. And indeed, we found that doctors were roughly 12 percent less likely to order more aggressive medications, such as antibiotics, if these options were grouped together, compared with when they were listed individually.”

I think that’s an excellent idea! Give the physician more information and the patient more options. Sounds great!

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Use Social Pressure and Physician Psychology to Achieve Goals

Another approach mentioned in the NYT article is:

“In one approach, doctors received a monthly email informing them of their performance relative to that of their peers. Those with the lowest inappropriate antibiotic prescribing rates were congratulated for being ‘top performers.’ Doctors who were not top performers were told ‘You are not a top performer.’ The email also included a personalized count of unnecessary antibiotic prescriptions and the count for a typical top performer. This ‘peer comparison’ approach almost completely eliminated inappropriate prescribing: from 19.9 percent in the pre-intervention period to 3.7 percent during the post-intervention period — an 81 percent reduction.”

An 81% reduction is impressive and significant!

Peer comparison is powerful because it taps into doctor’s egos. For fluoroquinolones, I think that guilt should be tapped into as well, and with the low-ranking notification should be a story of someone suffering from fluoroquinolone toxicity. These stories may be anecdotal, but they are real stories of people being devastated by these drugs.

Public Accountability

Another approach to curbing antibiotic use mentioned is:

“whenever doctors prescribed an antibiotic that was not clearly called for by the diagnosis, the electronic health record system asked them to provide a short ‘antibiotic justification note.’ The note would be entered into the patient’s medical record and would be visible to others. Introducing this speed bump into the work flow, along with the prospect of social accountability, reduced the inappropriate prescribing rate from 23.2 percent to 5.2 percent — a 77 percent reduction.”

Public accountability is a good thing. This could work well for curbing unnecessary fluoroquinolone prescriptions.

Start Curbing Antibiotic Overprescription by Curbing Fluoroquinolone Overprescription

The article concludes that, “Taken together, our studies suggest that simple and inexpensive tactics, grounded in scientific insights about human behavior, can be extremely effective in addressing public health problems.”

I think that the methods noted above could effectively cut fluoroquinolone use too.

Maybe trying to curb overuse of all antibiotics is too much to take on. Perhaps taking on overuse of one category of antibiotics at a time is an effective thing to do. I suggest that those who are interested in curbing antibiotic overprescription start with fluoroquinolones.

 

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48 Tips for Overcoming Insomnia

Insomnia is horrible and it can wreak havoc on all areas of your life. If you can’t sleep, you can’t think, and if you can’t think, you can’t do your job well. It puts your emotions on edge and relationships suffer. It can affect your appetite and sleep-deprived people will either eat too much or too little. Prolonged insomnia can have seriously detrimental effects on mental health, and after a while of not sleeping, people start to hallucinate.

Unfortunately, insomnia is something that many “floxies” suffer from. Fluoroquinolones inhibit the neurotransmitter GABA-A, “the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system.” Fluoroquinolones have similar effects on neurotransmitters to what happens when people go through benzodiazepine withdrawal–antagonism of the GABA-A receptors which leads to anxiety, psychosis, paranoia, paraesthesia, tinnitus, hypersensitivity to light and sound, tremors, suicidal ideation and tendencies, and INSOMNIA.

There is a vicious cycle when it comes to insomnia–if you can’t sleep, your anxiety and paranoia increase, which can make you even less able to sleep, and the cycle goes on.

Fortunately, many people have found relief from their insomnia. Here are some tips that people have provided for things that have helped them to sleep, and have relieved the cycle of fluoroquinolone-induced insomnia:

  1. Eliminate all sources of caffeine from your diet.
  2. Sleep in a completely dark room–either black-out your windows or set up a cot in a closet.
  3. Use ear-plugs.
  4. Melatonin.
  5. Visualize sleeping soundly in a peaceful place.
  6. Eat a banana before bed.
  7. EHT from Nerium.
  8. Cannabis.
  9. Eliminate alcohol from your diet.
  10. Calm Spirit Pills (Chinese Medicine).
  11. Meditation.
  12. Epsom salt baths.
  13. Borax baths.
  14. Baking soda baths.
  15. Prayer.
  16. A few spritz of magnesium oil spray and a couple of drops of Frankincense oil on a piece of cloth under a pillowcase.
  17. Kavinace PM.
  18. Benadryl.
  19. Tylenol PM.
  20. Herbal/Supplement sleep aids
  21. Honey with sea salt under the tongue.
  22. Valerian root.
  23. Low-dose naltrexone.
  24. EFT (Emotional Freedom Technique).
  25. Acupuncture.
  26. Zinc monomethionine.
  27. Magnesium.
  28. Tart cherry juice.
  29. Exercise 4+ hours before bedtime.
  30. Cut down on salt intake.
  31. Hydrochloric Acid (HCL) supplement.
  32. No screens (computer, phone, t.v.) before bed.
  33. Gaia Sound Sleep.
  34. Natural Calm Magnesium.
  35. 5HTP.
  36. Emperor’s Tea Pills (Chinese Medicine).
  37. Hypnotization (through an app).
  38. Bioidentical progesterone.
  39. Ambien.
  40. Benzodiazepines.
  41. Turn off wi-fi.
  42. Avoid soy.
  43. Sleep-restriction therapy.
  44. Listen to the radio on a foreign station or a boring station.
  45. Relaxing music.
  46. Silva Meditation For Deep Relaxation.
  47. Breathing Exercises.
  48. Don’t eat red-meat for dinner.

I hope that these tips help you! Insomnia can be debilitating and tortuous. I hope that you find some relief from your insomnia through using some of the methods mentioned above!

Sources:

  1. Toxicology Mechanisms and Methods, “Ciprofloxacin-induced neurotoxicity: evaluation of possible underlying mechanisms.
  2. British Journal of Clinical Pharmacology, “Neurotoxic effects associated with antibiotic use: management considerations

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Speaking at the Nov. 5 FDA Meeting About Fluoroquinolones

Please see the following for information about how to speak at the November 5, 2015 FDA meeting. Please contact Jennifer via the contact information listed below in order to sign up to be a speaker. Thank you to all who are willing to speak at the meeting!

On November 5, 2015, the committees will discuss the risks and benefits of the systemic fluoroquinolone antibacterial drugs for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis in patients who have chronic obstructive pulmonary disease, and uncomplicated urinary tract infections in the context of available safety information and the treatment effect of antibacterial drugs in these clinical conditions.

Meeting  location:

FDA White Oak Campus
10903 New Hampshire Avenue
Building 31 Conference Center
The Great Room (Rm. 1503)
Silver Spring, Maryland

Oral presentations from the public will be scheduled between approximately 1:00 p.m. and 2:30 p.m. on November 5, 2015. Please note that we will be accepting requests to speak at the Open Public Hearing session of this meeting through October 14, 2015.  If the unusual situation arises where more people wish to speak than can be reasonably accommodated during the scheduled Open Public Hearing session, we will conduct a lottery to identify (via a random process) those who will be speaking.  You/the speaker will be notified (by e-mail) on October 15, 2015 to confirm the request to speak.

In the meantime, please provide us the following information:

• Full contact information, including address

• Brief statement of the general nature of the evidence or arguments you wish to present

• Amount of time requested

• Any audio/visual requirements

• The organization(s) you will be representing, if any

Please let me know if you have any questions.  Thank you for your interest in the FDA’s Antimicrobial Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee.

Kind Regards,

Jennifer Shepherd, RPh.
LCDR, USPHS
Designated Federal Officer, AMDAC, Food and Drug Administration (FDA),Center for Drug Evaluation and Research (CDER), Office of Executive Programs (OEP), Division of Advisory Committee and Consultant Management (DACCM)
White Oak Building 31, Room 2417
10903 New Hampshire Avenue
Silver Spring, MD 20993
Main Telephone: (301) 796-9001 – Fax: (301) 847-8533
Email: AMDAC@fda.hhs.gov

 

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Advocacy Opportunity – FDA Meeting to Discuss Fluoroquinolones

ADVOCACY OPPORTUNITY 

The FDA (Food and Drug Administration) is holding a meeting on November 5, 2015 to discuss the benefits and risks of fluoroquinolones. Per the FDA notice, the agenda for the meeting is:

“The committees will discuss the risks and benefits of the systemic fluoroquinolone antibacterial drugs for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis in patients who have chronic obstructive pulmonary disease, and uncomplicated urinary tract infections in the context of available safety information and the treatment effect of antibacterial drugs in these clinical conditions.”

They are opening the meeting for public testimony and if you are in the Silver Spring, Maryland area I encourage you to attend the meeting and to testify at it. (I would love to go, but I’m in Colorado, so not exactly nearby.)

They are also accepting written testimony. Please send your story/testimony to Jennifer Shepherd, the contact person, by October 22, 2015. Jennifer’s contact information is:

Jennifer Shepherd, RPh.
Center for Drug Evaluation and Research
Food and Drug Administration
10903 New Hampshire Avenue
WO31-2417
Silver Spring, MD 20993-0002
Phone: 301-796-9001
Fax: 301-847-8533
E-mail: AMDAC@fda.hhs.gov

PLEASE take the time to tell your story to the FDA. The adverse effects of fluoroquinolones are too severe for it to be appropriate for them to be used for sinusitis or uncomplicated urinary tract infections. This is your opportunity to share your story directly with the FDA, and the committee that determines how fluoroquinolones are used.

More information can be found in these announcement links –

http://www.fda.gov/AdvisoryCommittees/Calendar/ucm465275.htm

https://www.federalregister.gov/articles/2015/10/01/2015-24836/joint-meeting-of-the-antimicrobial-drugs-advisory-committee-formerly-known-as-the-anti-infective

THANK YOU!!!

 

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Can Fluoroquinolones Activate Mast Cells?

What is the connection between fluoroquinolone toxicity and mast cell activation / histamine intolerance? Can fluoroquinolones trigger mast cell activation and histamine intolerance?

The symptoms of mast cell activation are similar to those of fluoroquinolone toxicity. According to Mastocytosis Society Canada, the symptoms of mast cell activation are:

skin lesions or sores, skin rash, spots, redness, hives, persistent fatigue, itching, flushing & severe sweating, joint, bone pain, headaches, tachycardia (racing heartrate), eyes tearing/dry, eye pain, persistent body/tissue pain, difficulty exercising, vertigo, episodes of low body temperature, unexplained Vitamin B12 deficiency, scents/odors/chemical reactions, difficult menses (females), numbness & tingling in face and extremities, skin feels on fire, unexplained anxiety, sudden drops in blood pressure, fainting, persistent diarrhea, vomiting, unexplained weight loss, cognitive impairment, sinus problems, chest pain, vision problems, hair loss, mouth sores, nausea, swelling & inflammation, odd reactions to insect stings, anesthesia difficulties, anemia, thyroid problems, decreased bone density, unexplained weakness, shortness of breath, sunlight sensitivity, temperature (hot/cold) sensitivity, difficulty with foods, drinks, anaphylactoid reactions, anaphylaxis, gastrointestinal pain, bloating, unexplained medication reactions, enlarged liver/spleen, liver/spleen/bladder/kidney pain, enlarged lymph nodes, frequent urination, recurring infections, neuropathic pain, constipation, iron deficiency, unexplained bruising, bleeding, malabsorption, intermittent tinnitus or hearing problems.

That’s a pretty comprehensive list of fluoroquinolone toxicity symptoms too. (Though, as I discussed with Dr. Wahls in episode 14 of The Floxie Hope Podcast, all of the multi-symptom, chronic diseases of modernity have more in common with each other than they don’t, and should probably all just be categorized as cellular dysfunction disorders and treated similarly.)

Several floxies who have been able to get a diagnosis from a doctor have come back with a diagnosis of mast cell activation, or a disease that is related to mast cells. For example, one floxie friend’s doctors have diagnosed him with eosinophilia, a disorder that is related to mast cells and histamine intolerance. Other floxies have been diagnosed as histamine intolerant, and instructed to go on a low-histamine diet. As noted above, many floxies have symptoms of mastocytosis, and it is possible that fluoroquinolones activate mast cells and trigger mastocytosis.

Mast cell disorders are considered to be rare, but, according to Mastocytosis Society Canada, “escalation in the prevalence of these patients worldwide has resulted in a flurry of medical research ongoing in numerous countries. This indicates that these disorders may not be rare, but rather have been commonly misidentified and unfortunately for patients worldwide, commonly undiagnosed. Since approximately 2005, every year there are new theories, classifications, and adjustments to the mastocytosis definitions due to escalation of patients presenting with these disorders worldwide.”

I found the following information connecting fluoroquinolones and mast cell activation / mastocytosis:

  • From the International Journal of Tissue Reaction’s article, Effect of levofloxacin and ciprofloxacin injection on permeability of the tail vein in mice and skin microvasculature in rats, “These results suggest that LVFX and CPFX increase vascular permeability through the induction of histamine release from mast cells in rodents.” (LVFX is levofloxacin and CPFX is ciprofloxacin.)
  • From the Journal of Pharmacy and Pharmacology’s article, Characterization of Histamine Release Induced by Fluoroquinolone Antibacterial Agents In-vivo and In-vitro, “Intravenous injection of levofloxacin and ciprofloxacin at 1–10 mg kg−1 produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg−1, whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells.” Note that in studies beagle puppies have been made lame by fluoroquinolones.
  • From the Archives of Toxicology’s article, Differential response of mast cells separated from various organs and basophils of dogs to the fluoroquinolone antimicrobial levofloxacin, “Histamine releases induced by the fluoroquinolone antimicrobial levofloxacin (LVFX) were investigated using mast cells separated from various organs and peripheral basophils of dogs, being the most susceptible species to quinolone derivatives, in both in vivo and in vitro systems. An intravenous infusion of LVFX at 30 mg/kg over a 30-min period produced endogenous histamine release from 5 min, and a maximum at 30 min, in which the plasma LVFX concentration was approximately 50 µM. A close correlation (r=0.87, n=20) between histamine and LVFX concentrations in plasma during the infusion was observed. In the in vitro study, LVFX at 30 µM or more caused histamine release from mast cells separated from the liver and skin, but not from the gastric mucosa, lung, and peripheral basophils. More exactly, the liver mast cells were most susceptible to LVFX among the organs tested. On the other hand, compound 48/80, a prototype histamine liberator, elicited the histamine release from the liver or skin mast cells at 10 µg/ml, and the calcium ionophore A23187 at 1 µM exhibited the histamine release from the mast cells derived from all organs examined. Histochemical analysis revealed that the liver and skin mast cells had positive reaction for both alcian blue and safranin staining, but the gastric mucosa and lung mast cells were only positive for alcian blue staining, indicating that LVFX preferably activated the connective tissue-type mast cells rather than the mucosal-type mast cells. The degranulation of the liver and skin mast cells brought about by either LVFX or compound 48/80, unlike the calcium ionophore A23187, was blocked by pretreatment with pertussis toxin, suggesting the involvement of pertussis toxin-sensitive G proteins. The results obtained from the canine experiments strongly suggest that LVFX induces histamine release from the connective tissue-type mast cells distributed mainly in the liver, somewhat in the cutaneous tissue, through the activation of pertussis toxin-sensitive G proteins.”

The articles noted above are all from animal studies, not human studies, but they show that fluoroquinolones can activate mast cells and histamine release in mammals, and it’s reasonable to think that they may do the same things to humans that they do to dogs. Also, the similarity between fluoroquinolone toxicity symptoms and mastocytosis symptoms, though not a smoking gun, indicate that further studies of the affects of fluoroquinolones on mast cells should be done.

A few good resources for people with mastocytosis, and it’s possible that floxies are in that category, are:

  1. Dr. Theoharides web site
  2. Mastocytosis Society Canada web site
  3. The Low Histamine Chef web site
  4. Alison Vickery’s web site

I suspect that mast cells are profoundly affected by fluoroquinolones and that mast cell activation is a big part of fluoroquinolone toxicity. The potential options, and mechanisms for fluoroquinolone toxicity, are mind-boggling. Add mast cell activation to the list.

 

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Pharmaceuticals Contraindicated with FQs

I’m not a doctor. If you want to know exactly what medications you should or shouldn’t take given your personal medical history, please ask your doctor. Please also know that these are not hard and fast rules for every floxie. Given that there is so little research into fluoroquinolone toxicity, there aren’t many definitive rules for what pharmaceuticals people can and cannot take post-flox. Following is information though, and with information, perhaps you can make a more informed choice about which drugs to take and which ones to avoid.

From the Cipro/ciprofloxacin warning label:

  • Corticosteroid drugs increase the risk of tendon ruptures (in the black box warning).
  • “Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug.” Drugs metabolized by CYP1A2 include Alosetron/Lotronex, Caffeine, Clozapine/Clozaril, Flutamide/Eulexin, Frovatriptan/Frova, Melatonin, Mexiletine/Mexitil, Mirtazapine/Remeron, Olanzapine/Zyprexa, Ramelteon/Rozererm, Rasaglinie/Azilect, Robinirole/Requip, Tacrine/Cognex, Theophylline, Tizanidine/Zanaflex, Triamterene/Dyrenium, Zolmitriptan/Zomig (Source).
  • “Concomitant administration with tizanidine is contraindicated”
  • “Concomitant administration of ciprofloxacin with theophylline decreases the clearance of theophylline resulting in elevated serum theophylline levels and increased risk of a patient developing CNS or other adverse reactions.”
  • “Ciprofloxacin also decreases caffeine clearance and inhibits the formation of paraxanthine after caffeine administration.”
  • “Ciprofloxacin should be avoided in patients with known prolongation of the QT interval, risk factors for QT prolongation or torsade de pointes (for example, congenital long QT syndrome , uncorrected electrolyte imbalance, such as hypokalemia or hypomagnesemia and cardiac disease, such as heart failure, myocardial infarction, or bradycardia), and patients receiving Class IA antiarrhythmic agents (quinidine, procainamide), or Class III antiarrhythmic agents (amiodarone, sotalol), tricyclic antidepressants, macrolides, and antipsychotics.”
  • “Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.”
  • “Hypoglycemia has been reported when ciprofloxacin and oral antidiabetic agents, mainly sulfonylureas (for example, glyburide, glimepiride), were co-administered, presumably by intensifying the action of the oral antidiabetic agent (see ADVERSE REACTIONS). The concomitant administration of ciprofloxacin with glyburide has, on rare occasions, resulted in severe hypoglycemia.”
  • Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in the serum.”
  • “Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin potentially leading to increased plasma levels of methotrexate.”
  • Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in shorter time to reach maximum plasma concentrations.”
  • NSAIDs – “Non-steroidal anti-inflammatory drugs (but not acetyl salicylic acid) in combination of very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies.”

fluoroquinolone-lawsuit-trulaw

There are many conditions that may (or may not) be related to fluoroquinolone toxicity that have “drugs to avoid” lists. Here are some of them:

There are a lot of questions about timing of drug administration that neither I, nor anyone else to my knowledge, know the answers to. It’s right there on the warning label that concurrent administration of ciprofloxacin and NSAIDs can induce convulsions (seizures), but does that mean that people who have taken ciprofloxacin in the past should avoid NSAIDs in the future? There is anecdotal evidence that NSAIDs should be avoided by floxies, but some people seem to handle them fine, and that’s valid anecdotal evidence too. When might it be safe for a floxie to take the drugs listed above? I don’t know the answer to that.

Another question that I don’t know the answer to is – Do adverse reactions to fluoroquinolones either uncover or cause another syndrome? Some of the possible syndromes that fluoroquinolone toxicity may or may not be related to are G6PD Deficiency and porphyria. Both G6PD Deficiency and porphyria can be brought on by adverse reactions to drugs. It’s possible that fluoroquinolone toxicity is related to these diseases, but I haven’t seen much evidence to support that assertion (so please just take it for what it’s worth).

I encourage everyone reading this to read the entire warning label for any drug you are prescribed, go over the potential benefits and risks with your doctor, and look up any drug you’re prescribed on www.askapatient.com and http://www.peoplespharmacy.com/. After that due diligence, I wish you luck with whatever decision you make. Know that fluoroquinolones are more dangerous than many, maybe most, drugs, and that sometimes pharmaceuticals are necessary, so try not to be too anxious about having to take one.

I hope this helps!

 

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Babies!

The floxie community is experiencing a baby boom. There are a lot of first-time moms and dads in the floxie community and I wanted to say CONGRATULATIONS to all of them!

The babies that have recently been born to floxie moms and dads are healthy, happy and beautiful. They are blessings to their parents and the world.

When I first got floxed, I was concerned about how my fluoroquinolone toxicity reaction would affect any future offspring I might have. It’s a worry that a lot of people of child-bearing age have. I was comforted by people like Briean, who has had 2 healthy children post-flox. I hope that all floxies find comfort in the smiling faces of the babies who have recently been born to floxed moms and dads. So far, all of the kids of floxies seem to be healthy and unaffected by the fluoroquinolone toxicity of their parents. Whatever made us vulnerable to getting floxed, or changes to our bodies as a result of getting floxed, don’t seem to be hurting the next generation.

Of course, it’s impossible to tell how a person will end up, or how healthy she or he will be in the long run, when she or he is only 6 months old, but, so far so good, as far as the health of babies born to floxed parents goes.

I have written about my fears about the intergenerational effects of fluoroquinolones (it seems like a particularly horrible idea to give topoisomerase interrupting drugs to people of child-bearing age). But it should be noted that my fears about the potential intergenerational effects of fluoroquinolones are just fears at this point—they have not been validated by any studies of intergenerational effects of fluoroquinolones. I whole-heartedly think that studies should be done. But the anecdotal evidence of lots of healthy, smiling babies being born to floxed parents, that is available now, is worth a lot. I hope that the healthy babies grow into healthy children and healthy adults—presumably, they will.

Should you, or I, or anyone else who has been floxed, have kids? I don’t think that there is any reason why a past history of fluoroquinolone toxicity should be taken into consideration when deciding whether or not to have kids, seeing as the babies who have been born to floxies are healthy. It should depend on whether or not this looks like something you want to sign up for:

Seriously? You do? Well, go for it then. 🙂

The knowledge that floxies have about gene SNPs, nutrition, antioxidants, etc. may even make their children more healthy than they would have been. Floxies know to avoid fluoroquinolones, and they will certainly never let their children get floxed. Avoiding fluoroquinolones is certainly a step in the direction of long-term health and happiness.

Again, CONGRATULATIONS to the floxie parents out there! Your babies are gorgeous! I hope that they live a long, happy, healthy, wonderful life and that they bring healing joy to your life! Give all your little ones a hug from me, and know that I wish them all the joy, love and health this world can bring.

Xoxo

-Lisa

 

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But Antibiotics Save Lives!!!

David Wolfe, a health, eco, nutrition and natural beauty expert (more information about him can be found HERE) posted the picture above on facebook.  He has more than 1,200,000 facebook followers and I greatly appreciate his help in spreading the word about the dangers of fluoroquinolones!  Many people commented on picture and told their story of how fluoroquinolones hurt them.  There are a lot of us out there, and the more the word gets spread, the more likely change is.

As always, there were some nay-sayers.  Honestly, there were a lot more people sharing their stories than there were nay-sayers, and I’m not suggesting that we all gang up on them, but I have some thoughts about the some of the nay-saying comments.  Here are some examples of the nay-saying comments:

“Want to go back to the dark ages before antibiotics?”

“If we didn’t have antibiotics…alot of people would die..”

“People who don’t believe in medicine should live on their own island of ignorance and watch their life expectancy drop to that of their intelligence.”

“Without antibiotics you can’t treat people with bacterial infections. Aka ur screwed. Pls don’t mislead the public. stick to quotes. My sincere request. Please.”

“Antibiotics have saved over 1 billion lives. Mr Wolfe’s irresponsible comments will cause deaths!!”

“WAIT! Are you trying to scare people off antibiotics now??? How many people would have to die of preventable illnesses before you retract this?”

Sigh.  Why do these people think that all antibiotics are the same?  Why do they think that all antibiotics are safe?  Why do they think that warning people about the dangers of fluoroquinolones equates to being anti-antibiotic?  Where is the grey area?  Can’t some antibiotics be appropriate for use in some circumstances but not others?  Can’t different antibiotics have different safety profiles?  Isn’t information about the dangers of drugs valuable so that people can make informed choices?  Doesn’t it matter that fluoroquinolones damage nerves, the musculoskeletal system, the eyes and kidneys?  Can’t that information lead to greater consumer knowledge and informed consent when fluoroquinolones are prescribed?  Can’t the dangers of fluoroquinolones be acknowledged without being “anti-antibiotic?”  Can’t we fight for prudent and appropriate use of all antibiotics (especially FQs) without negating the lives that have been saved by antibiotics (including FQs)?  GREY AREA, folks!  The world isn’t black and white.  Sigh.

A quote from my most recent post, “‘The 21st Century Cures Act’ Is On Its Way – Here’s Why You Haven’t Heard About It” seemed like an appropriate response to a lot of the nay-sayers.  Feel free to use this if you want it:

“A healthy and balanced microbiome (“the ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our body space”) is crucial for all areas of health, and a disturbed microbiome has been linked to all of the diseases of modernity, including mental health disorders, neurodegenerative diseases like Parkinson’s and Alzheimer’s, autoimmune diseases, inflammatory bowel disease and Crohn’s disease, mysterious diseases like fibromyalgia, autism, etc. And while there is acknowledgement of the role that a healthy microbiome plays in these diseases, researchers and journalists alike have been loath to acknowledge the role antibiotics have played in contributing to these diseases of modernity. No one wants to be anti-antibiotic. Everyone knows that antibiotics have saved millions of lives, but that doesn’t mean they are without consequences. And the good that penicillin has done doesn’t mean that all antibiotics are equally safe or effective. I can make a pretty thorough argument that fluoroquinolone antibiotics, like Cipro/ciprofloxacin and Levaquin/levofloxacin, drugs that work by “inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination,” are at least partially responsible for many of the diseases of modernity (more information can be found HERE, HERE and HERE). Fluoroquinolone antibiotics do not have the same safety profile as amoxicillin, and to assume that they do because both are categorized as antibiotics, is foolish on multiple levels.”

That’s my two cents of a response to the people who say things like the quotes above.  Also, quit giving carte blanche to the pharmaceutical companies if they label their dangerous drug as an antibiotic, because that’s just stupid.

Now I’m done.  🙂

 

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Hacking Fluoroquinolone Toxicity via the Nervous System

I recently read Hacking the Nervous System, about how vagus nerve tone is connected to chronic illness.

The vagus nerve is a huge nerve that connects the brain to the various organs throughout the body. Our autonomic nervous system (ANS) is controlled via the vagus nerve. It connects the digestive tract to the brain and when you feel butterflies in your stomach, that feeling is traveling from your stomach to your brain via your vagus nerve. Breathing and heart rate, as well as other ANS functions, are controlled through the vagus nerve.

The brain coordinates ANS functions using the vagus nerve, and how smoothly those functions are being coordinated is referred to as the “tone” of the vagus nerve.

Hacking the Nervous System goes over the hypothesis that inflammation is related to vagal nerve tone, and that vagal nerve tone has a lot to do with chronic, multi-symptom illnesses, like autoimmune diseases. I wonder if vagal nerve damage has something to do with fluoroquinolone toxicity, and I wonder if things that improve vagal tone can help floxies to heal. I suspect so on both counts.

Vagal nerve tone is important, and “Research shows that a high vagal tone makes your body better at regulating blood glucose levels, reducing the likelihood of diabetes, stroke and cardiovascular disease. Low vagal tone, however, has been associated with chronic inflammation.”

Little is known about how vagal tone relates to health. One of the scientists interviewed for Hacking the Nervous System stated, “We don’t even know yet what a healthy vagal tone looks like.” They are looking into it though, and vagal nerve stimulating implants are being used in clinical trials. (Read Hacking the Nervous System for more information about the implants.)

Improving Vagal Tone

Things that are less drastic and invasive than a vagal nerve stimulating implant can improve vagal tone. For example, meditation can improve vagal tone. “Those who meditated showed a significant rise in vagal tone, which was associated with reported increases in positive emotions. ‘That was the first experimental evidence that if you increased positive emotions and that led to increased social closeness, then vagal tone changed,’ Kok says.”

To drastically oversimplify a complex process, things that make you feel good, socially connected, happy, relaxed, etc. improve vagal tone. Conversely, stress and trauma decrease vagal tone. Many things that helped me through my fluoroquinolone toxicity journey were things that are purported to improve vagal tone – meditation, healing arts (e.g. dancing and music), mindfulness, acupuncture, chiropractic, and eliminating stressful stimuli from my life (e.g. getting off the internet). An article in Psychology Today, “How Does the Vagus Nerve Convey Gut Instincts to the Brain?” notes that, “Using positive self-talk and taking deep breaths is a quick and easy way to engage the vagus nerve and parasympathetic nervous system to calm yourself from both the top-down and from the bottom-up.”

Additionally, exercise also improves vagal tone. Playful exercise is best, but regardless, movement is good for vagal tone.

Vagal Tone and GABA Neurotransmitters

A decrease in vagal tone may be connected to damage to GABA neurotransmitters. The article in Psychology Today, “How Does the Vagus Nerve Convey Gut Instincts to the Brain?” notes that, “The most exciting discovery of this study is that under closer scrutiny of the rats’ brains, the researchers found that the loss of signals coming up from the abdomen via the vagus nerve altered the production of both adrenaline and GABA in the brain.” The article Selective antagonism of the GABAA receptor by ciprofloxacin and biphenylacetic acid published in the British Journal of Pharmacology noted that, “Ciprofloxacin (10–3000 μm) inhibited GABAA-mediated responses in the vagus nerve with an IC50 (and 95% CI) of 202 μm (148–275). BPAA (1–1000 μm) had little or no effect on the GABAA-mediated response but concentration-dependently potentiated the effects of ciprofloxacin by up to 33,000 times.” Let me highlight and reiterate: BPAA, which is a derivative or an NSAID, potentiated the harmful effects of ciprofloxacin on GABA receptors by up to 33,000 times. (WHOA!).

The ANS dysfunction that many floxies experience is likely connected to vagal nerve health, as the ANS is controlled via the vagus nerve.

girl ocean UNLOCK THE POWER OF YOUR VAGUS NERVE (4) (1)

A Hypothesis for Fluoroquinolone Toxicity

A possible hypothesis for fluoroquinolone toxicity is that people who get floxed have an underlying, dormant hiatal hernia (they’re pretty common) that is exacerbated by the FQ and the massive amount of oxidative stress induced in the gut by the FQ. The hiatal hernia irritates the vagus nerve and triggers ANS dysfunction that is self-perpetuating. The damage to the vagus nerve also alters the production of neurotransmitters, especially GABA, and hormones.

It’s possible, and I believe that the vagus nerve is a big part of the FQ toxicity puzzle. However, please know that I have not found much scientific research to support this hypothesis. Also, other possible causes for fluoroquinolone toxicity mentioned in the post, What is Fluoroquinolone Toxicity? have more supporting evidence supporting. However, all of these causes are not mutually exclusive, and may all play a role.

Measuring Vagal Tone

In Hacking the Nervous System it is noted that:

The strength of your vagus response is known as your vagal tone and it can be determined by using an electrocardiogram to measure heart rate. Every time you breathe in, your heart beats faster in order to speed the flow of oxygenated blood around your body. Breathe out and your heart rate slows. This variability is one of many things regulated by the vagus nerve, which is active when you breathe out but suppressed when you breathe in, so the bigger your difference in heart rate when breathing in and out, the higher your vagal tone.”

Another term for the relationship between breath and heart rate is respiratory sinus arrhythmia breathing (RSA breathing). I found the following passage from A Headache in the Pelvis to be interesting:

RSA breathing is a description of the relationship between heart rate and breathing and refers to the heart rate varying in response to respiration. RSA is a phenomenon that occurs in all vertebrates. You can experience the phenomenon of RSA by taking your pulse and noting that when you breathe in, the heart rate increases slightly and when you breathe out the heart rate decreases slightly. There is considerable research that indicates that when there is balance and health, the heart rate and the breath move robustly together as inhalation occurs, heart rate increases as exhalation occurs, heart rate drops.

Under circumstances of mental or physical disease the relationship between breathing and heart rate is disturbed. When individuals suffer panic attacks for instance, RSA is lower and disturbed. When they recover from panic disorders their RSA breathing becomes stronger, more balanced, and robust. The higher and stronger the heart rate variability is in relationship to appropriate respiration, the higher is the general level of health and well being. For example healthy children generally have very robust RSA breathing in which the heart rate can sometimes vary 40 beats or more between inhalation and exhalation.

Reduced RSA is thought to be an indicator of an adverse prognosis for people with heart disease. Generally disturbed RSA is indicative of early problems in the healthy functioning of the autonomic nervous system as it relates to a number of diseases. It has been suggested that one measure of the therapeutic effect or safety of a drug is whether it positively or negatively affects RSA.” (emphasis added).

Vagal tone and RSA breathing are either one and the same, or, at the very least, highly related. As doctors Wise and Anderson note in A Headache in the Pelvis, the effects of pharmaceuticals on RSA (or vagal tone) should be measured and noted, and those drugs that have deleterious effects on RSA should only be taken in extreme circumstances. The effects of fluoroquinolones on RSA breathing and vagal tone are unknown.

Coordinating Breathing with Heart Rate

I’m a huge fan of breathing exercises for health. The post Breathing Exercises for Health goes over some thoughts on breathing exercises for floxies. The easiest breathing exercise that I use is just saying, “OM” – take a deep breath in and let it out slowly while singing/chanting/groaning “OM.”

To get my heart and breath regulated, I took a Chinese herb called Suxiao Jiuxin Wan. It’s supposed to improve heart qi. (Heart qi? What? I’m not sure of this, but I suspect that “heart qi” is related to vagal nerve tone, but people who know more about this can either prove or disprove this notion.) Suxiao Jiuxin Wan has been shown to help people with angina and it calmed my racing heart dramatically. I’m not a doctor or Chinese herb specialist, so please do your own research, but it helped me immensely.

Conclusion

Fluoroquinolone toxicity is an incredibly complex disease with many facets. Is the nervous system involved? Absolutely. Is the vagus nerve involved? Almost certainly. But, unfortunately, not much research has been done on how fluoroquinolones relate to either the vagus nerve specifically or the nervous system generally.

Improving vagal tone has multiple health benefits for floxies and non-floxies alike. Most of the things that can be done to improve vagal tone are pretty simple and inexpensive. Meditate – be socially connected – exercise – do breathing exercises – minimize stress – think positively. None of those are magic bullets, they’re all processes and practices. They’re all good for you, free, and certainly worth a try.

 

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Warning: Fluoroquinolone Antibiotics May Ruin Your Life

Cipro warning label

Here is a new post on Hormones Matter:

WARNING: FLUOROQUINOLONE ANTIBIOTICS MAY RUIN YOUR LIFE

Chandler Marrs, founder of Hormones Matter, wisely asked, “We fight for better labeling, but is that really the right battle? How about safer medications? How about a better understanding of who is at risk and what percentage of people might experience those reactions? How about accountability when reactions occur?”

Indeed.

 

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Post-Ebola Syndrome Emerges In West Africa – Links To Bayer Explored

 

Very sadly, “post-Ebola syndrome” looks a lot like fluoroquinolone toxicity syndrome. Bayer pumped 3 million euros of Cipro into West Africa during the crisis. Now people are chronically ill with a “mysterious disease.” It should be noted that Cipro has never been shown to be effective at treating VIRUSES like ebola. It is an unapproved use. Sending millions of euros of Cipro to West Africa was a medical experiment that was, and is, criminal.

A post about this horrible situation is in Collective Evolution.

Post-Ebola Syndrome Emerges In West Africa – Links To Bayer Explored

 

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Studies Link Topoisomerase Interrupting Drugs to Autism

It has recently been discovered that, “chemicals or genetic mutations that impair topoisomerases, and possibly other components of the transcription elongation machinery that interface with topoisomerases, have the potential to profoundly affect expression of long ASD (autism spectrum disorder) candidate genes.”  (1)

Topoisomerases are enzymes that are essential for DNA and RNA replication and reproduction.  Without topoisomerase enzymes, DNA and RNA supercoiling fail to resolve correctly during cell division and gene transcription.  Topoisomerases are like oil to the DNA and RNA replication engine—making the process go smoothly.  Without topoisomerases, DNA and RNA supercoiling jams up and “over-heats,” causing transcription errors.  Topoisomerases are also “integral for gene expression, as they resolve DNA supercoiling that is generated during transcription.” (1)

DNA_replication_en.svg

Many pharmaceutical drugs inhibit topoisomerases.  Most of these drugs are chemotherapeutic agents such as topotecan, a drug used to treat various forms of cancer.  The most widely used topoisomerase inhibitors are fluoroquinolone antibiotics—Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin and Floxin/ofloxacin—drugs used to treat simple urinary tract, prostate, sinus and other infections.  The fluoroquinolone antibiotics that are in wide use were first patented in the late 1980s and their use increased steadily from then until now, with 26.9 million prescriptions for orally and IV administered fluoroquinolones written in 2011. (2)  A similar number of topically administered fluoroquinolone prescriptions have been written, and though orally and IV administered fluoroquinolones are not recommended for use in children because they cause cartilage lesions in juvenile animals (3), topically administered fluoroquinolones are approved for use in children as young as 6 months of age (4), and are regularly given to young children in the form of ear and eye drops.

Autism rates have been skyrocketing since the 1980s, with the most recent numbers out of the CDC stating that one in 68 American children is on the autism spectrum. (5)

prevalence-graph1

It is likely that a variety of environmental and genetic components has led to the staggering figure of 1 in 68 American children on the autism spectrum.  Studies have focused on vaccines (and there are vaccine injured children), but epidemiological studies have suggested that factors other than vaccines are likely at play.  Birth control pills, acetaminophen, antidepressants and other categories of drugs have been pointed to for their deleterious effects on the human brain, and their possible contributions to the increasing number of people on the autism spectrum.

STUDY SUMMARY AND IMPLICATIONS

In this article, I will go over some studies that point to topoisomerase interrupting drugs as a potential cause of autism.  The studies are out of the University of North Carolina at Chapel Hill—“Topoisomerases facilitate transcription of long genes linked to autism,” published in Nature (as well as the corresponding author manuscript), and “Topoisomerase 1 inhibition reversibly impairs synaptic function,” published in PNAS.  I will link these studies to the fact that fluoroquinolones are also topoisomerase interrupters.

The mechanism of action for Cipro/ciprofloxacin is:

“The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.”(6)

The mechanism of action for other fluoroquinolones—Levaquin/levofloxacin, Avelox/moxifloxacin, Floxin/ofloxacin, and their generic equivalents—are the same.

Why anyone thought that it was a good idea to give DNA disrupting chemotherapeutic drugs to children with ear infections is beyond my comprehension, but it happens every day.

Fluoroquinolone use has gone up hand in hand with autism rates.  As critics of all possible causes of autism are quick to point out, correlation does not mean causation.  While that criticism is true, the causes of autism are undoubtedly correlated with autism rates, and thus correlations should be examined.

The articles that I will be reviewing note that topoisomerase interrupting drugs profoundly affect the expression of genes related to autism.  A large number of the genes that have been found to be related to autism are particularly long and complex, and are related to neurotransmitter synaptic function and neurodevelopment.  The expression of these long genes is affected by topoisomerase interrupting drugs, as one may expect when noting that topoisomerases are necessary for gene transcription, and longer genes can more easily get mis-transcribed when exposed to topoisomerase interrupting drugs.

fluoroquinolone-lawsuit-banner-trulaw

Topoisomerase enzymes are expressed throughout the adult brain, and thus the connections between topoisomerase inhibiting drugs and neurodegenerative diseases should be explored along with connections between those drugs and autism.  It is noted in “Topoisomerases facilitate transcription of long genes linked to autism” that, “Our findings suggest that chemicals and genetic mutations that impair topoisomerases could commonly contribute to ASD and other neurodevelopmental disorders.”

Both “Topoisomerases facilitate transcription of long genes linked to autism” and “Topoisomerase 1 inhibition reversibly impairs synaptic function” examine the effects of topotecan, a topoisomerase 1 (TOP1) inhibitor, on autism related genes and synapses.  Studies of the effects of fluoroquinolones, topoisomerase 2 and 4 interrupters, have not yet been published.

It should be noted that the existing studies have looked at nuclear gene expression, and that the effects of topoisomerase interrupting drugs on the expression of mitochondrial and microbiome genes have not yet been explored.

The implications of “Topoisomerases facilitate transcription of long genes linked to autism” and “Topoisomerase 1 inhibition reversibly impairs synaptic function” are potentially huge given the wide-spread use of topoisomerase interrupting fluoroquinolones, both directly in humans and in agriculture.  If fluoroquinolones are conclusively linked to autism, their use in children and people of child-bearing age (exactly how gene expression is affected by topoisomerase interrupting drugs, and what the intergenerational effects may be, are not yet known) should be prohibited—effective immediately—regardless of what the average physician who knows little about the effects of topoisomerase inhibitors on gene expression thinks about the “excellent safety record” of fluoroquinolones as a class of drugs.

As a person who has been hurt by ciprofloxacin, a fluoroquinolone antibiotic, I am not without bias—but I do not think that it’s unreasonable to assert that all topoisomerase interrupting drugs should be strictly limited—especially if they’re connected in any way to autism or neurodegenerative diseases.

STUDIES LINKING TOPOISOMERASE INTERRUPTING DRUGS TO AUTISM

Topoisomerases facilitate transcription of long genes linked to autism” concludes that:

“Our data suggest that chemicals or genetic mutations that impair topoisomerases, and possibly other components of the transcription elongation machinery that interface with topoisomerases, have the potential to profoundly affect expression of long ASD candidate genes.  Length-dependent impairment of gene transcription, particularly in neurons and during critical periods of brain development, may thus represent a unifying cause of pathology in many individuals with ASD and other neurodevelopmental disorders.”

This conclusion has multiple levels of significance.  It involves a shift in thinking about ASD as either a genetic disorder or an environmentally caused disorder, to noting the interplay between genes and the environment (epigenetics).

The study is also significant in that it notes that genes that encode synaptic function and neurodevelopment, that are also related to autism, are particularly long and complex.  Those long and complex genes aren’t transcribed properly when topoisomerase enzymes are inhibited via pharmaceuticals.  When topoisomerase interrupting drugs impair gene transcription, expressions of long genes become impaired.

Whether or not the silencing of expression of particularly long genes through topoisomerase interrupting drugs is a possible unifying cause of autism spectrum disorders depends on the prevalence of topoisomerase interrupting drugs in our environment.  Topotecan, the topoisomerase 1 interrupter that was studied, is a chemotherapeutic drug that is only used in cancer patients, and is rarely used in pediatric patients.  Fluoroquinolone antibiotics, on the other hand, are topoisomerase interrupting drugs that are used commonly in the general population, including the pediatric population, and are even used in agriculture and thus are present in the food we eat, the soil our food is grown in and even the water we drink.

More than 20 million prescriptions for fluoroquinolones—topoisomerase interrupting drugs—have been written each year for more than two decades.  One is hard pressed to find an adult American who has not had at least one fluoroquinolone prescription in his or her lifetime.  Fluoroquinolone use has gone up hand in hand with incidence rates of autism.  As noted earlier, that correlation does not mean causation, but if topoisomerase interrupting drugs in our pharmacies and environment are a unifying cause of ASD (and other neurodegenerative diseases of modernity), fluoroquinolones would need to be the causal factor, not prudently used chemo drugs like topotecan.  Studies looking into this line of thinking are pending, and the similarities between fluorquinolones and chemotherapeutic topoisomerase interrupters have not escaped the attention of the researchers looking into the relationships between topoisomerases and autism.

The UNC researchers found that, “topotecan reduced expression of nearly all extremely long genes in mouse cortical neurons,” (1) and were able to reproduce the same results in human neurons.  Interestingly, not only was the expression of long genes suppressed, “topotecan increased expression of a majority of genes that were <67 kb in length, although the magnitude of this increase was very small for most genes.” (1)  The expression of long genes, those genes that are involved in encoding neural synapses, was downgraded, whereas the expression of shorter genes was up-regulated.

An example of a particularly long gene that is related to ASD whose expression is altered by topotecan is “Ubiquitin-protein ligase E3A (Ube3a), a gene that affects synaptic activity and that is deleted or duplicated in distinct neurodevelopmental disorders (Angelman syndrome and autism, respectively)” (7)  Ube3a is “normally expressed only from the maternal allele in neurons and regulates synaptic function.” (1)  However, in cells that have been exposed to topoisomerase interrupting drugs, the paternal allele of Ube3a is transcriptionally upregulated.  “Duplication of the chromosomal region containing maternal Ube3a is frequently detected in individuals with autism.”

Other particularly long genes are affected by topoisomerase interrupting drugs include:

“many genes down-regulated by topotecan are associated with synapses, cell adhesion, and neurotransmission.  Moreover, a number of those down-regulated long genes are associated with autism, including Neurexin-1 (Nrxn1; 1059 kb), Neuroligin-1 (Nlgn1; 900 kb) and Contactin-associated protein 2 (Cntnap2; 2,241 kb), genes that are well known to regulate inhibitory and excitatory synaptic function.” (7)

I wasn’t able to find any scholarly articles about the effects of fluoroquinolones on Nrxn1, Nlgn1 or Cntnap2.  However, it is hypothesized in “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology,” that all adverse reactions to fluoroquinolones are due to epigenetic mechanisms:

“The quinolones are a family of broad-spectrum antibiotics. They inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription. Eukaryotic cells do not contain DNA gyrase or topoisomerase IV, so it has been assumed that quinolones and fluoroquinolones have no effect on human cells, but they have been shown to inhibit eukaryotic DNA polymerase alpha and beta, and terminal deoxynucleotidyl transferase, affect cell cycle progression and function of lymphocytes in vitro, and cause other genotoxic effects. These agents have been associated with a diverse array of side-effects including hypoglycemia, hyperglycemia, dysglycemia, QTc prolongation, torsades des pointes, seizures, phototoxicity, tendon rupture, and pseudomembranous colitis. Cases of persistent neuropathy resulting in paresthesias, hypoaesthesias, dysesthesias, and weakness are quite common. Even more common are ruptures of the shoulder, hand, Achilles, or other tendons that require surgical repair or result in prolonged disability. Interestingly, extensive changes in gene expression were found in articular cartilage of rats receiving the quinolone antibacterial agent ofloxacin, suggesting a potential epigenetic mechanism for the arthropathy caused by these agents. It has also been documented that the incidence of hepatic and dysrhythmic cardiovascular events following use of fluoroquinolones is increased compared to controls, suggesting the possibility of persistent gene expression changes in the liver and heart.”(8)

Also, it has been known since 1996, when “Delayed Cytotoxicity and Cleavage of Mitochondrial DNA in Ciprofloxacin-Treated Mammalian Cells” was published in Molecular Pharmacology, that fluoroquinolones deplete mitochondrial DNA.  The article states, “The loss in mtDNA was associated with a delayed loss in mitochondrial function. Here, we report that the 4-quinolone drug ciprofloxacin is cytotoxic to a variety of cultured mammalian cell lines at concentrations that deplete cells of mtDNA.” (9)  Nuclear gene expression is linked to mitochondrial functioning and, “Mitochondria generate signals that regulate nuclear gene expression via retrograde signaling,” (10).  Fluoroquinolone induced mitochondrial DNA damage may lead to changes in nuclear DNA expression.

Fluoroquinolones are also known to affect neurotransmitters, particularly GABA neurotransmitters.  (11)  GABA neurotransmitters are responsible for regulation of inhibitory and excitatory synaptic function.  It is noted in “Topoisomerase 1 inhibition reversibly impairs synaptic function” that, “GABA-A receptor subunits are encoded by long genes.” And that, “multiple synaptic proteins encoded by long genes including cell adhesion molecules linked to autism and GABA receptor subunits, are depleted in topotecan-treated neurons.”

GABA receptors

Given that GABA receptors are critical for inhibitory and excitatory synaptic functioning, examining the role between GABA receptors, topoisomerases, topoisomerase inhibiting drugs, and attention deficit hyperactivity disorder (ADHD) is certainly warranted.  Many individuals with ASD also display symptoms of ADHD, and the interactions between GABA and glutamate receptors may be why many individuals with ASD find symptom relief through a gluten and casein free diet that is low in glutamate.

As the title of “Topoisomerase 1 inhibition reversibly impairs synaptic function” indicates, it was found that “the synaptic effects of topotecan are reversible” upon washout of the drug.  However, the complexity of neurotransmission is acknowledged in the discussion section of the article, where it is noted that, “adding back one synaptic cell-adhesion molecule would not likely restore the protein levels of all affected synaptic cell-adhesion molecules as well as multiple GABA-A receptor subunits.” It is also noted that, “transient TOP1 (topoisomerase 1) inhibition has the potential to impair brain function reversibly, whereas a persistent change in TOP1 activity has the potential to disrupt neurodevelopment and promote neurodegeneration.”  With limited exposure to a topoisomerase interrupting drug, the neurological effects appear to be reversible.  However, persistent exposure can cause more persistent harm.

Adult patients with fluoroquinolone toxicity syndrome often note that they were able to tolerate fluoroquinolones without experiencing adverse effects prior to getting “floxed.”  This tolerance threshold may indicate that fluoroquinolones somehow accumulate in cells and that the adverse effects of fluoroquinolones are amplified with each exposure.  It is also possible that mitochondrial DNA needs to cross over a damage threshold before resulting in adverse effects.  More about this can be found in the post, “The Fluoroquinolone Time Bomb – Answers in the Mitochondria.”

IS IT POSSIBLE THAT FLUOROQUINOLONE ANTIBIOTICS ARE RESPONSIBLE FOR MANY CASES OF AUTISM? 

The possibility hasn’t been explored, despite the documented effects of fluoroquinolones that line up with many of the symptoms and effects of autism.  In addition to the correlation between fluoroquinolone prescription rates and autism rates, and the points noted above about topoisomerase interrupting drugs changing the expression of autism related genes, fluoroquinolones also damage mitochondria (12)—and mitochondrial damage has been linked to autism (13) .  Fluoroquinolones also cause cellular leakage (14) and depletion of minerals (15) that are necessary for synthesis of minerals and vitamins that (deficiencies of) have been linked to autism (16).  Fluoroquinolones, as powerful antibiotics, are extremely destructive to the gut microbiome and gut microbiome health has also been linked to autism (17).

Even though a pretty good argument can be made for fluoroquinolones causing autism, if there is a relationship, it is not entirely clear-cut.  There are children who have been hurt by fluoroquinolones, but there are also children who have been administered fluoroquinolones without any apparent harm.  Like adults, children almost certainly have a tolerance threshold for fluoroquinolone use before they are injured.  Delayed adverse reactions (18) make recognition of symptoms of fluoroquinolone toxicity difficult to recognize, and recognition in the pediatric population is even more difficult because children have incompletely developed communication skills.  Studies that take into account delayed reactions and tolerance thresholds for fluoroquinolones have not been conducted on the adult population, much less the pediatric population, and thus it is unknown what the true effects of fluoroquinolones are.

It is possible that parental genes are altered by fluoroquinolone use and the damaged genes are passed on to children.  This possibility has not yet been explored, but, anecdotally, it does not appear to be a clear-cut relationship either.  Many mothers and fathers who have suffered from fluoroquinolone toxicity have had neurodevelopmentally normal children.  Some have had neurodevelopmentally challenged children though too, and it would be nice to see an actual study of the children of parents exposed to fluoroquinolones, as opposed to the anecdotes that are currently available.

Autism is a complicated disorder (or set of disorders) that likely has multiple environmental, genetic and epigenetic causes.  I strongly suspect that fluoroquinolones are part of the autism-cause-puzzle, but I also suspect that other cellular poisons compound the deleterious effects of fluoroquinolones on neural synapses, and can trigger autism.

Autism_Spectrum_Disorder-1

I noted above that adverse reactions to fluoroquinolones are often delayed.  Delayed adverse reactions to fluoroquinolones have been reportedly triggered by other stressors, including other pharmaceuticals (especially NSAIDs and steroids), benzodiazepine withdrawal, vigorous exercise, emotional stress, alcohol, hormonal changes and other things that can alter neurotransmitters and the autonomic nervous system.  The combined effects of fluoroquinolones and subsequent stressors have not yet been studied, despite (some) recognition of delayed adverse reactions to fluoroquinolones.

Given the indications of “Topoisomerases facilitate transcription of long genes linked to autism,” and “Topoisomerase 1 inhibition reversibly impairs synaptic function,” it is certainly prudent to explore whether or not fluoroquinolones affect gene expression similarly to topotecan.  Other drugs that inhibit topoisomerase activity, such as irinotecan and camptothecin, demonstrated similar effects to those of topotecan and thus the UNC researchers “speculate that other drugs that inhibit TOP1 or TOP2 enzymes could have similar effects on synaptic function.”  We shall see if their results show that fluoroquinolones affect the expression of long genes.  I’m betting that they will find that fluoroquinolones dramatically alter gene expression, especially after multiple uses and also especially when combined with NSAIDs.  Given the prevalence of both fluoroquinolone antibiotics and NSAIDs in our environment though, I hope that I am wrong.

It was never prudent for fluoroquinolones to be used as first-line antibiotics.  They are dangerous, DNA and RNA disrupting chemo drugs that should only be used in life-or-death situations, not as treatment for travelers’ diarrhea or sinus infections.  They’re topoisomerase interrupters.  They’re topoisomerase interrupters.  They’re topoisomerase interrupters.  They’re topoisomerase interrupters.  I’m not sure how many times I need to say that for people who know what topoisomerases are (those who went to medical school) to recognize that it is NOT APPROPRIATE TO GIVE TOPOISOMERASE INTERRUPTING DRUGS TO CHILDREN (or anyone else who isn’t dying).

A former biochemist friend noted, “I was stunned that people thought quinolones were perfectly safe. Coming through the ranks, I always thought, as was taught, that they were a last-ditch drug. There was absolutely no long-term research done with them, and apparently still isn’t.  But there sure was money involved.”

Long-term and intergenerational research need to be done on drugs that affect DNA before they are released into the public.  Neither long-term nor intergenerational studies were done on fluoroquinolones before flooding the market with them.  The odd intricacies of how fluoroquinolones affect people were not taken into consideration either—things like delayed effects, tolerance thresholds, drug and hormonal interactions, etc.

I’m hopeful that the UNC scientists that are looking at the interactions between topoisomerases and autism will start screaming about the deleterious effects of fluoroquinolones on our genes.  I hope that they have the resources to do the study with delayed adverse reactions and tolerance effects taken into consideration too.

We shall see.

I’m hopeful that the study will be well-done and, if not conclusive, interesting–and that it opens the door for more research.

I can’t say that I hope that fluoroquinolones are a unifying cause of autism spectrum disorders, because that would be too sad.

One thing that I’ve found through researching how fluoroquinolones damage human health, is an appreciation for how complex and multifaceted humans are.  Nothing happens in isolation.  There are feedback and feedforward loops within the body that compound the effects of a stimulus on one bodily system on another, there are interactions between drugs that can occur long after a drug “should” have cleared the body, the interactions between mitochondria and neurotransmitters and cellular signaling exist but little is known about them, and more.  It is difficult, if not impossible, for scientists to adequately take into account the incredible complexity of the human body.  What is not known cannot be taken into consideration, and don’t for a second think that we know “enough” about the human body to be throwing pharmaceuticals that are topoisomerase interrupters into the mix.

Fluoroquinolones never should have been approved for human use until long-term, intergenerational safety studies were performed.  They should be taken off of the market until those studies are done.  That won’t happen though.  Drugs aren’t taken off of the market unless they immediately kill a lot of people.  The damage that fluoroquinolones do is more nuanced than that.  If pharmaceutical makers can create a drug that is complex enough, and that can affect people in multiple different ways—through affecting gene expression—they can get away with just about anything.  Bayer and Johnson & Johnson have figured this out.  The FDA isn’t smart enough to protect the public.  Individuals need to be smart enough to protect themselves and their families—a difficult thing to do considering that some knowledge of biochemistry and genetics is necessary for protection against dangerous pharmaceuticals.

Fluoroquinolones are topoisomerase interrupters.  They’re topoisomerase interrupters.  They’re topoisomerase interrupters.  They’re topoisomerase interrupters.  They’re topoisomerase interrupters.  Repeat until someone who should know better shouts – “STOP.”

REMAINING QUESTIONS

The existing research into connections between topoisomerase interrupting drugs and autism spectrum disorders raises multiple questions.  It would be nice if some money, time, effort and other resources were devoted to answering these questions.

  1. What are the effects of fluoroquinolone antibiotics on nuclear, mitochondrial and microbiome gene expression?  What are the implications of these effects?
  2. Do topoisomerase interrupting drugs change gene expression of the person who takes them, the offspring of the person who takes them, or both?
  3. Do topoisomerase interrupting drugs increase a person’s chances of having a child with Autism? How?
  4. If a person takes a topoisomerase interrupting drug, is their DNA altered? If so, are the changes temporary or permanent?
  5. Are some people’s genes affected by these drugs more than others? What factors determine whether or not an individual’s genes are affected?
  6. Are DNA/gene alterations triggered by pharmaceuticals reversible? If so, how?
  7. What, if anything, can people who have taken these drugs do to discourage the expression of the ASD related genes?
  8. When would the administration of the drug happen to influence genes in a way that could trigger the genes associated with Autism – when a mother is pregnant or at any point before the child is conceived – or does the drug need to be directly administered to the person whose genes are altered?
  9. Do these drugs change gene expression in the ways that diet and music change gene expression or do they change DNA like Agent Orange? What level and scale are we talking about?

SOURCES:

  1. Ian F. King, et al. “Topoisomerases facilitate transcription of long genes linked to autismNature – author manuscript. 2013 Sep 5; 501(7465): 58–62.
  2. FDA Safety Announcement, “FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection” 08/15/2013
  3. Adam D. “Use of quinolones in pediatric patients.” Reviews of Infectious Diseases. 1989 Jul-Aug;11 Suppl 5:S1113-6.
  4. Ciprodex Warning Label
  5. CDC Newsroom Press Release, “CDC estimates 1 in 68 children has been identified with autism spectrum disorder” March 27, 2014
  6. FDA Warning Label for Cipro/Ciprofloxacin
  7. Mabb AM, et al. “Topoisomerase 1 inhibition reversibly impairs synaptic function.” Proceedings of the National Academy of Sciences of the United States of America, 2014 Dec 2;111(48):17290-5. doi: 10.1073/pnas.1413204111. Epub 2014 Nov 17.
  8. Antonei B. Csoka and Moshe Szyf. “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology.” Medical Hypotheses 73 (2009) 770–780
  9. JW Lawrence, et al. “Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells.” Molecular Pharmacology November 1996 vol. 50 no. 5 1178-1188
  10. Martin Pickard, et al. “Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogrammingProceedings of the National Academy of Sciences of the United States of America, 2014 Sep 23; 111(38): E4033–E4042.
  11. Pharmacology Weekly Newsletter, “What is the mechanism by which the fluoroquinolone antibiotics (e.g., ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin) can increase a patient’s risk for developing a seizure or worsen epilepsy?” August 31, 2009.
  12. Sameer Kalghatgi et al. “Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells.” Science Translational Medicine, 5, 192ra85 (2013)
  13. Suzanne Goh, et al. “Mitochondrial Dysfunction as a Neurobiological Subtype of Autism Spectrum Disorder – Evidence From Brain ImagingJAMA Psychiatry. 2014;71(6):665-671
  14. Marta Kicia, et al. “Comparison of the effects of subinhibitory concentrations of ciprofloxacin and colistin on the morphology of cardiolipin domains in Escherichia coli membranes.” Journal of Medicinal Microbiology, April 2012 vol. 61 no. Pt 4 520-524
  15. G Palu, et al. “Quinolone binding to DNA is mediated by magnesium ionsProceedings of the National Academy of Sciences of the United States of America, Vol. 89, pp. 9671-9675, October 1992
  16. Richard E. Frye, MD, PhD, and Daniel A. Rossignol, MD, FAAFP, “Cerebral Folate Deficiency in Autism Spectrum Disorders” Autism Science Digest: The Journal of Autism One. Issue 02.
  17. Jennifer G. Mulle, et al. “The Gut Microbiome: A New Frontier in Autism Research.” Current Psychiatry Rep. 2013 Feb; 15(2): 337.
  18. Jacquelyn K. Francis, BA and Elizabeth Higgins, MD, “Permanent Peripheral Neuropathy: A Case Report on a Rare but Serious Debilitating Side-Effect of Fluoroquinolone AdministrationJournal of Investigative Medicine High Impact Case Reports 1–4 © 2014 American Federation for Medical Research
  19. Thomas D. Gootz, et al. “Inhibitory Effects of Quinolone Antibacterial Agents on Eucaryotic Topoisomerases and Related Test SystemsAntimicrobial Agents and Chemotherapy. Jan. 1990, P. 8-12.
  20. Mukherjee, S. Sen, K. Agarwal, “Ciprofloxacin: mammalian DNA topoisomerase type II poison in vivo.” Mutation Research Letters. Volume 301, Issue 2, February 1993, Pages 87–92

 

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Cipro is no better than a PLACEBO at treating chronic prostatitis / chronic pelvic pain syndrome

It is noted in the book, A Headache in the Pelvis, that, “Ciprofloxacin, one of the most powerful antibiotics, on a long-term basis proves to be only as effective as a placebo” for treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS).

I just about fell out of my chair when I read that.

Ciprofloxacin, not only one of the most powerful antibiotics, but also one of the most dangerous antibiotics, is NO MORE EFFECTIVE THAN A PLACEBO for treatment of chronic prostatitis.  Despite their lack of effectiveness, “Quinolones, such as ciprofloxacin, are commonly used to treat CP/CPPS because of their excellent penetration into the prostate.”

Ciprofloxacin penetrates the prostate, and every cell in the body well, but that doesn’t seem like a good enough reason to give it out to the 9-12% of men who suffer from prostatitis if it is NO MORE EFFECTIVE THAN A PLACEBO in treating chronic prostatitis.

Let’s do a cost/benefit analysis of ciprofloxacin versus a placebo.

Placebo

Benefits:  Some potential alleviation of symptoms, as well as potential increases in physical and mental health scores.  (The placebo effect is amazing – it’s not the same as doing nothing.)

Costs:  The potential for “nocebo” effects exists – the experience of adverse effects based on the expectation of adverse effects.  A placebo is a sugar pill though, and the potential for adverse effects is negligible.

Ciprofloxacin

Benefits:  Some potential alleviation of symptoms, as well as potential increases in physical and mental health scores.  (Same potential benefits as the placebo.)

Costs:  Ciprofloxacin and other fluoroquinolones can kill people – DEATH is a potential effect.  If they don’t kill the patient, they can still structurally weakening of every tendon in one’s body, cause mitochondrial dysfunction and potentially increase the risk of all of the diseases related to mitochondrial dysfunction (including neurodegenerative and autoimmune diseases), lead to serious central nervous system adverse effects including seizures, anxiety, depression, suicidal ideation and intracranial pressure, cause liver and kidney failure, PERMANENT peripheral neuropathy, and more.  There is a 43 PAGE warning label for ciprofloxacin.  Many things are missing from the warning label, and a list of some of the adverse effects can be found HERE.  When patients are given ciprofloxacin, they are not only risking a single adverse effect listed on the warning label, they are risking multiple, devastating effects that may be permanent.

Opting for the sugar pill seems pretty reasonable—better, actually.

It is criminal to subject people to a drug as dangerous as ciprofloxacin for a condition that it isn’t effective at treating.  It is NOT a benign drug.  It is a topoisomerase interruptera chemo drug – and it should NOT be used frivolously.  Ciprofloxacin, and all the other fluoroquinolones, should only be used in life-threatening situations and they should NEVER be used for conditions that they are not proven effective at treating.  They should NEVER be used in situations where they have been shown to be no more effective than a placebo.

This isn’t rocket science.  Don’t give people dangerous drugs that don’t even have the potential for helping them.  It’s not hard.  But men with CP/CPPS are given ciprofloxacin, and other fluoroquinolones, as if they’re candy, to “treat” their condition.  It’s absurd.

The study that found that CP/CPPS is no more effective than a placebo was published in the Annals of Internal Medicine in 2004 and it was entitled “Ciprofloxacin or Tamsulosin in Men with Chronic Prostatitis / Chronic Pelvic Pain Syndrome: A Randomized, Double-Blind Trial.”  The article notes that:

“Chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is a common disorder and accounts for approximately 2 million visits to physicians annually in the United States.  The substantial impact of CP/CPPS includes bothersome lower urinary tract symptoms, sexual dysfunction, reduced quality of life, and increased health care expenditures.  The syndrome is diagnosed only on the basis of symptoms, principally pain or discomfort in the pelvis region.  No objective measures can help define the disease.  Although bacteria can infect the prostate, most men with prostatitis have a negative midstream urine culture, indicating that bacteria may not be the cause of their symptoms.”

“Because the cause of CP/CPPS is unknown, affected men receive many empirical therapies.  The 2 most common treatments prescribed by physicians are antimicrobial agents and a-adrenergic receptor antagonists, although there is little objective evidence to support their use.  Quinolones, such as ciprofloxacin, are commonly used to treat CP/CPPS because of their excellent penetration into the prostate and broad spectrum coverage for uropathogens and other organisms traditionally believed to be associated with the syndrome.” 

After completing a randomized, double-blind trial on men suffering from CP/CPPS, and comparing those who received ciprofloxacin, tamsulosin, a combination of both ciprofloxacin and tamsulosin, and a placebo, it was concluded that, “Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.”

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Ciprofloxacin, and other antibiotics, are given to men with non-bacterial prostatitis for no good reason whatsoever.  They are often given long courses as well – 6 to 12 weeks of the drugs.  That’s a long enough course for many of the men who are given these drugs to cross their tolerance threshold for the drugs and get floxed.

If ciprofloxacin was effective at treating CP/CPPS, perhaps it would be worth the risk of getting floxed.  But ciprofloxacin isn’t effective at treating CP/CPPS.  It’s no more effective than a sugar pill and it is beyond ridiculous and wrong to expose men to a dangerous drug that doesn’t even help them.

CP/CPPS has been shown to be treatable through the techniques outlined in A Headache in the Pelvis: A new understanding and treatment for prostatitis and chronic pain syndromes.  The effective treatments include trigger point therapy and concomitant relaxation training.  More information about the treatments can be found in the article, “6-Day Intensive Treatment Protocol for Refractory Chronic Prostatitis/Chronic Pelvic Pain Syndrome Using Myofascial Release and Paradoxical Relaxation Training,” as well as on the web site http://www.pelvicpainhelp.com/.

Many symptoms of CP/CPPS, and other pelvic pain syndromes, react well to relaxation training and appear to be a response to stress and anxiety.  “Chronic pelvic pain reflects tension in the pelvic floor, initiated or exacerbated by cycles of mental tension, anxiety and stress.”  Pelvic pain syndromes are no more a choice than other bodily manifestations of stress such as heart attacks, back pain or tension headaches.  The pain is real and it is not “in the patient’s head.”  The brain is not separate from the body though, and what is going on in the head can have bodily manifestations.

The effects of ciprofloxacin, and other fluoroquinolones, on neurotransmitters may exacerbate CP/CPPS and other diseases related to stress and anxiety.  Fluoroquinolones block GABA-A receptors.  GABA receptors are the neurotransmitters that induce a calming response.  When GABA receptors are blocked by fluoroquinolones, anxiety, insomnia, fearfulness, loss of confidence, loss of self, psychiatric illness and even seizures can result.  Floxed patients often report being unable to relax, a reduced threshold for stress, autonomic nervous system dysfunction, and other symptoms of GABA neurotransmitter dysfunction.  Fluoroquinolones activate the sympathetic nervous system and disrupt the balance between the sympathetic and parasympathetic nervous systems.

If CP/CPPS is primarily a response to anxiety, stress and disregulation of the sympathetic/parasympthetic nervous systems, ciprofloxacin may not only fail to improve chronic pelvic pain conditions, it may exacerbate them.

Prescribing ciprofloxacin, or any other fluoroquinolone, to patients with chronic pain and non-bacterial prostatitis, is not only not helpful – IT IS HARMFUL, and may exacerbate the condition it is prescribed to treat.

Post-script note – Many people, especially elderly women, are given fluoroquinolones to treat asymptomatic urinary tract infections after a urinalysis shows bacteria in their urine.  It has recently been noted that URINE ISN’T STERILE.  And again, people are getting floxed for no good reason.

Sources:

A Headache in the Pelvis, a New, Revised, Expanded and Updated 6th Edition: A New Understanding and Treatment for Chronic Pelvic Pain Syndromes by David Wise and Rodney Anderson

Alexander RB, et al. “Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial.” Annals of Internal Medicine, 2004 Oct 19;141(8):581-9.

Anderson RU, et al. “6-day intensive treatment protocol for refractory chronic prostatitis/chronic pelvic pain syndrome using myofascial release and paradoxical relaxation training.” The Journal of Urology, 2011 Apr;185(4):1294-9. doi: 10.1016/j.juro.2010.11.076. Epub 2011 Feb 22.

“What is the mechanism by which the fluoroquinolone antibiotics (e.g., ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin) can increase a patient’s risk for developing a seizure or worsen epilepsy?Pharmacology Weekly, ©2008 – 2014 Pharmacology Weekly, Inc.

 

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Study Finds that Ciprofloxacin Depletes Mitochondrial DNA

DNA replication fluoroquinolone Topoisomerase Interrupter

This post contains quotes from the article “Delayed Cytotoxicity and Cleavage of Mitochondrial DNA in Ciprofloxacin-Treated Mammalian Cells” that was published in Molecular Pharmacology in 1996.  It’s a good article.  It’s an interesting and damning article.  It’s a difficult article.  It would be nice if more people read it, and I wish that its implications were better understood and explored by research scientists and regular people alike.

Direct quotes from the article are in bold and italicized.  My commentary follows each quote.

“The loss in mtDNA was associated with a delayed loss in mitochondrial function. Here, we report that the 4-quinolone drug ciprofloxacin is cytotoxic to a variety of cultured mammalian cell lines at concentrations that deplete cells of mtDNA.”

Ciprofloxacin depletes mitochondrial DNA in mammalian cells.  It’s right there in black and white.  I have no idea why it didn’t strike anyone as alarming when it was published in 1996.  It sure is alarming now.

It should be noted that, “There is indeed experimental evidence that prolonged injury to mitochondria, such as that which typifies oxidative injury to mitochondrial DNA or to components of the electron transport chain (ETC), has to cross a certain threshold (or a number of thresholds) before cell damage or cell death becomes manifest.” (source)  And that mitochondrial damage is linked to “symptoms such as fatigue, muscle pain, shortness of breath, and abdominal pain can easily be mistaken for collagen vascular disease, chronic fatigue syndrome, fibromyalgia, or psychosomatic illness.” (source)  Mitochondrial dysfunction has been linked to multiple diseases of modernity including autoimmune diseases, neurodegenerative diseases, autism and “mysterious” diseases such as fibromyalgia and ME/CFS.

Also, as I’ve pointed out before, the FDA has noted in their internal documents that fluoroquinolones are toxic to mitochondria, and that mitochondrial damage is linked to many diseases, including neurodegenerative diseases.  More information about that can be found in the post, “FLUOROQUINOLONE ANTIBIOTICS DAMAGE MITOCHONDRIA – FDA DOES LITTLE

“Resistance was not due to a decrease in cellular drug accumulation, suggesting that ciprofloxacin cytotoxicity is caused by the loss of mtDNA-encoded functions.  Analysis of mtDNA from ciprofloxacin-treated cells revealed the presence of site-specific, double-stranded DNA breaks.”

Consequences?  Implications?  What happens when cytotoxicity is induced by DNA breaks?

“These results suggest that ciprofloxacin may be causing cytotoxicity by interfering with a mitochondrial topoisomerase Il-like activity, resulting in a loss of mtDNA.”

Many assert that fluoroquinolones only affect bacterial topoisomerases.  It turns out that mitochondrial topoisomerases are affected too.  Fluoroquinolones should be used as prudently and cautiously as all other topoisomerase interrupting drugs.  All the other topoisomerase interrupting drugs are chemo drugs that are only used to treat cancers.  To prescribe a drug that depletes mitochondrial DNA and affects human topoisomerases in order to treat urinary tract infections and traveler’s diarrhea is absurd, short-sighted and wrong.

It should also be noted that, “Our data suggest that chemicals or genetic mutations that impair topoisomerases, and possibly other components of the transcription elongation machinery that interface with topoisomerases, have the potential to profoundly affect expression of long ASD (autism spectrum disorder) candidate genes. Length-dependent impairment of gene transcription, particularly in neurons and during critical periods of brain development, may thus represent a unifying cause of pathology in many individuals with ASD and other neurodevelopmental disorders.” (source)

The team of scientists who wrote that last quote are looking at whether or not fluoroquinolones turn on genes that are related to autism.  The results of their exploration have not yet been published.

What is known though, is that topoisomerases are really important.  Duh–they’re the enzymes responsible for proper DNA and RNA replication—did someone think they were optional?  Interrupting topoisomerases with drugs is a really, really, really bad idea.

“Studies have also suggested that 4-quinolones may interfere with cell growth by inhibiting mammalian mtDNA replication (6, 11). Castora et al. (11) found that the 4-quinolone drugs nalidixic acid and oxolinic acid inhibited mtDNA replication in isolated rat liver mitochondria. These investigators inferred that this effect might be mediated by the inhibition of a mitochondrial topoisomerase II activity related to the bacterial enzyme DNA gyrase.”

Naladixic acid is the backbone of all fluoroquinolone antibiotics.  The quote speaks for itself.

 “We recently demonstrated that the 4-quinolone drugs nalidixic acid and ciprofloxacin cause a selective loss of mtDNA in drug-treated mammalian cells (6). The loss of mtDNA was associated with a decrease in mitochondrial respiration and an arrest in cell growth. These results suggested that inhibition of mammalian cell proliferation by 4-quinolone drugs might be caused by the selective depletion of mtDNA, resulting in compromised mitochondrial activity. We now report that ciprofloxacin causes a delayed cytotoxicity in cultured mammalian cells at concentrations that deplete cells of mtDNA.”

DELAYED CYTOTOXICITY!  When someone says that you “shouldn’t” be experiencing an adverse reaction to a fluoroquinolone weeks, months or even years after you took the drug, show them this.  Delayed cytotoxicity and mtDNA depletion–they’re right there.  Fluoroquinolones are NASTY drugs.  Why they are used frivolously is beyond my comprehension.

“We previously demonstrated that ciprofloxacin induces a selective depletion of mtDNA in mammalian cells. The depletion of mtDNA preceded a decrease in mitochondrial respiration and cell growth, suggesting that mtDNA was a primary target of drug action (6). Studies have recently shown that some cultured mammalian and avian cells can survive in the absence of mtDNA-encoded functions if the growth medium is supplemented with pyrimidines, pyruvate, and elevated concentrations of glucose (21-23). Cells deficient in mtDNA rely exclusively on glycolysis for energy.”

Hmmmmm…. So do our cells need/want more glucose??

And, again, I’d like to point out the clearly stated, “ciprofloxacin induces a selective depletion of mtDNA in mammalian cells.”

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“The apparent decrease in mtDNA cleavage at higher drug concentrations is reminiscent of the effect of DNA intercalating anticancer drugs on nuclear topoisomerase II enzymes (29, 30). Intercalating anticancer drugs such as 2-methyl-9-hydroxyellipticinium and Adriamycin have been shown to stimulate topoisomerase II cleavage at low concentrations but inhibit cleavage at high drug concentrations.”

Fluoroquinolones are chemo drugs.  All topoisomerase interrupters are chemo drugs.  Don’t give people chemo drugs to treat sinus infections.  It’s not a difficult notion.

http://www.collective-evolution.com/2014/10/15/fda-allows-chemo-drugs-prescribed-antibiotics/

http://www.hormonesmatter.com/cipro-levaquin-avelox-fluoroquinolones-chemo-drugs/

“The non-exonuclease-treated DNA contained both linear and nicked circular forms of mtDNA but did not contain closed circular supercoiled mtDNA (Fig. 8, lane A), suggesting that ciprofloxacin induces single- as well as double stranded protein-linked breaks in the mtDNA.”

Thanks for breaking my DNA, Bayer.

“The current results indicate that ciprofloxacin is not cytotoxic unless cells are continuously exposed to drug for a minimum of three or four cell doublings. In comparison, drugs that target nuclear topoisomerase II trigger an apoptotic type of cell killing, even after a short 2-hr drug exposure.”

Interesting.  What is the time-frame for cell doubling?  And I don’t think that the question has been definitively answered as to whether or not fluoroquinolones are stored in lipids, continuously exposing cells to damage, or not.

“Another possibility is that the growth inhibitory and cytotoxic effects of ciprofloxacin are caused by the inhibition of an essential mitochondrial function or functions. This is supported by the following observations: First, treatment of mammalian cells with ciprofloxacin results in a selective depletion of mtDNA, leading to a decrease in mitochondrial respiration (6). These mitochondrial events precede the drug induced loss in cell growth and viability (Ref. 6 and current results). Second, cells become resistant to ciprofloxacin when they are grown under conditions that do not require mtDNA encoded functions. Third, ciprofloxacin induces the formation of site-specific, protein-linked breaks in mtDNA, indicating the presence of a drug-sensitive mitochondrial topoisomerase Il-like activity.”

Given the connections between ciprofloxacin and mitochondrial damage–depleting mtDNA and decreasing mitochondrial respiration, and the connections between mitochondrial damage and multiple chronic, multi-symptom illnesses, it is not absurd to make the assertion that ciprofloxacin, and other fluoroquinolones, can cause those diseases (autoimmune diseases, neurodegenerative diseases, fibromyaligia, autism, ME/Chronic Fatigue Syndrome, etc.).

The article, “Mitochondria Resuscitation: The Key to Healing Every Disease” by Chris D. Meletis, N.D. is a succinct and illustrative look at how mitochondria are related to multiple areas of health.

It’s nice and dandy that “cells become resistant to ciprofloxacin when they are grown under conditions that do not require mtDNA encoded functions” but human beings don’t have a bunch of cells that live in petri dishes that can grow without requiring our mitochondrial DNA functions.  I wonder what happens when human cells attempt to adapt to resist ciprofloxacin and adapt by ceasing to require mtDNA encoded functions.  I bet you a buck that no one knows the answer to that question.

Cipro breaks mitochondrial DNA.  WHY WASN’T THIS REPORT PAID ATTENTION TO?  All of the results in it warrant fluoroquinolones being taken off of the market until further investigation can be done.  This is absurd.  I know that there are cases where fluoroquinolones can save lives, I get that, and I’m usually decently reasonable about not calling for their removal from the market.  But this article spooked me severely.  We, collectively, have NO CLUE what the consequences of depleting our mitochondrial DNA are.

“Neither cell growth nor viability seems to be affected until cells have undergone three or four cell doublings in the presence of ciprofloxacin (Ref. 6 and current results). During this time span, the content of mtDNA decreases >90%, suggesting that drug is causing a loss in cell growth and viability by interfering with mtDNA replication.”

Nasty drugs – but if you metabolize them fast enough, they’re less nasty – apparently.

“Ciprofloxacin, as well as several other 4-quinolone drugs, can cause significant unwinding of DNA”

It’s what they’re designed to do.  They’re topoisomerase interrupters.  The mechanism of action for ciprofloxacin is, “The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.” (source)  It doesn’t take a rocket scientist to realize that drugs that inhibit the DNA and RNA replication, transcription, repair and recombination are dangerous.  I hate the FDA for allowing these dangerous drugs to be used as antibiotics.  It’s ludicrous.

Delayed Cytotoxicity and Cleavage of Mitochondrial DNA in Ciprofloxacin-Treated Mammalian Cells” is not a hopeful article.  It is, frankly, a terrifying article.  More than 20 million prescriptions for fluoroquinolones are given out in Americans each year for the last couple decades, and that’s only a small portion of the prescriptions given worldwide.  What have we done to our collective mitochondrial DNA??  What are the consequences of depleting our mitochondrial DNA?  No one knows the answers to those questions.

Anyone who thinks that people aren’t sick with the diseases related to mitochondrial poisoning, isn’t looking very hard.  People are sick.  They’re in pain (peripheral neuropathy is thought to be caused by mitochondrial malfunctions), they’re depressed and suffering from even worse psychiatric disorders, they have heart conditions and metabolic disorders (source), ME/Chronic Fatigue Syndrome, autism, and many other misunderstood, chronic illnesses.  There are many potential culprits for the sorry state of human health in the 21st century, but fluoroquinolones aren’t even on the list according to most people.

FLUOROQUINOLONES DEPLETE MITOCHONDRIAL DNA, LEAD TO MITOCHONDRIAL DYSFUNCTION AND ALSO OBLITERATE THE MICROBIOME!

I’ll keep screaming it until I’m heard.

Back in 1992 it was noted that, “the interaction (of fluoroquinolones) with DNA is still of great concern because of the possible long-term genotoxicity of quinolone compounds, which are increasingly adopted as first-choice antibiotics for the treatment of many infections, and because it addresses the real mechanism of action of this class of molecules.”  (source)

I really wish that these warnings had been heeded.  Sadly, they’ve been ignored.

Our poor mitochondrial DNA.  I hope that mtDNA recovers and that the situation isn’t as dire as I suspect.  But the truth is, no one knows.  No one has a clue what the consequences of depleting mtDNA through unnecessary use of topoisomerase interrupting drugs are.

Floxies certainly know that the consequences of fluoroquinolones can involve a massive amount of pain and suffering.  It’s not okay.

Bayer, Johnson & Johnson, the FDA and everyone else involved with frivolously prescribing these drugs should be ashamed of themselves for failing to protect our mitochondrial DNA.  Topoisomerase interrupters should never have been approved for use as antibiotics.  It’s simply absurd.

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The Microbiome According to Michael Pollan

Cooked by Michael Pollan Microbiome

I recently read “Cooked: A Natural History of Transformation” by Michael Pollan.  You can buy it HERE and a portion of the proceeds will go to the QVF.  I recommend that you purchase it, not just because some money will go to the QVF, but because it is beautifully written, enjoyable, interesting, insightful and poignant.

On the surface, Cooked has very little, if anything, to do with fluoroquinolone antibiotic toxicity.  Cooked is about the transformation of raw ingredients into food when fire, water, air and earth are applied to those ingredients through the process we call cooking.  The section of Cooked that has to do with how things from the earth–bacteria, fungi, etc., are used to transform and “cook” food, is the section I am going to connect to fluoroquinolone antibiotic toxicity.

Fluoroquinolone antibiotics are like a nuclear bomb to the gut.  They obliterate the microbiome, killing both good and bad bacteria in the gut and throughout the body.  They lead to a massive amount of oxidative stress within the gut that further damages the balance of bacteria in the gut.  It is only because of lack of knowledge about the importance of the microbiome that Cipro/ciprofloxacin only has a 43 page warning label, not a 100 page warning label.  In Cooked, Michael Pollan goes over the importance of the microbiome.  He explains the microbiome better than I possibly could, so I’m going to highlight some of my favorite quotes from Cooked in this post.

“Could it be possible that the microbiota also affects mental function and mood, as some of the fermentos I met in Freesone claimed?  The idea no longer seems preposterous.  A recent study performed in Ireland found that introducing a certain probiotic species found in some fermented foods (Lactobacillus rhamnosus JB-1) to the diet of mice had a measureable effect on their stress levels and mood, altering the levels of certain neurotransmitters in the brain.  Precisely how the presence of a certain bacterium in the gut might affect mental function is unclear, yet the researchers found they could block the effect by severing the vagus nerve that links the gut to the brain.  Studies like this one make you wonder if it might someday be possible to cultivate, or garden, our microbiota, altering its makeup to improve our physical and possibly also our mental well-being.

Right now, of course, and for the last several decades at least, we have been assiduously doing exactly the opposite:  disordering the community of microbes in our bodies without even realizing it, much less  with any sense of what might be at stake.  Under the pressures of broad-spectrum antibiotics, a Pasteurian regime of ‘good sanitation,’ and a modern diet notably hostile to bacteria, the human microbiota has probably changed more in the last hundred years than in the previous ten thousand, when the shift to agriculture altered our diet and lifestyle.  We are only just beginning to recognize the implications of these changes for our health.”

A book that is on my reading list (but that I haven’t yet read) is “Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues” by Martin J. Blaser.  It’s supposed to be excellent.  It is about the diminishing diversity of our microbiota.

Back to Cooked:

“The average child in the developed world has also received between ten and twenty courses of antibiotics before his or her eighteenth birthday, an assault on the microflora the implications of which researchers are just beginning to reckon.  Like the pesticides applied to a farm field, antibiotics ‘work,’ at least in the short term.  Yet as soon as you widen the lens from a narrow focus on the ‘enemy species,’ you see that such blunt weapons inflict collateral damage to the larger environment, including, in the case of pesticides, the microbial community of the soil.  Resistant bugs and various other health problems soon emerge; the soil’s ability to nourish plants and help them withstand disease is also compromised, because the toxins have reduced the community’s biodiversity and thereby compromised its resilience.  As in the soil, so in the gut.  The drive for control and order ends up leading to more disorder.”

“An interesting question is why the body would enlist bacteria in all these critical functions, rather than evolve its own systems to do this work.  One theory is that, because microbes can evolve so much more rapidly than the ‘higher animals,’ they can respond with much greater speed and agility to changes in the environment–to threats as well as opportunities.  Exquisitely reactive and fungible, bacteria can swap genes and pieces of DNA among themselves, picking them up and dropping them almost as if they were tools.  This capability is especially handy when a new toxin or food source appears in the environment.  The microbiota can swiftly find precisely the right gene needed to fight it–or eat it.”

“Taken together, the microflora may function as a kind of sensory organ, bringing the body the latest information from the environment, as well as the new tools needed to deal with it.  ‘The bacteria in your gut are continually reading the environment and responding,’ says Joel Kimmons, a nutrition scientist and epidemiologist at the Centers for Disease Control and Prevention in Atlanta.  ‘They’re a molecular mirror of the changing world.  And because they can evolve so quickly, they help our bodies respond to changes in our environment.”

Bacteria gene-swap at the drop of a hat.  Isn’t that fascinating?  It also makes the fact that fluoroquinolones disrupt the process of bacterial DNA and RNA replication quite consequential.  I wrote this post about antibiotics altering bacterial DNA back in 2013 – http://www.collective-evolution.com/2013/10/23/genetically-modifying-humans-via-antibiotics-something-you-need-to-know/.  The consequences of altering bacterial DNA are still being explored.

Another book of Michael Pollan’s, “The Omnivore’s Dilemma: A Natural History of Four Meals” goes over the hazards of applying the industrial model to biological systems–specifically, the folly of using the industrial model to produce food when food production should be a biological, not an industrial, process.  The same is true for medicine.  The medical system treats people as machines with inputs and outputs and predictable outcomes based on those measured inputs and outputs.  It doesn’t work though.  Humans are biological systems with feedback and feedforward loops, genetic differences and epigenetic differences, nature and nurture differences, and more–that make conceptualizing humans as machines with predictable outcomes foolish and wrong-headed.  When land and animals are used to make food in an industrial, rather than biological, model, unsustainability, externalities and consequences result.  When biological systems are respected for the complex systems that they are, sustainability comes naturally.  Likewise, when human complexity is ignored and stupid, foolish, one-size-fits-all, industrial medicine prevails, consequences occur in place of health.  It turns out that consequences look a whole lot like chronic illness.  Whoops.

Lisa’s one-sentence summary of Cooked and The Omnivore’s Dilemma is – Don’t eat processed food.  Read the books for a more thorough explanation.  They’re both excellent.

 

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The Floxie Hope Podcast Episode 9 – Rick Radcliff

Rick Radcliff Floxie Hope Podcast

In Episode 9 of The Floxie Hope Podcast I had the opportunity to interview Rick Radcliff.  Rick is a long-time flox survivor.  He was hurt by Avelox/moxifloxacin ten years ago.

In the ten years that Rick has been a floxie, he has learned a lot about fluoroquinolone toxicity.  He reveals a lot of interesting information about the links between fluoroquinolone induced mitochondrial damage and thyroid health.  Balancing his hormones has helped him to improve immensely.

Please listen to Rick’s story and share it with your friends.  Thank you!

https://itunes.apple.com/us/podcast/floxie-hope-podcast/id945226010

http://www.floxiehopepodcast.com/episode-009-rick-radcliff/

As always, reviews of The Floxie Hope Podcast on iTunes are greatly appreciated!

 

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Media Coverage of Fluoroquinolone Antibiotic Dangers

WSB-TV 2 out of Atlanta, Georgia has run several news segments about the dangers of fluoroquinolone antibiotics – focusing on the death and destruction caused by Levaquin/levofloxacin.

A HUGE THANK YOU TO EVERYONE INVOLVED IN MAKING THIS POSSIBLE!  WSB-TV 2 producers and other staff, Jim Strickland, Kathy Dannelly, Donna Schultz, Jeff Stephens, Lynne Whitcopf, Dr. Keith Jeffords, Sandy Davis and everyone else who spoke up about the dangers of these drugs – THANK YOU!

Here are the video clips from WSB-TV 2 –

You can read the story here – http://www.wsbtv.com/news/news/local/local-woman-says-popular-antibiotic-killed-her-hus/njzwj/

Per The Quinolone Vigilance Foundation‘s facebook page, “QVF has just been informed moments ago by ABC2 WSB-TV that the number of shares from the news stories have increased from 2 million to 3.9 million.”  WOW!  Great job getting the word out!

Here is another story featuring Lynne Whitcopf and Dr. Keith Jeffords, and their stories of pain –

http://www.wsbtv.com/news/news/local/patients-suffer-devastating-side-effects-popular-a/nj4Br/

When a doctor reports that, “It was an amazing amount of pain, to the point that I couldn’t walk,” and has to crawl out of the hospital to avoid more fluoroquinolones, you KNOW that the situation is bad.

Sandy Davis sadly lost her husband Richard to levofloxacin.  Here is her story –

http://www.wsbtv.com/news/news/local/woman-says-popular-antibiotic-levofloxacin-killed-/nj5jY/

I’m so sorry for the pain that was experienced by all those who were interviewed.  I appreciate that each of you told your story of pain!  These stories are important!

 

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The Floxie Hope Podcast Episode 8 – Josh Arnold

Josh Arnold Floxie Hope Podcast

For Episode 8 of The Floxie Hope Podcast I had the opportunity to interview Josh Arnold.  Josh is insightful and wise and the lessons he learned from getting floxed are lessons that everyone should hear (they’re in the last quarter of the podcast).

Josh was only 25 when he got floxed by Cipro.  He had taken Levaquin without problems prior to getting floxed.  Two pills of Cipro pushed him over the edge of his tolerance threshold.  Josh went from being athletic and active to barely able to walk his dog after taking Cipro.  He has since battled his way back to health.  He describes his journey in the podcast.

You can listen to Josh’s story through these links:

http://www.floxiehopepodcast.com/episode-008-josh-arnold/

https://itunes.apple.com/us/podcast/floxie-hope-podcast/id945226010

Please subscribe to The Floxie Hope Podcast and leave a review on iTunes if you enjoy the episode.  Thank you!

 

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The Importance of the Microbiome

The bacterial cells in our body outnumber the human cells ten to one.  Additionally, within each eukaryotic (human) cell in our body, there are many (hundreds in many cells) mitochondria – ancient bacteria that got absorbed into non-bacterial cells and formed eukaryotic cells.  Bacteria are an important, vital part of us.  Bacteria affect every aspect of human health, including immune system regulation, digestion, personality, etc.  Additionally, disturbances in the make-up of the microbiome has been connected with multiple chronic diseases, including Parkinson’s Disease, Alzheimer’s Disease, diabetes, autism, autoimmune diseases, etc.

Given the importance of the bacteria that work symbiotically with us, and that ARE US, it drives me a little nuts when people minimize the harm in damaging the microbiome with pharmaceuticals.  If a drug “just” damages bacteria, but doesn’t damage eukaryotic cells directly, it hurts the person who takes the drug, because the bacteria within that person are a vital part of him/her and an integral part of his/her health.

Dismantling the DNA of bacteria (and mitochondria), and inducing massive amounts of oxidative stress (the Fenton Reaction) with fluoroquinolones is particularly stupid.

The above is elaborated upon in the following post on Hormones Matter:

THE HARMFUL EFFECTS OF ANTIBIOTICS ON THE HUMAN MICROBIOME

Thank you for reading it and for sharing it!

 

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Lisa’s Vacation to Costa Rica

CR Flower

 

Last week, my boyfriend and I went to Costa Rica for a little vacation.  It was a lot of fun!  🙂

I am mentioning my trip for two reasons.  First, if I didn’t respond to an email last week, it’s not because I’ve checked out and given up on the cause, it’s because I was on vacation.  Second, I think that people appreciate posts hearing about people living normally post-flox and post-recovery.

I was able to do all of the things in Costa Rica that I would have done on a similar vacation before getting floxed.  I did a zip-line tour of the jungle canopy.  I rode a horse.  I went on hikes.  I went swimming.  I drove all over creation.  I ate whatever food was in front of me (including Pringles – I was REALLY hungry, they were horrible and I don’t recommend them – but I ate them and was fine).  I drank pina coladas on the beach.  I walked across a hanging bridge that was 100 feet above a raging river and blowing in the wind – it was terrifying but it wasn’t any more terrifying than it would have been had I never gotten floxed.  I did the things that a non-floxed, not sick person would do on a week-long vacation in Costa Rica.  It was a good vacation.  It was a fun vacation.

I have fully returned to the level of health that I was before I got sick.  I hope that this post, and other posts like it, give you hope that you too can get back to a place of health post-flox.  I know that my story is not your story, and that everyone is different, but I hope that you too will someday be able to do adventure sports in the tropics – if that’s what you’re into.

There was a time when I wasn’t able to do the things that I did last week.  There was a time when I didn’t think that I would ever be able to do the things that I did last week.  But the memories of those fears have faded, and my capacity for movement and adventure has returned.

I’m lucky.  I know that I’m lucky and I don’t take it for granted at all.  I also know that some people aren’t as lucky as me and my heart aches for them.

When I was feeling lousy it was really nice to hear about people who were living well after recovering from FQ toxicity.  It felt good to read about people doing extraordinary, yet normal, things – getting married, having kids, getting a new job, going on a vacation, etc.  My ordinary/extraordinary adventure was a trip to Costa Rica.  Here are some pics:

CR Zipline

CR Tree

CR LB Beach

CR Beach

CR Hiking

CR Crocs

 

Random closing thought – my boyfriend and I forgot to change some Costa Rican money to US dollars before we got home.  Now we have about $30 worth of Costa Rican cash that is useless to us.  If anyone who is reading this is going to Costa Rica and can use it, I’ll send it to you – it’s not doing me any good and you’re welcome to it if you make it easy for me to get it to you.  🙂

Best,

Lisa

Photo Credit – Mark Palmer Photography

Fluoroquinolones and Dental Problems

Hormones Matter Logo2

This post, “Can Fluoroquinolone Antibiotics Cause Dental Problems?” published on Hormones Matter, is not very hopeful.  In fact, it’s quite frightening.  Many patient reports have been coming in lately about fluoroquinolone induced dental problems and teeth falling out.  Christopher’s story, on The Fluoroquinolone Wall of Pain is one of the stories highlighted.  Having all of your teeth fall out is a hefty price to pay for using an antibiotic – especially an antibiotic that is regularly prescribed for urinary tract and sinus infections.

I couldn’t find much in the way of journal articles about fluoroquinolone toxicity and dental problems.  If any of you find journal articles with dental problems listed as an effect of fluoroquinolones, please let me know.

The patient reports are quite compelling though – and frightening.

A couple people have mentioned that magnesium supplementation helps their post-flox teeth.  It’s probably a good thing to keep up.

On a personal note, I love my teeth.  Vanity is certainly at play, but I have really good teeth and I’d like to keep them.  I lost a tooth to internal resorbtion – basically, the root disintegrated for no reason – a long time before I took a FQ.  That stunk, for sure.  I can only imagine the horror of losing all of one’s teeth.  Hugs to those who are having post-FQ dental problems!

 

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The Floxie Hope Podcast Episode 4 – Holidays 2014

MPP-3090

Happy holidays, my friends!  Merry Christmas!  Happy Hanukkah!  Festive Festivus!  I hope that you have a wonderful, healing holiday season and a happy new year!  I know that 2014 was a difficult year for many of you, and I hope that 2015 is better!

Here is episode 4 of The Floxie Hope Podcast –

iTunes – https://itunes.apple.com/us/podcast/floxie-hope-podcast/id945226010

The Floxie Hope Podcast web site – http://www.floxiehopepodcast.com/episode4/

In episode 4 of The Floxie Hope Podcast I go over how difficult Christmas was when I was first floxed, and note how far I’ve come.  I also point out that there are some influential doctors and pharmacists reading Floxie Hope.  Keep screaming, my friends – people are listening!

I truly hope that the holidays are filled with love and laughter for each of you!
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The Floxie Hope Podcast Episode 3 – Rachel Brummert

RachelQVF

Rachel Brummert, Executive Director of the Quinolone Vigilance Foundation, is interviewed on Episode 3 of The Floxie Hope Podcast.  Rachel goes over her history with fluoroquinolone toxicity; and gives information on the history, mission and activities of the Quinolone Vigilance Foundation (QVF).

The QVF is engaged in research, advocacy, outreach and other activities related to helping victims of fluoroquinolone toxicity.  The Mission of the QVF is to understand and reduce Quinolone/Fluoroquinolone Toxicity as a cause of human suffering in the world.

Per the QVF’s web site, www.saferpills.org, they fulfill this mission by networking medical professionals and researchers; fostering, initiating, and directing fundamental research to discover underlying toxicity mechanisms; funding research that will produce the most promising results; translating new discoveries into effective medical practices, therapies and public health approaches; and develop and applying discovered knowledge to educate the medical community and help alleviate individual suffering.

You can learn more about the QVF through listening to Episode 3 of The Floxie Hope Podcast.  It is available through the following links:

iTunes – https://itunes.apple.com/us/podcast/floxie-hope-podcast/id945226010

Floxie Hope Podcast Web Site – http://www.floxiehopepodcast.com/floxie-hope-podcast-episode-003-rachel-brummert/

Thank you for listening!

Please share The Floxie Hope Podcast with your loved ones and help us to get the word out about the dangers of fluoroquinolones.  Thank you!

All reviews of The Floxie Hope Podcast on iTunes are appreciated!

Enjoy!

 

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The Floxie Hope Podcast Eposode 2 – Nick Luciano

Nick Luciano joined me for the second episode of The Floxie Hope Podcast.  In it, Nick describes his journey through fluoroquinolone toxicity induced by Cipro.  Nick went from being a law enforcement officer who worked out daily to being close to bed-bound.  He was unable to work for more than three months after taking Cipro.  He has since recovered most of his health.  His story of healing can be found here – https://floxiehope.com/nicks-story-recovery-from-cipro/

You can listen to Nick tell his story on the podcast through iTunes –

https://itunes.apple.com/us/podcast/floxie-hope-podcast/id945226010

Please subscribe via iTunes too, and you will automatically get The Floxie Hope Podcast downloaded to your phone or computer every time an episode comes out.

If you like this episode, please leave an iTunes review.  All reviews are appreciated!

You can also download this episode of The Floxie Hope Podcast through www.floxiehopepodcast.com

http://www.floxiehopepodcast.com/floxie-hope-podcast-episode-002-nick-luciano/

Thanks for listening, sharing, and spreading the word about fluoroquinolones!

 

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Off Label FQ Use – WTF are they thinking???

It has come to my attention that (some) doctors are prescribing Cipro to patients who are having adverse reactions to other drugs.

I am so flabbergasted by this that I’m close to speechless.

WHY would anyone think that it is appropriate to give a fluoroquinolone to someone who is experiencing an adverse reaction to a drug?!  NOWHERE in the literature for fluoroquinolones does it say that they should be used to treat adverse drug reactions.  It makes no sense.

I thoroughly disagree with fluoroquinolones being used as antibiotics in cases where there are other, safer, remedies that can be used.  They are too dangerous and it is a violation of the oath to “do no harm” to prescribe fluoroquinolones when there are safer antibiotics available.   But at least fluoroquinolones do kill bacteria.  Most doctors aren’t aware of how dangerous fluoroquinolones are, and they use them for the purposes for which they are indicated – urinary tract infections, prostatitis, sinusitis, typhoid, anthrax, and other bacterial infections.  There are even some articles that indicates that fluoroquinolones can be used as chemotherapeutic agents to kill cancer cells.  But there is NO REASON to think that they should be given to people who are experiencing adverse drug reactions.  It’s insane and it’s dangerous.  What in the world are these doctors thinking?!

Why would any doctor who has taken the Hippocratic Oath prescribe a drug that has a 43 PAGE warning label and a black box warning, for purposes other than those for which it is proven to be effective?  Why would a doctor who has taken a pharmacology class think that it is okay to give a topoisomerase interrupter to someone who doesn’t even have an infection (or cancer – topoisomerase interrupters are really only appropriate for use to treat cancer)?  Why are they ignoring the serious and severe adverse effects that are listed on the warning label?  Why are they handing out Cipro like it is candy?  Why are they giving drugs that deplete liver detoxification enzymes to people who are having an adverse reaction to another drug?  WHY?

Here is a video from a guy (a Veteran) who was given a prescription for Cipro after he went to the VA doctor’s office with an adverse reaction to Finasteride:

Another case is illustrated in this comment, which, frankly, broke my heart:

“The baby reacted badly to each vaccination, screaming throughout the night each time, and the doctor prescribed her cipro drops after each one. She can’t taste, and has many delays in speech, reading, learning, and physical development, even though she started off being very advanced in certain ways.”

WHY?

Why would a child (A CHILD) be given Cipro after she has had an adverse reaction to a vaccine?  To completely shut down her liver?  To shut down her kidneys?  To destroy her mitochondria?  To obliterate her microbiome?  To make sure that the microbial protection that her microbiome should give her blood-brain barrier is completely destroyed and the aluminum in the vaccines gets deep in there? (See post-script for sources.)

What kind of masochistic doctor does that to a child?

fluoroquinolone-lawsuit-banner-trulaw

There seems to be a strange and disturbing trend to give people Cipro for no justifiable reason – just ‘cause.  Bayer donated (aren’t they sweet?) 3.7 million Euros worth of Cipro to the countries of West Africa to help them deal with Ebola.  Ummm….. Ebola is a VIRUS.  In case it needs to be said, antibiotics do NOTHING to treat viral infections.  In fact, they can make viral infections worse by killing off the good bacteria in the microbiome that are fighting the virus.  If the doctors in West Africa are giving the people who are fighting Ebola Cipro, they are doing them no good.  Cipro can do plenty of harm too.  The warnings on the 43 page warning label aren’t a joke, and they’re not temporary.

The Western Medicine doctors in West Africa wonder why people don’t trust them and would rather go to a local Shaman.  Shoot, I’d rather go to a Shaman than be needlessly pumped full of Cipro.  The Cipro would definitely kill me, at least I’d have a chance of survival with the Shaman.

We’re in this bizarro world of Orwellian notions of drug safety.  The most dangerous drugs, like fluoroquinolones, are pushed as having “an excellent record of safety and efficacy.”  Just ignore the permanent peripheral neuropathy, severe psychiatric disturbances, mitochondrial dysfunction, cellular mineral chelation, antioxidant depletion, microbiome obliteration, etc. that they cause.  Those symptoms can happen weeks, months, or even years after administration of the drug, so it is pushed that fluoroquinolones are “safe” and that the multi-symptom, chronic illnesses that result from them are a “coincidence.”

Doctors are throwing Cipro at people who they don’t know how to deal with.  If you or your boyfriend/father/son is having bizarre psychiatric problems after taking Finasteride, or your child is reacting badly to a vaccine, they’ll be given Cipro.

Why?

I cannot for the life of me understand why.

Post Script – 

The findings published in Science Translational Medicine in the 2014 article, “The gut microbiota influences blood-brain barrier permeability in mice,” are fascinating and likely quite consequential.  The scientists/researchers found that gut microbiota influences blood brain barrier permeability.  Mice with a compromised (or nonexistent) microbiome showed more permeability in their blood brain barrier than mice with normal/healthy microbiomes.  Blood brain barrier permeability means that unwanted molecules and cells from the bloodstream can enter the brain.  Disturbing our microbiome with antibiotics, especially powerful chemotherapeutic antibiotics like fluoroquinolones, is quite consequential to the brain.

Here are some articles about the study:

Science Translational Medicine, “The gut microbiota influences blood-brain barrier permeability in mice

Translational Microbiome Research Forum, “Gut Microbiota Influences Blood Brain Barrier Permeability

NeuroScienceNews.com, “Gut Microbiota Influences Blood Brain Barrier Permeability

The Scientist, “Mother’s Microbes Protect Baby’s Brain: Bacteria in the gut of a pregnant mouse strengthen the blood-brain barrier of her developing fetus.

Karolinska Institute, “Gut microbiota influences blood-brain barrier permeability

 

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FDA Petitioned to Add Psychiatric Side Effects to Black Box Warning for Fluoroquinolones

Hormones Matter Logo2

In a survey of 94 people who experienced adverse reactions to Levaquin/levofloxacin, a fluoroquinolone antibiotic, 72% reported experiencing anxiety, 62% reported depression, 48% reported insomnia, 37% reported panic attacks, 33% reported brain fog and/or cognitive impairment, 29% reported depersonalization and/or derealization, 24% reported thoughts of suicide and 22% reported psychosis.

Psychiatric side-effects of fluoroquinolones are common.  Though many of the psychiatric adverse effects of fluoroquinolones are listed on the warning label, they are buried in the “Central Nervous System Effects” section.  Dr. Charles Bennett of the Southern Network on Adverse Reactions (SONAR), has submitted a petition to the FDA requesting that a black box warning about serious psychiatric adverse events be added to the Levaquin/levofloxacin warning label.

More information about the serious psychiatric adverse effects of fluoroquinolones can be found in this post –

PSYCHIATRIC SIDE EFFECTS OF FLUOROQUINOLONE ANTIBIOTICS

Please spread the word about the psychiatric problems that fluoroquinolones can cause.  The serious psychiatric adverse effects of fluoroquinolones are under-recognized.

People are suffering because they are not adequately warned about the dangers of fluoroquinolones.

Thank you for reading and sharing the post!

 

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Antibiotic Resistance – Can We Please Stop Being Stupid?

Can I just complain about how ridiculously STUPID the over-use of antibiotics in agriculture is?  Antibiotics are regularly used prophylactically in livestock in order to fatten up the animals and to compensate for the abhorrently unsanitary conditions in commercial feedlots.   Neither of those things are okay in the least.  They are appalling in themselves.

But if you don’t care that pigs, cows, chickens and turkeys are dirty and fat, you may say, “so what?”

The “so what” is that pathogenic bacteria are QUICKLY adapting to antibiotics and are getting stronger.  This is speeding up the process of antibiotic resistance among bacteria that can not only make livestock sick, but can also make humans sick.  When YOU get sick with one of these bacterial infections that is resistant to antibiotics, well, you may be screwed, because even fluoroquinolones don’t touch some of these nasty, antibiotic resistant, bacteria.

According to the CDC:

“Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections. Many more people die from other conditions that were complicated by an antibiotic-resistant infection.”

For a while the CDC, FDA and others, led by the pharma and big-ag lobbies, tried to BS (lie to) us all by saying that antibiotic resistance in livestock had nothing to do with antibiotic resistance to humans.  The 2013 CDC Report on Antibiotic / Antibmicrobial Resistance settled that argument as it noted that:

“Antibiotics are widely used in food-producing animals, and according to data published by FDA, there are more kilograms of antibiotics sold in the United States for food-producing animals than for people… This use contributes to the emergence of antibiotic-resistant bacteria in food-producing animals. Resistant bacteria in food-producing animals are of particular concern because these animals serve as carriers. Resistant bacteria can contaminate the foods that come from those animals, and people who consume these foods can develop antibiotic-resistant infections. Antibiotics must be used judiciously in humans and animals because both uses contribute to not only the emergence, but also the persistence and spread of antibiotic-resistant bacteria.”

Here is a good article in Wired explaining the CDC report – “CDC Threat Report: Yes, Agricultural Antibiotics Play a Role in Drug Resistance.”

The reports are in.  The scientific consensus has been stated.  Over-use of antibiotics in agriculture is hurting humans.  So, perhaps we should stop over-using antibiotics in agriculture.  That seems like a good idea.  Too bad the big-ag and pharma pockets are deep and they control the hearts and minds of legislators.  More info on that can be found here – http://www.healthline.com/health/antibiotics/politics-pork-and-poultry-why-legislation-has-not-passed

As bacteria in livestock become resistant to penicillin and sulfa antibiotics, fluoroquinolones will be used more frequently.  Fluoroquinolones already are being used in livestock, just not as frequently as other, safer, antibiotics.  But as bacteria become resistant to safer antibiotics, fluoroquinolone use will surely increase.  For humans as well, as antibiotic resistance increases, fluoroquinolone use will increase.  Doctors will have to pull out the “big guns” because the smaller ones will no longer work.

Antibiotic resistant bacteria are not only harming livestock and people, they are harming the earth itself.  The animals that are given antibiotics excrete those antibiotics (everybody poops – and pees) and the antibiotics go onto the earth / the soil.  This messes up the microbiome of the soil (yes, soil has a microbiome) and more antibiotic resistant bacteria thrive in the soil.  That’s the topic of THIS POST.  Our earth is, literally, getting floxed.  It’s going to get worse too, as stronger and stronger antibiotics become preferred in agriculture, because the traditional ones are no longer doing the job.  The fluoroquinolones will hurt the animals that they are given to, destroy the microbiome of the soil, and leave us Floxies with nothing to eat.  Great.

I wish I didn’t think this was going to happen in my lifetime, but I fear that it will.

The antibiotic arms race will likely continue, with increasingly powerful antibiotics being developed to compensate for antibiotic resistance.  Those synthetic antibiotics will likely have the same, or worse, devastating “side-effects” as fluoroquinolones.  Destruction of the microbiome and destruction of mitochondria is consequential for human health, animal health, and the health of the earth itself – the soil.  Though the importance of the microbiome is starting to be recognized, it may be too late to stop destroying our microbiome with antibiotics.  (The alternative is to fight pathogenic bacteria with helpful bacteria.)  We are accustomed to turning to drugs, and to wantonly killing bacteria.  I don’t see us stopping any time soon.

The bacteria will die – because there isn’t any political will to stop being foolish with antibiotics.  The insects (pests) will die – because there isn’t any political will to protect them from pesticides.  The bees will die – because corporate profits are, apparently, more important than our food supply.  The frogs will die – because no one understands non-linear hormonal responses.

Perhaps, with a painful number of human deaths from this ridiculousness, we’ll, collectively, stop being so stupid.  Maybe.  Because 23,000 human deaths per year (from antibiotic resistant bacteria) haven’t made policy-makers do squat about the over-use of antibiotics in agriculture.  Recommendations for prudent antibiotic use are put into place, but no actual changes are made.  Recommendations.  Recommendations will do nothing to solve this problem – nothing.

P.S. – Sorry for not being hopeful.  Here’s something I hope – I hope that the canaries in the coal mine are listened to.  That’s what we are – canaries.  Is anyone listening?

 

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The Earth is Floxed

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The use of antibiotics in agriculture is incredibly stupid on multiple levels. One level of stupidity to consider – the health of the microbiome of the soil is negatively affected by antibiotic treated animals excreting onto it. Soil has a microbiome. It’s not just ground up rocks. The health of the microbiome of the soil is necessary for healthy plants, and the over-use of antibiotics in agriculture is encouraging antibiotic resistance and pathogenic bacteria within soil.

Please read (and share) this post on Hormones Matter about how our soil is being affected by agricultural antibiotics:

THE EARTH IS FLOXED

Thank you!!!

Thank you for reading Floxie Hope!  I hope that all who read Floxie Hope gain insight, support, understanding and, most of all, HOPE.  If you would like to support Floxie Hope, all contributions will be greatly appreciated!  Click HERE to contribute to Floxie Hope.  Thank you!

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They Don’t Understand

It may be impossible for anyone who has not experienced fluoroquinolone toxicity to understand what it’s like.

It’s difficult for the person who is going through fluoroquinolone toxicity to explain that EVERYTHING is going wrong; and it is even more difficult for those around them to understand.

It’s beyond most people’s comprehension that a commonly prescribed antibiotic, maybe one that they themselves have taken, can cause debilitating pain, exhaustion, loss of mental capacity, inability to move, etc. in their formerly healthy loved one.  Most people think that antibiotics are benign, so they are unable to understand that an antibiotic destroyed the health of their spouse, friend, child, parent, etc.  They think, “it must be something else,” or “the drug should be out of your system by now,” or, simply, “what are you talking about?!” when you tell them that all of your health problems can be traced back to the antibiotic that you took to treat a urinary tract, or sinus, or prostate, or respiratory infection.

They don’t understand that the loss of health is real, that it is severe, and that it may last a while.

They trust doctors.  They trust the system.  They trust that the FDA is properly regulating drugs and protecting people from dangerous drugs.

They may not understand exactly how drugs work, but they think that someone does.  They believe that if a drug wasn’t safe, it wouldn’t be on the market.  They think that it wouldn’t have made it through the testing process if it wasn’t safe and better than drugs that are already available.  They think that the FDA has done a thorough and complete evaluation of all drugs that are on the market, and that if fluoroquinolones caused horrible adverse reactions in most people, they wouldn’t continue to be on the market.

They think that all drugs have side-effects, but those side-effects are rare.

They think that adverse drug reactions look like allergic reactions, and they think that you should immediately recover when the drug is “out of your system.”  They don’t understand that adverse drug reactions can manifest as multi-symptom chronic illness.

They don’t understand how you could suddenly be unable to walk, or think, or do the things that you used to be able to do with ease.

The fact that Floxies “look fine” makes it even more difficult to understand what a floxed loved one is going through.

They don’t understand how the tests could show that you’re “fine” when you say that you feel anything but “fine.”

They think that you’re a bit crazy, and probably a conspiracy theorist, when you wonder if other people who are suffering from mysterious, chronic illness may be suffering from fluoroquinolone toxicity too.  You see Floxies everywhere.  They don’t understand that.

They don’t understand the ups and downs, the relapses and the bad days following good days.

They don’t “get it” because they haven’t experienced it.  They don’t understand because they haven’t had to.  Their perception of the competence of the FDA and the medical system hasn’t been shaped by getting poisoned by an antibiotic that is assumed to have “an excellent record of safety and efficacy.”

I didn’t understand anything to do with fluoroquinolone toxicity before it happened to me.  If it had happened to a friend, family member or lover, I wouldn’t have understood.  I wouldn’t have “gotten it.”  I would have believed everything that I wrote above about belief, faith really, in the system that is supposed to make and keep us healthy.  I did believe everything that I wrote above.  And if a loved one had come down with fluoroquinolone toxicity, I probably would have continued to believe those things.  I would not have understood.  It took getting knocked down myself to understand – to really see and comprehend what a mysterious, pharmaceutical induced illness was like.

Many try to understand.  There are some loved ones of Floxies who work very hard to understand and support their sick loved ones.  They research and advocate for their spouse, child, parent or friend.  They listen with caring, compassion and kindness.  They do their best to be supportive and understanding.  They are wonderful, and greatly appreciated.

Most people, even really good people, don’t understand though.

On some level, it has to be okay.  It’s perfectly possible for them to still love and support you, without really “getting it,” without really understanding.

In order to maintain the relationships in your life, I think that it’s necessary to forgive them for not understanding.

They can’t understand.  It’s too bizarre.  It’s too foreign.  It’s too strange.  It’s too upsetting.

They still love you.  And you still love them.  So forgive them for not understanding.  Forgive them for not understanding your pain, or anxiety, or immobility.  Forgive them for not sharing your feelings of anger toward the system that allowed you to be poisoned.  Forgive them for not understanding how a drug could cause long-term damage to you.

Forgive them because you love them, and they love you.

They probably miss the old you – just like you miss the old you – and it’s probably hard for them to deal with the sick you – just like it’s hard for you to deal with the sick you.

This whole mess of fluoroquinolone toxicity is hard.  It’s hard for everyone involved.  It’s hardest for the people who have to deal first-hand with the pain and suffering that comes with getting poisoned.  It’s also hard for those who love Floxies to deal with.

Forgive them for not dealing with your sickness perfectly.  I’m guessing that you haven’t dealt with it perfectly either.  I know I didn’t.

We all want understanding.  We all want empathy and sympathy and compassion from those whom we are closest to.

Even if you can’t get that empathy from those whom you are closest to, because they just don’t understand, it is healing to forgive them.  They can’t understand because they haven’t been through it.  But you can give them understanding and compassion, because you understand their perspective.  After all, their perspective used to be your perspective.  You can forgive them for not understanding.  They may never understand how you are feeling and what you are experiencing, and that’s okay.  It must be okay.  Because you love them, and they love you, and they just want you to get better.

We grow when we forgive.  We heal when we forgive.  Forgiving is probably even necessary for healing and growth… and love.  Love is healing and it is necessary.  Forgiveness of those who don’t understand, who can’t understand, helps you to keep your heart open to love.

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Fluoroquinolone Induced Gene Upregulation and ROS

The article, “The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumonia” is difficult.  It’s not light reading.  I wish it was.  I wish the articles that have information about how fluoroquinolones affect cells were easy to understand and to read.  I wish that we had easy, simple answers about how fluoroquinolones lead to the myriad of adverse events that are listed on the FDA warning labels for them.  I wish that more was known about how fluoroquinolones work.  I wish that a list of definitions wasn’t necessary at the beginning of this blog post.  But this stuff is hard, and a list of definitions is necessary, so, hereyago (some definitions paraphrased from the Wikipedia article because it’s easiest and I’m not a biochemist – for more info, go to the wiki page, or elsewhere):

Reactive Oxygen Species (ROS):  “Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. ROS are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis.  However, during times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically. This may result in significant damage to cell structures. Cumulatively, this is known as oxidative stress. ROS are also generated by exogenous sources such as ionizing radiation.”  ROS can be incredibly nasty.  They can lead to cellular damage, including DNA damage, and are related to every chronic disease there is.  They’re also related to ageing.  As damage from ROS (also called oxidative stress and free radicals) accumulates, ageing and the diseases of old age occur.  Interestingly though, ROS are not all bad.  They serve as signaling mechanisms within cells and play a large role in turning genes on and off (epigenetics).  They need to be in balance.  If they’re not in balance, a whole lot of things can go wrong.  They’re kind of like tequila.  A shot of tequila mixed with lime juice and other goodies, is excellent in a margarita.  But if you drink the whole bottle, and then mix it with some whiskey, it’s really bad and destructive.  The ways that ROS work within cells is not linear and difficult to study.  Not a whole lot is known about ROS or how they affect human health.  The article, “Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production” has a really nice over-view of various ROS and their effects.  It’s easier to think of them as different  alcoholic drinks though.  Some are beer – pretty benign unless you have a ridiculous amount of them.  Others are potent – more like Everclear – and they can do a lot of damage to you quickly.

Fenton Reaction:  “Iron(II) is oxidized by hydrogen peroxide to iron(III), forming a hydroxyl radical and a hydroxide ion in the process. Iron(III) is then reduced back to iron(II) by another molecule of hydrogen peroxide, forming a hydroperoxyl radical and a proton. The net effect is a disproportionation of hydrogen peroxide to create two different oxygen-radical species, with water (H+ + OH–) as a byproduct.”  Basically, iron can “donate or accept free electrons via intracellular reactions and help in creating free radicals.”  Free radicals are ROS.  Some of the nastiest ROS are created in the Fenton Reaction – hydroxyl radicals and hydroperoxyl radicals.  (“Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production” has good info on both of those.)

Type II topoisomerases, gyrase and topoisomerase IV:  “Type II topoisomerases maintain DNA topology and solve the topological problems associated with DNA replication, transcription, and recombination (20). Gyrase introduces negative supercoils into DNA (21), whereas topo IV relaxes DNA and participates in chromosome partitioning (22). Chromosomal topology in Escherichia coli is maintained homeostatically by the opposing activities of topoisomerases that relax DNA (topo I and topo IV) and by gyrase.” (from “The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumonia”)

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You got all that?  Even the definitions are difficult.  Now onto some highlights of the article, “The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumonia.”

Basically, the researchers found that levofloxacin upregulated genes that are involved in iron uptake and triggered the Fenton reaction in certain bacteria.  The increase in reactive oxygen species that ensued contributed to the lethality of the levofloxacin.

There are a few interesting things that should be noted about this.  First, levofloxacin can upregulate genes.  How consequential is this?  Can eukaryotic genes be upregulated, or can only bacterial genes be upregulated?  What about mitochondrial genes?  What does upregulation of bacterial, mitochondrial and even eukaryotic nuclear genes do to the person who has taken levofloxacin?

Some interesting research is being conducted about the relationship between the microbiome and genetic, heritable traits.  This National Geographic article, “The Most Heritable Gut Bacterium is… Wait, What is That?” notes some of the relationships that are being explored.  Our genes can affect our microbiome, our microbiome can affect our genes, can the genes of our microbiome affect…. US?  Where does the microbiome stop and where do we begin?  Those are all questions that have not yet been answered.  Unfortunately, fluoroquinolones, like levofloxacin, are thoroughly messing up our microbiomes and even causing the upregulation/expression of certain genes.

The second thing of note from the article is that the upregulated genes caused the activation of the Fenton reaction in the bacterial cells.  Again, how does this affect our microbiome?  How does it affect US?  Hydroxyl radicals and superoxide anions are nasty ROS that damage everything in their wake.  What happens to the health of the microbiome, and the host (the person) when their gut is suddenly full of toxic ROS?  Leaky gut syndrome?  Autoimmune reactions?  The multi-symptom, chronic illness that is fluoroquinolone toxicity syndrome?

There is quite a bit of evidence that fluoroquinolones do to mitochondria what they do to bacteria – disrupt the process of DNA replication and reproduction and lead to destruction and cell death.  I think that mitochondrial destruction has a lot to do with fluoroquinolone toxicity.  However, I don’t think that the role of disruption of our microbiome and destruction of our gut bacteria should be overlooked.  The signaling that goes on within our microbiome, and between “us” and our microbiome, is critically important and poorly understood.  Triggering bacterial DNA destruction and death, upregulation of genes and the Fenton reaction – which leads to production of highly destructive ROS, is a very, very, very bad idea – even if it just stays within the microbiome.

The conclusion of “The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumonia” is that:

“In conclusion, we have shown for the first time that fatDCEB transcription is regulated by the supercoiling level. The primary effect of the interaction of LVX-topo IV is the upregulation of the operon by local increase in DNA supercoiling. This upregulation would increase the intracellular level of iron, which activates the Fenton reaction, increasing the concentration of hydroxyl radicals. These effects were observed before the inhibition of protein synthesis mediated by LVX. All these effects, together with the DNA damage caused by the inhibition of topo IV, would account for LVX lethality. The possibility to increase FQs’ efficacy by elevating the levels of intracellular ferrous iron remains open.”

Because, apparently, seeing the big picture of the symbiotic relationship between the microbiome and the rest of the organism (the person), isn’t the goal.  The goal is to kill bacteria.  It’s ridiculously short sighted.  Sigh.

Because we’re in Floxieville, there has to be a paradox.  Supplementing iron helped me more than just about anything else.  Iron is one of the few supplements that made me feel markedly better immediately after taking it.  Other Floxies have reported that their ferritin levels are low post-flox.  The role of the Fenton reaction in fluoroquinolone toxicity would lead one to think that iron should be the last thing that a Floxie might need or want.  It helped me though.  I had more energy and even my tendons felt better when I started supplementing iron.  I don’t know if this has something to do with the kind of iron in my supplement/body – FE3 or FE2 – or if the iron had been converted to other chemical compounds and I needed to replace it, or what.  I do know that, as I said in the beginning of this post, this stuff is hard.

The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumonia provides a good description of how fluoroquinolones work:

“The killing effect of FQs has been related to the resolution of reaction intermediates of DNA-FQ-topoisomerase complexes, which generates irreparable double-stranded DNA breaks (31). This could occur in E. coli by two pathways, one dependent on protein synthesis and the other independent of it. It has been shown that hydroxyl radical action contributes to FQ-mediated cell death occurring via a protein-dependent pathway (32). This result agrees with a recent proposal suggesting that, following gyrase poisoning, hydroxyl radical formation utilizing internal iron and the Fenton reaction (33) is generated and contributes to cell killing by FQs (34) as well as by other bactericidal antibiotics (35, 36). In this mechanism, proposed for Enterobacteriaceae (35, 37), the primary drug interactions stimulate oxidation of NADH via the electron transport chain that is dependent on the tricarboxylic acid cycle. Hyperactivation of the electron transport chain stimulates superoxide formation. Superoxide destabilizes the iron-sulfur clusters of enzymes, making Fe2+ available for oxidation by the Fenton reaction. The Fenton reaction leads to the formation of hydroxyl radicals that would damage DNA, proteins, and lipids (38), which results in cell death. Instead of a generalized oxidative damage, a recent study supports that the main action of hydroxyl radicals is the oxidation of guanine (to 8-oxo-guanine) of the nucleotide pool. The incomplete repair of closely spaced 8-oxo-deoxyguanosine lesions caused lethal double-strand DNA breaks, which would underlie much of the cell death caused by beta-lactams and FQs (39). However, recent investigations have questioned the role of hydroxyl radicals and intracellular iron levels in antibiotic-mediated lethality using antibiotic concentrations either similar to (40) or higher than (41) those used previously. The disparate results obtained using diverse antibiotic concentrations and times of treatment emphasize the complexity of the lethal stress response (42).”

Similar destruction happens in mitochondria.  As I mentioned though, even if it didn’t happen in mitochondria, and only happened in bacteria, that destruction and those reactions are horrible things to do to a person’s microbiome.  It is, after all, part of us.

All of the people at the FDA who think that it’s okay not to strictly regulate drugs that disrupt the process of DNA replication and reproduction, and lead to the upregulation of genes and induction of the Fenton reaction, which leads to high levels of highly reactive ROS, should be fired.  I’ve learned enough biochem in the last 3 years to know that induction of the Fenton reaction in any part of the body is a really bad idea.  The scientists at the FDA should be able to figure this out.

 

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Petitioning the FDA – Comments Needed

Floxie friends, I have one thing that I am asking you to do today.  And please, if you decide to do it, do it sooner rather than later.  Please go to THIS LINK and make a comment about how fluoroquinolones have hurt you.  Let the FDA know that the current warning label for fluoroquinolones is insufficient.  Let the FDA know that their own findings of fluoroquinolone caused mitochondrial toxicity need to be noted on the warning labels of fluoroquinolones.

Again, here is the link for the citizens’ petition, filed with the FDA, where comments about how a fluoroquinolone hurt you can be made –

http://www.regulations.gov/#!docketDetail;D=FDA-2014-P-0856

If you do nothing else today, please, please make comments on this petition.

Thank you!

HERE is the petition that I am asking you to comment on.

The petition was submitted by Dr. Charles Bennett, M.D., Ph.D., M.P.P.  Dr. Bennett is with the Center for Medication Safety and Efficacy and the Southern Network on Adverse Reactions (SONAR).  The Quinolone Vigilance Foundation facilitated much of the work that went into the petition.  I thank both Dr. Bennett and his colleagues, and the Quinolone Vigilance Foundation for their work!

The petition is to add “Possible Mitochondrial Toxicity” to the Levaquin label.  In the Warnings and Precautions section of the Levaquin/levofloxacin label, it should say:

Possible Mitochondrial Toxicity

Fluoroquinolones, including Levaquin, may cause Mitochondrial Toxicity due, in part, to an insufficiency of ATP. Mitochondrial conditions that are due to an insufficiency of ATP include developmental disorders of the brain, optic neuropathy, neuropathic pain, hearing loss, muscle weakness, cardiomyopathy, and lactic acidosis. Neurodegenerative diseases, like Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS) have been associated with the loss of neurons due to oxidative stress generated by reactive oxygen species (ROS) related to Mitochondrial Toxicity. Peripheral neuropathy, hepatoxicity, glucose disturbances, and phototoxicity may result from Mitochondrial Toxicity.

That language, by the way, is directly from the FDA document, “Disabling Peripheral Neuropathy Associated with Systemic Fluoroquinolone Exposure.”  The folks at the FDA know that fluoroquinolones have been shown to be toxic to mitochondria, this petition is asking them to do something about it.

It is also requested in the petition that the following black box warning be added to the Levaquin/levofloxacin warning label:

WARNING: POSSIBLE MITOCHONDRIAL TOXICITY

Fluoroquinolones may cause Mitochondrial Toxicity. Mitochondrial Toxicity has been implicated in conditions such as peripheral neuropathy, hepatoxicity, glucose disturbances, phototoxicity, developmental disorders of the brain, optic neuropathy, neuropathic pain, hearing loss, muscle weakness, cardiomyopathy, lactic acidosis, Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS).

Based on the severity of the effects of mitochondrial toxicity, it is being requested that:

  1. Levaquin label changes be made immediately.
  2. “Dear Doctor” letters be distributed regarding Levaquin label changes and requesting that physicians inform patients about the potential impact of “Possible Mitochondrial Toxicity” if they were previously prescribed this drug.

It is very important for all patients and medical professionals that this warning be added to the label of fluoroquinolones.  Please make your voice heard and support the petition with your comments.

THANK YOU!

 

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Unintended Consequences of Pharmaceuticals (Especially Fluoroquinolones)

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Before I started studying adverse drug reactions / biochem / cellular biology, I thought that there were people who had a pretty good grasp of how everything within the human body works. I was wrong about that – I was ignorant. It took a lot of research for me to realize that the body is so incredibly (beautifully) complex, and that systems are so unpredictably intertwined, that no one really grasps how it all works. We aren’t even close. But pharmaceuticals throw a wrench in many biochemical pathways whether we are aware of them or not. Ignorance is not bliss. The complexity of life is mind-bogglingly amazing. How ’bout we stop messing with it in ways that hurt us?

A post about how complex and interconnected all of our biological systems are, and about how messing up any or all systems with pharmaceuticals is probably not the best idea, can be found here –

SIDE EFFECTS AND UNINTENDED CONSEQUENCES OF POPULAR PHARMACEUTICALS

Many of the thoughts behind the post are based on THIS CHART.

There is nothing simple about biochemistry, but there is something that is beautiful and incredible about it.  All of those systems work together, and amazingly, they work together perfectly most of the time.  I find it to be mind-blowing and I’m a bit awe struck by what incredibly complex creatures we are.

Pharmaceuticals have the power to disrupt our biochemical systems.  I wish that we were using a bit more prudence with powerful concoctions that can hurt us in multiple ways.

 

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Repeated Use Doesn’t Make Fluoroquinolones Safe

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I posted “REPEATED USE DOESN’T MAKE FLUOROQUINOLONES SAFE” on www.hormonesmatter.com on 10/1/2014.  Please check it out and share it – thanks!!!

When doctors say things like, “I’ve prescribed fluoroquinolone antibiotics to hundreds of patients and I’ve never seen problems like yours. It’s a good drug with an excellent safety record.” it really irks me.  It irks me for the nine reasons listed, but the one that irks me most is that it’s so illogical.  Doing things wrong repeatedly does not make them right.  Thousands of prescriptions for Vioxx, Thalidomide and DES were written before they were taken off the market or restricted. I’m sure that the doctors who wrote those prescriptions thought that the drugs that they were prescribing were perfectly safe. They weren’t. Fluoroquinolones are not safe either. Lack of recognition of the severe adverse effects does not make them safe – it just means that doctors are as biased and blinded as anyone else. Look at the studies. Look at what Cipro, Levaquin and Avelox do to cells. Cellular destruction results in multi-symptom, chronic illness – in case that fyi is needed.

 

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Mitochondria, Neuropathy, HIV and Fluoroquinolones

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I wrote the following post and put it on one of my other sites, Mito Madness.

Mitochondria, Neuropathy, HIV and Fluoroquinolones

Though the damage done by fluoroquinolones to mitochondria is well documented, as is the connection between mitochondrial damage and many illnesses and maladies, the knowledge of the connections is not widespread.  Hopefully, some emerging research will change that.

Thank you for reading it!

Regards,

Lisa

 

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Shades of Grey – The Good and Bad of Fluoroquinolones

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Here is a new post about fluoroquinolones on Hormones Matter –

Shades of Grey – The Good and Bad of Fluoroquinolones

From it –

“Fluoroquinolones can do good, but they can do harm too. Categorizing things in terms of good or bad is the natural inclination of most people, but it’s never that simple for drugs. All drugs can do good, but they can do harm too – hence the list of side-effects that comes with each prescription. We can’t yet ask for drugs to only do good, and never do harm – that’s not the way the world works. But we can ask for dangerous drugs to be used appropriately. It is ONLY appropriate for fluoroquinolones to be used in life-or-death situations when other antibiotics aren’t effective. To use them flippantly, and when they aren’t entirely necessary, is inappropriate and a violation of the Hippocratic Oath.”

I hate that cipro hurt me.  I hate that fluoroquinolones hurt any of us.  But I still don’t think that they should be banned entirely.  It is not unreasonable to demand that they be used sensibly though.  The amount of collateral damage done by FQs is unacceptable.  Collateral damage should be minimized.  It’s not too much to ask for.

 

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Hidden Reactions: How Side-Effects of Cipro, Levaquin and Avelox Are Under-Recognized

lisa-bloomquist2 Baron and Budd

Adverse reactions to cipro, levaquin, avelox, floxin or any other fluoroquinolone, are tricky and difficult to recognize because of:

 

  • Delayed reactions
  • Tolerance thresholds
  • The absurdity of the severity of adverse reactions to fluoroquinolones

This post, published on the Baron & Budd web site, goes over information about those three things.

Hidden Reactions: How Side-Effects of Cipro, Levaquin and Avelox Are Under-Recognized

Please share it so that people can connect their pain to the culprit – Bayer and Johnson & Johnson.

 

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False Idols

Thou shall not worship false idols.

I’ve been thinking about the commandment not to worship false idols a lot since getting floxed.

We, as a society, and probably as individuals too, look to pills to fix us.  We look to pharmaceuticals to cure us when we are sick.  We worship the pills as if they are magical, and good, and as if they will remove all problems from our lives.  There is a systematic lack of questioning about whether or not drugs are actually good – whether the benefits outweigh the costs.  We have faith – blind, baseless faith – that all drugs do more good than harm, that adverse effects are transient and rare, that there is enough knowledge about the workings of the human body to anticipate how a drug is going to affect cells and how those effects are going to change the health and well-being of the person who takes them, etc.  (To their credit, scientists do try to make drugs safe and understand how they work – but there is a lack of willingness to admit that we know far too little about the workings of the human body to be messing with it like we are.)

We worship doctors as if they are Gods.

I wonder if there is something profoundly broken about this way of thinking.  And I wonder if there are some deep lessons to be learned in thinking about where our worshipping of false idols is taking us.

What happened in our floxed bodies is chemical.  I don’t think that any of us got sick because of God’s spite or vengeance, or because any of us worship the “wrong” God.  (There is NOTHING about getting poisoned that is your fault.  Nothing.)  Likewise, what it will take to fix us is chemical, and I don’t think that faith is going to be able to repair our broken cells.

But I also think that it is destructive and wrong to worship pharmaceuticals and doctors.  They can be helpful and they can be guides – but they are not Gods.

I used to believe that adverse reactions are rare, antibiotics are benign, when a drug does harm a doctor can fix it, the FDA is ensuring drug safety, diseases are well understood, the pharmaceutical industry is working hard to find cures to the ills that plague humanity, etc.  I no longer believe any of those things.  I have lost my faith.  Getting hurt – then gaining a little knowledge about how drugs work – will do that to you.

I don’t claim to know who or how (or even if) we should worship.

But I don’t think that pharmaceuticals or doctors should be worshipped.  They are powerful – there’s no denying that.  Unchecked power has never led to good though.  In politics, unchecked power leads to corruption and tyranny.  In medicine, unchecked power leads to poisoning – which leads to chronic disease and suffering.

Drugs aren’t the only false idol that are worshipped to the point of destruction and pain.  The oceans, rivers, land, animals and humans are being hurt in the pursuit of fossil fuels.  Money – the ultimate false idol – the one that none of us (myself included) seems capable of getting out from under the enchantment of – is pursued to the point of inducing pain, destruction and suffering of the earth and all her inhabitants.

When we, collectively (seriously, no individual blame here), worship false idols, we get poisoned.  Our earth and our bodies are being poisoned as we worship money and power and chemical concoctions that we don’t realize the consequences of.  It is a shame – a crying shame.  My heart and soul ache for us all.

 

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Cellular Oxidative Damage from Fluoroquinolones

Here are some thoughts about what is/was going on in our floxed bodies.

First, here’s my typical disclaimer.  I’m not a doctor or scientist.  I’m doing my best to put together this information, but I could be wrong.  I do my best to be right and I back up my assertions with peer-reviewed journal articles.

As I mentioned in Article Breakdown – “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria,” I believe that this paragraph describes much of what occurs in floxed cells:

“Increased steady-state levels of mitochondrial superoxide, arising from reduction of Sod2 activity in the Sod+/−mice (i.e., approximately half the wild-type activity), may be exacerbated by drugs that directly target the ETC [e.g., the complex I inhibitors flutamide and troglitazone (122)]. The increased amount of superoxide raises two considerations. First, superoxide that escapes dismutation to hydrogen peroxide cannot cross the inner mitochondrial membrane and can oxidize [Fe-S]-containing enzymes (e.g., aconitase and complex I/III subunits). Alternatively, superoxide can rapidly react with mitochondrial nitric oxide (NO) to form peroxynitrite (ONOO−). For example, the fluoroquinolone antibiotic trovafloxacin (TVX), a typical DILI (drug induced liver injury) associated drug, raises steady-state levels of NO in hepatocellular mitochondria (unpublished data). The mechanisms are not known, but TVX also increases cytosolic (non-ferritin-bound) Ca2+, likely activating the Ca2+-dependent mitochondrial NO synthase (123) to produce ONOO−. Peroxynitrite is dangerous for a number of reasons: i) under acidic conditions, it can be degraded to form the extremely reactive hydroxyl radical; ii) it may directly cause the nitration of aconitase, Sod2, and the [Fe-S]-containing subunits of ETC complexes; and iii) it can induce mitochondrial permeabilization (Figure 4B) (124). This superimposed oxidative/nitrative stress could ultimately push the cell across the threshold to observable injury.”

SUPEROXIDE DAMAGE OF MITOCHONDRIAL DNA

Superoxide is a powerful oxidant that is quite toxic.  Per “Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling,” “ROS are produced continuously as a by-product of aerobic metabolism.  Superoxide can be produced as a result of the one-electron reduction system within the mitochondrial electron transport chain.  Superoxide can then be converted into hydrogen peroxide (H2O2) by superoxide dismutase (the Mn isoform in the matrix and cu, Zn-superoxide dismutase in the cytosol).  H2O2 can be converted into highly reactive hydroxyl radicals (OH-) by the Fenton reaction, and can cause lipid peroxidation.” More info about superoxide can be found here – http://en.wikipedia.org/wiki/Superoxide

In properly functioning cells, superoxide dismutase (SOD) converts superoxide into hydrogen peroxide (H2O2) and water.  Unfortunately, fluoroquinolones deplete cellular SOD.  In “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients” it was found that, for human patients with urinary tract infections and treated with various fluoroquinolones, “There was substantial depletion in both SOD and glutathione levels particularly with ciprofloxacin.”

Without sufficient SOD, as noted above, superoxide “cannot cross the inner mitochondrial membrane and can oxidize.”  Oxidization within the mitochondrial membrane is harmful because it damages mitochondrial DNA (mtDNA) and starts the vicious cycle of oxidative damage to mitochondria.  (This “vicious cycle” theory is described in “Oxidative stress induces degradation of mitochondrial DNA” – “According to this theory, the production of ROS by mitochondria leads to mtDNA damage and mutations which in turn lead to progressive respiratory chain dysfunction and to a further increase in ROS production as a consequence of this dysfunction. The exponential escalation of these processes is commonly referred to as a ‘vicious cycle’, and the theory predicts that the rise in mtDNA mutations and ROS eventually reach levels that are incompatible with life.”  It should be noted that whether or not this theory is true for how aging works is contentious.  The vicious cycle of damage done by ROS does occur in mitochondria though.)

THE NITRIC OXIDE / PEROXYNITRITE (NO/ONOO-) CYCLE

Additionally, “superoxide can rapidly react with mitochondrial nitric oxide (NO) to form peroxynitrite (ONOO−).”  The ways in which peroxynitrite are dangerous are noted in the paragraph from “Mechanisms of Pathogenesis” at the beginning of this post.

Dr. Martin L. Pall, Professor Emeritus of Biochemistry and Basic Medical Sciences at Washington State University describes the NO/ONOO- (nitric oxide / peroxynitrite) cycle in his web site, http://www.thetenthparadigm.org/index.html.  Here is a diagram from The Tenth Paradigm describing the NO/ONOO- cycle –

ONOO cycle

Here is Dr. Pall’s description of the above diagram:

“Fig. 1 legend.  Vicious (NO/ONOO-) cycle diagram.  Each arrow represents one or more mechanisms by which the variable at the foot of the arrow can stimulate the level of the variable at the head of the arrow.  It can be seen that these arrows form a series of loops that can potentially continue to stimulate each other.  An example of this would be that nitric oxide can increase peroxynitrite which can stimulate oxidative stress which can stimulate NF-kappaB which can increase the production of iNOS which can, in turn increase nitric oxide.  This loop alone constitutes a potential vicious cycle and there are a number of other loops, diagrammed in the figure that can collectively make up a much larger vicious cycle.  The challenge, according to this view, in these illnesses is to lower this whole pattern of elevations to get back into a normal range.  You will note that the cycle not only includes the compounds nitric oxide, superoxide and peroxynitrite but a series of other elements, including the transcription factor NF-kappaB,  oxidative stress, inflammatory cytokines (in box, upper right), the three different forms of the enzymes that make nitric oxide (the nitric oxide synthases iNOS, nNOS and eNOS), and two neurological receptors the vanilloid (TRPV1) receptor and the NMDA receptor.”

The NO/ONOO- cycle provides a reasonable explanation for why it feels as if a bomb has gone off in the body of the floxie.  It also is an explanation as to why the adverse effects of drugs that damage mitochondria and cause oxidative stress are not transient.  There are feedback loops within the cells that perpetuate the damage.

Here is Dr. Pall’s table of signs of the NO/ONOO- cycle –

Explanations for Symptoms and Signs

Symptom/Sign Explanation based on elevated nitric oxide/peroxynitrite theory
energy metabolism /mitochondrial dysfunction Inactivation of several proteins in the mitochondrion by peroxynitrite; inhibition of some mitochondrial enzymes by nitric oxide and superoxide
oxidative stress Peroxynitrite, superoxide and other oxidants
PET scan changes Energy metabolism dysfunction leading to change transport of probe; changes in perfusion by nitric oxide, peroxynitrite and isoprostanes
SPECT scan changes Depletion of reduced glutathione by oxidative stress; perfusion changes as under PET scan changes
Low NK cell function Superoxide and other oxidants acting to lower NK cell function
Elevated cytokines NF-kappaB stimulating of the activity of inflammatory cytokine genes
Anxiety Excessive NMDA activity in the amygdala
Depression Elevated nitric oxide leading to depression; cytokines and NMDA increases acting in part or in whole via nitric oxide.
Rage Excessive NMDA activity in the periaqueductal gray region of the midbrain
Cognitive/learning and memory dysfunction Lowered energy metabolism in the brain, which is very susceptible to such changes; excessive NMDA activity and nitric oxide levels and their effects of learning and memory
Multiorgan pain All components of cycle have a role, acting in part through nitric oxide and cyclic GMP elevation
Fatigue Energy metabolism dysfunction
Sleep disturbance Sleep impacted by inflammatory cytokines, NF-kappaB activity and nitric oxide
Orthostatic intolerance Two mechanisms:  Nitric oxide-mediated vasodilation leading to blood pooling in the lower body; nitric oxide-mediated sympathetic nervous system dysfunction
Irritable bowel syndrome Sensitivity and other changes produced by excessive vanilloid and NMDA activity, increased nitric oxide
Intestinal permeabilization leading to food allergies Permeabilization produced by excessive nitric oxide, inflammatory cytokines, NF-kappaB activity and peroxynitrite; peroxynitrite acts in part by stimulating poly ADP-ribose polymerase activity

Sounds pretty familiar, doesn’t it?

STOPPING THE NO/ONOO- CYCLE

What can be done to stop the NO/ONOO- cycle?  How can one heal when cells are reinforcing the damage done to them over and over again?

Here are Dr. Pall’s recommendations – http://www.thetenthparadigm.org/therapy.htm

Additionally, a very smart and appreciated floxie noted in a comment on this site, that uric acid has been shown to decrease peroxynitrite.  Per the article, “Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis,” “Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO).”  (There has been some debate about whether floxies want to increase or decrease nitric oxide.  I think that we want to increase NO because too much of it is converted into peroxynitrite.  Here’s an article on how NO helps with tendon healing – “The role of nitric oxide in tendon healing.”)  Uric acid.  The stuff that causes kidney stones and gout – it’s a powerful antioxidant that scavenges peroxynitrite.

The role that uric acid plays in getting rid of toxic peroxynitrite makes sense to me on a personal level because of a couple of things that have made me feel significantly better post-flox – brewer’s yeast and uridine supplements.  Both brewer’s yeast and uridine are high in purines, which are converted into uric acid in the body.  I always thought that the purines and uric acid were a necessary evil and that the good done by brewer’s yeast had to do with its high amino acid and/or B vitamin content.  Now I’m thinking that the necessary evil was actually the active ingredient.

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Here are a couple more articles about the role of uric acid in peroxynitrite neutralization (thanks again to the floxie friend who pointed them out):

There is a very real risk of kidney stones and gout when consuming too many purines that lead to excess uric acid.  Even though brewer’s yeast has helped me immensely, I feel quite conflicted about it.  I don’t want a kidney stone and gout would probably make my flox-induced peripheral neuropathy look like a cake-walk.  Now that I’m feeling well, I’m probably going to cut way down on my brewer’s yeast consumption.  I really don’t know which are worse – the diseases of too much uric acid (kidney stones and gout) or the diseases of too little uric acid (“patients with MS have significantly lower levels of serum uric acid than controls” and peroxynitrite is associated with lots of other nasty diseases – like cancer and Alzheimer’s).  This isn’t exactly a great predicament.

Another consideration is that fluoroquinolones deplete cellular magnesium and proper amounts of cellular magnesium are necessary for 300+ enzymatic reactions.  (Fluoroquinolones may inhibit and deplete enzymes through means other than depletion of cellular magnesium too.)  If one doesn’t have the enzymes to metabolize uric acid, well, too much isn’t a good thing.  Too much peroxynitrite is bad too though.

I wish that the answers were more clear.  I hope that this post at least gave you some information with which you can make an informed decision!

In researching this post, I stumbled upon this interesting web site – http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/ROS.html  It is noted on the site that uric acid is an antioxidant and that, “Perhaps the long life span of some reptiles and birds is attributable to their high levels of uric acid.”  Bird shit and reptile blood are full of the stuff.  If there is a cure for fluoroquinolone toxicity, it’ll probably come from bird turds or alligator blood.  Great.

 

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