Tag Archives: neurotransmitters

Fluoroquinolone Toxicity Mimics Benzodiazepine Withdrawal – Beware

GABA “is the chief inhibitory neurotransmitter in the mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone” (source). 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.” (sourcesourcesource) Fluoroquinolones have also been shown to have similar effects on GABA neurotransmitters as benzodiazepine withdrawal (source).

The effects of fluoroquinolones on GABA-A neurotransmitters are the exact opposite of the effects of benzodiazepines, and, on a neurotransmitter level, they are the same as the effects of benzodiazepine withdrawal.

Symptoms of benzodiazepine withdrawal, AND fluoroquinolone toxicity, include:

  • sleep disturbances
  • irritability
  • increased tension and anxiety
  • panic attacks
  • tremors
  • difficulty with concentration
  • confusion and cognitive difficulty
  • memory problems
  • nausea
  • heart palpitations
  • headaches
  • muscular pain and stiffness
  • psychosis

And many other symptoms.

Both fluoroquinolone toxicity and benzodiazepine withdrawal are multi-symptom, chronic illnesses, for which there is no cure, and, despite significant research into both, the severity and complexity of both SYNDROMES is rarely acknowledged.

The following article does a brilliant job of connecting fluoroquinolone toxicity (syndrome) and benzodiazepine withdrawal (syndrome), and it gives a thorough explanation as to why people who have gone through benzodiazepine withdrawal should NEVER be prescribed fluoroquinolones. The article was originally published on the Benzodiazepine Information Coalition web site, www.benzoinfo.com, in October, 2016. It was written by Brad Verret, and I am grateful to him for the wonderful article.

Tragically, Brad Verret has passed away. I asked the editor of benzoinfo.com if I could re-publish it on floxiehope.com, and she said yes and noted that, “Brad wrote his articles to help as many people as possible. His intentions were to sound the alarm for benzodiazepine affected people to avoid that awful class of antibiotics, and he would have been pleased to help floxies avoid getting benzodiazepine injured.” She also noted that Brad was kind and smart and that he is missed dearly. I hope that his loved-ones see the use of his wonderful article as a tribute. Brad synthesized and interpreted the data about the effects of fluroquinolones and benzodiazepines on GABA-A thoughtfully and insightfully. This is a wonderful article, and Brad’s work is greatly appreciated! Please share it (or this entire post) far and wide – thank you!!

Hidden Dangers of Fluoroquinolone Antibiotics in the Benzodiazepine-Dependent Population

By Brad Verret

Whether it was for a sinus infection or bronchitis, most people have taken an antibiotic at some point in their lives. Antibiotics can be lifesaving medications but, like all other drugs, they come with risks. In particular, one specific class of antibiotic drugs called the fluoroquinolones carry serious risks that few people are aware of. In light of the growing epidemic of antibiotic resistance, each new generation of antibiotics has bolstered an enhanced degree of potency which can be viewed as both an asset and a liability. The fluoroquinolone class features a robust, broad-spectrum antibiotic effect and includes many popular drugs such as ciprofloxacin (Cipro), ofloxacin (Floxin), norfloxacin (Noroxin), levofloxacin (Levaquin), moxifloxacin (Avelox), and gemifloxacin (Factive).

Chemically speaking, the mechanism of action of the fluoroquinolones closely mirrors that of certain chemotherapy drugs, so it is rather unsettling that these powerful agents are sometimes prescribed for relatively benign infections that would probably resolve on their own or with a milder drug. One notable and unique risk of the fluoroquinolones is that, unlike most other antibiotics, they are neurologically active at commonly prescribed dosages. As an action secondary to their primary antimicrobial effect, they are capable of binding to certain receptors in the brain, spinal cord, and peripheral nervous system. The primary receptor type affected is the GABA-A receptor, which is the exact same receptor that benzodiazepines act on.[1]

When a fluoroquinolone binds to a GABA receptor, the result is the polar opposite of the effect of CNS depressants like benzodiazepines. Fluoroquinolones are antagonists of the GABA-A receptor, meaning that they prevent the binding of GABA and can displace other molecules bound to the receptor, such as benzodiazepines.[1] GABA is an inhibitory neurotransmitter and drugs which enhance its action, like benzodiazepines, cause sedation. The GABA receptor blockade caused by a fluoroquinolone results in a CNS stimulant effect, with neurological manifestations ranging from mild insomnia and agitation to hallucinations and seizures.[2] Anyone can suffer these side effects, but individuals prescribed benzodiazepines are notably much more prone to experiencing these adverse neuropsychiatric reactions.

The culprit is the GABA receptor downregulation imposed by benzodiazepine tolerance. When a benzodiazepine is given chronically (beyond 10 days) there are a series of downward compensatory mechanisms which seek to restore a neurological equilibrium in light of the overstimulation of GABA receptors by the drug. This results in GABA receptors becoming progressively less receptive to GABA over time following prolonged exposure to benzodiazepines.[3] Over time, the brain’s GABA-dependent systems are weakened and there is a heightened vulnerability to external influences which decrease the action of GABA.

A storm neural excitation ensues when a fluoroquinolone “unmasks” the GABA receptor downregulation associated with benzodiazepine tolerance. In addition, since they share the same target, fluoroquinolones are capable of competing with benzodiazepines for GABA receptor binding in a concentration-dependent manner. Studies have shown a complex interaction when a fluoroquinolone and a benzodiazepine are simultaneously bound to a GABA receptor. At high concentrations, fluoroquinolones are capable of displacing a portion of the benzodiazepine molecules bound to GABA receptors.[4]This displacement can precipitate an acute benzodiazepine withdrawal syndrome which is identical to that which would normally happen if an individual were to suddenly reduce their benzodiazepine dosage.

Imagine each GABA receptor as having a gas pedal and a brake pedal. The entire GABA receptor, with its imaginary gas and brake pedals, is anchored into the neuron whose pace it controls. GABA agonists like benzodiazepines act on the brake pedal and GABA antagonists like fluoroquinolones act on the gas pedal. When an agonist acts on the brake pedal, chloride ions flow through the receptor into the neuron. Chloride ions are like an electrostatic glue which slows the neuron down. When an antagonist acts on the gas pedal, the flow of chloride stops and the neuron speeds up.

When an agonist is present for a prolonged period of time, the brake pedal gradually becomes worn out. Additionally, the neuron will recruit chemical messengers to tune up the gas pedal so that the neuron can continue to move along at its desired pace. It might be a pace that provokes anxiety, but it is the precise pace which will allow the neuron to fulfill its purpose within the unique neural circuit it belongs to. After being chronically slowed down by benzodiazepines, neurons want to break free but are held back by the presence of the drug. They will progressively fight back harder and harder to overcome this pharmacological oppression. Fluoroquinolones unleash neurons from their chemical bondage by disengaging the brake and stepping on the gas pedal, causing a sort of neural short-circuit as the freed neurons begin to race out of control.

It has been shown that certain non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are capable of enhancing the GABA receptor blockade cause by fluoroquinolones, potentiating their neurotoxicity and exacerbating their CNS side effects.[5] NSAIDs are frequently co-prescribed with fluoroquinolone antibiotics for painful infections like sinusitis and urinary tract infections. Adding further insult to injury, some fluoroquinolones including ciprofloxacin (Cipro) are inhibitors of the CYP1A2 liver enzyme which is responsible for metabolizing caffeine and other xanthine alkaloids found in coffee, tea, and chocolate.[6] This commonly results in an increased sensitivity to the stimulating effects of caffeine when ciprofloxacin is taken. Hence, it is hardly a surprise that coffee drinkers who are prescribed a benzodiazepine are at an even higher risk for fluoroquinolone-induced seizures and neuropsychiatric disturbances.

It is an unfortunate truth that many healthcare practitioners outside the realm of neuroscience are unaware of these lesser-known facts about fluoroquinolone antibiotics. The fluoroquinolone-caffeine interaction is well documented but the fluoroquinolone-benzodiazepine interaction is not currently recognized in any of the current web-based drug interaction cross checking systems commonly used by healthcare consumers. Most pharmacists are not aware of the issue either, and will readily dispense fluoroquinolone prescriptions to benzodiazepine-dependent patients. This interaction is not consistently recognized yet it very consistently gets benzodiazepine-tolerant individuals into deep trouble. Studies have found that benzodiazepine-dependent individuals frequently experience depression, anxiety, psychosis, paranoia, severe insomnia, paraesthesia, tinnitus, hypersensitivity to light and sound, tremors, seizures, and suicidal thoughts upon exposure to fluoroquinolone antibiotics.[7] 

These symptoms are all consistent with acute benzodiazepine withdrawal syndrome. Furthermore, it may take several weeks or even months after discontinuing the fluoroquinolone for the affected individual to become symptom-free. This may be due to the long-term potentiation that occurs when excitatory glutamate-containing synapses are overstimulated by a deficit of GABA activity. Some individuals never return to their pre-fluoroquinolone state and they are commonly referred to as having been “floxed”. They are left with conditions including peripheral neuropathy, muscle weakness, cognitive dysfunction, new or worsened mental illness, and even paralysis which are all consistent with excitatory neurotoxicity (excitotoxicity) and brain damage.[8][9][10]

Taking all this into account, it is imperative that moving forward more healthcare professionals will become aware of and publicly acknowledge this dangerous interaction which has rendered normal, healthy people disabled. However, this alone is not enough. It is equally important that benzodiazepine-dependent individuals become aware of this interaction so that they can better advocate for themselves. It is well known that chronic benzodiazepine usage often creates chemical sensitivities which require the affected individuals to avoid a variety of foreign substances which most normal people can tolerate, and fluoroquinolones probably fall at the very top of that list.

All doctors should be aware that prescribing a fluoroquinolone to a benzodiazepine-dependent individual carries a serious risk for disability which could potentially be permanent. Fluoroquinolones should be contraindicated with chronic benzodiazepine exposure in nearly every scenario, including nonmedical benzodiazepine abuse. Clinicians should explore all alternatives before fluoroquinolones are considered. In rare cases where it has been determined that failing to administer a fluoroquinolone could result in death, benzodiazepine-dependent individuals should have their benzodiazepine dosages increased for the entire duration of fluoroquinolone therapy and until the drug is completely cleared from their system.

 

 

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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Treating Fluoroquinolone Anxiety

Free-floating, often severe, anxiety is a common symptom of fluoroquinolone toxicity.

Fluoroquinolones thoroughly mess up GABA neurotransmitters, and GABA “plays the principal role in reducing neuronal excitability throughout the nervous system.”  Here are a few articles that describe how fluoroquinolones negatively affect GABA – Article 1, Article 2, Article 3.

To put what fluoroquinolones do to GABA neurotransmitters into a framework, they basically throw people into protracted benzodiazepine withdrawal.  People who have gone through benzodiazepine withdrawal at any time in life should NEVER take a fluoroquinolone.  See “Benzodiazepine tolerance, dependency, and withdrawal syndromes and interactions with fluoroquinolone antimicrobials” for more information about how fluoroquinolones affect people who have a history of benzodiazepine use and withdrawal.

The things that help people through protracted benzodiazepine withdrawal may be helpful for floxies too.  GABA neurotransmitters and receptors have been iatrogenically damaged by both drugs, and they need to heal.  From what I understand, the Ashton Manual has a lot of good information in it about healing from benzodiazepine withdrawal.  Support sites like www.benzobuddies.org may also be helpful.

A very interesting review of supplements to treat anxiety (specifically benzodiazepine induced anxiety, but the advice is applicable to floxies too) can be found through this link –

http://www.longecity.org/forum/topic/54028-treating-anxiety-safely-effectively/

Additionally, Ruth has researched and written extensively about fluoroquinolone induced anxiety and I suggest reading her story – https://floxiehope.com/ruths-story-cipro-toxicity/ and listening to her podcast – https://floxiehope.com/2015/01/07/the-floxie-hope-podcast-episode-6-ruth-young/.  She also wrote some very interesting and insightful comments on my story starting about June 9, 2015 – https://floxiehope.com/lisas-recovery-story-cipro-toxicity/comment-page-13/#comments.

Ruth mentions supplementing uridine in her story:

I also have found that uridine works really well when I get that horrible insomnia and nothing else is helping. Uridine has it’s own receptors in the brain, so maybe it is a way floxies can bypass GABA receptor damage. I cannot prevent a relapse with it. I take it after the relapse starts, 500-750 mg with a fish oil capsule to help it work better. It’s something to have in reserve for those times you just want to crawl out of your own skin and you need to get some rest. Taking it every day did nothing for me. It has to be timed just right, at the moment that every time I’m starting to fall asleep symptoms are getting more intense and now I’m standing there by my bed with my skin just burning, knowing I am not going to sleep. A couple uridine and I’m out within thirty minutes.

It has recently come to my attention that uridine helps to reduce epileptic seizures and that increases free GABA, thus it has a calming influence. I have found it to be useful.

The things that helped me to get through cipro-induced anxiety are: 1. Acupuncture, 2. Meditation, 3. Stress reduction – especially flox related stress – that meant getting off the internet.

I went through a recent period of pain that induced anxiety. Kava helped me a lot. The longecity article recommends against kava, and I think that their concerns are valid. It is only for short-term use and it probably isn’t best for people who have had a history of benzo withdrawal. Personally, I’ve never had a benzo and I only needed to use kava for a short period of time.  It was a life-saver during the time I used it. Be careful with it though.

There is a vicious cycle when it comes to fluoroquinolone toxicity symptoms and anxiety.  Fluoroquinolone toxicity symptoms lead to stress and anxiety (it’s a pretty reasonable to be stressed and anxious when you’re suddenly in pain, you can’t move but when you do you tear tendons, you lose your memory, and suffer from chronic insomnia – to name just a few symptoms of fluoroquinolone toxicity), stress and anxiety negatively affect the autonomic nervous system (ANS) and lead to dysautonomia, ANS damage leads to more fluoroquinolone toxicity symptoms, which leads to more stress, and so on, and so on.

I don’t think that fluoroquinolone toxicity is “just” anxiety, but I do think that anxiety makes every symptom of fluoroquinolone toxicity worse.  I also think that there is nothing to be trivialized about anxiety.  It’s not a choice.  It’s the central and autonomic nervous systems going completely hay-wire, and both stress and anxiety can lead to serious health problems.

I know that anxiety makes you not want to do these things, but I also suggest trying really hard to do the simple things that make you healthy and happy. Sleep plenty. Enjoy your food. Laugh a lot. Be social. Hang out with a pet and/or children. Those things are healthy and they are healing. They’re easier said than done, but they’re certainly worth a try.

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In my opinion, it’s imperative for floxies to get stress and anxiety symptoms under control.  Neither stress nor anxiety are easy things to control, and, like I said earlier, it’s not a choice – it’s GABA neurotransmitter damage – but anything that can be done to reduce stress and anxiety will help the GABA neurotransmitters to heal, and will help the ANS and CNS to normalize.

Fluoroquinolone induced anxiety can be crawl-out-of-your-skin horrible, but it does get better.  Hang in there, my friends.

 

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