Fluoroquinolone Toxicity Study and P450

By SWA

The P450 System and Fluoroquinolone Antibiotics: A Detailed Examination

Fluoroquinolone antibiotics are among the most frequently prescribed medications globally for treating bacterial infections in humans and animals. These antibiotics are available in various forms, including pills, eye and ear drops, and intravenous solutions used in surgical settings. The most well-known fluoroquinolones include Cipro (ciprofloxacin), Levaquin (levofloxacin, now off the market), and Avelox (moxifloxacin), along with their generic counterparts.

Mechanism of Action and Adverse Effects

Fluoroquinolones work by inhibiting bacterial DNA gyrase and topoisomerase IV, enzymes critical for DNA replication and transcription. This mechanism, similar to that of chemotherapy agents, can result in severe, life-altering adverse health events. Since May 12, 2016, the U.S. Food and Drug Administration (FDA) has advised that fluoroquinolone antibiotics should be reserved for situations where no other treatment options exist. Both the FDA and the European Medicines Agency (EMA) have issued black box warnings about the potential for serious and irreversible side effects, including:

  • Central Nervous System: Risk of seizures, tremors, and psychosis.
  • Musculoskeletal System: Tendon disorders, spontaneous tendon ruptures, and myalgia.
  • Visual System: Vision disturbances and retinal detachment.
  • Renal System: Acute kidney injury.
  • Systemic Peripheral Neuropathy: Nerve damage leading to pain, burning, and tingling sensations.
  • Cardiovascular System: Risk of aortic aneurysm and dissection.
  • Metabolic System: Dysregulation of blood sugar levels, leading to diabetes or hypoglycemia.
  • Hepatic System: Hepatotoxicity, or liver damage.

Cytochrome P450 and Drug Interactions

Cytochrome P450 enzymes play a crucial role in the metabolism of various substances, including drugs, toxins, and endogenous compounds. Fluoroquinolones can interfere with these enzymes, leading to significant drug interactions and altered drug metabolism. This interference can result in increased toxicity or decreased efficacy of concomitantly administered medications, posing additional risks to patients.

Mitochondrial Dysfunction

Recent scientific work, particularly from Finland, has highlighted the potential for permanent mitochondrial damage caused by fluoroquinolones. Mitochondria are the powerhouses of cells, and their dysfunction can lead to a wide range of illnesses, from chronic fatigue to severe diseases such as dementia, Parkinson's disease, and cancers. A pivotal study from Finland revealed the following:

"Maintenance of topological homeostasis is vital for gene expression and genome replication in all organisms. Similar to other circular genomes, mitochondrial DNA (mtDNA) is known to exist in various topological forms, although their functional significance remains unknown. We report here that both known type II topoisomerases Top2α and Top2β are present in mammalian mitochondria, with especially Top2β regulating the supercoiling state of mtDNA. Loss of Top2β or its inhibition by ciprofloxacin results in accumulation of positively supercoiled mtDNA, followed by cessation of mitochondrial transcription and replication initiation, causing depletion of mtDNA copy number. These mitochondrial effects block both cell proliferation and differentiation, possibly explaining some of the side effects associated with fluoroquinolone antibiotics. Our results show for the first time the importance of topology for maintenance of mtDNA homeostasis and provide novel insight into the mitochondrial effects of fluoroquinolones."

Underreported Usage and Unrecognized Reactions

Despite the significant risks, fluoroquinolones are still widely used in surgical procedures, including Lasik and cataract surgeries, and as prophylactic measures. The general population and even many in the medical community remain largely unaware of the growing epidemic of severe, systemic, and simultaneous adverse reactions caused by these antibiotics. These reactions often go undiagnosed or misdiagnosed, exacerbating the problem and leading to prolonged suffering for affected individuals.

Conclusion

The use of fluoroquinolone antibiotics should be carefully considered, weighing the potential benefits against the risk of serious adverse effects. Greater awareness and education about the risks associated with these medications are essential for both healthcare providers and patients. Additionally, further research into the mechanisms underlying these adverse reactions, particularly the impact on mitochondrial function and the cytochrome P450 system, is crucial for developing safer therapeutic strategies.

 [1] Hangas et al. 12 October 2018. Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2. Nucleic Acids Research, Volume 46, Issue 18. Anu Hangas, Koit Aasumets, Nina J Kekäläinen, Mika Paloheinä, Jaakko L Pohjoismäki, Joachim M Gerhold, Steffi Goffart.

https://academic.oup.com/nar/article/46/18/9625/5088042?login=false 

List of drugs in the Fluoroquinolone class in all forms for humans and pets: fq100.org/drug-list

For toxicity warnings please visit our website: fq100.org

CIPRO LEVOFLOXACIN AVELOX ANTIBIOTIC SIDE EFFECTS MITOCHONDRIA DNA OXIDATIVE DAMAGE CHRONIC FATIGUE

Note: By reading my blog, you acknowledge that I do not provide medical diagnoses or treatments. The information provided is meant to answer frequently asked questions and is gathered from reputable scientific papers. 


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