Side Effects and Unintended Consequences of Popular Pharmaceuticals

After experiencing an adverse reaction to a popular antibiotic, ciprofloxacin, that involved destruction of my tendons, muscles, and cartilage, as well as my central, peripheral and autonomic nervous systems, I was left with questions that no one seemed to be able to answer – What did ciprofloxacin do to my body?  What happened that made it feel as if a bomb had gone off in me?  Why was I fine after taking ciprofloxacin once, but was far from fine after taking it a second time?  Why can some people tolerate ciprofloxacin and other fluoroquinolone antibiotics with no ill effects, but others can’t and are destroyed by a single prescription?  And the most important question of all – How could I put my body and mind back together again?

I scoured research journals for answers to these questions. The answers that I found were daunting.  I found that ciprofloxacin and other fluoroquinolone antibiotics are topoisomerase interrupters – meaning that they disrupt the enzymatic process of bacterial DNA replication (and mitochondrial DNA replication).  I found that fluoroquinolones deplete intracellular magnesium.  Depletion of intracellular magnesium has multiple health consequences including disruption of more than 300 enzymatic processes.  I realized that both enzyme depletion and magnesium depletion lead to mitochondrial dysfunction.  I found that mitochondrial dysfunction leads to high levels of oxidative stress and that oxidative stress wreaks havoc on multiple areas of health.  I discovered that the carboxylic acid molecule in fluoroquinolones can be metabolized into poisonous metabolites in the liver. I learned how feedback loops between multiple biological systems work together and those compensatory feedback loops make repairing damage difficult.

The more I learned about the complex interactions occurring in my body, the more I realized that the number of unknown factors is far greater than the number of known factors. I realized that, as much as I wanted easy answers and quick solutions, there were none available. Because of the complexity of the human body, as well as individual differences in both genetics and environment, I doubt that easy answers will ever be available. Any one of the many complex systems within the human body can be studied for a lifetime without knowing everything about it. The multiple systems within our bodies are interconnected, difficult to comprehend, poorly understood and truly amazing. Human life is astoundingly, beautifully, mind-bogglingly complex.

Mind Blowing Complexity 

This chart of metabolic pathways shows just one level of biochemical complexity in the human body. Click and take a look. Amazing, isn’t it?  I find the pathways to be both incredibly daunting and beautiful at the same time. As complex as that chart is, it doesn’t include everything. There are additional layers on top of it – genetics, epigenetics, equally complex charts about the microbiome, endocrine system, bioenergetics, etc.

Even though the metabolic pathways in the chart above are known (if they weren’t, they wouldn’t be in the chart), I suspect that the interactions between the metabolic pathways, and the connections between them and other complex systems, are not adequately considered in healthcare. How could they be? These pathways are so mind-blowingly complex, and so interconnected with layer upon layer of feedback and feedforward loops amplifying any disruption and miscalculation, that if we were to properly consider the ramifications of pharmaceutical alterations, no one would dare take most medications. We would recognize the limits of our abilities to predict and treat the inevitable unintended consequences of disturbing the balance within and among these systems. Since pharmaceuticals are a trillion dollar industry, it is safe to say that all of the potential effects of pharmaceuticals on these pathways are not fully considered.

Pharmaceuticals Disrupt Biochemical Pathways

Every pharmaceutical has an effect on those pathways. When the drug interacts with the metabolic pathways as expected, all parties involved are pleased. When the drug interacts in unexpected or unwanted ways, we say that there are “side-effects.” I wonder though, are there really side-effects, or is that just a more palatable expression about the limits of our understanding (and attention)? One could argue that if we paid more attention to the broader biological systems involved in human health, those “side-effects” would be entirely predictable. But we don’t. Instead we focus our medication efforts on narrowly defined targets, destroying a particular pathogen or amplifying or diminishing a specific cell cycle function, all the while ignoring that those processes are conserved systemically. Perturbations in one organism or one function, necessarily affects the entire system. Nothing happens in isolation.

If we were to consider the potential for drugs to initiate systemic reactions, and if the effects of drugs on metabolic pathways were properly regarded, fluoroquinolones and many other drugs and vaccines would not be on the market. But we don’t. Instead, we choose to believe that side-effects are rare and won’t happen to us. Those beliefs are bolstered by decades of marketing to physicians and patients, promoting the safety and efficacy of each drug, often long after science and the legal system have disputed those claims.

Fluoroquinolones, the drugs I know most about, deplete intracellular magnesium (note how many times you see Mg in the chart) and disrupt vital enzymatic processes (which are kind of important). Can you even imagine there not being unintended consequences to depleting vital minerals from a system that is as complex and interconnected as cellular biochemistry and metabolic pathways that determine human health?  I cannot imagine it, because after learning about how fluoroquinolones react in the body, I know too much to believe the marketing propaganda about any drug. Before my adverse reaction, however, I never gave the safety of antibiotics a second thought. It appears neither did my doctor, nor the millions of other physicians who have made the fluoroquinolone class of antibiotics the most prescribed and profitable antibiotics ever.

I know that there are some very smart scientists out there; people who are far more intelligent than I, who have a much better grasp of biochemistry – so why aren’t the dangers of fluoroquinolones more well-known? Why aren’t the side-effects entirely predictable? Why did I have to figure out all of this on my own, without help from the physician who prescribed the medication or the physicians I saw post reaction? Sadly, I have come to believe that most physicians and patients alike don’t want to recognize the complexity of human health; preferring instead to believe in our own intellectual supremacy. And as much as I appreciate the scientists who are doing the work on which I have based my assertions, I don’t think that there is anyone who understands the complex biochemical feedback loops sufficiently to guarantee that there won’t be unintended consequences when disrupting part of the system with a pharmaceutical.

Unintended Consequences

How can one avoid the unintended consequences that come with disruption of the biochemical interactions described in this chart?  Individualized medicine that takes into consideration genetic predispositions is one place to start, but it requires that we recognize the complexity of interacting systems and abandon our silver bullet approach to medicine. From where I sit, this is a long way off. Individualized medicine based on genetic predispositions barely exists. If we consider the complexity of a lifetime of environmental exposures, predicting how a particular drug will react in given individual is complex, if not impossible. For me, the most feasible way to avoid unintended disruptions and feedback loops is to avoiding pharmaceuticals (or at least use them very sparingly). Each medication has side-effects and unintended consequences. All drugs disrupt the very biochemical feedback loops necessary for keeping us healthy.

Avoid the Cause in Order to Avoid the Effect

Perhaps, I am the medical equivalent of a Luddite. Perhaps, I over-emphasize the harm done by pharmaceuticals and underestimate the good done by them because I was hurt by a drug. I see the unintended consequences of disrupting the delicate balance of biochemical pathways everywhere. All of the diseases of modernity can be traced to a disruption on the chart above (or maybe a disruption on the endocrine system chart, or the microbiome chart, or the epigenetics chart). People are sick; not cells in a petri dish – people. They are sick and they are suffering because of disruptions in their biochemistry.

These systems are complex. The feedback loops between systems amplify the complexity and make mistakes and miscalculations difficult (impossible) to correct.

Disruptions in our biochemistry result in disease.

We live in a world of unintended consequences. Does anyone else see it?

Information about Fluoroquinolone Toxicity

Information about the author, and adverse reactions to fluoroquinolone antibiotics (Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin and Floxin/ofloxacin) can be found on Lisa Bloomquist’s site, www.floxiehope.com.