This article is part one in a series exploring the history of fluoroquinolone antibiotics viewed from a unique perspective trying to uncover insights on their propensity for harm.  


The Fluoroquinolone (FQ) family of antibiotics harbors a dark side.  A very dark side. Thousands of people have fallen ill with adverse events after taking an FQ. Many of them experience devastating and progressive adverse symptoms which encompass symptoms ranging from psychiatric and sensory disturbances to problems with muscles, tendons and nerves.  For many these adverse events continue long after stopping the drug, becoming chronic, long lasting, and permanent.  Even more insidious is the ability of this family of drugs to cause adverse events long after stopping the medication.  One study recently uncovered that users could develop permanent peripheral neuropathy up to six months after stopping the medication (1).   

Despite all this, the FQ family of antibiotics continue to be commonly prescribed with over 32 million prescriptions in the U.S. alone in 2015 (2).  The FQs go by many trade names such as Levaquin, Cipro, Avelox, Floxin and more, with many now prescribed under their generic names.  In a study published last year, researchers reported that FQs are still the third most commonly prescribed antibiotic for adults (3).

As a sufferer of Fluoroquinolone Associated Disability (FQAD), I believe that this pharmaceutical family has an inherent flaw in its foundation, so to speak, that impacts how they interact with the human body.    Call it a gut feeling or an intuition, I believe this flaw runs out like a thread or as a spreading crack in the foundation of a large building.  This inherent weakness was present from the very beginning in nature and was subsequently carried forward through later generations. I also believe that any pharmaceutical that is developed from this core, or pharmacophore (the scaffold on which others are built), whether antibiotic, antimalarial, antiviral, or anti-tumor, is threatened by this inherent idiosyncratic flaw and that flaw can tragically affects the end user.

A Dark Side

I believe that we can go back and trace an under-appreciated thread of adverse interactions from the distance past to the present. This adverse side, or darker side, has always been present from our first exposure thousands of years ago and exists through today’s synthetic descendants and will probably exist well into the future.  Often times, this adverse interaction escapes notice by researchers and medical authorities, through its ability to hide in plain sight by mimicking other pathologies or separating cause and effect by delayed events, or late effects, that occur long after exposure.  It remains cloaked to both the professional and the end-user making it one of the deadliest instigators in modern history.

I have been dealing FQAD for well over twelve and a half years now. During that time, I have interacted with hundreds, if not thousands, who, like me, have found out the hard way that this family of drugs harbors a dark side.  Their stories are usually always the same; they were not aware that this family of drugs had such a propensity for harm, nor were they aware that, in many individuals, the chronic health symptoms did not go away upon discontinuation of the medication.  On the contrary and for many, the adverse events triggered chronic conditions that last indefinitely, disrupting, disabling and denying the ability of many individuals to live a productive life.  Also, to add final insult to injury, many professionals in the medical establishment deny that these drugs could even cause such problems. 

It is a serious question that begs asking, how in today’s enlightened and technologically driven society could a large portion of our society literally fall prey to an unseen enemy that is supposedly intended for good? Despite the outcry from thousands of victims, cautions the FDA, and ominous warnings from a few brave researchers, how could some of the world’s most prescribed medications be the suspect at the root of many of today’s modern vague, ill-defined mystery illnesses? The answers to these questions, which sound like chapter headings right out of a grand conspiracy novel, are staggering because the implications of such allegations, if true, are preposterous and deserve everyone’s attention.  Combine this with the unsettling fact that there are countless reports of discrimination, ridicule, ostracization and abuse experienced by patients, and even some medical professionals, who suggest these outlandish and absurd possibilities are.

Inspired Synthetics

The Fluoroquinolone antibiotics are compounds produced totally by synthesis.  However, like many synthetic drugs, they have their chemical basis as “natural product mimics”.  In other words, their chemical structure was synthesized based on chemical structures that are seen in the natural world or inspired by such structures.  Although tweaked and modified, without the original natural source as more than an inspiration these substances would not exist in the world today.

A pharmacophore is a part of a molecular structure that is responsible for a particular biological or pharmacological interaction that it undergoes. The Fluoroquinolones basic pharmacophore, or active structure, although synthetic, is based upon the quinoline ring system (4,5).

Keeping this in mind, let’s take a quick journey back in time and take a brief look at some pertinent history from a unique perspective: A perspective that goes back well before the conception of quinolone family of drugs. 

Andes Mountains

The Andes in South America are the longest continental mountain range in the world at about 4,300 miles long and varying between 120 to 430 miles wide with an average height of about 13,000 feet.  Our first stop takes us back a thousand years or more to the forests of the lower to mid-elevations on the eastern slopes of the Andes Mountains.  In that area, the healers of indigenous Quechua people used the bark from a medicinal woody tree for its healing properties. 

The bark of the tree when chewed or dried and powdered was used by the native people to relax muscles and stop shivering.  Unbeknownst to the native people at that time the shivering was probably caused by Malaria.  Moving forward, stories of the medicinal powers of this tree were noted in early journals of the Jesuits Priests in the 1500’s who served the area populated by the Quechua people.  Jesuits, who had long collected the bark in Peru, promoted its use wherever there were Jesuit missions. The Jesuit Priest Agostino Salumbro (1541-1642), is believed to be the first person who connected that the bark of this tree could be used for curing the symptoms of malaria.

Cinchona Tree

It is believed the woody tree’s name was based on the Spanish Countess of Chinchon, the wife of a viceroy of Peru.  According to folklore, she contracted malaria and the indigenous people persuaded her to bathe in a pond located beneath one of the trees.  She noted that the water tasted bitter and after a few days she was cured of malaria.  The Countess of Chinchon and her husband were credited with bringing the bark back to Spain although the exact facts surrounding this story are debatable.

Carl Linnaeus the Swedish botanist, physician, and zoologist, who laid the foundations for the modern biological naming scheme of binomial nomenclature named the tree, Cinchona, after her. Regionally, the bark was more commonly known by several other names such as Jesuits’ Bark, Peruvian Bark or Cardinal’s Bark (6,7).

Many natural treatments today are often looked upon as less harmful than man-made synthetic alternatives. Although this can be true in certain circumstances, it can also be a very dangerous assumption to make as natural substances can also carry the risk of adverse reactions and events, and the bark of the Cinchona tree was no different.   Though generally considered safe in low doses, the cinchona bark can cause what is known as cinchonism (8).   Cinchonism is a syndrome of adverse reactions and events tied to the bark that encompass severe headache, abdominal pain, convulsions, visual disturbances and blindness, auditory disturbances such as severe ringing in the ears, paralysis, and collapse.


Almost everyone in the world today has heard of Malaria.  Malaria is a mosquito-borne infectious disease that affects humans and some animals, and it is caused by parasitic protozoans.  Malaria causes very unpleasant symptoms that typically include fever, tiredness, vomiting, and headaches but in severe cases it can cause yellow skin, seizures, coma, or death. If not properly treated, people may have recurrences of the malarial symptom’s months later. In those who have recently survived an infection, reinfection usually causes milder symptoms with partial resistance developing.  However, if a person does not have continuing exposure to malaria, resistance usually disappears over months to years.

Malaria has always been a terrible plague for mankind and as recently as 2015 there were 296 million cases of malaria worldwide resulting in an estimated 731,000 deaths (6). Since it was considered such a scourge, a natural substance such as the bark of the Cinchona Tree, that seemed to cure, or at least treat, malaria, for many, was a Godsend. 

Uncovering Adverse Events

Just like trying to get an accurate picture of adverse events to pharmaceuticals today, getting an accurate picture of adverse events centuries ago to a natural substance is even harder, as a matter of fact, it is quite difficult.   But if we do a little detective work, we can peer behind the veil of bias and data gathering problems and piece together a rough adverse event profile which gives us a glimpse of a darker side of cinchona bark.  When we look at it in more detail, we see an adverse event profile that will ring true today for those familiar with both antimalarial and quinolone adverse event profiles and those unfortunate enough to personally experience them.

The first ‘official’ documentation that something was amiss was noted in The Journal of the American Medical Association, established in 1883. Documented in its September 1889 issue, a rarer and graver form of cinchonism was first noted.  It documented that the graver forms of cinchonism “may be due to a peculiar susceptibility of the individual.”   Interestingly, it goes on to say that “there is an indefinite area in which idiosyncrasy appears to determine toxicity, in which there can be no ‘a priori’ determination of the danger line.

In other words, some people could have adverse events related to the alkaloids of the cinchona bark and that these adverse events where idiosyncratic, not related to the size or frequency of the dose.  In an eerie foreshadowing, the article goes on to say that even though the general medical consensus shows that these severe adverse events are ‘thought’ to be rare by the medical establishment of the time (late 1800’s), there shows “indubitable evidence that their absolute frequency is by no means small.

In a déjà vu type of situation, the AMA journal goes on to state that “the general medical public has failed to properly appreciate these dangers…” even though intelligently documented and reported observations of adverse events have appeared in specific journals of the time.  

The adverse events described in the article focus mainly on severe visual damages, but they run the gamut to encompass many of the symptoms that we see today in anti-malarial and quinolone toxicity. Some of them are, severe vision problems, muscle spasms, epileptic convulsions, cardiac issues, circulatory disturbances, tinnitus, deafness, gastrointestinal problems, vagus nerve paralysis, and neurological symptoms described as “nervous perturbations.”(9)

History can teach us much, but it seems we humans fail to learn from history.  Edmund Burke was a British-Irish statesman said, “In history, a great volume is unrolled for our instruction, drawing the materials of future wisdom from the past errors and infirmities of mankind.” Whether by sheer ignorance, or blinded by the popularity of having a treatment, or other nefarious reasons, like today, the medical community of the time failed to appreciate the adverse events of cinchonism, even though they documented its existence and prevalence.


The popularity, or should I say notoriety, of the powers of the cinchona was initially spurred on by Jesuit priests. Supposedly, the planting of cinchona trees outside of South America was initiated by the Jesuits. Also, the constant need for malaria medicine motivated the British and Dutch to bring cinchona to their colonies by smuggling it out of the Spanish colonies and establishing plantations in Asia (10).

As scientific inquiry blossomed, researchers went on to discover the secrets that the Cinchona Tree’s bark held.  The tree is very medicinally active containing a variety of powerful alkaloid compounds.  These powerful alkaloids are chemically based on the quinoline ring pharmacophore and one of them became quite well known as the drug Quinine.

In 1820 French chemists Pierre-Joseph Pelletier (1788-1842) and Joseph-Bienaime Caventou (1795-1877) isolated quinine from cinchona bark (11). As I mentioned earlier, due to man’s expansion into the tropical areas of the world, Malaria became more recognized as a lethal disease worldwide. Because of Malaria’s prevalence, the potential dollar value of quinine inspired research into its finding a synthetic mass produced alternative.

After 1890 Quinine became the predominantly used alkaloid from the cinchona. One of the reasons for quinine’s popularity was due to a change in supply from the South American to Javan cinchona bark.  Javan cinchona bark became more readily available and it contained a higher proportion of the quinine alkaloid. Quinine is a white crystalline alkaloid that exhibits numerous medicinal properties such as having antipyretic (fever-reducing), antimalarial, analgesic, and anti-inflammatory properties and has a bitter taste.  On a side note, chemically, Quinine contains two major fused-ring systems: the aromatic quinoline ring (which we are interested in) and the bicyclic quinuclidine (12).

The science of synthetic organic chemistry underwent a revolution in the late 19th century, partly in response to the need for new mass produced antimalarials. Ironically, although fairly easy to isolate from the Cinchona tree, quinine is hard to for man to duplicate synthetically.  In 1856, William Henry Perkins, an 18-yr-old English chemist, set out determined to synthesize quinine. Perkins learned much but failed in quinine synthesis. If wasn’t until almost a hundred years later that Quinine was successfully synthesized in 1944 but because of difficulties in the process it still has never been synthesized on a commercially economic scale.

Quinine, because of its worldwide use for malaria was viewed as fairly innocuous substance by medical professionals and the general public alike.  So much so that it was used in drinks and the creation of ‘tonic water’ as a prophylaxis.  However, like cinchona bark Quinine has a dark side.

Quinine’s Dark Side

Adverse events to Quinine can be severe and life threatening. These adverse events, like those found in the cinchona bark and later synthetic ancestors, are of particular concern, because these reactions are not dose-related and their occurrence is unpredictable (13).  Often, patients never connected later health issues with their ingestion of quinine, often blaming it on other sources such as malaria. Reports of potentially fatal quinine hypersensitivity reactions, particularly quinine-induced thrombocytopenia, can occur rapidly within days or it can occur after months or years of use.

Adverse events of Quinine run the gamut and include, neurotoxic effects (headache, tinnitus, vertigo, visual disturbances, confusion, respiratory depression), gastrointestinal disorders (anorexia, nausea, vomiting, diarrhea, abdominal pain), cardiac conduction disorders (tachycardia, bradycardia, palpitations), blood disorders (hemolytic anemia, thrombocytopenia), hypersensitivity reactions (skin reactions, drug fever, bronchospasms), arthralgia, convulsions, hypotension, kidney failure, weakness and death. (14)

Looking back at documented adverse events from long ago we see paradoxes that exist still to this day. Often, adverse events to medication go unnoticed or unreported because they get blamed on the illness or the sickly state of the patient.  It seems that the drug is usually the last thing suspected for any adverse event in the short term and almost always long term.  It would be impossible to realize how many individuals suffered long term adverse events to these medicinal products based on the quinoline ring but in hindsight we can assume there were many.

Could this thread of idiosyncratic adverse events, tied to the quinoline ring structure, carry on downstream in certain robust pharmaceuticals that were mimicked off its structure? 

Join me in future parts of this series as we try to answer this question and more. 

Stay tuned to My Quin Story for the Dark History of the Fluoroquinolones part two:

Dye, Synthetic Antimalarials, and Pharmaceutical Giants
Coming Soon…

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