Fluoroquinolones: Their Connection to Older Anti-Malarial Drugs

This article was written in 2009 but still contains relevant information and has updated links. This article serves to document the information that links fluoroquinolones (FQ’s) with the older anti-malarial drugs that, in and of themselves, were/are known to be toxic.  This is a very basic overview in a nutshell for those who need to know.

A Visit With A Doctor

During a doctor’s appointment, I was had an interesting discussion about the FQ’s with a rheumatologist. This rheumatologist made the comment that he believed, based on his knowledge, that certain chemotherapy agents and anti-malarial drugs exhibited similar toxicity patterns. He had never heard of an antibiotic acting like chemotherapy, when I asked him about the FQ’s.  

After the conversation, my interest was piqued so I put on my Sherlock Holmes cap, something that every floxie does quite frequently, and started researching the origin of the FQ’s.  After revisiting the “Flox Report” it gave me some ideas where to start my investigations to research the link between FQ’s and anti-malarial drugs.

On The Trail

While researching, I ran across an article called “The New Quinolones: Back to the Future, by Julian Davies © 1989 The University of Chicago Press.” In this article the author stated that “the quinolones were discovered by accident as a side product in the synthetic preparation of an antimalarial agent.”

The older anti-malarials, the drugs that were discovered in the early 1900’s to fight against the spread of malaria in third world countries; they were very potent but very toxic drugs.  One older anti-malarial drug, Chloroquine, was discovered in 1934 at Bayer laboratories. This drug later became the drug from which the FQ’s were indirectly based off of.

It is important to note that chloroquine was initially ignored for a decade because it was considered too toxic to use in humans. Chloroquine was “re-discovered” during World War II by the United States because of it was desperate to find a treatment for malaria (1).  It is my conjecture that nothing changed about the toxicity of Chloroquine, the U.S. Government just changed it’s definition of toxicity so as to be able to use the drug to combat the scourge of Malaria that the G.I.’s were facing in WWII. 

The Fluoroquinolone/Chloroquine Connection

In a 2008 medical journal listed on Pubmed titled “Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America” the author’s state: 

“The pharmacore of the fluoroquinolones and chloroquine are similar. In fact the origins of the quinolone class are from the use of chloroquine as an antimalarial. A compound isolated from the commercial preparation of chloroquine was modified to produce the first marketed quinolone, nalidixic acid. Fluorine was subsequently added to produce the fluoroquinolones, resulting in both an increase in potency and spectrum.”

Both FQ’s and Chlororquine are based off of the quinoline pharmacophore. 

This article interestingly relates that because of the use of chloroquine in tropical countries there are strains of bacteria that are becoming resistant to FQ’s.  In other words, because they use chloroquine so much for malaria in tropical countries, there are actually strains of bacteria that are becoming resistant to the FQ’s because of their close chemical composition! 

Chloroquine As Chemotherapy

Remember earlier when the rheumatologist said that he was familiar with anti-malarials and chemotherapeutic agents having the same toxicity patterns?  Sure enough.  Just like the FQ’s (2), scientific evidence also supports the use of chloroquine in the treatment of cancer (3).  Another commonality between the FQ’s and Chloroquine. 

Chloroquine A Toxic Cousin To The FQ’s

What is the significance of all of this? Well for floxed individuals it is important to know that Chloroquine, in and of itself, can be a nasty drug.  It has a laundry list of adverse events that are similar to those of floxing,  including, gastrointestinal problems especially stomach ache, skin problems including alopecia, itching, and rashes, headache, nervous system problems including psychosis, depersonalization, serious concentration problems, depression, anxiety, confusion, dizziness and peripheral neuropathy, cardiac problems including Qtc prolongation,  and severe eye toxicity including blurred vision, extra ocular muscle palsies and retinal toxicity, Hemolysis with G6PD deficiency.

Chloroquine Can Remain In The Body For A Long Time

Chloroquine is very slowly excreted from the body. It has been detected in the plasma, red blood cells, and urine of patients 5 years after their last known ingestion (4,5).   If you think about it, that is pretty shocking that this toxic drug can remain in the body for up to five years or longer in measurable doses!

Summing It Up

The fluoroquinolones and chloroquine are chemical cousins.  The share a common point in that they are based off of the quinoline pharmacophore.  To get a complete picture of the ancestry of these drugs (FQ’s and antimalarials) even further please read my article  The Dark History of the Fluoroquinolones: Part 1.

I have been asked if it is safe to take chloroquine or any of the other anti-malarials from this family of drugs after being floxed?  My answer would be to use extreme caution if it is necessary.  I have had reports (not many) of floxies taking Hydroxychloroquine (Plaquenil) for Lupus and reporting no toxicity. Plaquenil is suppose to be less toxic than Chloroquine (6). If you are faced with this decision, please make sure that your doctor is aware that you had an adverse event to the FQ’s and even bring up that they are ‘chemical cousins,’so to speak.   Maybe there would be a safer alternative available. There are many sites on the internet discussing the toxicity of the anti-malarials that are based in the same chemical family, such as chloroquine and lariam, for those who want to do the research.   Much of the harm that has been done by these drugs have been done to military members who took these drugs (7).

Related article from FQ FAQS: Are the FQ’s Failed Chemotherapy Drugs?

Back to: A Coronavirus Question: Chloroquine After FQ’s?