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I read a claim (I can't find the source) that fluoroquinolone antibiotics are actually chemotherapy drugs, or maybe to be more specific, are "chemotherapeutic." Is this claim true? Additionally, if true, does this claim apply to all antibiotics, or only fluoroquinolones?

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    $\begingroup$ Chemotherapy of what? Chemotherapy literally means using of chemicals to treat a disease/condition. All drugs are chemotherapeutics, technically. $\endgroup$ – WYSIWYG Apr 20 '18 at 10:11
  • $\begingroup$ I think what the OP is asking here is whether fluoroquinolines may be used to treat cancer. Although chemotherapy may be defined as the use of chemical substances to treat disease, a common usage is "especially : the administration of one or more cytotoxic drugs to destroy or inhibit the growth and division of malignant cells in the treatment of cancer" $\endgroup$ – user1136 Sep 7 at 11:07
  • $\begingroup$ For example, according to this ref by E.M Scholar, fluoroquinolines also inhibit mammalian type II DNA gyrase (topoisomerase II) "which is the target of several anticancer drugs, such as etoposide". So, it seems to me, the question is: have fluoroquinolines been used therapeutically to treat cancer? I don't know the answer, but I can't believe that some medic somewhere hasn't tried (and charged for the privilege) $\endgroup$ – user1136 Sep 7 at 11:31
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Short answer: Yes, fluoroquinolones are chemotherapy drugs

In layman's terms, fluoroquinolone antibiotics kill human cells as they divide. Fluoroquinolones are a class of drug called "topoisomerase interrupters." Every drug in this class is directly labeled as a chemotherapy drug except fluoroquinolones.

This is not well known by the medical community and is in part why irreversible damage from fluoroquinolone antibiotics is not well understood.

Long answer: Fluoroquinolones are definitely chemotherapy drugs, and they're dangerous

A refresher on how fluoroquinolones work, in case you slept through molecular pharmacology 🙂:

If you want you can skip this first section and instead watch YouTube: Fluoroquinolones: Mechanisms of Action and Resistance

How topoisomerase works

Bacterial cells have double helix DNA, meaning two strands twisted around each other. When bacterial cells divide, the two DNA strands are separated (untwisted), and eventually each side is turned back into a full double helix, making two copies.

If you think of a tightly twisted rope (representing double helix DNA) and start to pull the two ends apart, the rope will twist tighter and tighter and eventually you can't untwist it further. Nature's fairly primitive solution is an enzyme called topoisomerase.

  • topo-: dealing with topology, as in the structure of the DNA
  • -isomerase: a class of enzymes (enzymes are usually bundles of proteins)

The job of topoisomerase is to cut the the double helix DNA strand, untwist it, and then glue it back together.

There are several types of topoisomerase, which we'll come back to.

How fluoroquinolones kill bacteria

Fluoroquinolones bind to the glueing action of topoisomerase. So, as part of normal cell division, topoisomerase cuts a DNA strand, untwists it, then tries to glue it back together. However, fluoroquinolones block the gluing action ("plug the glue bottle"), so the cell literally cuts up its own DNA. Insidious, isn't it?

Don't human cells have topoisomerase?

Yes, since humans have two sets of DNA, let's focus on one at a time.

How fluoroquinolones kill human mitochondria

Human mitochondria are bacteria, and they do contain double helix DNA and topoisomerase. So why don't fluoroquinolones kill mitochondria? Trick question: they do, and it's worse than that.

Human mitochondria keep around backup copies of their mtDNA (we often call mitochondrial DNA "mtDNA" to distinguish it) to use when there are replication errors in DNA synthesis. Fluoroquinolones "deplete" mtDNA, meaning irreversibly destroy backup copies. The organelle desperately tries to pull in backup copies as it cuts up its own mtDNA during replication, and may die, or may become permanently damaged.

Insidious, isn't it?

Many other studies have proven that fluoroquinolones kill human mitochondria as they divide. Interrupting topoisomerase isn't the only way they kill mitochondria, but it's an important one.

How fluoroquinolones kill human eukaryotic cells

Human "eukaryotic" cells (cells with a nucleus, such as tissue cells) also have topoisomerase. So why don't fluoroquinolones kill eukaryotic cells? Trick question, they do:

Compared to an [actual DNA poison], ciprofloxacin produced comparable dose-dependent SCE frequency increases

(an SCE, "sister chromatid exchange" is a marker for how genetically damaged a cell is)

and

topoisomerase type II and DNA gyrase are physiological targets for [ciprofloxacin]

Insidious, isn't it?

Like mitochondria, topo binding is a small part of the kaleidoscope of how fluoroquinolones cause permanent cellular damage, but it's an important one.

As you can imagine, fluoroquinolones killing a cell's main source of energy (mitochondria), while also causing the cell to irreversibly destroy its own DNA lead to human cells dying as they try to divide divide

Even clearer: Compared to other chemo drugs

There are several oral chemotherapy drugs on the market, one of which is Topotecan (notice the topo-?). Here's how they work:

Topoisomerase I inhibitors: Ironotecan, topotecan

Topoisomerase II inhibitors: Amsacrine, etoposide, etoposide phosphate, teniposide

And, as linked in the earlier study, fluoroquinolones are topoisomerase II inhibitors. (They probably bind to other forms of topo, but we don't know for sure).

Even clearer: Fluoroquinolones are used for chemotherapy

There are a few "novel" studies using fluoroquinolones as chemotherapy drugs. In this study, ciprofloxacin is used to target leukemia cells.

Why are chemotherapy drugs used as antibiotics?

When (non-fluorinated) quinolone antibiotics were first invented in the 60s-70s, we didn't know about mitochondrial DNA, and certainly not how fluoroquinolones affect mitochondria.

Don't fluoroquinolones have a good safety profile?

No.

Fluoroquinolones were released in the 70s, but the FDA warning for permanent nerve damage wasn't added until 2013. Because the symptoms of permanent fluoroquinolone damage are so outrageous (permanent nerve damage, tendons spontaneously rupturing, organ failure, psychosis, and dozens more). Doctors simply didn't know (and still don't know) to look for the symptoms, so they aren't documented.

There have been other fluoroquinolones that had "good" safety profiles, passed all medical standards, and then were promptly removed from the market after they started killing patients outright. One such drug, temifloxacin, was removed because it caused so many cells to die that the kidneys became clogged, killing patients.

The fluoroquinolones on the market are all able to, and have, killed patients through multiple mechanisms, but it's more rare, and the permanent damage symptoms are not connected by doctors.

All fluoroquinolones have the same core method of action, and all have a fluorine moiety allowing them to penetrate anywhere in the human body ("hard to reach" infections), so even though the current ones haven't been removed from the market, it doesn't follow that they are safe.

Why continue to prescribe them?

I sincerely believe that if doctors understood how fluoroquinolones worked, they would stop prescribing them, and use them only in life or death situations. The FDA has already advised never to use fluoroquinolones for "uncomplicated" infections, but this advice is not known nor heeded.

If only doctors read studies from over 10 years ago:

In view of the present genotoxicity, ciprofloxacin should be administered with caution.

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    $\begingroup$ Holy moley... what an answer! I will take some time to digest it $\endgroup$ – TimTom Jan 13 '18 at 23:08
  • $\begingroup$ I can't upvote answers (yet?) but thanks a lot! could you also answer about other antibiotics? $\endgroup$ – TimTom Jan 14 '18 at 18:51
  • $\begingroup$ "The FDA has already advised never to use fluoroquinolones for "uncomplicated" infections, but this advice is not known nor heeded." How do you know? How many doctors have you asked about this? $\endgroup$ – anongoodnurse Jan 15 '18 at 2:22
  • $\begingroup$ 23 so far by my count? $\endgroup$ – Andy Ray Jan 15 '18 at 3:03
  • $\begingroup$ So, 23 doctors you've asked admitter that they used fluoroquinolones for "uncomplicated" infections? Or admitted they used fluoroquinolones? There's a difference. $\endgroup$ – anongoodnurse Jan 15 '18 at 17:05
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Yes they are chemotherapeutic drugs. They enter the cells and destroy the mitochondria of the cell and it can no longer produce energy. Problem is these antibiotics target all cells whether they are healthy or not so they are systemically poisoning your whole body. Hence the wide variety of problems reported by patients who have taken them. They are commonly given along with a steroid such as Prednisone. Unfortunately, those patients often suffer more acute damage.

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We're looking for long answers that provide some explanation and context. Don't just give a one-line answer; explain why your answer is right, ideally with citations. Answers that don't include explanations may be removed.

  • $\begingroup$ Your reasoning is not entirely correct. Please cite reliable references. If you don't improve your answer, it will be deleted. $\endgroup$ – WYSIWYG Apr 20 '18 at 10:22

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