Old Quinolones – The Dead May Rise Again

In March of 2014 an article appeared on Nature.com which is a leading science journal outlet.  The article, “Unexpected link between an antibiotic, pannexin channels and apoptosis”, highlighted an unexpected discovery between an older fluoroquinolone, trovafloxacin, which was removed from clinical use due to toxicity, mainly liver toxicity, and the body’s little understood pannexin proteins.

Pannexin proteins, in part, function as a signal beacon to direct or point apoptoticcell death activity of the immune system.  Pannexin communication to the immune system allows for an “ordered’ disassembly of a cell during the apoptotic (programmed cell death) process. Basically pannexin helps control the timing in which dying cells literally fall into pieces.

Apoptosis

Apoptosis is programmed cell death.  It is a very tightly controlled, highly active and voluminous process involved in roughly 1 million cell deaths per second in the human body.  It is body’s orderly response to cell changes that range from eliminating older cells, diseased cells, and even removing cells from between fingers and toes during the embryonic process.  A malfunctioning apoptotic process has been implicated in a variety of diseases.   In this case the researchers believed that trovafloxacin’s interference in the apoptotic process through pannexin inhibition led to its marked liver toxicity.

Pannexins

For those who do not know about pannexins, in very oversimplified laymen’s terms, they are a subsection of a larger family of proteins called innexins. Pannexins are glycoproteins, commonly referred to as Panx1, Panx2, and Panx3.  Basically, they form channels, or as I like to think of them, small passageways between the membranes of a cell that allow the passage of small molecules.

There is some solid knowledge on the basic roles of pannexins but much of their function in the human body is quite hypothetical.   Researchers believe there are very important in neuronal metabolism specifically neurochemistry involving the hippocampus.   Their dysfunction can play a role in certain neurological cancers.

Antibiotic Use Still Out of Control

Despite cautions issued by a great number of organizations about the overuse of antibiotics, their use in society goes on unabated.  Although many physicians are becoming more conservative in antibiotic use, I hear stories daily about antibiotics prescribed without any due diligence on the physician’s part.

Recently the FDA found that total sales of medically important antibiotics, i.e. the types that are also needed for human medicine, have increased 16% between 2009 and 2012 and comprise a whopping 70% of those that are used.  In other words, those antibiotics that are deemed to be critically important or highly important by FDA are also among those increasingly sold for livestock use.

Antibiotics, Not the Benign Drug We Previously Thought

I grew up in the miracle age of penicillin.  When we were kids the ‘pink liquid’ handed out by the doctor was a very common sight.  I adopted a benign view of antibiotics, along with most of society and the medical community.  Little did we realize the biological monster that was being created.  Science is just now starting to realize what so many have long suspected, antibiotic use is destroying and permanently altering the microbiome of the human body, not to mention its biological impact on nature itself

In the U.S., antibiotic resistance caused more than two million illnesses in 2013, according to a report by the Centers for Disease Control and Prevention, and an estimated 23,000 deaths, adding up to more than $20 million in healthcare costs.  We are losing the war against superbugs that we have created because of our own reckless antibiotic use.

Antibiotic use has delivered a one-two punch.  It has fostered the rise of superbugs (really nothing more than bacteria that have a natural resistance to the action of antibiotics), in addition it has created Antibitoic Resistancelong term health problems in many that are now just coming to light. As a matter of fact, many non-antibiotic pharmaceuticals contribute to the rise of super bugs. A subject that I wrote about here.

Nicole Allan wrote in The Atlantic in early 2014, “As a result, pharmaceutical companies have found antibiotics to be less worthwhile investments than drugs for chronic illnesses.”  Since pharmaceutical companies are abandoning their quest for new antibiotics, researchers are looking for ways to repurpose older toxic antibiotics.

How Does Pannexin Inhibition Tie In?

Kodi S. Ravichandran, PhD, one of the authors of the “Unexpected link between an antibiotic, pannexin channels and apoptosis” paper explains the thinking quite clearly.  In an interview with the University of Virginia Health System, where he is a researcher, he stated “The increase of drug resistance to antibiotics is one of the biggest threats to human health in the next 10 years. Yet the number of new antibiotics that are developed is extremely few. The reason a number of the older antibiotics have been shelved is toxicity. So perhaps if we better understand how this toxicity arises in those molecules, and by removing the bad parts and keeping the good parts, we might be able to find more usable antibiotics.”

This approach sounds good but let’s dig a little deeper. On the UVA website the synopsis of the pannexin research is a hope to use the information on how trovafloxacin blocks these channels to re-engineer it and other antibiotics in the quinolone family to lessen toxicity concerns.

Remember, there have been several members of the quinolone family removed from use because of toxicity.   The main thrust of this discovery is to use the knowledge to re-engineer the previously deemed toxic quinolones.   For the average person and typical medical professional this all sounds great but for those who know just how toxic the current formulary of quinolones are, it gets more controversial.

I called the University of Virginia School of Medicine, Dept. of Pharmacology and was unable to speak with Dr. Ravichandran directly but spoke to a research assistant who spoke to me on condition of anonymity.  When asking me why I was inquiring, I told the person that I was interested in their pannexin research and that I might write a blog article regarding the repurposing of old quinolones.    I was told that if I write an article I must leave their name out, which I honored, even though they said nothing controversial from their end.  Their comments were basically a synopsis of their research.

The assistant reiterated that on the surface the research showed that surprisingly, in contrast to trovafloxacin, two other structurally related quinolone antibiotics ciprofloxacin and levofloxacin did not block PANX1-dependent dye uptake.  In other words Cipro and Levaquin did not show an affinity for blocking or inhibiting pannexin.   The assistant told me that “if we can re-engineer older quinolones to achieve the same level of efficacy and safety that Levaquin and Cipro have shown, the results will be ground breaking.”

Prior to calling I had read the paper thoroughly again.  I politely told the assistant that I still believe that they are too quick to dismiss Levaquin and Cipro as a non-player in pannexin inhibition.  Modern FQ’s interfere with apoptosis in ways that have not been clearly identified yet and have been shown to interfere with other apoptotic signaling proteins.  Cancer research has shown that there is a caspase/pannexin-1-independent mechanism and current FQ’s such as Cipro and Levaquin have been found to increase activated caspase-3, a marker of apoptosis, with confirmatory apoptotic changes on electron microscopy. As a matter of fact there are diverse pro-apoptotic drugs, including topoisomerase inhibitors, kinase inhibitors, and proteasome inhibitors that induce functional activation of Panx1 channels via caspase-3. At this point the assistant was suspecting me of being something other than what I actually am and the conversation came to an abrupt but polite end, with the assistant telling me that I would have to speak to Dr. Ravichandran directly for more information.  I am still waiting a call back.

It’s a Matter of Viewpoint

Obviously I pick and choose my arguments regarding FQ’s to those that are most efficacious and this was neither the time nor place.  My goal was to understand their mindset behind the research and for me it was revealed. Despite boatloads of documents pointing FQ’s to be toxic on many levels, we are still fighting an enemy that has its mindset back to the days of the ‘pink liquid’.  When researchers have the mindset that the current usable formulary of FQ’s is a goal to reach based on safety and efficacy then the premise of their research is flawed.

These researchers, like many others, believe their cause is just and true and in some ways it is.   They are guided by the need to defeat an enemy that man is responsible for unleashing and they believe their research will save countless lives.  What they do not realize is that their research may also have the unintended consequence of disabling countless lives as well.

Despite those who think that we are winning the media battle about the toxicity of FQ’s, their use in our society is increasing.  Not just because of increased antibiotic use, which is problematic, but because of the broad chemical properties of the FQ’s themselves.  In cancer they have found use as adjunctive therapy and several new chemotherapeutic agents are currently being developed based on the FQ pharmacore.  Now because of societal factors and the lack of development of new antibiotics coupled with a new vigor of reengineering, we face yet another controversial front as researchers seek to repurpose or re-engineer FQ’s of the past.

Not that re-engineering is a bad thing; after all, many things in our society havePill Grave been successfully re-engineered for the betterment of mankind, including medications. It happens all the time.  Who knows, maybe we’ll get lucky and some researcher will uncover a tidbit that further helps us understand the adverse reactions these drugs inflict. But, as far as I can see, these new directions in FQ research are all based on the deadly assumption that the current FQ’s are, for the most part, safe and efficacious and that the current adverse reaction rate is an acceptable collateral outcome.  That genie is hard to get back in the bottle.

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...damaged by fluoroquinolones in 2007 at age 46. Prior to, a healthy law enforcement official. Now an amateur FQ researcher, author, and blogger.

3 Responses

  1. ANNA says:

    Hi David,

    Once again your research into the real damage FQ cause, and your devotion to finding the truth is commendable. Thank you, David ! This article truly does explain the mindset out there about FQ, and the uphill battle that we all face in getting help from the medical field. I for one, am very damaged with severe Small Fiber Peripheral Neuropathy in my feet /legs/ fingers/ hands/arms from 10 Levaquin pills given with Prednisone to me in March 2013 for a re-check after bronchitis where I was just coughing a little bit, but was well really. I was 67 years old then and should not have been given it as I have CFIDS too , Not one Neurologist will actually admit that it was caused from “the safe Levaquin” even though the FDA even stated in August 2013 that it could cause permanent PN ! My life is devastated, and all the disability, pain and suffering I go through cannot change the mindset out there. So, I like all of us, do my best, and trust in God, and pray that I can survive the years I have left . Thank you again for your devotion to the truth .

    God bless you & heal you,
    Anna

  2. Barbara Siron says:

    Hello Anna! How are you doing today? No new symptoms I pray. Seems a never-ending battle for us seniors and all who have floxed. I, too, was 67 when floxed by Levaquin (with CFS also) but back in’86 I took Cipro and did not know what was going on with me. Was having horrible panic attack, feeling like I was all hear, strange brain feelings, swelling feeling and something like something eating my bran weird and miserable feeling. horrible nausea and strange pain, awful anxiety Was taken to ER several times thinking I was having a heart attack due to tachycardia and had that awful needle in my wrist to see if I was having heart attack. Was bed-ridden for a full year and lost tons of weight from not being able to eat. It was horrible Found a rheumatolgist after 8 years of misery, who did natural way of healing and he gave me an intravenous vitamin shot and therapeutic Vit. C not knowing yet about the Fluoroquinolone toxicity problem So all of these years I was floxed and didn’t know it. I gained strength and whenever I overdid it which was really just ordinary tasks, I was back in bed again and started having MS symptoms several years ago. These set-backs were intermittent all of these years. Then in the end of 2012 I caught pneumonia and was given Levaquin pills with Prednisone and whcih wasn’t working and was hosipitalized and given Levoquin I.V. for four days and sent home with another prescription of Lev. I did not fill it as I was having a strange and very uncomfortable feeling in heart and stomach. Called Pharmacy and he said it wasn’t from the Levaquin a lot he knew! I got on-line and did some research. Oh brother! I was shocked. And as you know now it is a daily struggle with new things. I wanted to tell you, new friend ( I hope!) that I take St. John’s Wort for nerve pain an excellent herb. I still take high doses of VIt. C, Turmeric, and put cayenne added to soups and my V-8 juice everyday several times a day. I take DE (food-grade diatomaceous earth) powder every day to keep my intestines clean. Another wonderful natural powder. No need for any other cleanser for colon! No need for colonics. It is also helpful for heart-burn You don’t want to take any of these acid-reducing drugs out here NEVER! Also, I am a huge herb drinker, i.e. Hibiscus and Olive Leaf and other herbs for tea. Everyday also. You can contact me on my e-mail if you want more info. Just wanted to give you some quick things and to encourage you in your walk with The Lord God and His Son Who love and care for us. You are the first senior I have seen on all the posts who have similar issues as I. — hope to hear from you Anna Love in Christ our Lord and Savior, Barb Siron e-mail: bjsbarbee@yahoo.com

  3. ANNA says:

    Hello Barbara,

    Thank you so much, dear lady ,for reaching out to me with this kind and caring message. I did email you on 11-7-14. Please check your spam or junk email to see if my message went there by mistake. God bless you Barbara, and may He continue to heal you, and keep you close to His heart.

    Blessings,
    Anna

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