As a drug safety advocate specializing in quinolone antibiotics, namely the fluoroquinolones (FQ’s), I have learned about both the history and the chemical compositions of this drug family. Because of this, I am very familiar with the chemical links to the quinoline pharmacophore including the anti-malarial drugs in this class.

Based on everything I have learned over that time and have seen other’s personal experiences, I am not a proponent of any pharmaceutical that is based on the quinoline pharmacophore. 

My research has led me to believe there is something inherently wrong with the all drugs that are based on this substrate.  It can be shown, going all the way back to the natural alkaloid from the cinchona tree, that there is a thread of idiosyncratic toxicity that is poorly understood that spreads out like a crack in the foundation.  This idiosyncratic toxicity loosely affects all of the drugs based off of this platform.  Again, this includes all the quinolone antibiotics and the quinoline antimalarials, more specifically chloroquine, hydroxychloroquine, and mefloquine.

Antimalarials, COVID-19, and Safety Concerns

Trump COViD 19 Briefing
Dr Eric Topol

Dr Eric Topol

Recently, chloroquine and a similar drug, hydroxychloroquine (plaquenil), showed encouraging signs in small, early tests against the coronavirus, COVID-19. Yet those preliminary studies sparked intense interest after President Donald Trump tweeted that hydroxychloroquine plus an antibiotic could be “one of the biggest game changers in the history of medicine” and should “be put in use immediately.” He cited a French study that gave the combo to only six patients.

It is a very weak study … leaving us in suspension of whether the combination strategy has any merit,” said Dr. Eric Topol, a cardiologist and head of the Scripps Research Translational Institute in San Diego.

But the drugs have do have major side effects, one reason scientists that know about them don’t want to give them without evidence of their value, even in this emergency. 

Meghan May

Chloroquine is an extremely toxic drug with a terrible side effect profile. Hydroxychloroquine is far safer, but its side effects are still significant,” Meghan May, a microbiologist at the University of New England College of Osteopathic Medicine in Biddeford, Maine, wrote recently in an email.

Nevertheless, excitement about treating the new coronavirus with malaria drugs has garnered massive media attention after the mention from President Trump.

Chloroquine seems to work by acting as an “ionophore” and helping zinc to enter the cell to inhibit viral replication.  Something I wrote about here

Right now, the evidence that they may help the broad population is thin, and a run on the drugs is complicating access for a select group of people who need them for rheumatoid arthritis or lupus.

Sounding the Alarm About Antimalarial Use

Dr. Remington Nevin

The Quinism Foundation has warned of a risk of sudden and lasting neuropsychiatric effects from the use of antimalarial quinolines against COVID‑19, and has urged policy makers, physicians, and members of the public to be alert to such effects.

“The same endosomotropic properties that likely underlie the effectiveness of quinoline antimalarial drugs such as chloroquine and hydroxychloroquine against the virus may also underlie their dangers, ” said Dr. Remington Nevin, MD, MPH, DrPH, a Johns-Hopkins trained psychiatric epidemiologist and drug safety expert and former U.S. Army public health physician, who now serves as Executive Director of The Quinism Foundation. “These are not safe drugs.

Read their official press release here: The Quinism Foundation Warns of Dangers from Use of Antimalarial Quinolines Against COVID‑19

Safer Way of Dealing with COVID-19

On such safer way to deal with COVD-19 is outlined in this article from Italy.

It is the asymptomatic carriers that are mainly responsible for spreading the disease. If you successfully locate them via readily available testing and subsequently quarantine them for a reasonable period of time, you can stop the spread of this virus in its tracks.

Deadly Assumption

Driven by media hype, the general public and even medical researchers, often make the assumption that because a drug has been around for a long time it has an acceptable toxicity profile.  In other words, if it has passed the test of time, it is acceptable for use.  In reality, nothing could be further from the truth, especially with quinoline based pharmaceuticals.

Antimalarial quinolines have been commonly prescribed in the past, but it is important to note that a substantial number of patients need to discontinue the drugs early owing to the development of serious adverse events.

Like quinolone antibiotics, quinoline antimalarials display idiosyncratic toxicity that can cause adverse events with irreversible consequences, even when used at relatively low doses.  It is important to note that it is usually never known ahead of time who is susceptible to these adverse events and often when a patient experiences them, it is too late, and the adverse events do not stop after discontinuation.

“During any outbreaks of epidemic and pandemic levels, there is hardly any time left for new drug development and clinical trials,” said Sunit K. Singh, PhD, a professor of molecular immunology & virology and head of the molecular biology unit at Banaras Hindu University’s Institute of Medical Sciences in Varanasi, India. Therefore clinicians will turn to trying existing drugs, known as “repurposing.”

The CVOID-19 presents society with a desperate situation.  In desperate times humans often resorts to desperate measures.  History is replete with lessons that caution against resorting to haste in times of desperation because during these times well-meaning cures can become the cure that kills instead.