Number of Drugs Suggested in Search for COVID-19 Cure Cause for Concern

Mohamed A. Bayorh, PhD, Department of Pharmacology

My personal opinion about COVID-19 and some of the challenges associated with the treatment needed to save lives.

I am convinced that part of the answers to the COVID-19 puzzle is embedded in the recent discoveries made by Italian scientists who did extensive autopsies on people killed by the virus. Their assertion was that the treatment used involved a tremendous overload of unneeded medical equipment that are extremely bulky, expensive and may have contributed to the large number of fatalities. To them the current pandemic may be slightly less than the monster we thought it to be initially.

The large number of drugs being suggested for the treatment of COVID-19 is a major concern to all physicians and scientists including pharmacologists. The most frequently referred to drugs are the antimalarial drugs (chloroquine and hydroxychloroquine) that are seldomly used because of their significant toxicities, which include retinal and arrhythmogenic effects.

These drugs can significantly prolong action potential duration (QRS and QT intervals) in the heart and may cause “Torsade de pointes.” This arrhythmia is akin to ventricular tachycardia, which can lead to ventricular fibrillation, which can cause heart failure and eventually death. Thus, it appears as if the minor antiviral effects of these drugs are being exploited to treat a complex viral effect or a disseminated intravascular coagulation problem.

One of the dangers associated with the use of these drugs is the lack of detailed clinical studies on their effectiveness in the treatment of COVID-19. Thus, the significant toxicities of these agents may limit their beneficial effects on the treatment of COVID-19. The complications created by the renowned French researchers initially suggesting using one set of nonsteroidal anti-inflammatory agents (e.g. paracetamol, acetaminophen) over another set of NSAIDS such as ibuprofens, was a mistake. There were no detail clinical studies to warrant such an action. Commercially, it creates a significant injustice in promoting one set of drugs over others in the absence of a valid FDA approval.

I am not saying that all actions of the two sets of drugs should be the same just because they both inhibit the synthesis of prostaglandins, mostly derived from the fatty acid arachidonic acid. The implication of the Renin-Angiotensin Aldosterone System drugs in the actions of COVID-19 is also very interesting. These drugs are among the most recently prescribed for treatment of hypertension but they are not widely prescribed for blacks – providers usually prescribe thiazides and calcium channel blockers instead. The RAAS drugs are used to reduce the availability and/or the actions of Angiotensin 2 on its receptors.

Drugs that inhibit the synthesis of ANG such as captopril or ANG 2 receptor blockers like losartan are less effective in blacks but used widely by whites because the drugs are more effective in situations of high ANG-2 levels as is observed in whites compared to blacks. A very prominent side effect of ACE inhibitors like captopril is dry cough similar to that seen in COVID-19 patients. Interestingly, the antihypertensive effects of the ANG 2 receptor blockers is not associated with dry cough. There may be additional factors that are associated with the actions of COVID-19 and the dry cough produced by ACE inhibitors that are not clear at this stage.

The competition to develop safe therapeutic drugs and vaccines for COVID-19 is in high gear and several drugs are currently under clinical trials. Therefore, we should have a few drugs in the near future and vaccines in a year or so from major pharmaceutical companies. I hope that the above information will shed some light on the basic understanding of some of the mechanisms involved in the actions of some of the drugs that have been implicated in the current pandemic.