About Covid-19 Medications…

What questions will USMLE and COMLEX ask you in your upcoming exams?
Why, among so many drugs in the market have only a handful gotten the world’s attention as potential remedies for COVID-19?
What are the reasons for selecting and mechanisms of actions of the proposed drugs for treating COVID-19?
Why hydroxychloroquine is used for treating COVID-19?

Coronavirus Treatment Acceleration Program (CTAP)

Dr. E: It is not uncommon for researchers to race against time to identify new medications and to evaluate the efficacy of the commonly used co-morbidity drugs in decreasing morbidity and mortality of new diseases such as COVID-19. The impetus for this type of approach is in part supported by Coronavirus Treatment Acceleration Program (CTAP), and in part by the assumption that the most common comorbidities of any ailment are by far the most common culprits for the patients’ prognosis. For this reason, from the onset of the current pandemic we have witnessed a worldwide outpouring of hypotheses and researches targeting established treatments of comorbidities and closely-related viral families as quick fixes for minimizing the mortality and severity of COVID-19.

There must be a rationale for targeting certain drugs:  There are four major criteria used by most scientists and pharmacologists for coming up with workable medications against COVID-19. These are: (1) drugs that act on viruses with close genetic makeup; (2) building on the experience of China in dealing SARS virus; (3) random use of current antivirals with the hope that one of them may work; and (4) trying drugs that are used to treat COVID’s comorbidities.

What would we like to do today? Today, I like us to focus our attention on hydroxychloroquine that is well-known as HCQ. This drug satisfies three of the rationales that I just cited. Beneatha, if you are ready, let’s begin with our first question! Do you know what conditions are commonly treated by hydroxychloroquine?

Beneatha:  I know that hydroxychloroquine has classically been used to treat malaria. I took a complete dose of it during the summer of my junior undergrad year that I had to travel to India. Last year, I heard that it is used for treating rheumatoid arthritis. Now, I am hearing that it is one of the suggested drugs for treating COVID-19 as well.

Dr. E: You are correct! Hydroxychloroquine has become such a global celebrity these days, in part, because of its use for treating two common comorbidities of the COVID-19 that require ongoing or so-called “tertiary preventative management”. These two are lupus erythematosus, that is our famous SLE, and rheumatoid arthritis. I guess jumping is a common trend these days! COVID-19 has jumped from bats, to snakes and pangolins, and then to humans! Meanwhile, hydroxychloroquine that used to only treat malaria, has moved on to treat rheumatoid arthritis, and now it has become a candidate for treating COVID-19!

Beneatha:  I am starting to get a feel for how the sciences of epidemiology, biostatistics, microbiology, and pharmacology can cooperate for conquering certain diseases.

Dr. E: I trust that you may be interested to know why hydroxychloroquine as a treatment for lupus and rheumatoid conditions, has become a candidate for reducing the morbidity and mortality of the COVID-19. Aren’t you?

Beneatha:  You read my mind!

Dr. E: I will get to it soon, but for now I would like to share the following relevant statistics with you: 1% of world’s population have rheumatoid arthritis; 9-10% have diabetes; 5-10% have asthma; and 24-26% have hypertension. To orient you even better, in 2008, American Heart association reported that cardiovascular deaths represented 30 percent of all global deaths. Also, 70% of all cancers occur in people over 50; every sixth death in the world is due to cancer, and cancer is the second most common cause of death after cardiovascular diseases. Oh, I forgot to mention an important one; I forgot our elderly population! To give you a very conservative number, about 10% of our population are older than 65 years.  This population, due to frailty, is a lot more vulnerable to environmental risks than our general population. To make it even more sensible, the aforementioned comorbidities are all killers of the people, but when they team up with the COVID-19, their fatality rate skyrockets. As a result, it’s not unusual for researchers to target drugs that are commonly used for treating the most common comorbidities of the COVID-19.

Do you know what is the term that best describes, the concept of using or investigating an existing drug for new therapeutic purposes?

Beneatha: I didn’t know that there is a term for it! What is it?

Dr. E: It is known as drug repositioning or drug repurposing. This is a quick way to try a drug that has a well-established record track, for a new purpose to save time, money, and lives. Of course, they don’t just pick these drugs at random, and there must be some scientific rationale for these choices. One such rationale, as we just said it, is their utility in managing the comorbidities. As you can guess a good example is also the use of hydroxychloroquine and chloroquine that are classic anti-malarial drugs, for treating COVID-19.

Beneatha: How did it even occur to anyone’s mind to use hydroxychloroquine among myriads of other drugs for this purpose?

Dr. E: Actually, the precedent was established by the severe acute respiratory syndrome or SARS virus epidemic in China in 2002-2003. SARS virus that is also known as SARS-CoV or SARS-CoV-1, is structurally and functionally similar to SARS-CoV-2, the causative agent of COVID-19. Both viruses are nasty coronaviruses that have learned to jump from being a bat disease to become a human disease. SARS-CoV-1 and SARS-CoV-2 are both known as beta coronaviruses. This is to differentiates them from the classic and more benign human corona virus that we have known for quite a long time as one of the major causes of the common cold. Our good old corona virus is actually an alpha coronavirus!  

Can you name another nasty beta coronavirus?

Beneatha: Crown prince of…

Dr. E: Stop it right there; no jokes or politics! We’re working on the science of medicine now! 

Beneatha: Dr. E, didn’t you recently say that you are outraged to see our sciences being marred with the politics? Didn’t you say that scientifically correct and politically correct seems to have intermingled; they are increasingly dictated by autocratic politicians; and more than ever they are guiding the directions of our sciences? 

Dr. E: I might have! Guess what! I feel saddened to say this, but I’m in power now and this is my blog, so whatever I say overrides everything else! I know that you can name another nasty beta coronavirus for me. Make me happy and show me that you can!

Beneatha: While you got distracted, I googled it, and I came up with MERS!

Dr. E: Lovely! At times it just doesn’t matter how you do it, as long as you just do it! Middle East Respiratory Syndrome, or MERS is the other beta corona. It surfaced in the middle east and Saudi Arabia in 2012. It is hypothesized that it jumped from bats, its natural reservoir, to camels, and then to humans. Yes, MERS is the other beta-corona, just remember b” for the “bad”!

So why did I go to so much lengths to talk about all these?

Beneatha: I guess, they must be related to hydroxychloroquine! Are they?

Dr. E: Correct! Although we didn’t hear or care much at our country about the other two bad or beta coronas, they caused much panic at their own times in China and Saudi Arabia. Guess what was one the meds that was presumed to work on both?

Beneatha: They way that you posed it, I think, it must be “HCQ”!

Is it Possible?

Dr. E unintendedly jumps from physics to metaphysics…

Dr. E: Correct! Hydroxychloroquine and its buddy chloroquine were both presumed to work against SARS.  I tell you–I wish you were asking from me, why haven’t we developed any decisive treatment for SARS? Had we done it; we might have not been in the mess that we have to deal with now!  Didn’t we do it because it just went away on its own? I guess to a large extent this may be true! If so, I would love to believe in supernatural forces and hope that this may also happen to COVID-19! Wow–wouldn’t that be great if COVID just goes away the way that SARS and MERS did! If so, a big proportion of our frenzy about the COVID-19 may turn to be unfounded. Is it possible that some supernatural forces are teaching us a lesson about humanity? Look at our earth, it is breathing again! Is this a sign? Is it possible that a supernatural force is forcing us to sacrifice 2% of our entire worldwide population to save our mother Earth? SARS erupted in China, a country that used to be the cornerstone of polluting our earth, and as a result extinguishing so many species of our earthly co-habitants! MERS surfaced in Saudi Arabia, the source of fossil fuel for polluting our entire globe! We didn’t learn our lessons back then because we said it’s theirs and not ours! But we’re all in this together now!

Beneatha: Dr. E!  HELLO!

Dr. E: Thank you Beneatha! I know, I started daydreaming! Extraordinary matters at times force us to lose our sanity! Where did I leave the track of my thoughts? Okay, I got it! I wanted to say that it is evident to any sensible person that people with comorbidities are at a higher risk for almost any ailment that one can imagine. More importantly, they are extremely at risk for any new contagious infections.  Deep in my gut I feel that all sensible physicians would agree that COVID-19 can potentially affect all exposed individuals, at least as badly as the influenza virus does. Why? Simply because likewise influenza it is an extremely contagious disease!

Humanity at its Best: A Lesson from History!

Development of influenza vaccine was one of the milestones of the 20th century!

The fact that influenza doesn’t kill as many people these days is simply because we have put all our humanity at work to develop vaccines against it. The first influenza vaccine was developed in 1930s. During World War II, influenza vaccine saved the lives of so many of our soldiers. In 2003 we developed our first generation of predictive influenza vaccines that annually safeguards our at-risk population against influenza.

For your information, a predictive vaccine, like influenza vaccine assumes that a rascal like influenza can modify its structure, or more specifically, its virulence factor, to avoid our body’s immune system. Most medical students are familiar with the concepts of antigenic drift and shift that are inherent to influenza virus family, and allows them to bypass our immune defenses. These discussions are utterly important but beyond the scope of our current conversations. To sum the influenza story up; based on the typing of the influenza strains that have been affecting people during the immediate-prior flu seasons, we have been able to develop new vaccines to safeguard us during our current flu seasons. We should bear in mind that the COVID-19 is altogether something new and far worse than the influenzas that we have gradually learned to live along their sides. The fact that the coronavirus family jumps so readily, likewise influenza, from one animal to another, and then to the humans, guide any sensible person to believe that we must have astringent methods of surveillance in place to keep these rascals constantly under our radar. I think it is helpful for our morale if we assume a positive attitude and look forward to the bright day when everyone can be vaccinated against the COVID-19! If any, please don’t take away my dream! At this moment the best gift that anyone or any country can give to the humanity is a safe and effective Covid-19 vaccine! I just hope that you don’t say that I am a dreamer (click here)!

Here are a few million-dollar questions that we have to yet answer today: (1) What attribute of COVID-19’s infection prompts usage of hydroxychloroquine against it and against rheumatoid arthritis? (2) Why some clinicians have proposed usage of hydroxychloroquine with or without azithromycin, that is known as Z pack for COVID-19’s treatment? (3) What is the most dreaded consequence of prophylactic and unwarranted use of hydroxychloroquine?

Let us begin with answering our first question. How is it that a medication that works on rheumatoid arthritis can also work on the COVID-19?

Beneatha: I have no clue!

Dr. E: The classic proposed causes of death from COVID-19 have been acute respiratory distress syndrome (ARDS) and cytokine storm that results from overproduction of interleukin 1 (IL-1) and 6 (IL-6), and tumor necrosis factor (TNF).These cytokines cause a serious septic shock-like picture for the patients. Do you know what is the jazzy term that we have coined for these three cytokines?

Beneatha: Sorry, no clue again!

Dr. E: They are known as proinflammatory cytokines! Their overproduction causes increased vascular hyperpermeability, widespread thrombosis, and multiorgan infarctions and failure. The thrombotic causes of death as a result of these cytokines may very well be due to disseminated intravascular coagulation (DIC) that is a common finding with the cytokine storm. Current management of COVID patients with ARDS among other things involve intubation and frequent positional rotation of the patients. It is, however, the management of cytokine storm that relies on the administration of the hydroxychloroquine. Okay, let me see if you can reconcile hydroxychloroquine, rheumatoid arthritis, and cytokine storm of the COVID-19?

Beneatha: …cytokine…what!

Dr. E: Did I lose you? I asked if you could reconcile HCQ, rheumatoid arthritis and cytokine storm of COVID-19! You know what; what if I give you a 5-minute break to run up-N-down the stairways for three times, and then come back with an answer to me!

5 minutes later…

Beneatha (still panting): I think I got the answer! I guess hydroxychloroquine must have some sort of immune-suppressant or anti-inflammatory functions!

Dr. E: Bravo! Do you see how exercise can act as food for your thoughts!

Beneatha: Having you as my mentor, I must have known it by heart now, but I know that I have a lazy and sluggish nature!

Dr. E: Did you say lazy nature! Guess what! I want you to run up-N-down the stairways for two more times! I will give you three minutes—go now!

3 min later…

Dr. E: Well, you’re back!  No more defeating thoughts! Never ever say that you’re lazy! What did I say!

Beneatha (still panting): I will never ever say that I’m lazy!

Dr. E: Otherwise, you know what! Next time it’s going to be 5 times!

Beneatha: I promise!

Dr. E: Great, that’s a deal! I want you to listen carefully to this one: Hydroxychloroquine is believed to substantially decrease pro-inflammatory markers and cytokines! Do you remember the three major proinflammatory cytokines that we just talked about them?

Beneatha: IL-1 and IL-6 and … and… cancer… something like cancer necrosis…I got it! TUMOR NECROSIS FACTOR!

Dr. E: Great! Hydroxychloroquine is believed to reduce all three, and as a result it reduces inflammation!

Beneatha: The talk of interleukins reminded me again that my knowledge of immunology needs tons of tune-ups!

Dr. E: Remember, the other day that we’ve been venting over the Covid-19 and chanting “Testing, Testing, Testing…! That day I donated a copy of my immunology book and a complete set of my immunology videos to pupils of medical wisdom across the globe (Click)!

Beneatha: I remember clearly! It was towards the end of the day and right before you wrapped up our session!

Dr. E: I was not talking to you! I was talking to her!

Beneatha: Who!

Dr. E: …that inquisitive female medical student who is listening to what we’re talking about!

Okay, enough of these side-tracks! What is the descriptive term that we’ve assigned to drugs like hydroxychloroquine that is used in the management of rheumatoid arthritis and SLE?

Beneatha: I know this one! It is…disease modifying…anti-rheumatic drugs…DMARDs! 

Dr. E: Bingo! Now, the tougher concept to understand is the mechanism of anti-inflammatory function of hydroxychloroquine. This is the mechanism that makes HCQ a suitable medication for both rheumatoid arthritis and COVID-19. It is also a highly likely question that may show up on your upcoming medical board examination!

It is believed that HCQ preferentially inhibits toll-like receptor 9, that is also known with the acronym of TLR9. These important receptors are expressed on the outer membrane of the cells of our immune system. In particular they are prevalent on our first-responder immune cells such as dendritic cells, macrophages, natural killer cells, and other antigen (or pathogen) presenting cells. TLR9 preferentially binds DNA of the bacteria and viruses, and triggers signaling cascades that lead to a pro-inflammatory cytokine response. It is also shown that cancer, infection, and tissue damage can all modulate and activate TLR9 expression and activation. Of course, as you may guess now, TLR9 is also an important mediator in autoimmune conditions such as rheumatoid arthritis, SLE, and Sjogren’s disease.

Well, we established the role of HCQ in the management of explosive proinflammatory cytokine release. Now our challenging question is “how does the antimalarial function of HCQ allows it to have antiviral and antiCOVID-19 activity?”

Beneatha: I think whatever HCQ does to knock down the malarial agents should also work for knocking down the viruses! Am I correct?

Dr. E: Yes, you are! Do you recall the name of two vicious coronaviruses that haunted people in China and Saudi Arabia before COVID-19? Do you also know the names the nasty diseases that they cause? We just talked about them!

Beneatha:  The first disease was severe acute respiratory syndrome caused by SARS coronavirus that plagued China in…I guess, 2003-ish. Its causative corona was named SARS-CoV, but after COVID-19 got into the mix, its name was refined to SARS-COV-1, to distinguish it from SARS-COV-2 that causes COVID-19. The other virus that has jumped from bats to camels in Saudi Arabia was MERS-COV! The disease that it caused was Middle East Respiratory Syndrome (MERS). I think it plagued Saudi Arabia and Qatar in 2012-2013!

Dr. E: I’m impressed! Your memory works like a clock! 

Beneatha: I remember the isolated facts quite well, but I have a hard time to relate those facts to big pictures.  I’ve noticed that I remember the answers to “what” types of questions much better than “why” types of questions. One of my problems with national medical board exams is that I’m spending more energy on memorizing facts instead of learning why things are this way or that way!

Dr. E:  If you focus part of your time and energy on mastering mechanisms of actions and pathophysiology, you will be able to greatly improve your odds against your upcoming medical board exam!  

Do you remember what I said is by far the best piece of work among the available review books for acing the Step 1 USMLE and Level 1 COMLEX exams?

Beneatha: I clearly remember it! I remember that you said you love, Dr. Thomas Brown, the brilliant man who put it all together! I am clearly visualizing the cover of his book that you gave to me!

Dr. E:  I can clearly see through your mind—you have this image on your mind–don’t you!

This review book has been adored by Dr. E from the time that it was published! It is by far the best kept secret from under-performers in the world history of medical board prep!

Beneatha: OMG! Dr. E you’re psychic!  

Okay enough of this! We went onto so many tangents, that I totally forgot why we ended up here again!

Beneatha: You asked me about the two other nasty corona viruses that have plagued China and Saudi Arabia! 

Dr. E: Oh yes! I wanted to say that those two coronaviruses provided the precedent for using HCQ to treat SAR-COV-2! Of course, as you can tell we do still need to figure out what is the mechanism of action of the HCQ that makes it a suitable medication for treating malaria and coronaviruses!

Beneatha: All I can say is that I’m all ears!

Dr. E: Viruses and malarial agents such Plasmodium falciparum or Plasmodium vivax are tinny organisms. Roughly about 200 to 500 viruses can fit into one human cell. The malarial organisms or Plasmodia are much bigger than the average viruses, but much smaller than the human cells. Depending on the stages of their life cycle, anywhere from a few and up to 40 Plasmodia can fill-up the cells that they commonly parasitize.  Do you recall what two types of human cells are commonly infested by the Plasmodia organisms such Plasmodium falciparum?

Beneatha: Liver and red blood cells!

Dr. E: Bravo! So now we need to think of an intracellular immunological mechanism that allows HCQ to knock down viruses and Plasmodia alike!

How does HCQ knock down malaria? A classic explanation for effects of HCQ on malaria is that after it enters the red blood cells, it uses the globin or the protein part of hemoglobin within its vacuoles or lysosomes to convert it to its own proteins. For simplicity, you may think of the lysosome or vacuole of the one-celled organisms to be comparable to the stomach of the human body. They digest and break whatever enters them! Note that Plasmodium has no use for the heme moiety of the hemoglobin of our red blood cells, as it is very toxic. What does it do with it? It converts it to non-toxic crystals that are called hemozoin. When a person takes HCQ, it enters the Plasmodial vacuoles as uncharged molecule, and within the acidic intra-vacuolar environment it becomes charged with hydrogen ions (H+), and then gets trapped. The charged trapped HCQ then makes a complex with heme that is extremely toxic and causes lysis of the red blood cells together with the malaria organisms inside them. I personally believe that this is by far the most sensible mechanism for antiviral and anti-COVID effects of the HCQ. When a virus, let us say SARS-COV-2, enters the human cells, it is engulfed by our lysosomes. When patients receive HCQ, it enters into our lysosomes, raises the pH, and knocks down the SARS-COV-2.

There are also some talks in the literature about effects of HCQ on sialic acid receptors. Have you heard of these receptors?

Beneatha: I have heard of sialic acid, but don’t know how it relates to all these!

Dr. E: Well, many viruses such as influenza, mumps, and corona use glycoprotein receptors on human cells that are linked to sialic acid. These receptors play important roles in allowing the viruses to inject their particles into our cells. It is believed that HCQ inhibits sialic acid synthesis and as result it has a generalized blocking effect against a broad spectrum of viruses, including the corona viruses.

Moreover, it is further believed that HCQ inhibits an enzyme called quinine reductase 2. Have you heard of this enzyme?

Beneatha: OMG Dr. E! I have no clue!

Dr. E: This enzyme is believed to cause synthesis of sialic acid. Inhibition of sialic acid formation by HCQ causes loss of receptors that are used for viral entry into our cells!

Do you recall that sometime ago there was so much fuss about the use of Losartan, an antihypertensive medication, for treating COVID-19 patients?

Beneatha: Yes, I do! I was curious about how it was related to COVID-19!

Dr. E: There has been some talk in literature about attachment of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptors and using them as their portal of entry into the cells. Of course as you tell a big chunk of our immunology-related information is highly speculative at the moment. Nevertheless, the good news is that the science of immunology is currently one of the fastest growing medical disciplines, and we are learning at a very high pace as we go on.

Well, back to the ACE receptors; they are mainly expressed in the lung, but they are also present on the heart and kidney cells. It is hypothesized that HCQ interferes with the glycosylation of the ACE2 receptors and distorts their structures.  Net result is blockade of attachment of the COVID-19 virus to the lung cells. Do you recall from your cardiac pharmacology that losartan, one of our famous antihypertensive drugs, functions as an ACE receptor inhibitor?

Beneatha: Yes, I do!

Dr. E: I guess this helps you to understand why some scientists have proposed Losartan for COVID-19’s treatment. It plays a dual role, not only it treats hypertension that is a comorbidity for COVID-19, it also inhibits ACE2 receptors that are believed to be the portal of entry into the cells for the COVID-19!

Beneatha:  Earlier we mentioned Z-Pak! Why do they use Z-Pak together with HCQ in patients with COVID-19 infection?

Dr. E: This is in my opinion just a crazy combination that makes sense only in a pandemonium! As you recall Z-Pak or azithromycin is an antibacterial. I guess the combo use of it is due to the fact that any type of respiratory ailments can be a comorbidity for COVID-19!

Put yourself in the shoes of a frontline ER doctor in New York city for a moment! Imagine a patient among so many other desperate patients who is presented with fever and pulmonary symptoms! I know about your immediate clinical suspicion, had it been during the pre-COVID era!

Beneatha:  Bacterial pneumonia!

Dr. E: Bravo to you again! 

During those good old times, you might have also had a reasonable time to order a few diagnostic tests for your patient.

What is the most commonly used drug against most bacterial pneumonia?

Beneatha:  Is it Zee…Pak!

Dr. E: Most docs agree with you! Would you consider pneumonia to be a comorbidity for the COVID-19?

Beneatha:  Yes, I do!

Dr. E: Bravo! Now imagine yourself in the same hectic emergency room in the New York city amidst the Covid-19 frenzy. This time the emergency room is filled with many Covid-19 patients looking up to you as their only savior! Do you have time to test for the bacterial causes of pneumonia? Of course not! Your goal is to save one more life! If the patient happens to have bacterial pneumonia, azithromycin may most likely work for him. If not, azithromycin has a rap for being relatively safe, so it may not hurt or hurt as much! What is then the most frugal next step for you? To give HCQ with an add-on Z-Pak and moving to your next patient!

Just never forget that extra-ordinary situations call for extra-ordinary measures!

Beneatha:  Wow, I can imagine how crazy things may be in the COVID frontlines! My heart goes for all the healthcare professionals!

Dr. E, do you remember that I said earlier, that once I took a complete dose of HCQ during my undergrad trip to India? I remember that back then I took one HCQ pill about a week before my trip and then one pill each week thereafter, for the entire duration of my trip! I also think that I took one final pill one week after my return to the US! I don’t recall any adverse reactions at the time.  If so, then, why is there so much fuss about the side effects of hydroxychloroquine?

Center for Disease Control (CDC) suggests precautions against malaria during peak seasons in India!

Dr. E: Good question! Hydroxychloroquine has a more established effect on malaria. It may work on patients with early symptoms of COVID-19. However, the idea that people prophylactically can take them is absurd! Do you recall the major antiarrhythmics that we’ve covered in our cardiology prep course? Do you recall quinidine? What was the class of it?

Beneatha: I know this very well! I love memorizing facts! I know that you are utterly appalled by reducing the science and art of medicine to trivia and jeopardy-like endeavors! 

Dr. E: You are correct! A good physician must be a logician. S/he must be a master of analytical reasoning, and not a regurgitator of isolated pieces of facts. In the world that we live in today, all sorts of information are available to anyone who has a smart handheld device, and this practically includes the entire world, physicians, and non-physicians alike! The two organizations that own the USMLE and COMLEX examinations must be well-aware of this and apply it to the design of their exams, and if not, then it’s about time for them to close their shops.

The unfortunate catch is that when you search the medical terms or phrases on the internet you will come-up with myriads of pieces of information; some are factual, and some are fictitious. Why? Because everyone with a handheld device can shoot a sensible or non-sensible piece of information onto the worldwide web. As a result, the entire medical ballgame has turned into a trivial game with so many contradictory concepts and propositions! To avoid personal contradictions, it then appears natural if we subscribe only to certain social media outlets that agree with our overall beliefs. As a result, we often fail to consider the truth or falsity, rationality, or irrationality of the information that our favorite outlets force-feed us. Amidst all these frenzies, physicians who employ their unbiased analytical and logical minds for drawing their own judgments based on their own coherent medical frameworks will become our rightful medical science leaders!

Beneatha: I see why I love Dr. Fau…

Dr. E: Stop it right there again; no politics! We’re working on the science of medicine now! 

On second thought, I don’t blame you! I love my good old pal, Dr. Tom Brown. “Hey man, if you can hear me, “thank you so much for helping so many medical students of mine with their USMLE and COMLEX prep!”

Beneatha: Dr. E, I know how passionate you are about him and his Secrets book! I fell in love with his book at first sight!

But Dr. E I just can’t take my mind off your outrage against seeing the science being marred with the politics! 

Dr. E: I understand! But let us not think about these issues today.

Okay! We went a little in tangents again! But you’re not off the hook yet! What was the antiarrhythmic class of quinidine?

Beneatha: Class IA!

Dr. E: Bravo! What is the prototype of class 1A?

Beneatha: Quinidine!

Dr. E: Great! What is the most dreaded and fatal consequence of using quinidine?

Beneatha: Myocardial toxicity!

Dr. E: What is the term that best describes cardiac rhythm abnormality that results from elongation of QT interval due to quinidine? I give you a hint! It starts with the letter “T”!

Beneatha: Torsades de pointes!

Dr. E: That’s correct! Torsades de pointes that is abbreviated as TdP causes palpitation, dizziness, fainting, ventricular tachycardia, and at times, heart attack! Do you know another important cardiovascular side effect of HCQ?

Beneatha: I’m sorry, I can’t recall!

Dr. E: Your hint is that it causes widespread bleeding and increases the bleeding time!

Beneatha: Got it! Thrombocytopenia!

Dr. E: Correct! Can thrombocytopenia as a result of HCQ kill you?

Beneatha: Yes! Especially if we take HCQ with blood thinners such as aspirin!

Dr. E: Do you see any similarities between hydroxychloroquine and quinidine?

Beneatha: Their names look alike!

Dr. E: Actually, hydroxychloroquine, quinidine, and quinine (another antimalarial drug) are all related drugs.  Have you heard of the proverb that birds of same feather flock together?

Beneatha:  Yes, I have!

Dr. E: Do you think that hydroxychloroquine, quinidine, and quinine can cause heart attack?

Beneatha:  Yes, I clearly see it now!

Dr. E: What do you see?

Beneatha:  I see that they all can cause heart attack!

Dr. E: Lovely! Having said all these, what two groups of populations do you think are at a higher risk for dreaded consequences of hydroxychloroquine?   

Beneatha: Those with heart and bleeding problems!

Dr. E: Bravo! Do know of any medication that has no side effects?

Beneatha: No! Actually, you mentioned that in one of our former meetings!

Dr. E: Bravo!

I have good news for you! Let’s leave it here for today! You just take a good care of yourself and stay away from the COVID!

Beneatha:  You clarified so many concepts for me! Thank you so much and have a lovely weekend!

Dr. E


Also known as "Dr. Testbuster", Dr. Eftekar (Dr. E) is the founder, head coach and lead lecturer of the medical board training programs at Northwestern Medical Review. A unique attribute of Dr. E is his well-rounded academic background that, in addition to the science of medicine, extends over several other disciplines such as physiology of aging and longevity, philosophy of science and medicine, and integrated kinesiology.

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    If hydroxychloroquine (HCQ) has been working for so many years for so many people who’ve been travelling to malaria-infested areas, how come it has suddenly become so unsafe! Is it only unsafe in people with overt or covert risk factors for HCQ? Is it only unsafe in people with cardiac arrhythmias or bleeding tendencies?

    Do you want to know how my conversation with Beneatha continued the day after? Well here we go!

    Dr. E: Beneatha, if you have to go back to India during a malaria season, would you take HCQ prophylactically?
    Beneatha: Of course, I will! It worked for me then—it will most likely work now!
    Dr. E: What if God forbid, you notice that your nose-poke test shows that you are positive for Covid-19, would you go for HCQ?
    Beneatha: Of course, I will!
    Dr. E: I will go for it too! How about if your nose-poke test shows that you are negative for Covid-19, would you go for HCQ?
    Beneatha: Of course, NOT!
    Dr. E: Bravo! Life is more pleasant if we live it with less medications!

    Dr. E Reply

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