What drug companies did not want you to know about Aspirin and Advil in asthma and COPD?

What you are about to read in our blog will most likely change your entire outlook about these meds!

Beneatha: In mid-March and when Corona erupted, the household rumor was that Advil and Aspirin may predispose us to COVID-19 infection. What I cannot understand is how Aspirin and Advil are related to COVID-19, and what makes Tylenol a better choice compared to them?

Dr. E: The truth is that only part of what you’ve heard is correct, but the devil is in the details, which are for most part concealed from the laypersons. The unqualified generalizations that are loudly and widely broadcast by people in social media only add fuel to the frenzy. The public’s panic mostly stems from widespread use of Aspirin and Advil as anti-inflammatory and anti-thrombotic agents by so many people across the globe. Meanwhile, drug companies that make Tylenol (acetaminophen) are provided with a once in lifetime opportunity to promote their own products at the expense of the other two. Let me say it, and let me say it out loud, these three drugs and the long list of their look-alikes come with so much baggage that their producers wish that you may never learn about them.

Beneatha: The way you say it makes me think that there are a lot more about these than meets our eyes and ears!

Dr. E: You’re right! COVID-19 has already revealed so much about our shortcomings. It has disclosed our insatiable greed, egocentrism, hypocrisy, and corporate immorality. What makes me so furious is that with all our claims to superiority and humanity, the morbid COVID-19 was the one who exposed our public health flaws. But wait a minute! I see a dim light at the end of this doomed tunnel! Let’s look at it this way: All those frontline health professionals, all those 1.6 million people who contracted COVID-19; all those 350,000 who got it, suffered through and recovered from it; and all those 100,000 people who died because of it, are all our heroes; aren’t they? Let the whole world hear you–aren’t they? Their pains, sufferings, and lives were not meant to be in vain. As of today, April 17^th, our heroes have revealed so much about the filthy nature of our politics, the unethical practices of our health insurance and pharmaceutical industries, the grid and cruelty of our fossil fuel industry, and so much more. If you’ve lost a loved one to COVID-19, you may be comforted just little to know that our health professional heroes and those who are constantly working on the streets to maintain  our wellbeing at our homes, are getting suffocated so that the entire humanity can breathe for many years to come. They are sacrificing their health and their lives so that our airs, our skies, and our oceans breathe again. More importantly, and to relate these to your current concern, they helped us to appreciate the hazards of so many seemingly safe over-the-counter medications.

Beneatha: Dr. E, you are the master of suspense! The way you lay the foundation gives me the feeling that there are a lot of nasty things about these three drugs than what hits the eyes of the public. I just can’t wait to hear them!

Dr. E: You’re right! I was suffocating; thank you for allowing me to vent a little!

Let us focus on our current issue! Do you recall what public health professionals used to say from the outset about the people who are at risk of dying from COVID-19?

Beneatha: They said that it is more serious and fatal for people with comorbidities!

Dr. E: Bravo! Do you recall the most common comorbidities that were named?

Beneatha: I recall old age, chronic obstructive pulmonary diseases (COPD), diabetes…

Dr. E: Sorry to interrupt you, can you name a few COPD conditions?

Beneatha: The first three that come to mind are emphysema, bronchitis, asthma!

Dr. E: Great! Let us get back to your list of comorbidities! Can you add any more?

Beneatha:  Let me see, I already named COPD, diabetes, and old age! A couple more are rheumatoid arthritis, and systemic lupus erythematosus, and…I know a few more…

I think kidney diseases, hypertension, cardiovascular and cerebrovascular diseases… well, I can’t recall any more! No, wait, two more came to my mind; immune deficiency and undergoing cancer chemotherapy!

Dr. E: Can you add one more that only applies to our country? I will give you a hint! As of today, this segment of our society, which represents about 12% of our total population, has suffered the highest COVID-19 fatality rate compared to other segments of our population.

Beneatha: I think you are referring to African Americans; am I correct?

Dr. E: I wish I could have been able to say “no”, but you are correct! I feel utterly ashamed to call it a comorbidity. But I just hope that this could get our attention, could shake up our conscience, and could move us even just a little to the RIGHT side of our history.

Beneatha: I do see it clearly now! Also, I see how comorbidities can be different for various populations.

Dr. E: Great! Let us now focus on your list of COVID-19 comorbidities. I am not sure if you noticed it or not, but you practically named the most common conditions that majority of our people over 65 are suffering from, and they account for most recurrent doctor visits in our country as well. Do you know what’s the jazzy term that we have coined for the type of intervention or prevention that we provide for them to delay their complications or to restore their optimal functions? I give you a hint, it is not primary prevention! It is…!

Beneatha: Tertiary prevention!

Dr. E: Bingo! This type of prevention focuses on people who are already affected by a disease. It aims at enhancing the quality of their lives by decreasing disability, reducing and delaying complications, and gradually restoring their optimal functioning through constant surveillance, rehabilitation and lifestyle modifications. To relate this all to what I am about to say, these conditions are the dream-come-true for the pharmaceutical companies. They know very well that patients, let say, who have diabetes, are doomed to use their products for the rest their lives!

Beneatha: Getting to know you better over time as my mentor, I know that you are about to relate these to Tylenol, Aspirin, and Advil. All I can say is that I’m all ears!  

Dr. E: Okay, here we go! Asthma and COPD are common respiratory-related issues, aren’t they?

Beneatha: Yes, they are!

Dr. E: Common cold, influenza, pneumonia and COVID-19 are all respiratory-related issues, aren’t they?

Beneatha: Yes, they are!

Dr. E: Almost everyone knows about the nonsteroidal anti-inflammatory drugs or the so-called, NSAIDs! We take ibuprofen that is marketed as Advil and Motrin; acetaminophen that is known as Tylenol; and acetylsalicylic acid that is widely known as aspirin for so many conditions. I bet you know of so many who take one or the other, and you can name their most common usages as well, can’t you?

Beneatha: Dr. E I’d rather say I know of no one who doesn’t take them! I know of so many in my family and among my friends who take one or the others for so many reasons. They take them for fever, muscle ache, joint ache, toothache, headache, menstrual cramps, and common cold, in addition to certain specific conditions such stroke, risk of blood clotting, and diabetes. I almost forgot to say that some of my friends use cocktails of these NSAIDs with antihistamines as sleeping pills.

Dr. E: So, our next anticipated question is why do so many people so readily take these drugs?

Beneatha: I guess its because of their widespread availability. They are sold almost anywhere…gas stations, grocery stores, convenient stores, supermarkets, and highway rest areas!

Dr. E: What do people assume when they see these meds that require no prescriptions everywhere?

Beneatha: They are safe! They are approved by the FDA for over-the-counter sales! They are almost like grocery items, and people can pick them up with chewing gum while they’re peeking at the gossip magazines in the checkout lanes of the grocery stores!

Dr. E: You just hit the nail on the head! Let us now focus on why there are widespread positives for Tylenol, and cons for Aspirin and Advil, as they relate to COVID-19! Are you ready for a little technical talk?

Beneatha: I’m all ears!

Dr. E: COVID-19 is so far best classified as a respiratory culprit and it is placed among a few look alike conditions that range in terms of severity from common cold to influenza, and SARS. The most bothersome presentation of the disease appears to be dyspnea or difficult breathing, and the top two common causes of death from it have been acute respiratory distress syndrome (ARDS) and septic shock. I am more concerned about the respiratory distress and ARDS today as they relate to NSAIDs, Asthma, COPD and COVID-19 symptoms. But before getting there, I want to dismiss one of the erroneous kitchen table issues related to these–are you ready for it?

Beneatha: Dr. E! You turned me into ears again!

Dr. E: Aspirin and Advil DO NOT cause corona infection! By the same token, Tylenol is not the treatment for corona. So, what’s the scientific fuss about them? Tylenol, Aspirin and a few less-commonly-known-by-the-public NSAIDs, in contrast to Tylenol (acetaminophen) can induce bronchospasm or tightening of the airways. Of course, as you can tell everything is a matter of degrees! A bronchoconstriction of up to 5% may be imperceptible by most people during normal daily activities. In contrast, bronchoconstrictions of 55% or much higher, may asphyxiate people to death. Do you recall what population, in general, has the most widely documented and debated issues related to the use of Advil and aspirin?

Beneatha: Asthmatics!

Dr. E: Correct! This doesn’t mean that other people do not get bronchoconstriction with Aspirin or Advil. Of course, as we will see the mechanism NSAID-induced bronchospasm shortly, they all do! However, they only get a minor and imperceptible bronchial tightening. Asthmatics on the other hand, and to begin with, have some chronic degrees of bronchoconstriction that when is added to NSAID-induced spasms may choke them. Now, if we add into the mix a nasty respiratory disease like COVID-19 that screws up the alveolar and gas-exchange surfaces, the fatality rate for the patients will reach to 98% or more!

Beneatha: Dr. E, is it fair to assume that Tylenol and Aspirin are comorbidities for COVID-19 patients?

Dr. E: Bravo again! In a sense, we can consider them to be minor comorbidities in non-asthmatic and non-COPD general population!

I guess having said all this we may now look at the pathophysiology of NSAID-induced bronchospasm. I like to point the following diagram to you. But before doing it, I like to hear your first impression about it, did I do a good job on it?

Beneatha: It’s awesome! I have seen so many of your medical illustrations, I just love them as they cut to the heart of what you explain for medical professionals. I know that people commonly don’t care much about the history of medical board preparation, but if they do, they know you as the father of osteopathic board prep! What goes without saying is that you’re the first person who introduced uplifting mnemonics and cartoons into medical board prep review notes and courses. In my opinion, the medical board industry that is now flooded with animations, cartoons, and study aids, owes as much to your pioneering vision, as the cartoon and animation industry owe theirs to Walt Disney.

Dr. E: Thanks Beneatha! I just hope you didn’t say all that so that I take it lighter on you as I will be delving into the higher level of mechanism of actions of NSAIDs!

Beneatha: LOL!

Dr. E: If you look at the diagram it shows that inflammation or cell membrane damage causes release of cell membrane phospholipids and local activation of the enzyme, phospholipase A2, and as result formation of an important fatty compound, the arachidonic acid. Two enzymes then act on the arachidonic acid—cyclooxygenase that is a fast-acting one, and lipoxygenase that is a slow-acting enzyme. Products of cyclooxygenase in different tissues of the body are prostaglandins, prostacyclins and thromboxanes. Products of lipoxygenase are leukotrienes. These four products that are collectively known as eicosanoids, play many important local physiological functions and bodily chores for us.

Wait a minute…stop it NOW!

Beneatha: Stop what? What did I do?

Dr. E: Yawning! Haven’t you heard they say it’s contagious! I’m worried that you may put my diehard fans to sleep!

Beneatha: I’m so sorry!

Dr. E: Sorry is not enough! Didn’t you say a few minutes ago that I am the Master of Medical Mnemonics! The father of this…father of that…who did you say I was the father of?

Beneatha:  Osteopathic medical board preparation!

Dr. E: I love the ring of it! My only problem with it is that it makes me look too old, which isn’t so, because deep inside I feel that I’ve just started kicking! Do you know what was the year and how old was I at the time?

Beneatha: Wasn’t it 1986?

Dr. E: Correct! Now can you also say when was the time that the first osteopathic medical board prep class was offered in the world? Where was its location? Who did put it all together for generations of medical students to benefit from board prep services thereafter?

Beneatha: 1986! At Michigan State University in East Lansing, Michigan. It all began with a visionary man named Dr. E!

Dr. E: Wow! Don’t know why I love so much the way that you put it! Did you say I was the father of what?

Beneatha:  …Osteopathic medical board preparation!

Dr. E: I just wanted you to say it out loud again as I love the way it sounds!  But didn’t you also say that I was the first person who introduced mnemonics in its modern sense into the medical board prep courseware?

Beneatha:  Yes, I did!

Dr. E:  Well, I have a good mnemonic for you so that you never ever forget that you’ve promised not to yawn again while I’m talking! I want you look at the picture that you admired so much, and tell me what does normally thromboxane do, and what types of cells or tissues make it?

Beneatha: Dr. E this is tortuous, but I know that you have my best in mind and want me to learn these concepts. It is produced by the platelets in the blood! Forms clots and stops bleeding!

Dr. E: That’s correct! Now suppose that a patient makes too many blood clots and she is at risk for deep vein thrombosis, myocardial infarction, or stroke, do you see a reasonable use for ibuprofen, or more importantly for Aspirin in these patients?

Beneatha: I clearly see why they may take these NSAIDs to safeguard against stroke, deep vein thrombosis or myocardial infarction!

Dr. E: Look at the picture and tell me what does prostaglandins normally do in the body? But before doing so, I want to make sure that you understand that I have only outlined major functions of the prostaglandins and the other three eicosanoids for their relevance to my talks!

Beneatha: I clearly understand! Prostaglandins are the main cause of inflammatory pain, but they block stomach acid secretion, and act as a safeguard against stomach ulcers!

Dr. E: Great! Assuming that pain management is by far the most desired effect of NSAIDs for the people, can you tell what is the most troublesome consequence of inhibition of prostaglandins for the patients?

Beneatha: They unleash stomach acid and predispose to stomach ulcers!

Dr. E: Great! Now, tell me what do prostacyclins do, and what will happen if we block their effects by the NSAIDs?

Beneatha: They normally dilate blood vessels. They oppose thromboxane’s thrombotic effects. Wow, I now clearly see how the use of NSAIDs reverse this effect, and why in patients with myocardial infarction and stroke this may not be desirable.

Dr. E: All I can tell you, because you are one my favorite students, is that there is no medication that has no baggage!

Okay, let us now zero on leukotrienes. What is the enzyme that facilitates their formation? What are their functions, and what will happen if we reverse these functions with NSAIDs?

Beneatha: Lipoxygenase does it. They increase bronchial tone. They cause tissue inflammation and localized edema. They are involved in the etiology of asthma and allergic rhinitis. Awe, they seem to have so much undesirable effects!

Dr. E: You can say it out loud again! They are also claimed to be involved in the etiology so many other conditions such as rheumatoid arthritis, asthma, aspirin-exacerbated respiratory disease (AERD), inflammatory bowel disease, and acute respiratory distress syndrome (ARDS). Speaking of ARDS and Asthma–do you recall what was one of the major causes of death from COVID-19?

Beneatha: Didn’t you say ARDS!

Dr. E: Correct! Now I guess it’s about time for us to relate COVID-19, Advil, Aspirin, and asthma to our story! Let’s begin with this question: By looking at the picture, can you tell me what would be the dreaded consequence of taking Aspirin and Advil for any reason by asthmatics?

Beneatha: They block the cyclooxygenase enzyme. They result in accumulation of arachidonic acid and stimulation of lipoxygenase enzyme, and as result they induce bronchospasm, inflammation, and edema formation.

O dear! They choke patients who are already suffocated by the COVID-19! They promote ARDS! They cause bronchoconstriction! Awe! I guess in a sense they act as comorbidities for COVID-19!

Dr. E: You are correct! In a sense Advil and Aspirin can be considered as controllable risk factors for COVID-19, but as you indicated in contrast to asthma, we can modify them or stop taking them. 

Beneatha: I guess this is the reason why they suggest that if we must take an NSAID for any reason, Tylenol is by far much better for asthma, ARDS and COVID-19! But how does Tylenol work?

Dr. E: I’m not sure if you know it or not, but Tylenol is known as an atypical NSAID. In contrast to other NSAIDs such as aspirin that work locally and on peripheral tissues, Tylenol works in the brain, and most likely at the level of hypothalamus and spinal cord. There, it centrally decreases prostaglandin’s output and as result decrease pain, lower the body temperature, and reduce fever. However, given that it does not act on cyclooxygenase, it does not have anti-inflammatory effects of Aspirin and Advil.

Beneatha: Dr. E, do we have any medication that can reduce fever, pain, and inflammation, and can help patients who have asthma or rheumatoid arthritis?

Dr. E: Look at the first picture, and you tell me!

Beneatha: O dear! Why I couldn’t I see it before–glucocorticosteroids such as hydrocortisone are awesome for this purpose!

Dr. E: You are correct! Do you remember that I said there is no drug that has no baggage? Do you know what is the most dreaded consequence of abusing Tylenol?

Beneatha: Is it something related to liver function?

Dr. E: Correct! It causes a serious and life-threatening liver toxicity and failure!

Beneatha: What is the mechanism of liver toxicity with Ty…

Dr. E: Stop it right there–I have a webinar meeting with one of my students who is scheduled to take her USMLE CK exam in early June. So, let’s talk about this at a different occasion. For now, just remember that in our next meeting we will delve into drugs that are proposed for treating COVID-19!