Study Hacks: How to Memorize Drug Side Effects

I am often asked by students how to study and retain drug information. Given the "drinking from a fire hose" environment of pharmacy school, this is understandable. Although the internet and online databases have put a lot of information at our fingertips, there's still a lot of drug information you must memorize in order to graduate and become a successful pharmacist.

When I was a student asking the same "how do I remember all of this!?" questions to my professors, the general response I got was some variation of the immersion principle (i.e. study harder). For me anyway, this worked to a point, but eventually, I started noticing diminishing returns. I experimented and came across the following process. This article will focus specifically on drug side effects, but it can be applied to just about anything. These "learning by deconstruction" techniques are what got me through pharmacy school (not to mention the NAPLEX and BCPS exams).

Learning by Deconstruction

Start by breaking down how side effects happen. What are the causes? Take the general overview of "side effects" and break it into its individual parts. We can use toxicology studies to help us with this. In general, there are 4 main "causes" of drug toxicity (and hence, side effects):¹

1. Mechanism-Based (you'll often see these broken down into "On-Target" and "Off-Target" effects)

2. Toxic metabolites

3. Immune/hypersensitivity reaction to the drug

4. Idiosyncratic reactions

With that basic framework in mind, let's look at each category separately. Afterwards, we'll explore some useful tips and tricks for memorization.

1. Mechanism-Based

The first step is to understand the pharmacology of the drug itself. For any given drug, the majority of its side effects are usually some offshoot of its mechanism of action. It might be the drug working "too well" or it might be the drug binding to the correct receptor in the wrong tissue. If you truly learn pharmacology (and the related pathophysiology), then "memorizing" side effects is easy. It almost becomes unnecessary because you can use reason to figure out most potential side effects.

Mechanism-based side effects are broken down further into "on-target" and "off-target" effects. Going a step further, on-target effects are categorized by where they occur (either the intended tissue or in an unintended tissue).

For example, a "classic" side effect of non-selective beta blockers is asthma exacerbation. This is an on-target effect because beta receptors are being appropriately blocked but it's in an unintended tissue (the lungs instead of the heart). Another side effect of beta blockers is bradycardia, another on-target effect. This time, however, it's in the intended tissue.

For off-target effects, let's look at diphenhydramine. It's "supposed" to bind to H1 receptors, but many of its side effects stem from the fact that it also binds to (and blocks) cholinergic receptors. This leads to the classic anticholinergic effects such as dry mouth and urinary retention.

How do you memorize all of this? These side effects usually extend to the entire class of drugs. So you might learn in class or in a package insert that lisinopril can cause a dry, hacking cough. By learning the mechanism of that reaction (bradykinin build up secondary to ACE inhibition), you can now reason that every ACE inhibitor can cause a dry hacking cough. This is a class-wide side effect. Another example is how all NRTIs can cause both lactic acidosis and hepatic steatosis via mitochondrial toxicity.

You can learn mechanism-based side effects "once" for one drug, and you now know it for all other drugs in the same class. You can make a note card (or similar list) of these on and off-target effects. That will help you see the forest for the trees and connect the dots of the big picture.

2. Toxic Metabolites

Another kind of side effect is due to toxic metabolites. As a point of caution, I would not necessarily include active metabolites in this categorization (active metabolites would usually fall under the mechanism-based categorization). Toxic metabolites are substances that can accumulate and cause cellular damage from the normal process of drug metabolism. An example you're likely familiar with is N-acetyl-p-benzoquinone imine (NAPQI): the toxic metabolic product of acetaminophen. As you come across toxic metabolites in your studies, keep a list of them on a notecard and review it periodically. To make it even more useful, you can also include the treatment or medical intervention for dealing with toxic metabolites (such as N-acetylcysteine for NAPQI).

3. Immune/Hypersensitivity Reactions

Immune reactions to drugs are somewhat rare, but severe when they do occur.

While there is a theoretic risk of any drug causing hypersensitivity, you'll make the memorization process a lot easier on yourself if you single out the most common offending agents.

Here again, it's best to take a class-wide approach. I recommend making a list of drugs (and drug classes) that commonly cause immune reactions. For example, my own list includes penicillins,

sulfa drugs

, taxanes, and pretty much every monoclonal antibody. Additionally, I include drugs where we might test for human leukocyte antigen (HLA). Drugs like abacavir (HLA-B*5701) and carbamazepine (HLA-B*1502) have a very high risk of an immune reaction if given to individuals positive for the respective HLA.

4. Idiosyncratic Reactions

For idiosyncratic reactions, I find (again) that the best practice is to group drugs together that can cause a certain reaction. For example, you might make a list of drugs that can prolong QTc interval (fluoroquinolones, macrolides, antipsychotics, 5-HT3 antagonists, etc...) and drugs that can cause hyperkalemia (ACE inhibitors, ARBs, aldosterone antagonists, aliskiren, heparin, SMT/TMP, etc...). These drugs don't necessarily need to be in the same class. In fact, I think it's best if you throw in any drug that applies as you come across it. This serves a few purposes. First, and most importantly, it forces you to connect the dots. We learn things in a modular format in pharmacy school.

It's tempting to "learn and dump" the information and to not realize how connected and similar medicine can be. Having a list of drugs grouped together by side effect forces you to make some of those connections (and it allows you to be mindful of synergistic drug-drug interactions). Secondly, every time you add something to one of your side effect lists, you'll naturally review the other drugs already on the list. This repetition is crucial and will help strengthen your drug info foundation.

Useful Memorization Tricks

One of my favorite "study hacks" is to memorize the exceptions to a rule. An example I like to use here is the renal dosing of

antibiotics

. There are only a small handful of commonly used antibiotics that don't require a renal adjustment. The "rule" here then, is to monitor kidney function for every antibiotic. Then, you can make a list of exceptions to the rule. It's much easier to memorize these few outliers than it is to try to remember the massive list every antibiotic that requires a renal adjustment. There are many examples of drugs that are exceptions to the rule that you can use when you're studying. For example

• Abacavir is the only NRTI that does not require a renal adjustment
• Ethambutol is the only drug in the RIPE regimen for tuberculosis that does not cause liver damage
• Captopril is the only ACE inhibitor dosed 3 times daily (and is the only one used in hypertensive urgencies)

You can create many such exception lists to aid you in your studying.

With those core tips out of the way, there are a couple of other memorization tricks you can explore if you're interested. I'm not even sure if I realized I was using these tricks at the time, but 2 tricks that worked for me in pharmacy school were making personal associations with drugs and placing post-it notes all over my apartment.

I later found out that there are some legit cognitive principles behind both of these (the Baker-baker paradox for making associations, and the Method of loci for my post-it notes). To give you an idea of how powerful these can be, I still remember the brand name for rifapentine (Priftin), that it is dosed weekly for latent TB infection, and that it's generally avoided for active TB, all because it was on a yellow post-it note on my refrigerator door. I have not encountered (or even thought about) rifapentine since the infectious disease test I took in a therapeutics module 5 years ago.

These studying techniques are useful for many things besides side effects. I hope they will be as useful to you as they have been to me.

References

1. Guengerich, F. Peter. Mechanisms of Drug Toxicity and Relevance to Pharmaceutical Development. Drug Metab. Pharmacokinet. 2011; 26(1): 3-14. Accessed from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707670/