SPOILER ALERT! Medications have side effects
Posted on February 3, 2017 by Joe Jensen
A novel no one wants to read
We’ve all been there before: We visit the doctor, receive a prescription, and visit the pharmacy to fill the prescription. If the doctor is a good doctor and the pharmacist is a good pharmacist, we expect to learn a little about the medication, like how to take it and which side effects (if any) we should anticipate. Luckily for us, doctors and pharmacists don’t go over each and every side effect listed for the medication, since reading War and Peace usually takes less time. Why is that?
Risk vs benefit
First, it’s important to know that with any medication (or any medical procedure, but we’ll stick with medications here) there are benefits and there are risks. Unfortunately, there isn’t a perfect medication with all benefit and no risk--yes, even those two ibuprofen you took for your last headache pose a risk, albeit a small risk if taken in limited quantity. For medications, risk is more widely known as adverse effects or side effects. These can range from mild nausea to life threatening agranulocytosis (a dangerously low white blood cell count that interferes with your body’s ability to fight infections). Sometimes these side effects are both serious AND relatively common, in which case the Food and Drug Administration (FDA) issues their strongest “Black Box Warnings” that are clearly labeled on the medication. One of the main jobs of any physician is to determine whether the benefit of any medical intervention outweighs the risk. That’s not always an easy task as the risk can take many different forms.
The many faces of side effects:
- Too much of a good thing: Insulin is an injectable medication that diabetic patients use to lower their blood sugar to the normal range that our bodies. The benefits include lowering the risk of heart disease, kidney disease and even eye disease. However, too much insulin is NOT a good thing and the side effect of hypoglycemia (low blood sugar) can cause sweating, shakiness, dizziness and even seizures.
- Drug-drug interactions: This could be an entirely different topic altogether and can be especially difficult for doctors to manage when patients are on many medications. For instance, warfarin is a medication that thins the blood to prevent blood clots after strokes or specific types of heart disease. Too thin and there is a higher risk of bleeding. Not thin enough and clots can form or be thrown to the brain or the lungs. This medication is closely monitored with a routine lab test, but its levels can be impacted by other medications like antibiotics, supplements like St. John’s Wort, or even green leafy vegetables! All of these act on the same pathway in the body that processes warfarin making its side effects that much more difficult to manage.
- Alternative pathway: Benadryl is a medication commonly used for allergies, hives and rashes. While its principal effect takes place against a molecule called histamine (a class of medications commonly known as antihistamines), its side effects act against a separate pathway called the cholinergic pathway causing dry mouth and throat, increased heart rate, pupil dilation, urinary retention, constipation, and, at high doses, even hallucinations or delirium.
- Same pathway different effect: Albuterol is an inhaled medication used by people with lung diseases like asthma and COPD. This medication principally acts on what is called a Beta2 receptor (with some Beta1 activity) in the lungs causing the small airways to dilate allowing people to breathe easier. These same receptors are actually found in the heart as well, and if not all the medication is fully inhaled, systemic absorption can cause an increased heart rate, tremor, and anxiety.
- Dose-dependent toxicity: Many medications fall into this category, and that is why properly dosing and timing medications is extremely important. One example is something as benign as tylenol. Tylenol relieves minor aches, pains and even fever. However, when taken too frequently or at inappropriate doses it can cause liver damage that is sometimes severe enough to require a transplant.
- The great unknown: It may be hard to believe, but there remains a high degree of uncertainty in the field of medicine as the body still holds on to some of its mystery. Over 14 million Americans are currently taking some form of cholesterol lowering medication from a drug family called statins. For reasons unbeknownst to researchers, somewhere between 4-12% of people experience muscle pain while taking these medications and often stop the medication because of its side effect. There are theories as to why this happens, but no one knows for sure. This is like the dose-dependent toxicity category in that many medications fit here.
Before we can answer why those lists of medication side effects are SO long, we need to understand how new medications are created in the first place. These steps include:
- Discovery and development. This takes place in a research laboratory.
- Preclinical research. This drug testing takes place both in research laboratories and with animals.
- Clinical Research. This phase takes place with humans to determine first, if they are safe and then if they are effective.
- FDA review. FDA review teams thoroughly examine all of the submitted data related to the drug or device and make a decision to approve or not to approve it.
- Post-Market Safety Monitoring. The FDA monitors all drug and device safety once products are available for use by the public.
(See the FDA website for more details on the above steps.)
The birth of side effects
As you may have guessed, side effects are born at Step 3, but not in the way you may think. When completing clinical trials for safety and efficacy, pharmaceutical companies are required to track all “side effects” reported by patients participating in the trial. For example, let’s say you are participating in a drug trial for a new pill that hopes to restore vision to 20/20. While taking that pill you spend a day outside on your feet in 80 degree weather without drinking much water. When the day ends, you are likely to feel fatigued with a bit of a headache. Just like that, two side effects were born before your very eyes. Whether or not these were directly related to the drug itself is unimportant. What is important is the number of times side effects are reported. You can now begin to imagine why these lists of “side effects” get so long since at the end of that same 80 degree day your feet were swollen and you felt a bit dizzy too. Two more!
Further side effect monitoring takes place in Step 5 after the drug is deemed safe to use. The clinical research completed is inherently limited since not everyone that will use the drug can test it. In this way, the frequency of side effects can be over or under-reported based on the testing population. Along the same lines, the ultra-rare but very serious side effects can be missed altogether. One of the most notable post-market drug recalls in FDA history was the drug Thalidomide, which was used to prevent nausea in pregnant women but ended up causing terrible birth defects. Another example was Fen-Fen, a weight-loss drug from the 1990s that caused significant heart disease.
This show brought to you by the new wonder-drug!
So next time you’re sitting down watching TV when the 90 second commercial for the next wonder drug comes on with the last 30 seconds dedicated to the rapid-fire listing of the common and serious side effects, you’ll now know why those lists are assembled, what they mean, and how to best weigh the risks and benefits together with your doctor.