NSAIDs-not-so-safe

Note:  This is the second in a series of blogs that will be written by Erik Borgnes of Team Epic USA.  Stay tuned for more very insightful and informative content.  I am thrilled to have Erik sharing his wisdom with us in 2015

OTC Analgesics and Athletes

Over the counter medication (OTC) isn’t candy. How’s that for an opener? In other words, it’s unwise to pop them in your mouth like Tic-Tacs at the earliest signs of muscle soreness or at the expectation of soreness or fatigue in an upcoming sporting event – something which happens all too frequently because after all, they’re over the counter medications and likely harmless, right? Wrong.

About a year ago, when I was going through my usual stacks of cases in the radiology department, I was viewing images of a 17 yr old high school runner who had collapsed about 15 minutes into her 5k race, then had persistent nausea and vomiting and had to be helped across the finish line. Initial thoughts in the Emergency Department was that this was cardiac related – maybe some anomaly with her heart structure or function that she was born with and which came to light at that time, but focus soon turned towards her kidneys due to a lab test that suggested her kidneys were only functioning at about 1/3 of what was normal. There was some skepticism about this lab result. Why was a young healthy runner suddenly in renal failure?   Shortly thereafter, I put on my cape and performed a renal ultrasound exam, and lo and behold, her kidneys both looked abnormally bright on the images – which supported the kidney failure idea. She was indeed in acute kidney failure, but from what? After further questioning the patient and her mother, I learned that she had popped two regular ibuprofen tablets the night before and two more in the morning shortly before her running race. Knowing that ibuprofen is a nonspecific selective inhibitor of cyclooxygenase . . . actually, I had to refresh myself on it’s mechanism of action and all that ‘stuff’… Long story short, here’s the gist of what happened: our bodies need to feed a continuous supply of blood to our brains, our hearts, and our kidneys because these are the most vital of the vital organs. Blood flow to other organs like our intestines, muscles, skin, can be turned up and down like the volume knob on a radio. When we exercise intensely, as did this high school girl, our bodies can choose to limit blood flow to organs that can do fine with lower volumes of blood flow like our intestines and muscles that aren’t in use. The thing with Ibuprofen, though, is that it blocks the signal that keeps the kidneys in that special category of vital organs. So, during the race, as she was pushing a large volume of blood to her running muscles, nonvital organs had their volume knobs turned down and the ibuprofen blocked the signal that said “keep the kidney arteries wide open” and that put her into a type of renal failure called acute tubular necrosis. Vital means vital. Sacrifice the carotid arteries and you stroke. Sacrifice the coronary arteries and you have a heart attack and / or an arrhythmia and promptly die. Sacrifice the renal arteries and you go into acute renal failure. Now, acute renal failure isn’t always catastrophic, and healthy people usually recover from it with a few days of hospitalization and fluids. Symptoms of acute renal failure are usually that of confusion, nausea, and vomiting and they aren’t short lived, meaning that the symptoms don’t just go away after a short rest and after a few swigs of sports drink as it takes some time for the renal arteries to first recover their blood flow and then to recover from the inflammation and swelling before they can begin functioning again. While it should be obvious that going into acute renal failure on land isn’t immediately life threatening, how about if you’re quite a distance from shore in a surfski? Good luck getting back to shore while you’re nauseous, vomiting, and dizzy.

Some people are probably genetically susceptible to acute renal failure from ibuprofen, but there are other acquired conditions that can render one susceptible as well and one might not know if and when they are susceptible or not. And, how would one know if they’re in the susceptible “pool” or not? I don’t think that you do until it happens one day and even then, chances aren’t great that you or your caregiver will connect the dots between ibuprofen use and your symptoms unless you have your labs checked.

Acetominophen is not an anti-inflammatory medication like the other two in this article – it’s more of an analgesic (pain reducer) and antipyretic (fever reducer). Of interest, though, is that it’s oftentimes thought of as a safer alternative to the others because it’s the “go to “ medication for infants and children, it doesn’t cause stomach ulcers, and it’s “the number one doctor recommended,” according to ads. However, one thing that sets it apart from the others is its toxicity.

What’s interesting – and scary – about acetominophen is how close the toxic dose is to the recommended dose. The maximum recommended daily dosage used to be 4000 mg per day but was updated in 2012 to a maximum of 3000 mg per day, which is about four servings of two 325 mg tablets. Now, say you’ve really got a bad headache or your workout was really hard and left you quite sore, or you figure you’re a big person and you have this feeling that the recommended daily dose is likely a bit conservative, and after all, it’s nonprescription, right? So, when the directions say take 2 tablets, you take 3 or 4… Then get this: In 2006, Watkins, et al. showed in healthy volunteers that you could induce liver injury (read: liver toxicity) by dosing acetominophen at 1000 mg every 6 hours. That’s 3 tablets every 6 hours compared to the maximum recommended dose of 2 tablets every 6 hours – to get liver damage. Continue that schedule for several days and you’re in trouble. Add a few of your favorite alcoholic beverages during those evenings, maybe one or more of a long list of medications or supplements that are also simultaneously processed by the liver, and you could find yourself in big trouble. Acetaminophen is far and away the leading cause of acute liver failure in the United States and accounts for nearly one-half of all cases. But, rest comfortably in knowing that death from acetominophen induced liver failure is only about 2%, and the need for liver transplant is about the same – 2%.   Acetominophen’s margin of safety can also be looked at this way: According to the FDA, in the USA between 2000 and 2009, the accidental substitution of children’s acetominophen for infant’s acetaminophen resulted in at least 20 infant deaths.

It’s difficult to find information on where the lower limits of acute aspirin toxicity reside, but Rick Kingston, PharmD, has course information online that suggests that chronic toxicity begins at about 100 mg / kg / day, so about twenty-four 325 mg tablets per day which is about six 325 mg tablets every 6 hours for a normal size adult. Six tablets of aspirin every four hours seems like a lot of pills to swallow and I think one would have to be a bit thick or wreckless to dose on that schedule for very long. Aspirin, however, still ranks at the top of poison fatalities in the U.S., but from what I read, that’s primarily a consequence of intentional ingestion / suicide, which probably means that the general public thinks that aspirin has a low margin of safety and can be deadly. So, oddly enough, marketing campaigns by acetominophen companies that tout it as being the one that “hospitals trust most” leads to aspirin overdoses and thus lives saved as these poor souls reach for aspirin and not acetominophen…

Way back when I was a college student and a bit short on wisdom, (not that I’ve completely recovered from doing knuckleheaded things…) I went on a road trip with three friends to Dallas, Texas to run a marathon. I had banged up my knee the day before we departed playing soccer, and I could hardly walk on it. But, like any level headed college student, I wasn’t going to let all my training go to waste and I figured that I could take refuge in an OTC medication that I picked up at the local drug store – extra-strength Exedrin – which is a combination of aspirin, acetaminophen, and caffeine. Extra strength because my knee was hurting “extra” badly. Again, long story short: several tablets during the drive there, again before our 2 a.m. turn-in, and again with our 5 a.m. breakfast, and with the lack of sleep keeping me confused and blurry-eyed as to how many pills I’d ingested…Needless to say, I tasted the toxic levels of caffeine via my salivary gland secretions at the 1 mile water stop, felt my heart beating out of my chest the whole race, and had an ‘out of body’ experience at mile 24 when I found myself unable to coordinate my legs with my desire to walk let alone run. All told, I had eaten 12 tablets in the previous 12 hours which amounts to a load of 780 mg caffeine, 3000 mg aspirin, and 3000 mg of acetaminophen. Alone, the dose of acetaminophen borders on being severely toxic in that short of time frame, and coupled with the aspirin and dehydration . . . I was lucky they didn’t take me away in an ambulance – though I’m still rather annoyed that I didn’t finish the race.

Other interesting tidbits: Muscle repair and hypertrophy may be negatively affected by NSAIDs (ibuprofen, acetominophen, aspirin) according to several, though not all, studies. In layman’s terms, it seems that the soreness from training and weight lifting is because of muscle inflammation and free radical generation and those chemicals signal the muscle to repair and adapt so as to get stronger. So, keep that in mind as something to avoid if you value training to get stronger and faster as opposed to training only for social reasons. You might also want to re-think your high antioxidant post-workout smoothie, too.

The take home message here is that even though NSAIDS, like those mentioned above, might be available without a prescription and widely used and have an acceptable safety profile, think twice before you reach for them before or after training or if taking them on a regular basis. As always, your mileage may vary compared with another’s, and if you must succumb to the pills, don’t be tempted into thinking that you can get away with upping the dosages, even by just a little bit, because you might find yourself in trouble sooner than you think.

Tagged with →