APAPAPAPAPAP

Gobbledygook? No, acetaminophen, also known by paracetamol or in this post, APAP. FYSA I do not have any affiliation with any name brands in this post. The ubiquitous Tylenol, with many other brand names is common on store and bathroom shelves and hospital MARs across the world. Back pain? Pop a few APAP. Tweak your shoulder? APAP. Fever and chills? Can you say APAP? The car driving slow in the left lane giving you a headache? Don’t throw the APAP at them just take it PO. 

For pain control, acetaminophen is widely used and considered a very safe medication by many healthcare and non healthcare people. The indications are pain and fever alone or combined with NSAIDs or opioids, and it can be give. PO, rectally, and IV with some studies on IM being conducted as well. As we learn that more PO medications may be as effective as IV versions, so PO APAP is actually more effective that IV. 

In a previous post I talked about some pain control methods and discussed the benefits of adding APAP to other pain control methods. Part of this is not understood but could be due to the different properties of each. For example, the different cyclooxygenase or COX pathways spot different prostaglandins which affect pain perception. While APAP is a pain reliever/antipyretic, opioids alter the perception of pain, and NSAIDs, like their name suggests, reduces inflammation with the pain relief aspect. There may also be synergistic effects as well. 

So what? As mentioned above, APAP is ubiquitous so it is likely that anyone working in healthcare will have to administer it or deal with its effects on patients. The first thing to discuss is how it is metabolized, which is via the liver. As such the most well known and possibly the most dangerous adverse effect is hepatic damage. Given that many people view APAP as not a medication but like a vitamin in their use, it is important to ask about so more meds that use the liver are not given, or the doses can be adjusted. The other potential issue is  it’s use in other common OTC and prescription preparations. For example, prescription opioids often have APAP in the same pill, cold and “flu” drugs are often cocktails of decongestants, antihistamines and APAP, and others like Excedrin combine APAP with ASA and caffeine  

Long term use, concomitant use of liver metabolized drugs, prior hepatic injury, and alcohol use are just a few conditions that place the user at higher risk for the above adverse effect. Is alcohol use ever a good thing when mixed with drugs? 

Chronic use can cause changes in electrolyte levels and alterations in blood counts; anemia, low sodium and calcium, hyperglycemia, and increase creatinine and liver function tests. These effects are relatively rare and keeping the daily dose below the 4g maximum recommended is the easiest way to reduce the risk. However with liver issues, this should be lower. 

Ok, so keep it under 4g and watch out for liver damage. What else? Keep in mind that unlike NSAIDs, APAP has no anti inflammatory properties. So maybe favor the former for sprains and all that. Another thing is that GI bleeding risks are lower with APAP than NSAIDs, though there still is a risk. 

What about over 4g? Can you overdose? APAP overdose causes a painful and protracted episode of acute liver failure, nausea, vomiting, pain, and possible acute kidney injury. While this may be from unintentional or intentional ingestion of APAP alone, many overdoses are caused by recreational opioid use since they are commonly combined with APAP. The treatment for this is supportive care and N-acetylcysteine, though liver transplant may be needed depending on the level of damage  

There are controversial aspects as well, looking at the impact of APAP on autism when used in pregnancy, CV adverse events, and kidney cancer. Those I will not argue cause I don’t know enough but maybe later. 

Ok  that’s my speal on the good ol acetaminophen. If you would be so kind to check out the podcast and share this or the podcast, I would be very grateful. Love y’all. 

References 

Acetaminophen from StatPearls at the NIH National Library of Medicine 

Image of the chemical structure of a acetaminophen from PubChem

Public awareness of acetaminophen and risks of drug induced liver injury: Results of a large outpatient clinic survey from PlosOne by Mitchell et al., 2020

The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews from the Medical Journal of Australia 2021 by Saheed et al.

Nonopioid pharmacological management of acute low back pain: A level I of evidence systematic review by Baronici et al. in the Journal of Orthopedic Research  from February 2023.

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