#453: Four Things to Fear About NSAIDs

On mobile? Listen here or straight from your favorite podcast player.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in both prescription and over-the-counter (OTC) forms. In this lesson, you’ll learn how NSAIDs work, what conditions they are used to treat and four big risks that come with these popular medications.

What are NSAIDs and how do they work?

The class of drugs known as NSAIDs work similarly to reduce inflammation, fever, and pain by inhibiting cyclooxygenase (COX) enzymes which decreases prostaglandin synthesis.

There are two types of COX enzymes – COX-1 and COX-2. Note that prostaglandins associated with COX-1 enzymes play a key role in protecting the gastric epithelium and maintaining both kidney function and platelet aggregation. This will come into play later when we discuss the biggest risks when taking NSAIDs. Most drugs in this class are nonselective and inhibit both COX-1 and COX-2. However, there are a few NSAIDs (and only one in the U.S.) that are selective for COX-2, which means they have different side effects than those that also inhibit COX-1.

Common examples of NSAIDs

There are quite a few medications within this drug class and that’s because there are several subtypes of NSAIDs based on their chemical structure and COX selectivity. Some of the most common you will see include: 

• Aspirin – Commonly used to treat fever, pain, and to reduce risk for cardiovascular events and stroke. You will even see aspirin used in patients with acute ischemic stroke and myocardial infarction. 
• Indomethacin – One very specialized use of indomethacin is as a tocolytic to stop preterm labor. It is also used to treat patent ductus arteriosus in preterm infants.
• Ibuprofen and naproxen – These are very common medications used to treat pain.
• Meloxicam – This is a prescription-only NSAID used to treat the symptoms of arthritis.
• Ketorolac – This is another prescription-only NSAID used to treat moderate to severe acute pain and is commonly used in the postoperative period.
• Diclofenac – Available in both oral and topical formulations, diclofenac is used primarily to treat inflammatory conditions such as arthritis. 
• Celecoxib – As a selective COX-2 inhibitor, celecoxib is commonly used in the treatment of arthritis and is safer to use in patients with a history of GI bleeding. Celecoxib is currently the only COX-2 inhibitor available in the U.S. 

The “quadruple threat” of NSAIDs

Even though NSAIDs are very commonly used, it’s important to not underestimate the potential and significant risks. Use of NSAIDs can cause gastrointestinal, renal, cardiovascular and hematologic complications.

GI risks – Because most NSAIDs inhibit COX-1, they reduce the prostaglandins that protect the stomach lining. This makes patients more vulnerable to developing peptic ulcers and GI bleeds. This explains why a patient with a history of peptic ulcers  or GI bleeding would likely be prescribed celecoxib (a selective COX-2 inhibitor) instead of a medication like ibuprofen or meloxicam. Note that the bleeding from peptic ulcers can be significant, and even lead to death. To learn more about GI bleeds, check out this article here.

Renal risks – Since prostaglandins also play an important role in kidney function, NSAIDs should be avoided in those with renal insufficiency and used with caution in those taking a diuretic. Consequences of renal damage associated with NSAIDs include hypertension, fluid imbalance, electrolyte imbalance, acute renal failure and nephrotic syndrome.

Cardiovascular risk – Excluding aspirin (which can be cardioprotective), NSAIDs can increase the risk of hypertension, myocardial infarction, atrial fibrillation and even thrombotic events such as stroke or DVT. 

Hematologic risk – Due to their antiplatelet activity, NSAIDs are also associated with higher risk for bleeding. This is most pronounced in those with a history of gastric ulcers and patients with existing coagulopathy (such as hemophilia or thrombocytopenia), but can also come into play postoperatively or in cases of trauma. Postoperatively, you will often see ketorolac used, but only for a short period of time (typically less than 5 days).

Strategies for safer NSAID use

Some tips for utilizing NSAIDs more safely include:

• Using the lowest effective dose for the shortest duration.
• Advocate for concurrent PPI prescription to help protect the gastric mucosa – in fact there is a combination medication, Vimovo, that includes naproxen and esomeprazole for this very reason!
• Consider alternatives such as acetaminophen, topical NSAIDs and non-pharmacologic pain interventions.

Want more pharmacology topics? Check out Fast Pharmacology, an audio-based program (with printable study guides) where I teach pharm concepts in five minutes or less!

_____________________________________

The information, including but not limited to, audio, video, text, and graphics contained on this website are for educational purposes only. No content on this website is intended to guide nursing practice and does not supersede any individual healthcare provider’s scope of practice or any nursing school curriculum. Additionally, no content on this website is intended to be a substitute for professional medical advice, diagnosis or treatment.

References:

Alfaro, R. A., & Davis, D. D. (2025). Diclofenac. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK557879/

Amin, S. B., Handley, C., & Carter-Pokras, O. (2007). Indomethacin Use for the Management of Patent Ductus Arteriosus in Preterms: A Web-Based Survey of Practice Attitudes Among Neonatal Fellowship Program Directors in the United States. Pediatric Cardiology, 28(3), 193–200. https://doi.org/10.1007/s00246-006-0093-1

Arif, H., & Aggarwal, S. (2025). Salicylic Acid (Aspirin). In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK519032/

Di, J., Xi, Y., Qi, L., Zhao, Y., Guo, Z., Yang, N., & Xiang, C. (2025). Beyond pain relief: the thrombosis threat of celecoxib. Therapeutic Advances in Drug Safety, 16, 20420986251347354. https://doi.org/10.1177/20420986251347354

Drugs.com. (2023, August). Vimovo: Uses, Dosage & Side Effects. Drugs.Com. https://www.drugs.com/vimovo.html

Ghlichloo, I., & Gerriets, V. (2025). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK547742/

Mahmoodi, A. N., Patel, P., & Kim, P. Y. (2025). Ketorolac. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK545172/

Mayer, C., & Apodaca-Ramos, I. (2023). Tocolysis. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK562212/

Mayo Clinic. (2025a). Celecoxib (oral route) – Side effects & dosage. Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/celecoxib-oral-route/description/drg-20068925

Mayo Clinic. (2025b). Diclofenac (oral route) – Side effects & dosage. Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/diclofenac-oral-route/description/drg-20069748

Mayo Clinic. (2025c). Indomethacin (oral route) – Side effects & dosage. Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/indomethacin-oral-route/description/drg-20069700

Mayo Clinic. (2025d). Meloxicam (oral route) – Side effects & dosage. Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/meloxicam-oral-route/description/drg-20066928

Saad, J., & Mathew, D. (2025). Nonsteroidal Anti-Inflammatory Drugs Toxicity. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK526006/

Last Updated on January 6, 2026 by Maureen Osuna, MSN, RN