NSAIDs, or nonsteroidal anti-inflammatory drugs, are a class of medications that reduce pain, lower fever, and fight inflammation. They’re among the most widely used drugs in the world, available both over the counter and by prescription. If you’ve ever taken ibuprofen for a headache or naproxen for a sore knee, you’ve used an NSAID.
How NSAIDs Work in Your Body
Your body produces a group of chemicals called prostaglandins whenever tissue is damaged or irritated. These chemicals trigger inflammation, amplify pain signals, and raise your body temperature. NSAIDs work by blocking the enzymes (called COX-1 and COX-2) that your body needs to produce prostaglandins. By cutting off that production, NSAIDs reduce swelling, ease pain, and bring down fever.
The catch is that prostaglandins aren’t purely harmful. COX-1 enzymes also produce prostaglandins that protect the lining of your stomach and help your blood clot normally. COX-2 enzymes are more specifically involved in inflammation and pain. Most common NSAIDs block both enzymes, which is why they work well for pain but can also cause stomach problems. Some prescription NSAIDs are designed to target mainly COX-2, which offers a similar level of pain relief with a lower risk of stomach damage.
Common Over-the-Counter and Prescription NSAIDs
You can buy three NSAIDs without a prescription in the United States:
- Aspirin (Bayer, St. Joseph)
- Ibuprofen (Motrin, Advil)
- Naproxen sodium (Aleve)
Prescription NSAIDs are typically stronger or designed for specific conditions. Common ones include celecoxib (Celebrex), diclofenac (Voltaren), indomethacin, and ketorolac. Celecoxib is the most widely prescribed COX-2 selective NSAID, meaning it targets inflammation more precisely while being somewhat gentler on the stomach.
What NSAIDs Are Used For
NSAIDs treat a broad range of conditions. At lower doses, they primarily relieve pain and reduce fever from headaches, colds, flu, menstrual cramps, and minor injuries. At higher doses, they also reduce the inflammation behind conditions like rheumatoid arthritis, osteoarthritis, gout, and tendinitis. For arthritis specifically, prescription-strength ibuprofen dosing can range from 1,200 mg up to 3,200 mg per day, split across several doses. That’s significantly more than the over-the-counter amount, and it’s enough to suppress the chronic inflammation driving joint damage.
NSAIDs are also commonly used after surgeries, dental procedures, and sports injuries to manage short-term pain without resorting to opioid painkillers.
How Aspirin Differs From Other NSAIDs
Aspirin is technically an NSAID, but it behaves differently in one important way. It permanently disables the COX-1 enzyme in platelets, the blood cells responsible for clotting. Other NSAIDs only block the enzyme temporarily. This permanent effect is why low-dose aspirin (81 mg) is sometimes used to prevent heart attacks and strokes in people at high cardiovascular risk. It keeps blood from clotting too easily.
This distinction matters if you’re taking both aspirin and another NSAID. Ibuprofen, for example, can interfere with aspirin’s ability to bind to platelets if the two are taken at the same time, potentially reducing aspirin’s heart-protective benefit.
Stomach and Digestive Risks
The most common side effect of NSAIDs is damage to the stomach and upper digestive tract. Because these drugs block COX-1, they reduce the protective mucus lining of the stomach, leaving it vulnerable to acid. Minor symptoms like heartburn and nausea are common. More seriously, 15% to 30% of people who take NSAIDs long-term develop ulcers visible on endoscopy. Of those ulcers, 2% to 4% lead to complications like bleeding or perforation.
These aren’t trivial numbers. In one clinical trial studying naproxen, nearly 28% of patients developed an ulcer during the study period. The risk goes up if you’re over 65, if you drink alcohol regularly, if you take blood thinners, or if you’ve had stomach ulcers before. COX-2 selective NSAIDs like celecoxib carry a lower risk of stomach damage compared to non-selective NSAIDs, which is one reason doctors prescribe them for people who need long-term anti-inflammatory treatment.
Heart, Blood Pressure, and Kidney Risks
The FDA has strengthened its warnings about cardiovascular risks from non-aspirin NSAIDs. The risk of heart attack and stroke increases even with short-term use, and it can begin within the first few weeks of regular use. Higher doses taken for longer periods carry the greatest risk. People who already have heart disease face the highest danger, but even those without a history of heart problems are not immune.
NSAIDs can also raise blood pressure and, over time, contribute to heart failure. For the kidneys, these drugs reduce blood flow to the organs by suppressing prostaglandins that help regulate it. Occasional use in a healthy person is generally fine, but regular use can gradually impair kidney function, especially in people who already have reduced kidney capacity or who are dehydrated.
Who Should Avoid NSAIDs
Pregnant women should not take NSAIDs at 20 weeks of pregnancy or later. The FDA issued this recommendation because these drugs can reduce amniotic fluid levels, which can cause complications for the baby. After 30 weeks, the risk increases further because NSAIDs can cause premature closure of a blood vessel in the fetal heart. The one exception is low-dose aspirin (81 mg), which is sometimes prescribed during pregnancy for specific conditions like preeclampsia prevention.
People with a history of stomach ulcers or gastrointestinal bleeding should use NSAIDs with caution or avoid them. The same goes for people with significant kidney disease, uncontrolled high blood pressure, or heart failure. Some people with asthma experience worsened symptoms or even severe reactions when taking aspirin or other NSAIDs, a condition sometimes called aspirin-exacerbated respiratory disease. If you’ve ever had an asthma flare after taking ibuprofen or aspirin, other NSAIDs will likely trigger the same response.
Using NSAIDs Safely
For occasional use at over-the-counter doses, NSAIDs are effective and well tolerated by most people. The key is using the lowest effective dose for the shortest time needed. Taking them with food can help reduce stomach irritation, though it doesn’t eliminate the risk entirely.
If you find yourself reaching for ibuprofen or naproxen daily for more than a week or two, that’s worth a conversation with a healthcare provider. Long-term use shifts the risk profile considerably, and there may be better options depending on the underlying cause of your pain. For people who do need ongoing NSAID therapy, doctors sometimes add a stomach-protecting medication to reduce the chance of ulcers.