NSAIDs, or nonsteroidal anti-inflammatory drugs, are a class of medications that reduce pain, lower fevers, and fight inflammation. They’re among the most widely used drugs in the world, available both over the counter and by prescription. Common examples include ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin (Bayer). While they’re effective and generally safe for short-term use, NSAIDs carry real risks that are worth understanding before you reach for them regularly.
How NSAIDs Work in Your Body
Your body produces compounds called prostaglandins at sites of injury or illness. Prostaglandins trigger inflammation, amplify pain signals, and raise your body temperature. NSAIDs block the enzyme responsible for making these compounds, called cyclooxygenase (COX). With less prostaglandin production, you get less swelling, less pain, and lower fever.
There are two forms of the COX enzyme. COX-1 is active all the time and handles housekeeping tasks: protecting the stomach lining, supporting kidney blood flow, and helping blood platelets clump together for clotting. COX-2 ramps up mainly in response to tissue damage and drives the inflammatory response. Most traditional NSAIDs block both forms, which is why they relieve inflammation but also cause side effects in the stomach and kidneys.
Common Types of NSAIDs
Three NSAIDs are available without a prescription in the United States:
- Ibuprofen (Advil, Motrin)
- Naproxen sodium (Aleve)
- Aspirin (Bayer, St. Joseph)
Prescription-strength options include celecoxib (Celebrex), diclofenac (Voltaren), indomethacin (Indocin), and ketorolac (Toradol), among more than 20 available NSAIDs. The main practical differences between them are how long they last in your system, how potent they are, and which COX enzyme they target.
Selective vs. Traditional NSAIDs
Celecoxib is the best-known “selective” NSAID. It preferentially blocks COX-2, the enzyme tied to inflammation, while largely leaving COX-1 alone. The intended benefit is fewer stomach problems, since COX-1 is the enzyme that helps protect the stomach lining and supports normal platelet function. Traditional NSAIDs like ibuprofen and naproxen block both enzymes without much distinction.
Selective COX-2 inhibitors do cause fewer ulcers than traditional NSAIDs, but they carry the same kidney risks and similar cardiovascular concerns. For people at high risk of stomach bleeding, a COX-2 inhibitor combined with a stomach-protecting medication offers the greatest gastrointestinal safety.
Aspirin Is Different
Aspirin stands apart from other NSAIDs in one important way: it permanently disables the COX enzyme rather than blocking it temporarily. Other NSAIDs bind to COX reversibly, so their effects wear off as the drug leaves your system. Aspirin’s irreversible action is why low-dose aspirin (81 mg) is used to prevent blood clots in people at risk for heart attack or stroke. Platelets can’t make new COX enzymes, so a single dose of aspirin affects clotting for the entire lifespan of those platelets, roughly 7 to 10 days.
One critical safety note: aspirin should not be given to children or teenagers, particularly during flu or chickenpox. It’s linked to Reye’s syndrome, a rare but serious condition that causes swelling in the liver and brain. The only exception is when a doctor specifically prescribes aspirin for a chronic condition like Kawasaki disease.
Stomach and Digestive Risks
The most common side effect of NSAIDs is damage to the digestive tract. Prostaglandins produced by COX-1 play a protective role in the stomach: they maintain blood flow to the stomach lining, stimulate mucus production, promote bicarbonate secretion that neutralizes acid, and reduce acid output. When NSAIDs suppress these prostaglandins, the stomach becomes more vulnerable to its own acid.
This can range from mild heartburn to serious ulcers and life-threatening bleeding. The risk increases with higher doses, longer use, older age, and a history of stomach problems. If you need to take an NSAID regularly, a proton pump inhibitor (a common type of acid-reducing medication) can significantly lower the chance of developing ulcers.
Heart Attack and Stroke Risk
All non-aspirin NSAIDs carry a boxed warning from the FDA about increased risk of heart attack and stroke. This risk applies even to people without prior heart disease, though those with existing cardiovascular problems or risk factors face greater danger. The risk increases with longer use and higher doses, which is why the FDA recommends using the lowest effective dose for the shortest time possible. Taking aspirin alongside another NSAID does not reduce this cardiovascular risk, and it actually increases the chance of stomach bleeding.
How NSAIDs Affect Your Kidneys
Your kidneys rely on prostaglandins to maintain adequate blood flow, especially when your body is under stress from dehydration, heart failure, or blood pressure changes. NSAIDs block those prostaglandins, which can reduce blood flow to the kidneys and impair their filtering ability. For most healthy, well-hydrated people taking occasional doses, this isn’t a problem. The risk becomes significant in specific situations.
People most vulnerable to NSAID-related kidney injury include older adults, anyone with existing kidney disease or heart failure, and people with high blood pressure. The combination of an NSAID with a diuretic (water pill) and a blood pressure medication that acts on the renin-angiotensin system is particularly risky. A follow-up study of nearly 80,000 patients found a strong association between this triple combination and kidney damage. Selective COX-2 inhibitors like celecoxib carry the same kidney risks as traditional NSAIDs.
Drug Interactions to Know About
NSAIDs interact with several commonly prescribed medications. If you take lithium for a mood disorder, NSAIDs can raise lithium levels in your blood by reducing how quickly your kidneys clear it. Ibuprofen and naproxen both cause this effect, though the degree varies widely from person to person. Indomethacin appears to have the strongest effect on lithium levels. Aspirin, interestingly, does not seem to raise lithium levels in a clinically meaningful way.
NSAIDs can also reduce the effectiveness of blood pressure medications and diuretics, and they increase bleeding risk when combined with blood thinners.
NSAIDs During Pregnancy
The FDA warns against using NSAIDs from 20 weeks of pregnancy onward. At that stage, the baby’s kidneys are producing most of the amniotic fluid, and NSAIDs can impair fetal kidney function. This leads to dangerously low amniotic fluid levels, sometimes appearing as soon as 48 hours after starting the medication. Low-dose aspirin (81 mg) is an exception and is sometimes specifically recommended during pregnancy for conditions like preeclampsia prevention. All other NSAIDs should be avoided in the second half of pregnancy unless a doctor determines the benefit clearly outweighs the risk and monitors amniotic fluid levels closely.
Practical Guidelines for Safe Use
For short-term pain relief in otherwise healthy adults, over-the-counter NSAIDs are effective and reasonably safe when used as directed. Naproxen lasts longer than ibuprofen, so it requires fewer doses per day, which some people find more convenient. When choosing between the two, neither is clearly superior for pain relief; the best choice often comes down to how your body responds.
Taking NSAIDs with food can reduce stomach irritation, though it doesn’t eliminate the risk of ulcers with prolonged use. If you find yourself reaching for NSAIDs most days for more than a week or two, that’s a signal to explore other approaches rather than continuing to increase your exposure to these risks. The core principle from the FDA applies broadly: use the lowest dose that works, for the shortest time you need it.