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 medications in the world, available both over the counter and by prescription. The most familiar examples are ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin.
How NSAIDs Work
Your body produces chemicals called prostaglandins at sites of injury or illness. Prostaglandins trigger inflammation, swelling, and pain, and they also raise your body temperature during a fever. NSAIDs block the enzyme responsible for making prostaglandins, called cyclooxygenase (COX).
There are two forms of this enzyme. COX-1 is always active and helps maintain the stomach lining, supports kidney function, and plays a role in blood clotting. COX-2 ramps up specifically during inflammation. Most NSAIDs block both forms to varying degrees. That’s why they’re effective at reducing pain and swelling but can also cause stomach and kidney side effects: they’re partially shutting down protective functions along with the inflammatory ones.
Aspirin is unique among NSAIDs because it permanently disables the COX enzyme in platelets (the blood cells involved in clotting), which is why low-dose aspirin is sometimes used to prevent heart attacks. Other NSAIDs only block the enzyme temporarily.
Common Over-the-Counter NSAIDs
Three NSAIDs are widely available without a prescription:
- Ibuprofen (Advil, Motrin): fast-acting, typically lasts 4 to 6 hours per dose
- Naproxen (Aleve): longer-lasting, with effects that can stretch 8 to 12 hours
- Aspirin (Bayer): the oldest NSAID, also used at low doses for cardiovascular protection
All three reduce pain, fever, and inflammation. The practical differences come down to how long they last and how they affect your stomach. Naproxen’s longer duration means fewer doses per day, which some people find more convenient for ongoing pain. Ibuprofen’s shorter duration gives you more control over timing.
Prescription NSAIDs
When over-the-counter options aren’t enough, doctors can prescribe stronger NSAIDs or specialized versions. Common prescription NSAIDs include celecoxib (Celebrex), diclofenac (Voltaren in prescription strength), indomethacin, fenoprofen, and ketorolac. Celecoxib is notable because it selectively targets COX-2, the inflammation-specific enzyme, while mostly leaving COX-1 alone. This selective approach generally causes fewer stomach problems, though it still carries cardiovascular risks.
What NSAIDs Are Used For
NSAIDs treat a broad range of conditions tied to pain and inflammation. For short-term use, they’re commonly taken for headaches, muscle strains, menstrual cramps, dental pain, and minor injuries. For chronic conditions, they’re a mainstay in managing osteoarthritis, rheumatoid arthritis, and other inflammatory joint diseases. Prescription doses for arthritis can range considerably higher than what you’d take for a headache.
They’re also used after surgeries and injuries to control both pain and swelling simultaneously, something that acetaminophen (Tylenol) cannot do on its own.
NSAIDs vs. Acetaminophen
Acetaminophen is often grouped with NSAIDs in the pain reliever aisle, but it works differently and isn’t an NSAID. While both appear to block prostaglandin production, acetaminophen only does so in the central nervous system. It can reduce pain and fever, but it does not reduce inflammation anywhere in the body. If you have a swollen joint, a sprained ankle, or arthritis flare, acetaminophen won’t address the swelling the way an NSAID will.
On the other hand, acetaminophen tends to cause fewer stomach problems. For people who can’t tolerate NSAIDs, it’s often the go-to alternative for basic pain relief.
Stomach and Digestive Risks
The most common side effects of NSAIDs involve the digestive system. Because these drugs reduce the prostaglandins that protect your stomach lining, they can cause irritation, heartburn, nausea, and in more serious cases, stomach ulcers. Endoscopic studies show that 20 to 30 percent of regular NSAID users develop ulcers, though up to 85 percent of those ulcers never progress to the point of causing noticeable symptoms.
The serious complications, including stomach bleeding, perforation, or obstruction, occur in roughly 2 to 4 percent of people who take NSAIDs continuously for a year. For people at higher risk (older adults, those with a history of ulcers, or people taking blood thinners), that rate can climb to 10 percent per year. Taking NSAIDs with food or using a stomach-protecting medication can help reduce this risk.
Heart and Blood Pressure Risks
NSAIDs can raise both systolic and diastolic blood pressure, and they increase the risk of heart attack and stroke. The FDA requires all prescription NSAID labels to carry a warning about this cardiovascular risk, noting that it can appear early in treatment and tends to increase with higher doses and longer use. People who already have heart disease or risk factors for it face a higher absolute risk.
The mechanism involves a shift in the balance between two prostaglandin-related chemicals. One promotes blood clotting and constricts blood vessels, while the other relaxes blood vessels and discourages clotting. NSAIDs, to varying degrees, tip that balance toward clotting and vessel constriction. This is also why NSAIDs are not to be used around the time of coronary artery bypass surgery.
Low-dose aspirin is the exception here. Because of the way it permanently blocks clotting in platelets, it’s actually used to protect against heart attacks in certain patients, the opposite effect of what other NSAIDs tend to cause.
Kidney Effects
Your kidneys rely on prostaglandins to regulate blood flow and manage salt and water balance. When NSAIDs suppress those prostaglandins, your kidneys can retain more fluid, which contributes to the blood pressure increases mentioned above. In people with already reduced kidney function, or in anyone who is dehydrated, NSAIDs can cause further impairment. Long-term, high-dose use poses the greatest risk to kidney health.
Aspirin and Children
While ibuprofen is commonly used for children’s fevers and pain, aspirin should not be given to children or teenagers. Aspirin use during viral illnesses in young people is linked to Reye’s syndrome, a rare but serious condition in which blood sugar drops, ammonia levels rise, the liver swells with fat buildup, and dangerous brain swelling can occur. Other NSAIDs like ibuprofen do not carry this specific risk.
How to Use NSAIDs Safely
For occasional use, like a few days for a headache or muscle strain, NSAIDs are generally well tolerated in healthy adults. The risks climb with dose and duration. A few practical guidelines help minimize problems:
- Use the lowest effective dose for the shortest time needed
- Take them with food to reduce stomach irritation
- Don’t stack NSAIDs, meaning don’t take ibuprofen and naproxen at the same time, as they work through the same pathway and the side effects multiply
- Stay hydrated, especially during exercise or hot weather, to protect kidney function
- Be cautious combining with blood thinners, as NSAIDs already affect clotting and can increase bleeding risk
If you need daily pain relief for weeks or longer, the risk profile changes significantly, and the choice of medication, dose, and protective strategies becomes more important.