NSAIDs — Nonsteroidal Anti-Inflammatory Drugs — are among the most widely used medications in the world. Available both over the counter and by prescription, they are used to relieve pain, reduce inflammation, and lower fever. Common NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve), aspirin, celecoxib (Celebrex), and diclofenac (Voltaren). Despite their widespread use, NSAIDs carry important risks that users should understand.

How NSAIDs Work

NSAIDs work by blocking enzymes called cyclooxygenase (COX-1 and COX-2). These enzymes produce prostaglandins — chemical messengers that promote inflammation, pain, and fever. By inhibiting COX enzymes, NSAIDs reduce the production of prostaglandins, thereby decreasing inflammation, pain, and fever. COX-2 selective NSAIDs (such as celecoxib) were developed to reduce gastrointestinal side effects by more specifically targeting the inflammatory enzyme while sparing the stomach-protective one.

Common Uses and Benefits

• Acute pain relief – headaches, dental pain, menstrual cramps, muscle aches, minor injuries
• Inflammatory conditions – rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout, and bursitis
• Post-surgical and post-procedural pain – often used as part of multimodal pain management
• Back and neck pain – effective for acute episodes, particularly when inflammation is involved
• Fever reduction – all NSAIDs are effective antipyretics
• Cardiovascular protection (aspirin only) – low-dose aspirin is used for prevention of heart attack and stroke in select high-risk patients

Types of NSAIDs

• Over-the-counter: ibuprofen (Advil, Motrin), naproxen sodium (Aleve), aspirin
• Prescription non-selective: diclofenac, indomethacin, meloxicam, ketorolac, piroxicam, nabumetone
• COX-2 selective (prescription): celecoxib (Celebrex) — designed to reduce GI risk while maintaining anti-inflammatory effect
• Topical NSAIDs: diclofenac gel (Voltaren) — applied directly to painful joints, offering localized relief with less systemic absorption

Potential Risks and Side Effects

While effective, NSAIDs carry a range of potential risks, particularly with long-term or high-dose use:

• Gastrointestinal effects – the most common concern; NSAIDs can irritate the stomach lining, leading to stomach upset, ulcers, and gastrointestinal bleeding. Taking NSAIDs with food, milk, or a proton pump inhibitor (PPI) can reduce this risk
• Cardiovascular risks – most NSAIDs (except aspirin) increase the risk of heart attack and stroke, particularly at higher doses and with longer use. This risk is elevated in people with pre-existing heart disease
• Kidney effects – NSAIDs reduce blood flow to the kidneys and can cause fluid retention, elevated blood pressure, and kidney damage, especially in older adults or those with pre-existing kidney disease
• Blood pressure – NSAIDs can raise blood pressure and reduce the effectiveness of antihypertensive medications
• Bleeding – NSAIDs inhibit platelet function, increasing bleeding risk. This is particularly relevant before surgery or in people taking blood thinners
• Liver effects – rare but possible with long-term use
• Allergic reactions – some individuals develop hives, asthma, or anaphylaxis in response to NSAIDs
• Pregnancy risks – NSAIDs are generally not recommended after 20 weeks of pregnancy due to risk of fetal kidney problems and premature closure of a fetal heart vessel

Who Should Use NSAIDs with Caution

NSAIDs may not be appropriate — or require close medical supervision — for people with:

• A history of stomach ulcers or GI bleeding
• Heart disease, heart failure, or history of heart attack or stroke
• Chronic kidney disease
• High blood pressure (hypertension)
• Liver disease
• Aspirin-exacerbated respiratory disease (AERD/aspirin-sensitive asthma)
• Pregnancy (especially second and third trimesters)
• Use of blood thinners such as warfarin or newer anticoagulants

Safe Use Guidelines

• Use the lowest effective dose for the shortest time needed
• Always take with food or milk to reduce stomach irritation
• Do not combine multiple NSAIDs
• Do not exceed the recommended daily dose on the label
• Talk to your doctor before using NSAIDs regularly if you have any chronic medical conditions
• Consider topical NSAIDs (diclofenac gel) for localized joint pain — they are as effective as oral NSAIDs for some conditions with far less systemic risk