Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Related Agents

Generic and Brand Names

• Propionic Acids
• fenoprofen (Nalfon)
• flurbiprofen (Ansaid)
• ibuprofen (Motrin, Advil)
• ketoprofen (Orudis)
• naproxen (Naprosyn)
• oxaprozin (Daypro)
• Acetic Acids
• diclofenac (Voltaren, Cataflam)
• etodolac (Lodine)
• indomethacin (Indocin)
• ketorolac (Toradol)
• nabumetone (Relafen)
• sulindac (Clinoril)
• tolmetin (Tolectin)
• Fenamates
• meclofenamate
• mefenamic acid (Ponstel)
• Oxicam Derivatives
• meloxicam (Mobic)
• piroxicam (Feldene)

Disease Spotlight: Primary Dysmenorrhea

Primary dysmenorrhea is cramping pain in the lower abdomen just before or during menstruation, with no other disease such as endometriosis behind it. The etiology is not precisely understood, but most symptoms trace to the uterine prostaglandin PGF2a, which drives uterine contractions, ischemia, and sensitization of nerve endings. Prevalence runs as high as 90 percent and is common among younger women, and OTC NSAIDs relieve many cases.

Therapeutic Action

NSAIDs inhibit prostaglandin synthesis, which produces their anti-inflammatory, analgesic, and antipyretic effects. They block two enzymes, cyclooxygenase (COX) 1 and 2, which sit in all tissues and take part in blood clotting, the stomach lining, and sodium-water balance in the kidney. COX-1 turns arachidonic acid into prostaglandins as needed, while COX-2 activates at sites of trauma or injury when more prostaglandins are required, so NSAIDs block inflammation before all the signs and symptoms develop. Acetaminophen works differently: it acts directly on the thermoregulatory cells in the hypothalamus to cause sweating and vasodilation that release heat. The mechanism behind its analgesic effect has not been identified.

Indications

Use NSAIDs to relieve the signs and symptoms of rheumatoid arthritis and osteoarthritis, to relieve mild to moderate pain, to treat primary dysmenorrhea, and to reduce fever. Acetaminophen treats mild to moderate pain and fever in children and often replaces NSAIDs or salicylates. It appears in many combination products and can cause severe, fatal liver toxicity in high doses. It is also used for influenza, for prophylaxis in children receiving diphtheria-pertussis-tetanus (DPT) immunizations, and for the musculoskeletal pain of arthritis.

Pharmacokinetics

Here are the characteristic interactions of NSAIDs and the body in terms of absorption, distribution, metabolism, and excretion:

Contraindications and Cautions

Allergy to NSAIDs or salicylate; allergy to sulfonamides (contraindication with celecoxib); CV dysfunction or hypertension (prostaglandin effects vary); peptic ulcer or known GI bleeding (potential to worsen bleeding); pregnancy or lactation (risk to neonate or mother); renal or hepatic dysfunction (altered metabolism and excretion); and any other known allergies, which signal increased sensitivity.

Adverse Effects

CNS: headache, dizziness, somnolence, fatigue. CV: hypertension. GI: nausea, dyspepsia, GI pain, constipation, diarrhea, flatulence. Hematologic: bleeding, platelet inhibition, and bone marrow depression.

The two effects that carry an FDA boxed warning are the most important to teach and monitor. All prescription non-aspirin NSAIDs carry a strengthened warning that they raise the risk of serious cardiovascular thrombotic events, including heart attack and stroke, which can occur as early as the first weeks of use and rise with higher doses and longer use (FDA Drug Safety Communication, 2015). They also carry a boxed warning for serious gastrointestinal bleeding, ulceration, and perforation, which can occur without warning. The guidance is to use the lowest effective dose for the shortest time needed (FDA, NSAIDs patient and provider information).

Interactions

Loop diuretics lose diuretic effect, and beta-blockers lose antihypertensive effect. Ibuprofen can drive lithium toxicity. With acetaminophen specifically, oral anticoagulants increase bleeding and chronic ethanol ingestion raises the risk of toxicity.

Nursing Considerations

Nursing care for patients on NSAIDs is the same as for patients taking anti-inflammatory agents.

Frequently Asked Questions

How do NSAIDs actually work? They inhibit cyclooxygenase (COX-1 and COX-2), the enzymes that make prostaglandins. Blocking prostaglandin synthesis gives the anti-inflammatory, analgesic, and antipyretic effects, but it also explains the GI and kidney side effects, since those same prostaglandins protect the stomach lining and regulate renal blood flow.

What is the biggest safety concern with NSAIDs? Two FDA boxed warnings drive the monitoring: serious cardiovascular events (heart attack and stroke) that can start within the first weeks of use, and serious GI bleeding, ulceration, and perforation. Use the lowest effective dose for the shortest time, and screen for cardiac and GI history first (FDA Drug Safety Communication, 2015).

How is acetaminophen different from an NSAID? Acetaminophen relieves pain and fever but has no meaningful anti-inflammatory effect, and it does not carry the same CV and GI risk. Its defining danger is liver toxicity at high doses, especially with chronic alcohol use or accidental combination-product overlap.

Who should avoid NSAIDs? Patients with active peptic ulcer or GI bleeding, significant cardiovascular disease or uncontrolled hypertension, renal or hepatic dysfunction, NSAID or salicylate allergy, and those who are pregnant or lactating. A sulfonamide allergy specifically contraindicates celecoxib.

Why do NSAIDs interact with lithium and some blood pressure drugs? By cutting renal prostaglandins, NSAIDs reduce the effect of loop diuretics and the antihypertensive effect of beta-blockers, and they can drive lithium toxicity by reducing its clearance. Check the medication list before starting an NSAID.

Can NSAIDs help menstrual cramps? Yes. Primary dysmenorrhea is largely driven by the uterine prostaglandin PGF2a, so prostaglandin-blocking NSAIDs relieve many cases, which is why OTC options work well for cramping pain.