NSAIDs

Technically includes aspirin, but generally refers to aspirin substitutes.

Pharmacology: Anti-inflammatory (inhibition of prostaglandin synthesis); analgesic (variable); antipyretic (variable); antiplatelet (cyclooxygenase inhibition that is reversible); inhibition of prostaglandin synthesis (mostly COX-1, some COX-2 and/or lipoxygenase).

Pharmacokinetics: Protein-bound; hepatic metabolism; half-life 1-5 hrs (ibuprofen, indomethicin, flurbiprofen, ketoprofen); half-life >10 hrs (diflunisal, suldinac, naproxen, carprofen, piroxicam);

Adverse effects

• GI toxicity: Dyspepsia, bleeding, ulceration, perforation (misoprostol used to prevent ulceration; H2 antagonists also helpful).

• Fluid retention: Due to inhibition of PGE synthesis leading to decreased renal blood flow (aspirin, indomethicin, phenylbutazone).

• Nephrotoxicity

• Hypersensitivity: Contraindicated in patients with nasal polyps, angioedema, or bronchospastic response to aspirin.

• Blood dyscriasis: Agranulocytosis and aplastic anemia (phenylbutazone).

• CNS effects: Tinnitus, dizziness, anxiety, drowsiness, confusion.

• Hepatic toxicity

• Dermatological: Steven-Johnson syndrome.

Drug interactions: Reduced effects of antihypertensives and diuretics; increased lithium or methotrexate toxicity; potentiation of anticoagulants; displacement of protein-bound drugs; phenylbutazone mya inhibit or induce microsomal enzymes.

Ibuprofen – Inhibits COX-1/2 approximately equally. Elederly patients and patients with CAD are at risk for ibuprofen-associated renal impairment; may be used to reduce risk of Alzheimer’s disease.

Indomethacin – High incidence of dose-related toxic effects; inhibits COX-1>2; may reduce leukotriene synthesis; severe headache is a common side effect; used to treat several condition and to promote closure of patent ductus arteriosus; contraindicated in pregnancy; reserved for later use.

Ketoprofen – Inhibits both COX and lipoxygenase; used for OA and RA; does not alter warfarin or digoxin activity.

Ketorolac – IV; strong analgesic.

Naproxen – Long half-life; especially effective for termination and prevention of migraine.

Phenylbutazone – Oldest and most toxic NSAID.

Piroxicam – Longest half-life.

Sulindac – Prodrug that must be converted to sulfide in liver; long half-life (enterohepatic circulation).

Category: Pharmacology Notes