Pharmacology C8

MOA: Irreversibly blocks COX-1/COX-2 --> drops prostaglandins & TXA_2.

Toxicities: GI bleed, salicylism (tinnitus/hyperventilation), metabolic acidosis in overdose.

High-Yield: Low dose (<300 mg): antiplatelet for platelet lifetime. Avoid in kids (Reye syndrome) and peptic ulcers. High dose (>4 g): zero-order kinetics.

MOA: Selective COX-2 inhibitor; preserves COX-1.

Toxicities: High MI/thrombosis risk, fluid retention/edema, and acute renal failure.

High-Yield: Same efficacy as traditional NSAIDs but with reduced GI toxicity. Does not affect plateletsleeding time. Strictly avoid if history of MI exists.

MOA: Inhibits CNS prostaglandin synthesis; weak peripheral COX effect.

Toxicities: Fatal hepatotoxicity (10 - 15gdose) and renal necrosis; risk increases with alcohol.

High-Yield: No anti-inflammatory/antiplatelet effect. Choice for kids with viral infections (prevents Reye). NAPQI metabolite depletes glutathione; treat with N-acetylcysteine.

MOA: Nonselective COX inhibitors (acetic acids). Indomethacin decreases granulocyte movement into inflamed areas.

Toxicities: severe GI toxicity and hematologic reactions. Sulindac side effects are identical but less severe.

High-Yield: Highly potent; preferred for acute gout attacks

MOA: Nonselective COX inhibitor with potent analgesic properties.

Toxicities: High risk of fatal peptic ulcers, GI bleeding/perforation, and renal damage.

High-Yield: Only parenteral NSAID; restricted to short-term (< 5 days) moderate-to-severe postoperative pain management. Avoid in chronic inflammation.

MOA: Prostaglandin PGE_1 analog.

Toxicities: GI cramping and diarrhea.

High-Yield: Co-prescribed with NSAIDs to prevent gastric/duodenal ulcers. Decreases acid/pepsin secretion and boosts mucosal barriers.

MOA: Binds tubulin --> blocks microtubule assembly (mitotic poison). Disrupts granulocyte mobility, stopping migration and crystal phagocytosis.

Toxicities: Acute: severe GI toxicity. Chronic: myopathy, neutropenia, aplastic anemia, alopecia. Contraindicated in pregnancy.

High-Yield: Used at low doses for prophylaxis of recurrent gout attacks.

MOA: Xanthine oxidase inhibitors; block hypoxanthine -->xanthine --> uric acid to drop production.

Toxicities: Rashes/hypersensitivity; can precipitate acute gout attacks at initiation (needs prophylaxis).

High-Yield: 1st-line for chronic gout. Allopurinol converts to oxypurinol (irreversible suicide inhibitor); preferred in renal insufficiency or stone history. Febuxostat is a newer, more effective nonpurine inhibitor.

MOA: Uricosuric agents; block renal tubular reabsorption of uric acid to accelerate excretion and lower plasma levels.

Toxicities: High risk of uric acid stone formation in the urinary tract.

High-Yield: 1st-line choice only for chronic gout with reduced urinary excretion of uric acid. Avoid aspirin because it slows renal uric acid secretion and blocks these effects.

MOA: Recombinant urate oxidase (uricase) that converts uric acid to allantoin.

Toxicities: Infusion reactions, anaphylaxis.

High-Yield: Given via IV infusion for aggressive chronic gout. Allantoin is 5 to 10 times more soluble than uric acid, preventing crystal deposition and facilitating renal excretion

MOA: Non-biologic, cytotoxic DMARD. Reduces the number of immune cells available to sustain the inflammatory cascade.

Toxicities: Bone marrow suppression, mucosal ulcerations, hepatic fibrosis, and severe teratogenicity.

High-Yield Info: Considered a first-line, foundational non-biologic DMARD for Rheumatoid Arthritis. Because of its cytotoxic profile, it is also widely used in cancer treatments.

MOA: Biologic DMARDs acting as TNF-a antagonists.

Toxicities: Serious infection risk (e.g., latent TB reactivation) and injection site reactions.

High-Yield: Etanercept is a recombinant protein blocking TNF signaling. Given parenterally as second-line therapy for severe RA when non-biologic DMARDs/NSAIDs fail to halt progressive joint destruction.