FA Musculoskeletal, Skin, and Connective Tissue Flashcards
MSK, skin, connective tissue chapter pharm from USMLE Step 1 First Aid 2014.
Aspirin Mechanism
Irreversibly inhibits COX-1 and COX-2 by covalent acetylation, which ↓ production of TXA2 and prostaglandins
Aspirin Use
Low dose (<300mg/day): ↓ platelet aggregation Intermediate dose: (300-2400mg/day): antipyretic and analgesic High dose (2400-4000mg/day): anti-inflammatory
Aspirin Toxicity
Gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial nephritis, upper GI bleeding. Risk of Reye syndrome in children with viral infection. Stimulates respiratory centers, causing hyperventilation and respiratory alkalosis.
NSAIDs
Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac
NSAID Mechanism
Reversibly inhibit COX-1 and COX-2, blocking PG synthesis.
NSAID Use
Antipyretic, analgesic, anti-inflammatory. Indomethacin used to close PDA.
NSAID Toxicity
Interstitial nephritis, gastric ulcer (PGs protect gastric mucosa), renal ischemia (PGs vasodilate afferent arteriole).
COX-2 inhibitor
celecoxib
COX-2 inhibitor (celecoxib) Mechanism
Reversibly inhibit COX isoform 2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain. Spares COX-1, which helps maintain gastric mucosa (should not have corrosive effects of other NSAIDs). Spares platelet function (TXA2 production is COX-1 dependent).
COX-2 inhibitor (celecoxib) Use
Rheumatoid arthritis, osteoarthritis; patients with gastritis or ulcers.
COX-2 inhibitor (celecoxib) Toxicity
↑ risk of thrombosis. Sulfa allergy.
Acetaminophen Mechanism
Reversibly inhibits COX, mostly in CNS. Inactivated peripherally.
Acetaminophen Use
Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in children with viral infection.
Acetaminophen Toxicity
Overdose produces hepatic necrosis; metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote – regenerates glutathione.
Chronic gout drugs
Allopurinol, febuxostat, probenecid