Musculoskeletal Pharmacology Flashcards
Acetaminophen
MOA: Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
Use: Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in children with viral infection.
Adverse Effects: Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic byproducts in liver.
Toxicity Tx: N-acetylcysteine
Aspirin
MOA: NSAID that irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation → ↓ synthesis of TXA2 and prostaglandins. ↑ bleeding time. No effect on PT, PTT. Effect lasts until new platelets produced.
Use: Low dose: ↓ platelet aggregation.
Intermediate dose: Antipyretic and analgesic.
High dose: Anti-inflammatory.
Adverse Effects: Gastric ulceration, salicyism (vertigo, tinnitus, hearing loss). Chronic use can lead to acute renal failure, interstitial nephritis, GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Causes respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis
Celecoxib
MOA: Reversibly inhibits specifically COX-2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain; spares COX-1, which helps maintain gastric mucosa. Spares platelet function as TXA2 production is dependent on COX-1.
Use: Rheumatoid arthritis, osteoarthritis.
Adverse Effects: ↑ risk of thrombosis. Sulfa allergy.
NSAIDs (ibuprofen, naproxen, indomethacin, ketorolac, diclofenac, meloxicam, piroxicam)
MOA: Reversibly inhibits COX-1 and COX-2. Block prostaglandin synthesis.
Use: Antiypretic, analgesic, anti-inflammatory. Indomethacin used to close PDA.
Adverse Effects: Interstitial nephritis, gastric ulcer, renal ischemia.
Leflunomide
MOA: Reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis. Suppresses T cell proliferation.
Use: Rheumatoid arthritis, psoriatic arthritis.
Adverse Effects: Diarrhea, hypertension, hepatotoxicity, teratogenicity.
Bisphosphonates (Alendronate, ibandronate, risedronate, zoledronate)
MOA: Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity.
Use: Osteoporosis, hypercalcemia, Paget disease of bone, metastatic bone disease, osteogenesis imperfecta.
Adverse Effects: Esophagitis, osteonecrosis of jaw, atypical stress fractures.
Teriparatide
MOA: Recombinant PTH analog given subcutaneously daily. ↑ osteoblastic activity.
Use: Osteoporosis. Causes ↑ bone growth compared to antiresorptive therapies.
Adverse Effects: Transient hypercalcemia
Allopurinol
MOA: Competitive inhibitor of xanthine oxidase. ↓ conversion of hypoxanthine and xanthine to urate. ↑ concentrations of azathioprine and 6-MP.
Use: Chronic gout. Also used in lymphoma and leukemia to prevent tumor-associated urate nephropathy.
Febuxostat
MOA: Inhibits xanthine oxidase.
Use: Chronic gout
Pegloticase
MOA: Recombinant uricase that catalyzes metabolism of uric acid to allantoin (a more water-soluble product).
Use: Chronic gout
Probenecid
MOA: Inhibits reabsorption of uric acid in PCT (also inhibit secretion of penicilin).
Use: Chronic gout
Adverse Effects: Can precipitate uric acid calculi
Colchicine
MOA: Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and degranulation.
Use: Acute and chronic gout.
Adverse Effects: GI side effects
Etanercept
MOA: TNF-α inhibitor. Fusion protein (receptor for TNF-α + IgG1 Fc), produced by recombinant DNA
Use: Rheumatoid arthritis, psoriasis, ankylosing spondylitis.
Adverse Effects: Predispose to infection, including reactivation of latent TB.
Infliximab, adalimumab
MOA: Anti-TNF-α monoclonal antibody.
Use: Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriasis.
Adverse Effects: Predispose to infection, including reactivation of latent TB.
Rasburicase
MOA: Recombinant uricase that catalyzes metabolims of uric acid to allantoin.
Use: Prevention and treatment of tumor lysis syndrome.
