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Pharmacology — Mechanisms — USMLE Step 2 CK Notes
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Autonomic pharmacology is the backbone
- Know receptor → G-protein → second messenger for every autonomic receptor
- Alpha-1 (Gq, IP3/Ca), alpha-2 (Gi, ↓cAMP), beta-1/2 (Gs, ↑cAMP), M1/M3 (Gq), M2 (Gi)
Enzyme-cofactor and toxin pairings the exam loves
- ACE inhibitor → bradykinin accumulation → cough and angioedema; ARBs spare it
- Isoniazid → depletes vitamin B6 → neuropathy; give pyridoxine
- Cholera toxin activates Gs; pertussis toxin inactivates Gi — both raise cAMP
- Diphtheria and Pseudomonas exotoxin A both inactivate elongation factor 2
Pharmacokinetics essentials
- Loading dose = target concentration × volume of distribution; independent of clearance
- Maintenance dose depends on clearance
- Zero-order (constant amount): alcohol, phenytoin, aspirin at high dose
- First-order (constant fraction): most drugs
Classic drug-adverse-effect flags
- Anti-histone antibodies → drug-induced lupus (hydralazine, isoniazid, procainamide)
- Amiodarone → pulmonary fibrosis, thyroid dysfunction, corneal deposits
- Aminoglycosides → nephrotoxic and ototoxic
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