Usmle Step 1 High Yield Pharmacology

Hepatic CYP2E1 oxidizes APAP → toxic NAPQI metabolite. Glutathione normally detoxifies; in overdose glutathione is depleted → centrilobular hepatic necrosis.

N-acetylcysteine — replenishes glutathione.

Irreversible COX-1 / COX-2 inhibitor → ↓ thromboxane A₂ in platelets (antithrombotic) + ↓ prostaglandins (analgesic, antipyretic, anti-inflammatory).

Mixed: respiratory alkalosis (early — direct medullary stimulation) + anion-gap metabolic acidosis (later — uncoupled oxidative phosphorylation).

Cough (↑ bradykinin), angioedema, hyperkalemia, creatinine bump, teratogenic.

Block AT1 receptor instead of ACE → no bradykinin increase → no cough, less angioedema. Same K+/Cr risks.

Severe bradycardia, AV block, decompensated heart failure, severe asthma (esp. non-selective).

β₁-selective: metoprolol, atenolol, esmolol, bisoprolol ('A through M = β1-selective except carvedilol/labetalol').

HMG-CoA reductase inhibitor → ↓ cholesterol synthesis. Side: myopathy/rhabdomyolysis (esp. + fibrate), hepatotoxicity.

Inhibits vitamin K epoxide reductase → ↓ active vitamin K → ↓ synthesis of factors II, VII, IX, X (1972) and proteins C, S.

Vitamin K (slow, hours-days); fresh frozen plasma or 4-factor PCC for urgent reversal.

Activates antithrombin III → inactivates thrombin (IIa) and factor Xa. Monitor with aPTT.