Pharmacology accounts for roughly 15–20% of Step 1. Unlike pathophysiology, which requires deep mechanistic reasoning, pharmacology rewards systematic memorization — but only if you learn the right framework.
The Pharmacology Framework: What to Know for Every Drug
For every drug class, learn in this order: (1) Mechanism, (2) Clinical indication, (3) Key toxicities and side effects, (4) Contraindications, (5) Classic Step 1 question trigger. Do not learn all drugs at once — learn by system alongside your Pathoma review.
Cardiovascular Pharmacology
Antihypertensives — First-Line
| Drug class | Mechanism | Key toxicity | Contraindications |
|---|---|---|---|
| ACE inhibitors (-pril) | Block ACE → ↓ angiotensin II → vasodilation, ↓ aldosterone | Dry cough (bradykinin), angioedema, hyperkalemia, teratogenic | Pregnancy, bilateral renal artery stenosis |
| ARBs (-sartan) | Block AT1 receptor directly | Same as ACEi except NO cough; still angioedema risk | Pregnancy |
| Thiazide diuretics (HCTZ) | Block NaCl cotransporter in DCT | Hypokalemia, hyperuricemia, hyperglycemia, hypercalcemia, hyperlipidemia | Gout (relative) |
| Ca²⁺ channel blockers (dihydropyridines) | Block L-type calcium channels in vascular smooth muscle | Peripheral edema, reflex tachycardia | Heart failure (use with caution) |
| Beta-blockers (-olol) | Block β1 (heart): ↓HR, ↓contractility, ↓renin | Bradycardia, AV block, bronchoconstriction, masks hypoglycemia | Asthma, COPD (non-selective), decompensated HF (initially) |
Antiarrhythmics — Vaughan Williams Classes
| Class | Drug examples | Mechanism | Key toxicity |
|---|---|---|---|
| Ia | Quinidine, procainamide, disopyramide | Na+ channel block (moderate); prolongs QT | Quinidine: cinchonism, torsades; procainamide: drug-induced lupus |
| Ib | Lidocaine, mexiletine | Na+ channel block (fast on/off); post-MI arrhythmia | CNS toxicity (lidocaine): seizures, tremor |
| Ic | Flecainide, propafenone | Na+ channel block (slow off); no structural heart disease | Proarrhythmic in structural heart disease |
| II | Beta-blockers (metoprolol, esmolol) | Decrease SA/AV node conduction | Bradycardia, hypotension |
| III | Amiodarone, sotalol, ibutilide | K+ channel block; prolongs AP duration + QT | Amiodarone: pulmonary fibrosis, hepatotoxicity, thyroid dysfunction, corneal deposits, photosensitivity, blue-gray skin |
| IV | Verapamil, diltiazem | Block L-type Ca²⁺ channels in SA/AV node | Bradycardia, constipation, AV block; contraindicated in WPW |
Antibiotics: The High-Yield Mechanisms and Toxicities
| Drug class | Mechanism | Classic toxicity | Notes |
|---|---|---|---|
| Beta-lactams (penicillins, cephalosporins, carbapenems) | Inhibit transpeptidase (PBP) → block cell wall synthesis | Hypersensitivity (anaphylaxis); cross-reactivity ~1–2% | Clavulanic acid inhibits beta-lactamase |
| Vancomycin | Binds D-Ala-D-Ala → inhibits cell wall synthesis | Red man syndrome (histamine release, infuse slowly), nephrotoxicity, ototoxicity | For MRSA, C. diff (PO) |
| Aminoglycosides (gentamicin, tobramycin) | Bind 30S ribosome; irreversible inhibition | Nephrotoxicity, ototoxicity (vestibular then cochlear), teratogenic | Synergy with beta-lactams for enterococcal endocarditis |
| Tetracyclines (doxycycline) | Bind 30S; inhibit aminoacyl-tRNA binding | Photosensitivity, GI upset, chelation (no dairy/antacids), teratogenic (teeth/bones) | Atypicals, Rickettsia, Lyme, acne |
| Macrolides (azithromycin) | Bind 23S rRNA of 50S; block translocation | GI motility (motilin agonist), prolonged QT, drug interactions (CYP3A4) | Atypicals, community-acquired pneumonia, H. pylori (clarithromycin) |
| Fluoroquinolones (-floxacin) | Inhibit DNA gyrase (topoisomerase II) and IV | Tendon rupture (especially Achilles), QT prolongation, cartilage damage (children), CNS effects | Gram-negative coverage; UTI, respiratory |
| Metronidazole | Forms free radicals that damage DNA | Disulfiram-like reaction with alcohol, metallic taste, peripheral neuropathy | Anaerobes, H. pylori, C. diff (PO), Giardia, Trichomonas |
Psychiatric Pharmacology
Antidepressants
SSRIs — first-line for depression, anxiety, OCD, PTSD, panic disorder. Side effects: sexual dysfunction, GI upset, serotonin syndrome (with MAOIs/triptans), SIADH, increase in suicidality in adolescents (first 2 weeks).
TCAs (amitriptyline, nortriptyline) — block NE + serotonin reuptake + muscarinic, H1, alpha-1 receptors. Toxic dose: sodium channel blockade → wide QRS, arrhythmias, seizures. Treat overdose with sodium bicarbonate. Also good for neuropathic pain, bedwetting.
MAOIs (phenelzine) — last-line; hypertensive crisis with tyramine (aged cheese, wine), serotonin syndrome with SSRIs or meperidine. 2-week washout required.
Bupropion — blocks NE + dopamine reuptake. Lowers seizure threshold. No sexual side effects. Used for smoking cessation and depression (not for bulimia — seizure risk).
Pharmacokinetics Essentials
Zero-order kinetics: Rate of elimination is constant regardless of concentration. PEAZ — Phenytoin, Ethanol, Aspirin (high dose), Zero-order = PEAZ. Drug accumulates rapidly when concentration is high.
First-order kinetics: Rate proportional to concentration. Most drugs. Constant half-life. After 4–5 half-lives: 94–97% of drug eliminated; same time to reach steady state.
Volume of distribution (Vd): Low Vd = stays in plasma (large, charged, protein-bound). High Vd = distributes to tissues (lipophilic, small). High Vd drugs are not removed by dialysis.
Clearance: CL = Vd × ke. Renal clearance reduced in elderly → dose adjustments required for renally cleared drugs.
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