Master Pharmacology
for USMLE Step 1

What the USMLE Step 1 Tests in Pharmacology

USMLE Step 1 Pharmacology tests the ability to select appropriate drug therapy based on mechanism of action, adverse effects, and clinical context. Candidates must demonstrate knowledge of first-line treatments for common conditions (e.g., hypertension, diabetes, asthma, infections), drug interactions, and contraindications. Questions often present a patient with specific comorbidities (e.g., renal impairment, pregnancy, heart failure) and require choosing the safest or most effective agent. You must also interpret dose adjustments, recognise toxicities (e.g., digoxin toxicity, aminoglycoside nephrotoxicity), and apply pharmacokinetic principles (e.g., volume of distribution, clearance, half-life) to clinical scenarios. Emphasis is on rational prescribing and safety.

High-Yield Concepts

• ACE Inhibitors vs ARBs in Hypertension and Heart Failure: First-line for hypertension in diabetes with proteinuria (e.g., lisinopril, losartan). ACE inhibitors (e.g., captopril) cause cough and angioedema; ARBs are alternatives. In heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%), both reduce mortality. Avoid in pregnancy (teratogenic) and bilateral renal artery stenosis (risk of acute kidney injury). Monitor potassium and creatinine.
• Beta-Blockers in Heart Failure and Myocardial Infarction: Metoprolol succinate, bisoprolol, and carvedilol are first-line in stable HFrEF (LVEF ≤40%) to reduce mortality. After MI, beta-blockers (e.g., atenolol) reduce reinfarction risk. Avoid in acute decompensated heart failure (pulmonary oedema), asthma (bronchospasm), and bradycardia. Bisoprolol is cardioselective; carvedilol has alpha-blocking effects.
• Metformin in Type 2 Diabetes: First-line oral agent for type 2 diabetes. Mechanism: decreases hepatic gluconeogenesis. Contraindicated if eGFR <30 mL/min/1.73m² due to lactic acidosis risk. Also avoid in severe liver disease, acute heart failure, and during iodinated contrast studies (hold 48h pre/post). Common side effects: gastrointestinal upset, metallic taste.
• Penicillin Allergy and Cephalosporin Cross-Reactivity: True IgE-mediated cross-reactivity between penicillins and cephalosporins is low (≈1-3%) but exists, especially with first-generation cephalosporins (e.g., cephalexin). For patients with severe penicillin allergy (anaphylaxis), avoid cephalosporins; use alternatives like macrolides (azithromycin) or fluoroquinolones (levofloxacin). Non-IgE reactions (rash) do not contraindicate cephalosporins.
• Warfarin Monitoring and Reversal: Target INR 2.0-3.0 for most indications (e.g., atrial fibrillation, DVT). For mechanical mitral valve, target 2.5-3.5. Reversal: vitamin K (oral/IV) for INR 4.5-10 without bleeding; fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) for life-threatening bleeding. Major drug interactions: antibiotics (metronidazole, ciprofloxacin) and antifungals (fluconazole) potentiate warfarin.
• Statins in Primary and Secondary Prevention: First-line lipid-lowering therapy. Indications: clinical atherosclerotic cardiovascular disease (ASCVD), LDL ≥4.9 mmol/L (190 mg/dL), diabetes age 40-75 with LDL 1.8-4.9 mmol/L (70-189 mg/dL), or 10-year risk ≥7.5% (US guidelines). Use high-intensity statin (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) for ASCVD. Monitor liver enzymes and CK if myopathy suspected.
• Inhaled Corticosteroids in Asthma: First-line controller therapy for persistent asthma (e.g., beclometasone, fluticasone). Stepwise approach: low-dose ICS for mild persistent, add long-acting beta-agonist (LABA, e.g., salmeterol) if uncontrolled. Rescue therapy: short-acting beta-agonist (SABA, e.g., salbutamol). ICS side effects: oral candidiasis, dysphonia. Rinse mouth after use.
• Opioid Equianalgesic Dosing and Toxicity: Morphine 10 mg IV = morphine 30 mg oral = hydromorphone 1.5 mg IV = oxycodone 20 mg oral. Toxicity: respiratory depression (rate <8/min, pinpoint pupils). Reversal: naloxone 0.4-2 mg IV, repeat every 2-3 min. Avoid naloxone in chronic opioid users (precipitates withdrawal). Monitor for serotonin syndrome if combining with MAOIs or SSRIs.

Common Traps in Pharmacology Questions

• Confusing ACE inhibitor cough with ARB cough: ARBs do not cause cough because they do not increase bradykinin levels.
• Thinking beta-blockers are contraindicated in all heart failure: they are first-line in stable HFrEF, only avoided in acute decompensation.
• Assuming metformin is safe in all renal impairment: it is contraindicated if eGFR <30 mL/min/1.73m² due to lactic acidosis risk.
• Believing all cephalosporins are contraindicated in penicillin allergy: cross-reactivity is low except for first-generation agents.
• Forgetting that warfarin reversal with vitamin K takes 24-48 hours; use FFP or PCC for immediate reversal in bleeding.
• Mixing up high-intensity and moderate-intensity statins: atorvastatin 40-80 mg and rosuvastatin 20-40 mg are high-intensity; simvastatin 20-40 mg is moderate.

How to Revise Pharmacology for the USMLE Step 1

Prioritise drug mechanisms, adverse effects, and first-line choices for common chronic diseases (hypertension, diabetes, heart failure, asthma, dyslipidaemia). Focus on drug interactions (e.g., warfarin-antibiotics, statin-fibrates) and contraindications in pregnancy, renal/hepatic impairment. Questions are often framed as clinical vignettes with a patient's history, lab values, and comorbidities; choose the safest drug or identify the toxicity. Practise dose adjustments (e.g., renally cleared drugs like gentamicin) and recognising classic toxicity patterns (e.g., metformin lactic acidosis, opioid respiratory depression). Use flashcards for drug classes and side effects. Emphasise antibiotics: spectrum, resistance mechanisms, and adverse effects (e.g., fluoroquinolone tendonitis).

Practise it: MedLumen has 30 Pharmacology questions for the USMLE Step 1, each with a full explanation and references.