Master Pharmacology
for USMLE Step 1
Access 30+ high-yield questions tailored for the 2026 syllabus. Includes AI-powered explanations and performance tracking.
Core Concepts
Pharmacology for USMLE Step 1 covers drug-body interactions.
- Pharmacokinetics (ADME):
- Absorption: Bioavailability (F), first-pass metabolism.
- Distribution: Volume of Distribution (Vd = Dose/Cp). High Vd for lipid-soluble drugs. Protein binding reduces free drug.
- Metabolism: Liver (CYP450, Phase I/II). Prodrugs require activation.
- Excretion: Kidney. Clearance (Cl). Half-life (t1/2). Steady state ~4-5 t1/2.
- Kinetics: First-order (constant fraction, most drugs) vs. Zero-order (constant amount, e.g., alcohol, phenytoin).
- Pharmacodynamics:
- Receptors: Ligand-gated, G-protein, enzyme-linked, intracellular.
- Agonists/Antagonists: Agonist (activates), Antagonist (blocks). Competitive vs. Non-competitive.
- Dose-Response: Potency (left shift, less drug for effect) vs. Efficacy (max effect, higher curve).
- Therapeutic Index (TI): TD50/ED50. High TI = safer.
- Tolerance/Tachyphylaxis: Decreased drug response over time.
- Drug Interactions: PK (ADME alteration, e.g., CYP450 inducers/inhibitors) or PD (additive, synergistic, antagonistic).
- Adverse Drug Reactions (ADRs):
- Type A: Dose-dependent, predictable.
- Type B: Dose-independent, unpredictable (allergic, idiosyncratic).
- Teratogenicity: Fetal harm (e.g., ACEi, Warfarin, Isotretinoin).
Clinical Presentation
- Therapeutic Effects: Manifestations of desired drug action (e.g., lowered BP, pain relief).
- Common Side Effects: Predictable from MOA.
- Anticholinergic: Dry mouth, blurred vision, urinary retention, constipation, confusion.
- Adrenergic: Tachycardia, tremors, anxiety.
- CNS: Sedation/excitation, dizziness.
- GI: Nausea, vomiting, diarrhea.
- Drug Toxicity: Exaggerated effects or organ damage (e.g., hepatotoxicity, nephrotoxicity).
- Allergic Reactions: Rash, urticaria, anaphylaxis.
Diagnosis (Gold Standard)
Assessing drug effect, toxicity, or interaction.
- Therapeutic Drug Monitoring (TDM): Measuring plasma drug concentrations for narrow therapeutic index drugs (e.g., Lithium, Digoxin, Phenytoin, Aminoglycosides, Vancomycin).
- Clinical Assessment: Comprehensive history (meds, OTCs), physical exam, symptom evaluation.
- Laboratory & Imaging: Organ function tests (LFTs, BUN/Cr), ECG.
- Dechallenge/Rechallenge: Confirming drug role in adverse events.
Management (First Line)
Managing drug-related issues.
- Dose Adjustment: Titrate based on efficacy, side effects, patient factors (renal/hepatic function, age).
- Switch Medications: For intolerable side effects or therapeutic failure.
- Supportive Care: Symptom management.
- Specific Antidotes: Reversing overdose/toxicity (e.g., Naloxone for opioids, Flumazenil for benzodiazepines, Acetylcysteine for acetaminophen).
- Discontinuation: For severe/life-threatening ADRs.
- Patient Education: Crucial for adherence, side effect recognition.
Exam Red Flags
- Narrow Therapeutic Index Drugs: TDM, toxicity, interactions (Warfarin, Lithium, Digoxin, Phenytoin, Theophylline).
- CYP450 Interactions: Inducers (Rifampin, Phenytoin, Carbamazepine); Inhibitors (Grapefruit juice, Macrolides, Azoles, Ritonavir).
- Organ-Specific Toxicities:
- Hepatotoxicity: Acetaminophen (OD), Isoniazid, Statins, Valproic acid.
- Nephrotoxicity: Aminoglycosides, NSAIDs, ACE inhibitors, Amphotericin B, Vancomycin.
- Ototoxicity: Aminoglycosides, Loop diuretics, Cisplatin.
- Cardiotoxicity: Doxorubicin (dilated CM), Amiodarone, TCAs (QT).
- Pulmonary Fibrosis: Amiodarone, Bleomycin, Methotrexate.
- Myelosuppression: Chemo, Chloramphenicol, Methotrexate.
- Teratogenic Drugs (Pregnancy Contraindications): ACEi/ARBs, Warfarin, Isotretinoin, Methotrexate, Phenytoin, Valproic acid, Tetracyclines, Lithium, Thalidomide.
- Key Antidotes: Naloxone (opioids), Flumazenil (benzos), N-acetylcysteine (acetaminophen), Protamine (heparin), Vit K (warfarin), Fomepizole (methanol/ethylene glycol).
- MAO Inhibitors: Hypertensive Crisis (tyramine foods), Serotonin Syndrome (SSRIs, SNRIs).
Sample Practice Questions
A 58-year-old male with a history of hypertension and well-controlled asthma presents to his primary care physician for routine follow-up. His blood pressure is consistently elevated despite lifestyle modifications. The physician is considering initiating a beta-blocker. Which of the following beta-blockers would be the *most appropriate* choice for this patient?
A 55-year-old male with newly diagnosed type 2 diabetes mellitus is started on metformin. He asks his physician how this medication helps to lower his blood sugar. Which of the following is the primary mechanism by which metformin achieves its therapeutic effect?
A 68-year-old male is brought to the emergency department after accidentally taking a double dose of his heart medication. He is hypotensive (BP 80/50 mmHg), bradycardic (HR 45 bpm), and his blood glucose level is 60 mg/dL. He reports feeling dizzy and weak. On examination, he is lethargic but arousable. Which of the following is the most appropriate initial pharmacological treatment to specifically address the myocardial depression and hypoglycemia refractory to IV fluids and atropine?
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