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 68-year-old male presents to the emergency department with sudden onset shortness of breath and pleuritic chest pain. A CT pulmonary angiography reveals multiple bilateral pulmonary emboli. He is started on intravenous unfractionated heparin and warfarin. Which of the following best describes the mechanism of action of warfarin?
A 68-year-old male is admitted to the ICU with severe gram-negative sepsis. He is empirically started on a broad-spectrum antibiotic regimen including IV tobramycin. After several days, he complains of tinnitus and experiences a decrease in his hearing acuity, confirmed by audiometry. Lab tests also show a rise in serum creatinine. Which of the following is the *most likely* mechanism underlying these adverse effects?
A 68-year-old male with a history of atrial fibrillation on warfarin therapy presents to the emergency department with new-onset epistaxis and easy bruising over the past 24 hours. He reports taking ibuprofen 400 mg three times daily for the past three days due to exacerbation of chronic knee pain. His INR is found to be significantly elevated at 5.5 (therapeutic range 2.0-3.0). Which drug interaction is most likely responsible for his current presentation?
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