Usmle Step 1 High Yield Pharmacology Practice Exam

Question 1 Usmle Step 1 High Yield Pharmacology

Sildenafil mechanism and major contraindication?

PDE5 inhibitor → increased cGMP → smooth muscle relaxation in corpus cavernosum. Contraindicated with nitrates → severe hypotension. Also can cause blue-tinted vision, hearing loss. Class III K-blocker + non-selective beta-blocker. Used for AFib/flutter. Major risk: torsades de pointes from QT prolongation. Phenoxybenzamine — irreversible non-selective alpha antagonist (used pre-op for pheochromocytoma). Phentolamine — reversible non-selective alpha antagonist (treats MAOI–tyramine crisis and extravasation of norepinephrine). Anticholinergic (mydriasis, dry), cardiac (wide QRS, VT), CNS (seizures, coma). Treat QRS widening with sodium bicarbonate.

Question 2 Usmle Step 1 High Yield Pharmacology

Succinylcholine mechanism and key cautions?

LMWH: predictable PK, longer half-life, sub-Q, mostly anti-Xa; monitor only in renal failure/obesity. Less HIT risk. Depolarizing NMJ blocker — Phase I block, ACh receptor agonist. Contraindicated in hyperkalemia, denervation injuries, burn patients, malignant hyperthermia history, muscular dystrophy (increased K+ release). Pyrimidine analog → blocks thymidylate synthase → decreased dTMP. Toxicities: myelosuppression, mucositis, hand-foot syndrome, photosensitivity. Anastrozole, letrozole, exemestane — block conversion of androgens to estrogens. First-line for postmenopausal ER+ breast cancer. Side: osteoporosis, arthralgias.

Question 3 Usmle Step 1 High Yield Pharmacology

Buspirone mechanism and use?

Inhibit prostaglandin-mediated afferent arteriolar dilation → decreased GFR, especially in volume-depleted/elderly/CHF/CKD patients. Can cause acute interstitial nephritis and papillary necrosis. 5-HT1A partial agonist. Used for generalized anxiety disorder. No sedation, no dependence, no withdrawal, no respiratory depression. Takes 1-2 weeks for effect. Same mechanism; carboplatin — more myelosuppressive (esp. thrombocytopenia), less nephro/ototoxic. Dose by Calvert formula using GFR. Irreversible alpha-blocker given before pheochromocytoma surgery to control BP. Volume expansion then beta-blocker (never beta first — unopposed alpha → hypertensive crisis).

Question 4 Usmle Step 1 High Yield Pharmacology

Aspirin overdose acid-base picture?

Non-benzodiazepine GABA-A agonist (BZ-1 selective) — minimal muscle relaxation, less dependence. Overdose reversed by flumazenil. Use short-term. GABA-A potentiation (mainly) → loss of consciousness; rapid onset/offset. Major AE: propofol infusion syndrome (acidosis, rhabdomyolysis, cardiac failure) with prolonged high-dose use; hypotension on induction. Class III antiarrhythmic → increased K efflux → prolongs action potential. Used for pharmacologic cardioversion of atrial flutter/fibrillation. Risk of torsades. Mixed: respiratory alkalosis (early — direct medullary stimulation) + anion-gap metabolic acidosis (later — uncoupled oxidative phosphorylation).

Question 5 Usmle Step 1 High Yield Pharmacology

SSRIs vs SNRIs?

Generates free radicals → DNA strand breaks. Pulmonary fibrosis is dose-limiting toxicity; worsened by O2. Used in Hodgkin (ABVD), testicular cancer. Irreversible AChE inhibitor → increased ACh at NMJ and synapses → DUMBBBELS: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Salivation, Sweating. Treat with atropine + pralidoxime. SSRIs: serotonin only (fluoxetine, sertraline, escitalopram).
SNRIs: serotonin + norepinephrine (venlafaxine, duloxetine). ↓ hepatic gluconeogenesis (AMPK activation). Doesn't cause hypoglycemia as monotherapy.

Question 6 Usmle Step 1 High Yield Pharmacology

Heparin reversal?

Irreversible alpha-blocker given before pheochromocytoma surgery to control BP. Volume expansion then beta-blocker (never beta first — unopposed alpha → hypertensive crisis). Topoisomerase II inhibitor → DNA double-strand breaks. Toxicities: myelosuppression, secondary AML (with translocation t(15;17)), hypersensitivity. Class III (K-blocker) with all-class properties. Toxicities: pulmonary fibrosis, thyroid (hyper/hypo), corneal deposits, blue-gray skin, hepatotoxic. Protamine sulfate.

Question 7 Usmle Step 1 High Yield Pharmacology

Ibutilide mechanism and use?

Vecuronium, rocuronium, cisatracurium. Reversal: sugammadex (cyclodextrin, binds rocuronium) or neostigmine + glycopyrrolate. Anti-VEGF monoclonal antibody. Used in many solid tumors. Side: HTN, proteinuria, poor wound healing, bleeding, thrombosis, GI perforation. Irreversible alpha-blocker given before pheochromocytoma surgery to control BP. Volume expansion then beta-blocker (never beta first — unopposed alpha → hypertensive crisis). Class III antiarrhythmic → increased K efflux → prolongs action potential. Used for pharmacologic cardioversion of atrial flutter/fibrillation. Risk of torsades.

Question 8 Usmle Step 1 High Yield Pharmacology

DOAC for atrial fibrillation?

BCR-ABL tyrosine kinase inhibitor → used in CML. Also c-KIT → GIST. Side: fluid retention, hepatotoxicity, myelosuppression. Direct oral anticoagulants: apixaban, rivaroxaban (anti-Xa); dabigatran (direct thrombin). No INR monitoring. -gliflozin (empagliflozin, dapagliflozin, canagliflozin). Block glucose reabsorption in proximal tubule. Side: UTI, euglycemic DKA, volume depletion. Cardiovascular & renal benefit. Benztropine — muscarinic antagonist (muscle rigidity, tremor). Amantadine — increases dopamine release, NMDA antagonist (used for levodopa-induced dyskinesia).

Question 9 Usmle Step 1 High Yield Pharmacology

Rasburicase indication and mechanism?

Recombinant urate oxidase → converts uric acid to allantoin (soluble). Used for tumor lysis syndrome. Contraindicated in G6PD deficiency. Furosemide. Blocks Na-K-2Cl in thick ascending loop. Side: hypokalemia, hypocalcemia, ototoxic in high IV doses, hyperuricemia. CYP3A4 inhibitor + P-gp inhibitor → increased warfarin levels (bleed) and increased digoxin levels (toxicity). Also displaces digoxin from tissues. Activates A1 receptors → increased K conductance → hyperpolarizes AV node → transient AV block. Used for SVT. Effects last ~10 seconds; contraindicated in WPW with AFib (can precipitate VF).

Question 10 Usmle Step 1 High Yield Pharmacology

Doxorubicin mechanism and dose-limiting toxicity?

Interstitial pneumonitis / pulmonary fibrosis — dry cough, dyspnea. Most dangerous non-cardiac toxicity. Get baseline CXR and PFTs; stop drug if suspected. Mixed: respiratory alkalosis (early — direct medullary stimulation) + anion-gap metabolic acidosis (later — uncoupled oxidative phosphorylation). Nephrotoxic (fluoride release) — historical agent, rarely used now. Topoisomerase II inhibitor → DNA strand breaks. Cardiotoxicity — dose-dependent dilated cardiomyopathy. Prevent with dexrazoxane (iron chelator).

Question 11 Usmle Step 1 High Yield Pharmacology

Memantine mechanism?

Vitamin K (slow, hours-days); fresh frozen plasma or 4-factor PCC for urgent reversal. Fentanyl ~100x more potent than morphine, rapid onset, short duration. Used in anesthesia, transdermal for chronic pain, and abused (esp. with cocaine). CYP3A4 inhibitor + P-gp inhibitor → increased warfarin levels (bleed) and increased digoxin levels (toxicity). Also displaces digoxin from tissues. Uncompetitive NMDA receptor antagonist — used in moderate-to-severe Alzheimer disease. Often combined with donepezil.

Question 12 Usmle Step 1 High Yield Pharmacology

Drugs causing QT prolongation?

β₁-selective: metoprolol, atenolol, esmolol, bisoprolol ('A through M = β1-selective except carvedilol/labetalol'). Macrolides (azithro), fluoroquinolones, methadone, antipsychotics, ondansetron, antiarrhythmics. Avoid stacking; check baseline ECG. Central alpha-2 agonist → decreased sympathetic outflow. Used for HTN, ADHD, opioid withdrawal. Major SE: rebound hypertension on abrupt stop; dry mouth, sedation. Monoclonal antibody against HER2. Causes reversible cardiomyopathy (not dose-dependent like doxorubicin) — monitor LVEF.

Question 13 Usmle Step 1 High Yield Pharmacology

Mechanism of acetaminophen toxicity?

Hepatic CYP2E1 oxidizes APAP → toxic NAPQI metabolite. Glutathione normally detoxifies; in overdose glutathione is depleted → centrilobular hepatic necrosis. Long-acting mu agonist + NMDA antagonist; long, variable half-life (risk of accumulation). Used for opioid maintenance and chronic pain. QT prolongation. Stabilizes microtubules → prevents depolymerization → mitotic arrest. Major toxicity: peripheral neuropathy and myelosuppression; can cause hypersensitivity (give premeds). Phenoxybenzamine — irreversible non-selective alpha antagonist (used pre-op for pheochromocytoma). Phentolamine — reversible non-selective alpha antagonist (treats MAOI–tyramine crisis and extravasation of norepinephrine).

Question 14 Usmle Step 1 High Yield Pharmacology

Cyclosporine / tacrolimus mechanism?

Competitive mu-opioid receptor antagonist. Reverses opioid overdose (respiratory depression). Short half-life — may need re-dosing, esp. with methadone. Calcineurin inhibitors → block IL-2 transcription in T-cells. Side: nephrotoxic, HTN, neurotoxic, gum hyperplasia (cyclosporine). Topoisomerase II inhibitor → DNA strand breaks. Cardiotoxicity — dose-dependent dilated cardiomyopathy. Prevent with dexrazoxane (iron chelator). mu-opioid receptor agonist. Side: respiratory depression, miosis, constipation, tolerance, dependence. Histamine release can cause hypotension/bronchospasm.

Question 15 Usmle Step 1 High Yield Pharmacology

Nephrotoxicity mechanism of NSAIDs?

Inhibit prostaglandin-mediated afferent arteriolar dilation → decreased GFR, especially in volume-depleted/elderly/CHF/CKD patients. Can cause acute interstitial nephritis and papillary necrosis. Hyper GLUC (glucose, lipid, uric acid, calcium); hypo NaKMg. Non-benzodiazepine GABA-A agonist (BZ-1 selective) — minimal muscle relaxation, less dependence. Overdose reversed by flumazenil. Use short-term. Can cause acute drop in GFR in bilateral renal artery stenosis (kidneys depend on AngII to maintain GFR). A small creatinine rise is acceptable; stop if rise >30%.

Question 16 Usmle Step 1 High Yield Pharmacology

Malignant hyperthermia trigger and treatment?

Activated by viral thymidine kinase → triphosphate → chain terminator in viral DNA. Targets HSV/VZV; nephrotoxic if not hydrated. Crosslinks DNA. Major toxicities: nephrotoxicity (give amifostine / aggressive hydration), ototoxicity, peripheral neuropathy, severe N/V (highly emetogenic). NMDA antagonist. Dissociative anesthesia, bronchodilation, increased BP/HR (sympathomimetic), minimal respiratory depression. Causes emergence reactions / hallucinations; useful in pediatrics, trauma, field anesthesia. Triggered by succinylcholine / volatile anesthetics in RyR1 mutation → sustained Ca2+ release → hyperthermia, rigidity. Treat with dantrolene (blocks ryanodine receptor).

Question 17 Usmle Step 1 High Yield Pharmacology

Febuxostat compared to allopurinol?

Binds tubulin → inhibits microtubule polymerization → impairs neutrophil chemotaxis. Main toxicity: GI (diarrhea, N/V); long-term myelosuppression. Also a xanthine oxidase inhibitor (non-purine), used in allopurinol intolerance. Carries higher CV death warning vs allopurinol. Vitamin K (slow, hours-days); fresh frozen plasma or 4-factor PCC for urgent reversal. Central alpha-2 agonist (false neurotransmitter). Drug of choice for HTN in pregnancy. Risk of hemolytic anemia (Coombs positive).

Question 18 Usmle Step 1 High Yield Pharmacology

Metoclopramide mechanism and risk?

D2 receptor antagonist (prokinetic). Risk of extrapyramidal symptoms / tardive dyskinesia; acute dystonia treatable with diphenhydramine/benztropine. Non-selective beta-blockers increase triglycerides, decrease HDL. Cardioselective beta-blockers have less effect. Rapid: lispro, aspart, glulisine.
Short: regular.
Intermediate: NPH.
Long: glargine, detemir, degludec. Furosemide. Blocks Na-K-2Cl in thick ascending loop. Side: hypokalemia, hypocalcemia, ototoxic in high IV doses, hyperuricemia.

Question 19 Usmle Step 1 High Yield Pharmacology

Inhaled anesthetic potency vs speed of onset?

Direct renin inhibitor → decreased Angiotensinogen → AngI conversion. Used for HTN. Risk of hyperkalemia, renal dysfunction, angioedema (don't combine with ACE-I/ARB). Potency = MAC (minimum alveolar concentration) — inverse to potency. Speed of onset governed by blood:gas partition coefficient (lower = faster, e.g. nitrous oxide). Alpha-2 antagonist + 5-HT2/3 antagonist. Increases NE and 5-HT. Side: sedation, weight gain, increased appetite (anti-H1, anti-5-HT2C). Fewer sexual side effects than SSRIs. Benztropine — muscarinic antagonist (muscle rigidity, tremor). Amantadine — increases dopamine release, NMDA antagonist (used for levodopa-induced dyskinesia).

Question 20 Usmle Step 1 High Yield Pharmacology

Bethanechol mechanism and use?

COX-1 inhibition → decreased protective gastric prostaglandins (PGE2, PGI2) → decreased mucus/bicarbonate/blood flow → ulceration. Direct arteriolar vasodilator. Side: lupus-like syndrome, reflex tachycardia, fluid retention (give with beta-blocker + diuretic). Used in pregnancy. Type II: antibodies to heparin-PF4 complex → paradoxical thrombosis + ↓ platelets ~5-10d after heparin start. Stop heparin; switch to argatroban/bivalirudin. Direct muscarinic agonist (resistant to AChE). Used for postoperative urinary retention and neurogenic ileus. Contraindicated in obstruction.

Question 21 Usmle Step 1 High Yield Pharmacology

Statin mechanism and side effect?

-gliflozin (empagliflozin, dapagliflozin, canagliflozin). Block glucose reabsorption in proximal tubule. Side: UTI, euglycemic DKA, volume depletion. Cardiovascular & renal benefit. HMG-CoA reductase inhibitor → ↓ cholesterol synthesis. Side: myopathy/rhabdomyolysis (esp. + fibrate), hepatotoxicity. Nephrotoxic + ototoxic. Concentration-dependent killing; once-daily dosing reduces toxicity. Loop/thiazide diuretics cause hypokalemia → increased digoxin binding and toxicity. Give K+ supplementation or K-sparing diuretic with digoxin.

Question 22 Usmle Step 1 High Yield Pharmacology

Metformin contraindication?

Direct renin inhibitor → decreased Angiotensinogen → AngI conversion. Used for HTN. Risk of hyperkalemia, renal dysfunction, angioedema (don't combine with ACE-I/ARB). Both are NO donors. Dinitrate requires hepatic first-pass → shorter acting with tolerance issues; mononitrate is active metabolite, longer acting. Cleaves SNARE proteins → blocks ACh release at NMJ. Used for spasticity, blepharospasm, strabismus, migraine prophylaxis, cosmetics. Botulism food poisoning from C. botulinum. Renal dysfunction (eGFR <30) — risk of lactic acidosis.

Question 23 Usmle Step 1 High Yield Pharmacology

Botulinum toxin mechanism and clinical use?

Inhibits dihydrofolate reductase → decreased purine/thymidylate synthesis. Leucovorin (folinic acid) rescue. Side: hepatotoxicity, pulmonary fibrosis, mucositis, myelosuppression, nephrotoxicity. Activated by viral thymidine kinase → triphosphate → chain terminator in viral DNA. Targets HSV/VZV; nephrotoxic if not hydrated. Cleaves SNARE proteins → blocks ACh release at NMJ. Used for spasticity, blepharospasm, strabismus, migraine prophylaxis, cosmetics. Botulism food poisoning from C. botulinum. Central alpha-2 agonist → decreased sympathetic outflow. Used for HTN, ADHD, opioid withdrawal. Major SE: rebound hypertension on abrupt stop; dry mouth, sedation.

Question 24 Usmle Step 1 High Yield Pharmacology

Benztropine vs amantadine in parkinsonism?

Antibodies to presynaptic voltage-gated Ca2+ channels → decreased ACh release. Increases with repeated stimulation (vs MG worsens). Often associated with small cell lung cancer. Treat with 3,4-diaminopyridine. PDE5 inhibitor → increased cGMP → smooth muscle relaxation in corpus cavernosum. Contraindicated with nitrates → severe hypotension. Also can cause blue-tinted vision, hearing loss. Activated by viral thymidine kinase → triphosphate → chain terminator in viral DNA. Targets HSV/VZV; nephrotoxic if not hydrated. Benztropine — muscarinic antagonist (muscle rigidity, tremor). Amantadine — increases dopamine release, NMDA antagonist (used for levodopa-induced dyskinesia).

Question 25 Usmle Step 1 High Yield Pharmacology

Raloxifene mechanism and use?

Central alpha-2 agonist → increased presynaptic inhibition of motor neurons. Used for spasticity (esp. MS, spinal cord injury). Monitor LFTs. Benztropine — muscarinic antagonist (muscle rigidity, tremor). Amantadine — increases dopamine release, NMDA antagonist (used for levodopa-induced dyskinesia). SERM — agonist on bone (treats osteoporosis), antagonist on breast (BC chemoprevention), no endometrial stimulation. Risk: DVT. Avoid with SSRIs/MAOIs/other serotonergic drugs → serotonin syndrome. Avoid in patients with CAD, stroke, PVD (vasoconstriction).

Question 26 Usmle Step 1 High Yield Pharmacology

Aliskiren mechanism?

Carbidopa = peripheral DOPA decarboxylase inhibitor → decreased peripheral conversion of L-DOPA to dopamine → decreased peripheral side effects and increased CNS L-DOPA availability. Competitive benzodiazepine antagonist. Use: reverse benzodiazepine overdose. Risk: precipitates seizures in chronic users, especially with TCA co-ingestion. Alkylating agent — crosslinks DNA. Toxicities: hemorrhagic cystitis (give MESNA), SIADH, myelosuppression, secondary malignancies (bladder, leukemia). Direct renin inhibitor → decreased Angiotensinogen → AngI conversion. Used for HTN. Risk of hyperkalemia, renal dysfunction, angioedema (don't combine with ACE-I/ARB).

Question 27 Usmle Step 1 High Yield Pharmacology

Etomidate — distinctive adverse effect?

Protamine sulfate. COX-1 inhibition → decreased protective gastric prostaglandins (PGE2, PGI2) → decreased mucus/bicarbonate/blood flow → ulceration. Bradykinin accumulation → vasogenic edema of face, lips, tongue, airway. Higher incidence in black patients; life-threatening → stop drug permanently, switch to ARB (still some cross-reactivity). Adrenal suppression via 11beta-hydroxylase inhibition → decreased cortisol. Useful in hemodynamic instability but avoid in sepsis due to increased mortality.

Question 28 Usmle Step 1 High Yield Pharmacology

Metoprolol selective vs propranolol?

Long-acting opioid antagonist. Used for alcohol use disorder and opioid dependence maintenance. Non-selective beta-blockers increase triglycerides, decrease HDL. Cardioselective beta-blockers have less effect. Same mechanism; carboplatin — more myelosuppressive (esp. thrombocytopenia), less nephro/ototoxic. Dose by Calvert formula using GFR. Beta-1-selective → preferred in asthma/COPD and diabetics (less bronchospasm, masks hypoglycemia less). Loses selectivity at high doses.

Question 29 Usmle Step 1 High Yield Pharmacology

Hydroxychloroquine main toxicities?

D2 receptor antagonist (prokinetic). Risk of extrapyramidal symptoms / tardive dyskinesia; acute dystonia treatable with diphenhydramine/benztropine. Pyrimidine analog → blocks thymidylate synthase → decreased dTMP. Toxicities: myelosuppression, mucositis, hand-foot syndrome, photosensitivity. Dihydropyridines (amlodipine, nifedipine) — vascular selective, cause reflex tachycardia, no negative inotropy. Non-DHPs (verapamil, diltiazem) — cardiac effects: negative inotropy/chronotropy/dromotropy, constipation (verapamil). Retinopathy (bull's-eye maculopathy), QT prolongation, hemolysis in G6PD deficiency, neuromyopathy. Used in SLE, RA. Get baseline and annual ophthalmology exam.

Question 30 Usmle Step 1 High Yield Pharmacology

Phenoxybenzamine pre-op use?

Celecoxib — selective COX-2 inhibitor. Lacks aspirin's antiplatelet effect; carries increased cardiovascular/thrombotic risk. Irreversible alpha-blocker given before pheochromocytoma surgery to control BP. Volume expansion then beta-blocker (never beta first — unopposed alpha → hypertensive crisis). Inhibit prostaglandin-mediated afferent arteriolar dilation → decreased GFR, especially in volume-depleted/elderly/CHF/CKD patients. Can cause acute interstitial nephritis and papillary necrosis. Anastrozole, letrozole, exemestane — block conversion of androgens to estrogens. First-line for postmenopausal ER+ breast cancer. Side: osteoporosis, arthralgias.

Question 31 Usmle Step 1 High Yield Pharmacology

Cisplatin mechanism and main toxicities?

Crosslinks DNA. Major toxicities: nephrotoxicity (give amifostine / aggressive hydration), ototoxicity, peripheral neuropathy, severe N/V (highly emetogenic). Retinopathy (bull's-eye maculopathy), QT prolongation, hemolysis in G6PD deficiency, neuromyopathy. Used in SLE, RA. Get baseline and annual ophthalmology exam. Blocks proximal tubule reabsorption of uric acid → increased urate excretion. Uricosuric. Ineffective if GFR reduced; risks urate stones. Recombinant BNP → vasodilation, natriuresis. Used acutely in decompensated heart failure. Limited by hypotension and questionable mortality benefit.

Question 32 Usmle Step 1 High Yield Pharmacology

Beta-lactam allergy — risk with cephalosporins?

Non-selective beta-blockers increase triglycerides, decrease HDL. Cardioselective beta-blockers have less effect. Monoclonal antibody against HER2. Causes reversible cardiomyopathy (not dose-dependent like doxorubicin) — monitor LVEF. Na-channel blockers. IA: quinidine, procainamide — slow phase 0, ↑ APD.
IB: lidocaine — fast off, ↓ APD.
IC: flecainide — strongest Na block, no APD change. Avoid IC post-MI. Historically quoted ~10%; modern estimates closer to 1-2% with 1st-gen cephalosporins, lower with 3rd/4th-gen.

Question 33 Usmle Step 1 High Yield Pharmacology

Bevacizumab mechanism and main toxicities?

Irreversible AChE inhibitor → increased ACh at NMJ and synapses → DUMBBBELS: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Salivation, Sweating. Treat with atropine + pralidoxime. Monoclonal antibody against HER2. Causes reversible cardiomyopathy (not dose-dependent like doxorubicin) — monitor LVEF. Class III (K-blocker) with all-class properties. Toxicities: pulmonary fibrosis, thyroid (hyper/hypo), corneal deposits, blue-gray skin, hepatotoxic. Anti-VEGF monoclonal antibody. Used in many solid tumors. Side: HTN, proteinuria, poor wound healing, bleeding, thrombosis, GI perforation.

Question 34 Usmle Step 1 High Yield Pharmacology

6-Mercaptopurine / azathioprine mechanism?

Activates A1 receptors → increased K conductance → hyperpolarizes AV node → transient AV block. Used for SVT. Effects last ~10 seconds; contraindicated in WPW with AFib (can precipitate VF). Purine analogs → decreased purine synthesis. 6-MP/azathioprine metabolized by xanthine oxidase — avoid with allopurinol (toxicity). Azathioprine is a prodrug → 6-MP. Depolarizing NMJ blocker — Phase I block, ACh receptor agonist. Contraindicated in hyperkalemia, denervation injuries, burn patients, malignant hyperthermia history, muscular dystrophy (increased K+ release). Same mechanism; carboplatin — more myelosuppressive (esp. thrombocytopenia), less nephro/ototoxic. Dose by Calvert formula using GFR.

Question 35 Usmle Step 1 High Yield Pharmacology

MAOI dietary warning?

LMWH: predictable PK, longer half-life, sub-Q, mostly anti-Xa; monitor only in renal failure/obesity. Less HIT risk. Celecoxib — selective COX-2 inhibitor. Lacks aspirin's antiplatelet effect; carries increased cardiovascular/thrombotic risk. Causes vasoconstriction → prolongs anesthesia and reduces systemic absorption/bleeding. Risk: ischemia at end-arterial sites (fingers, toes, nose, penis) — avoid. Avoid tyramine-rich foods (aged cheese, cured meats, wine) — hypertensive crisis.

Question 36 Usmle Step 1 High Yield Pharmacology

Methadone pharmacology distinctions?

Long-acting mu agonist + NMDA antagonist; long, variable half-life (risk of accumulation). Used for opioid maintenance and chronic pain. QT prolongation. Non-benzodiazepine GABA-A agonist (BZ-1 selective) — minimal muscle relaxation, less dependence. Overdose reversed by flumazenil. Use short-term. Competitive mu-opioid receptor antagonist. Reverses opioid overdose (respiratory depression). Short half-life — may need re-dosing, esp. with methadone. GABA-A positive allosteric modulator → increased frequency of Cl- channel opening. Reversed by flumazenil. Long-acting vs short-acting (lorazepam vs midazolam).

Question 37 Usmle Step 1 High Yield Pharmacology

Methotrexate mechanism and key toxicities?

Celecoxib — selective COX-2 inhibitor. Lacks aspirin's antiplatelet effect; carries increased cardiovascular/thrombotic risk. Benztropine — muscarinic antagonist (muscle rigidity, tremor). Amantadine — increases dopamine release, NMDA antagonist (used for levodopa-induced dyskinesia). Inhibits dihydrofolate reductase → decreased purine/thymidylate synthesis. Leucovorin (folinic acid) rescue. Side: hepatotoxicity, pulmonary fibrosis, mucositis, myelosuppression, nephrotoxicity. Blocks voltage-gated Na+ channels on nerves (esp. from puffer fish). Causes ascending paralysis, paresthesias, respiratory failure — no antidote, supportive care.

Question 38 Usmle Step 1 High Yield Pharmacology

Sacubitril/valsartan (Entresto) mechanism?

β₁-selective: metoprolol, atenolol, esmolol, bisoprolol ('A through M = β1-selective except carvedilol/labetalol'). Sacubitril = neprilysin inhibitor → increased BNP, ANP, CNP (vasodilation, natriuresis). Combined with ARB for HFrEF. Do not combine with ACE-I (angioedema risk) — 36h washout. Hyper GLUC (glucose, lipid, uric acid, calcium); hypo NaKMg. Na-channel blockers. IA: quinidine, procainamide — slow phase 0, ↑ APD.
IB: lidocaine — fast off, ↓ APD.
IC: flecainide — strongest Na block, no APD change. Avoid IC post-MI.

Question 39 Usmle Step 1 High Yield Pharmacology

Warfarin mechanism?

Inhibits vitamin K epoxide reductase → ↓ active vitamin K → ↓ synthesis of factors II, VII, IX, X (1972) and proteins C, S. Also a xanthine oxidase inhibitor (non-purine), used in allopurinol intolerance. Carries higher CV death warning vs allopurinol. Type II: antibodies to heparin-PF4 complex → paradoxical thrombosis + ↓ platelets ~5-10d after heparin start. Stop heparin; switch to argatroban/bivalirudin. Carvedilol, metoprolol succinate, bisoprolol reduce mortality in HFrEF by blocking chronic sympathetic-driven remodeling.

Question 40 Usmle Step 1 High Yield Pharmacology

Aromatase inhibitors — examples and use?

Generates free radicals → DNA strand breaks. Pulmonary fibrosis is dose-limiting toxicity; worsened by O2. Used in Hodgkin (ABVD), testicular cancer. Central alpha-2 agonist → decreased sympathetic outflow. Used for HTN, ADHD, opioid withdrawal. Major SE: rebound hypertension on abrupt stop; dry mouth, sedation. Carbidopa = peripheral DOPA decarboxylase inhibitor → decreased peripheral conversion of L-DOPA to dopamine → decreased peripheral side effects and increased CNS L-DOPA availability. Anastrozole, letrozole, exemestane — block conversion of androgens to estrogens. First-line for postmenopausal ER+ breast cancer. Side: osteoporosis, arthralgias.

Question 41 Usmle Step 1 High Yield Pharmacology

Nesiritide mechanism?

Andexanet alfa. Block AT1 receptor instead of ACE → no bradykinin increase → no cough, less angioedema. Same K+/Cr risks. Inhibit prostaglandin-mediated afferent arteriolar dilation → decreased GFR, especially in volume-depleted/elderly/CHF/CKD patients. Can cause acute interstitial nephritis and papillary necrosis. Recombinant BNP → vasodilation, natriuresis. Used acutely in decompensated heart failure. Limited by hypotension and questionable mortality benefit.

Question 42 Usmle Step 1 High Yield Pharmacology

5-Fluorouracil mechanism and toxicities?

Anticholinergic (mydriasis, dry), cardiac (wide QRS, VT), CNS (seizures, coma). Treat QRS widening with sodium bicarbonate. Severe bradycardia, AV block, decompensated heart failure, severe asthma (esp. non-selective). Avoid with SSRIs/MAOIs/other serotonergic drugs → serotonin syndrome. Avoid in patients with CAD, stroke, PVD (vasoconstriction). Pyrimidine analog → blocks thymidylate synthase → decreased dTMP. Toxicities: myelosuppression, mucositis, hand-foot syndrome, photosensitivity.

Question 43 Usmle Step 1 High Yield Pharmacology

Prostaglandin analogs for glaucoma?

5-HT1A partial agonist. Used for generalized anxiety disorder. No sedation, no dependence, no withdrawal, no respiratory depression. Takes 1-2 weeks for effect. Latanoprost (PGF2alpha analog) → increased uveoscleral outflow. Side: iris hyperpigmentation, eyelash growth, periorbital fat atrophy. Increased bradykinin (normally degraded by ACE) accumulates in airways → dry, nonproductive cough. Switch to ARB. BCR-ABL tyrosine kinase inhibitor → used in CML. Also c-KIT → GIST. Side: fluid retention, hepatotoxicity, myelosuppression.

Question 44 Usmle Step 1 High Yield Pharmacology

Amiodarone class and toxicities?

Class III (K-blocker) with all-class properties. Toxicities: pulmonary fibrosis, thyroid (hyper/hypo), corneal deposits, blue-gray skin, hepatotoxic. Amitriptyline, nortriptyline, imipramine, clomipramine, doxepin. Side: anticholinergic, orthostatic hypotension (alpha-1 block), sedation (H1), QT prolongation, weight gain. Topoisomerase II inhibitor → DNA strand breaks. Cardiotoxicity — dose-dependent dilated cardiomyopathy. Prevent with dexrazoxane (iron chelator). Stabilizes microtubules → prevents depolymerization → mitotic arrest. Major toxicity: peripheral neuropathy and myelosuppression; can cause hypersensitivity (give premeds).

Question 45 Usmle Step 1 High Yield Pharmacology

Sotalol class and key toxicity?

Adrenal suppression via 11beta-hydroxylase inhibition → decreased cortisol. Useful in hemodynamic instability but avoid in sepsis due to increased mortality. 5-HT1B/1D receptor agonist → cranial vasoconstriction. Contraindicated in patients with CAD / Prinzmetal angina / uncontrolled HTN (vasospasm). Causes vasoconstriction → prolongs anesthesia and reduces systemic absorption/bleeding. Risk: ischemia at end-arterial sites (fingers, toes, nose, penis) — avoid. Class III K-blocker + non-selective beta-blocker. Used for AFib/flutter. Major risk: torsades de pointes from QT prolongation.

Question 46 Usmle Step 1 High Yield Pharmacology

Pralidoxime (2-PAM) mechanism and use?

Class III (K-blocker) with all-class properties. Toxicities: pulmonary fibrosis, thyroid (hyper/hypo), corneal deposits, blue-gray skin, hepatotoxic. Interstitial pneumonitis / pulmonary fibrosis — dry cough, dyspnea. Most dangerous non-cardiac toxicity. Get baseline CXR and PFTs; stop drug if suspected. Andexanet alfa. Regenerates AChE after organophosphate poisoning before aging occurs. Combined with atropine; doesn't reverse CNS effects.

Question 47 Usmle Step 1 High Yield Pharmacology

Ganciclovir vs acyclovir?

Block voltage-gated Na+ channels on nerve axons → no action potential. Amides (lidocaine, bupivacaine) — metabolized in liver; esters (procaine, tetracaine) — plasma AChE, PABA allergy cross-reactivity. Ganciclovir is the CMV drug — much more potent against CMV, but more myelosuppressive. Stabilizes microtubules → prevents depolymerization → mitotic arrest. Major toxicity: peripheral neuropathy and myelosuppression; can cause hypersensitivity (give premeds). Cough (↑ bradykinin), angioedema, hyperkalemia, creatinine bump, teratogenic.

Question 48 Usmle Step 1 High Yield Pharmacology

Ondansetron mechanism and major risk?

Long-acting benzo (diazepam, chlordiazepoxide) tapered slowly. Avoid abrupt discontinuation → seizures, delirium, death. Flumazenil contraindicated. 5-HT3 antagonist. Used for chemo/radiation/post-op nausea. Major risk: QT prolongation (FDA warning) → avoid with other QT-prolonging drugs. Selective alpha-1 antagonist → vasodilation. Used for HTN and PTSD-related nightmares. First-dose orthostatic hypotension — start low. Rapid: lispro, aspart, glulisine.
Short: regular.
Intermediate: NPH.
Long: glargine, detemir, degludec.

Question 49 Usmle Step 1 High Yield Pharmacology

SGLT2 inhibitors examples and effects?

Na-channel blockers. IA: quinidine, procainamide — slow phase 0, ↑ APD.
IB: lidocaine — fast off, ↓ APD.
IC: flecainide — strongest Na block, no APD change. Avoid IC post-MI. AChE inhibitor → increased ACh → useful in myasthenia gravis and reversing NMJ block. Glycopyrrolate is added to prevent muscarinic effects (bradycardia, GI cramps). Alpha-2 antagonist + 5-HT2/3 antagonist. Increases NE and 5-HT. Side: sedation, weight gain, increased appetite (anti-H1, anti-5-HT2C). Fewer sexual side effects than SSRIs. -gliflozin (empagliflozin, dapagliflozin, canagliflozin). Block glucose reabsorption in proximal tubule. Side: UTI, euglycemic DKA, volume depletion. Cardiovascular & renal benefit.

Question 50 Usmle Step 1 High Yield Pharmacology

Aminoglycoside (gentamicin) toxicity?

Alpha-2 antagonist + 5-HT2/3 antagonist. Increases NE and 5-HT. Side: sedation, weight gain, increased appetite (anti-H1, anti-5-HT2C). Fewer sexual side effects than SSRIs. Muscarinic antagonist → blocks parasympathetic (especially vagal) tone. Used for bradycardia (esp. symptomatic) and preop to dry secretions. Side: mydriasis, hyperthermia, dry mouth, urinary retention. Potency = MAC (minimum alveolar concentration) — inverse to potency. Speed of onset governed by blood:gas partition coefficient (lower = faster, e.g. nitrous oxide). Nephrotoxic + ototoxic. Concentration-dependent killing; once-daily dosing reduces toxicity.