Title: Usmle Step 1 High Yield Pharmacology — LearnCoachAssist

Q: Mechanism of acetaminophen toxicity?
A: Hepatic CYP2E1 oxidizes APAP → toxic NAPQI metabolite. Glutathione normally detoxifies; in overdose glutathione is depleted → centrilobular hepatic necrosis.

Q: Antidote for acetaminophen overdose?
A: N-acetylcysteine — replenishes glutathione.

Q: Aspirin mechanism?
A: Irreversible COX-1 / COX-2 inhibitor → ↓ thromboxane A₂ in platelets (antithrombotic) + ↓ prostaglandins (analgesic, antipyretic, anti-inflammatory).

Q: Aspirin overdose acid-base picture?
A: Mixed: respiratory alkalosis (early — direct medullary stimulation) + anion-gap metabolic acidosis (later — uncoupled oxidative phosphorylation).

Q: ACE inhibitor side effects?
A: Cough (↑ bradykinin), angioedema, hyperkalemia, creatinine bump, teratogenic.

Q: ARBs differ from ACE-Is how?
A: Block AT1 receptor instead of ACE → no bradykinin increase → no cough, less angioedema. Same K+/Cr risks.

Q: Beta-blocker contraindications?
A: Severe bradycardia, AV block, decompensated heart failure, severe asthma (esp. non-selective).

Q: Cardioselective beta-blockers?
A: β₁-selective: metoprolol, atenolol, esmolol, bisoprolol ('A through M = β1-selective except carvedilol/labetalol').

Q: Statin mechanism and side effect?
A: HMG-CoA reductase inhibitor → ↓ cholesterol synthesis. Side: myopathy/rhabdomyolysis (esp. + fibrate), hepatotoxicity.

Q: Warfarin mechanism?
A: Inhibits vitamin K epoxide reductase → ↓ active vitamin K → ↓ synthesis of factors II, VII, IX, X (1972) and proteins C, S.

Q: Warfarin reversal?
A: Vitamin K (slow, hours-days); fresh frozen plasma or 4-factor PCC for urgent reversal.

Q: Heparin mechanism?
A: Activates antithrombin III → inactivates thrombin (IIa) and factor Xa. Monitor with aPTT.

Q: LMWH (enoxaparin) vs heparin?
A: LMWH: predictable PK, longer half-life, sub-Q, mostly anti-Xa; monitor only in renal failure/obesity. Less HIT risk.

Q: Heparin reversal?
A: Protamine sulfate.

Q: HIT (heparin-induced thrombocytopenia)?
A: Type II: antibodies to heparin-PF4 complex → paradoxical thrombosis + ↓ platelets ~5-10d after heparin start. Stop heparin; switch to argatroban/bivalirudin.

Q: DOAC for atrial fibrillation?
A: Direct oral anticoagulants: apixaban, rivaroxaban (anti-Xa); dabigatran (direct thrombin). No INR monitoring.

Q: Dabigatran reversal?
A: Idarucizumab.

Q: Apixaban/rivaroxaban reversal?
A: Andexanet alfa.

Q: Insulin types — onset rapid vs intermediate vs long?
A: Rapid: lispro, aspart, glulisine.
Short: regular.
Intermediate: NPH.
Long: glargine, detemir, degludec.

Q: Metformin mechanism?
A: ↓ hepatic gluconeogenesis (AMPK activation). Doesn't cause hypoglycemia as monotherapy.

Q: Metformin contraindication?
A: Renal dysfunction (eGFR <30) — risk of lactic acidosis.

Q: SGLT2 inhibitors examples and effects?
A: -gliflozin (empagliflozin, dapagliflozin, canagliflozin). Block glucose reabsorption in proximal tubule. Side: UTI, euglycemic DKA, volume depletion. Cardiovascular & renal benefit.

Q: GLP-1 agonists?
A: -glutide (semaglutide, liraglutide). ↑ insulin (glucose-dependent), ↓ glucagon, slow gastric emptying. Weight loss benefit. Side: GI, pancreatitis risk.

Q: Thyroid storm treatment?
A: β-blocker (propranolol) + PTU/methimazole + iodine (Lugol's) + corticosteroids. Treat fever; supportive care.

Q: Anti-TB drug side effects?
A: Isoniazid: hepatotoxic, peripheral neuropathy (give B6).
Rifampin: orange body fluids, CYP inducer.
Ethambutol: optic neuritis.
Pyrazinamide: hepatotoxic, hyperuricemia.

Q: Aminoglycoside (gentamicin) toxicity?
A: Nephrotoxic + ototoxic. Concentration-dependent killing; once-daily dosing reduces toxicity.

Q: Vancomycin red man syndrome?
A: Histamine release from rapid infusion — flushing, pruritus. Slow infusion; not a true allergy.

Q: Beta-lactam allergy — risk with cephalosporins?
A: Historically quoted ~10%; modern estimates closer to 1-2% with 1st-gen cephalosporins, lower with 3rd/4th-gen.

Q: SSRIs vs SNRIs?
A: SSRIs: serotonin only (fluoxetine, sertraline, escitalopram).
SNRIs: serotonin + norepinephrine (venlafaxine, duloxetine).

Q: Serotonin syndrome triad?
A: Autonomic instability (BP, HR, sweat), neuromuscular (clonus, hyperreflexia), altered mental status. Stop offending drug, supportive, cyproheptadine if severe.

Q: MAOI dietary warning?
A: Avoid tyramine-rich foods (aged cheese, cured meats, wine) — hypertensive crisis.

Q: Lithium toxicity and antidote?
A: Tremor, confusion, ataxia, seizures. Antidote: hemodialysis for severe levels.

Q: Drugs causing QT prolongation?
A: Macrolides (azithro), fluoroquinolones, methadone, antipsychotics, ondansetron, antiarrhythmics. Avoid stacking; check baseline ECG.

Q: Loop diuretic prototype and mechanism?
A: Furosemide. Blocks Na-K-2Cl in thick ascending loop. Side: hypokalemia, hypocalcemia, ototoxic in high IV doses, hyperuricemia.

Q: Thiazide side effects (HCTZ)?
A: Hyper GLUC (glucose, lipid, uric acid, calcium); hypo NaKMg.

Q: Spironolactone vs eplerenone?
A: Both: K-sparing aldosterone antagonists. Spironolactone causes gynecomastia (anti-androgen); eplerenone doesn't.

Q: Class IA, IB, IC antiarrhythmics?
A: 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.

Q: Amiodarone class and toxicities?
A: Class III (K-blocker) with all-class properties. Toxicities: pulmonary fibrosis, thyroid (hyper/hypo), corneal deposits, blue-gray skin, hepatotoxic.

Q: Cyclosporine / tacrolimus mechanism?
A: Calcineurin inhibitors → block IL-2 transcription in T-cells. Side: nephrotoxic, HTN, neurotoxic, gum hyperplasia (cyclosporine).

Q: Acyclovir mechanism?
A: Activated by viral thymidine kinase → triphosphate → chain terminator in viral DNA. Targets HSV/VZV; nephrotoxic if not hydrated.

Q: Ganciclovir vs acyclovir?
A: Ganciclovir is the CMV drug — much more potent against CMV, but more myelosuppressive.

Q: NSAID that preferentially inhibits COX-2 and lacks antiplatelet effect?
A: Celecoxib — selective COX-2 inhibitor. Lacks aspirin's antiplatelet effect; carries increased cardiovascular/thrombotic risk.

Q: Why is aspirin avoided in children with viral infection?
A: Risk of Reye syndrome — hepatic encephalopathy with mitochondrial dysfunction after aspirin during viral illness (esp. influenza/varicella).

Q: Mechanism of GI bleeding from NSAIDs?
A: COX-1 inhibition → decreased protective gastric prostaglandins (PGE2, PGI2) → decreased mucus/bicarbonate/blood flow → ulceration.

Q: Nephrotoxicity mechanism of NSAIDs?
A: Inhibit prostaglandin-mediated afferent arteriolar dilation → decreased GFR, especially in volume-depleted/elderly/CHF/CKD patients. Can cause acute interstitial nephritis and papillary necrosis.

Q: First-line for acute gout flare?
A: NSAIDs (indomethacin, naproxen). Alternatives: colchicine (within 24h) or glucocorticoids.

Q: Colchicine mechanism and main toxicity?
A: Binds tubulin → inhibits microtubule polymerization → impairs neutrophil chemotaxis. Main toxicity: GI (diarrhea, N/V); long-term myelosuppression.

Q: Allopurinol mechanism and key interaction?
A: Xanthine oxidase inhibitor → decreased uric acid synthesis. Azathioprine interaction: azathioprine metabolized by xanthine oxidase → increased 6-MP levels → myelosuppression.

Q: Febuxostat compared to allopurinol?
A: Also a xanthine oxidase inhibitor (non-purine), used in allopurinol intolerance. Carries higher CV death warning vs allopurinol.

Q: Probenecid mechanism?
A: Blocks proximal tubule reabsorption of uric acid → increased urate excretion. Uricosuric. Ineffective if GFR reduced; risks urate stones.

Q: Rasburicase indication and mechanism?
A: Recombinant urate oxidase → converts uric acid to allantoin (soluble). Used for tumor lysis syndrome. Contraindicated in G6PD deficiency.

Q: Morphine mechanism and main adverse effects?
A: mu-opioid receptor agonist. Side: respiratory depression, miosis, constipation, tolerance, dependence. Histamine release can cause hypotension/bronchospasm.

Q: Naloxone mechanism and clinical use?
A: Competitive mu-opioid receptor antagonist. Reverses opioid overdose (respiratory depression). Short half-life — may need re-dosing, esp. with methadone.

Q: Naltrexone clinical uses?
A: Long-acting opioid antagonist. Used for alcohol use disorder and opioid dependence maintenance.

Q: Methadone pharmacology distinctions?
A: Long-acting mu agonist + NMDA antagonist; long, variable half-life (risk of accumulation). Used for opioid maintenance and chronic pain. QT prolongation.

Q: Buprenorphine distinguishing features?
A: Partial mu agonist + kappa antagonist. Ceiling effect on respiratory depression. Suboxone = buprenorphine + naloxone to deter IV misuse.

Q: Tramadol mechanism and seizure risk?
A: Weak mu agonist + inhibits 5-HT and NE reuptake. Lowers seizure threshold; risk of serotonin syndrome with SSRIs/MAOI.

Q: Fentanyl vs morphine potency and clinical use?
A: Fentanyl ~100x more potent than morphine, rapid onset, short duration. Used in anesthesia, transdermal for chronic pain, and abused (esp. with cocaine).

Q: Diphenoxylate/atropine (Lomotil)?
A: Opioid agonist + atropine. Used for diarrhea. Atropine added to discourage abuse (causes anticholinergic effects at high doses).

Q: Ondansetron mechanism and major risk?
A: 5-HT3 antagonist. Used for chemo/radiation/post-op nausea. Major risk: QT prolongation (FDA warning) → avoid with other QT-prolonging drugs.

Q: Metoclopramide mechanism and risk?
A: D2 receptor antagonist (prokinetic). Risk of extrapyramidal symptoms / tardive dyskinesia; acute dystonia treatable with diphenhydramine/benztropine.

Q: Benztropine vs amantadine in parkinsonism?
A: Benztropine — muscarinic antagonist (muscle rigidity, tremor). Amantadine — increases dopamine release, NMDA antagonist (used for levodopa-induced dyskinesia).

Q: Donepezil mechanism and major side effect?
A: Acetylcholinesterase inhibitor → increased ACh at synapse. Used in Alzheimer dementia. Main SE: bradycardia, syncope, GI upset, vivid dreams.

Q: Memantine mechanism?
A: Uncompetitive NMDA receptor antagonist — used in moderate-to-severe Alzheimer disease. Often combined with donepezil.

Q: Riluzole indication?
A: ALS — inhibits glutamate release / NMDA effects. Modestly prolongs survival.

Q: Levodopa with carbidopa rationale?
A: Carbidopa = peripheral DOPA decarboxylase inhibitor → decreased peripheral conversion of L-DOPA to dopamine → decreased peripheral side effects and increased CNS L-DOPA availability.

Q: Selegiline mechanism?
A: MAO-B inhibitor (selective at low doses). Used in early Parkinson disease. At higher doses loses selectivity → tyramine risk.

Q: Sumatriptan mechanism and contraindication?
A: 5-HT1B/1D receptor agonist → cranial vasoconstriction. Contraindicated in patients with CAD / Prinzmetal angina / uncontrolled HTN (vasospasm).

Q: Propranolol — which receptors and clinical uses?
A: Non-selective beta-blocker (beta-1 + beta-2). Used for HTN, angina, migraine prophylaxis, performance anxiety, portal HTN, thyroid storm symptoms.

Q: Metoprolol selective vs propranolol?
A: Beta-1-selective → preferred in asthma/COPD and diabetics (less bronchospasm, masks hypoglycemia less). Loses selectivity at high doses.

Q: Prazosin mechanism and main use?
A: Selective alpha-1 antagonist → vasodilation. Used for HTN and PTSD-related nightmares. First-dose orthostatic hypotension — start low.

Q: Phenoxybenzamine vs phentolamine?
A: 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).

Q: Clonidine mechanism and key side effect?
A: Central alpha-2 agonist → decreased sympathetic outflow. Used for HTN, ADHD, opioid withdrawal. Major SE: rebound hypertension on abrupt stop; dry mouth, sedation.

Q: Methyldopa mechanism and use in pregnancy?
A: Central alpha-2 agonist (false neurotransmitter). Drug of choice for HTN in pregnancy. Risk of hemolytic anemia (Coombs positive).

Q: Hydralazine mechanism and key side effects?
A: Direct arteriolar vasodilator. Side: lupus-like syndrome, reflex tachycardia, fluid retention (give with beta-blocker + diuretic). Used in pregnancy.

Q: Nitroprusside mechanism and cyanide risk?
A: Releases NO → vascular smooth muscle relaxation. Metabolized to cyanide (risk with prolonged/high-dose infusion or renal failure). Treat cyanide toxicity with hydroxocobalamin or sodium thiosulfate.

Q: Nitroglycerin mechanism and clinical features?
A: Releases NO → venodilation (preload reduction) at low doses; arterial at high doses. Used for angina. Headache, reflex tachycardia, tolerance.

Q: Isosorbide mononitrate vs dinitrate?
A: Both are NO donors. Dinitrate requires hepatic first-pass → shorter acting with tolerance issues; mononitrate is active metabolite, longer acting.

Q: Digitalis (digoxin) mechanism and effect on ECG?
A: Inhibits Na/K-ATPase → increased intracellular Na → decreased Na/Ca exchanger → increased intracellular Ca → increased inotropy. ECG: scooped ST depression (Salvador Dali mustache).

Q: Digoxin toxicity signs and treatment?
A: GI (N/V), yellow-green vision (xanthopsia), arrhythmias (PVCs, AV block). Toxicity increased by hypokalemia. Treatment: digoxin immune Fab (Digibind) for severe toxicity.

Q: Digoxin interaction with diuretics?
A: Loop/thiazide diuretics cause hypokalemia → increased digoxin binding and toxicity. Give K+ supplementation or K-sparing diuretic with digoxin.

Q: Milrinone mechanism and clinical use?
A: Phosphodiesterase III inhibitor → increased cAMP → inotropy + vasodilation (inodilator). Used in acute decompensated heart failure; increases mortality with long-term use.

Q: Dobutamine mechanism and use?
A: Beta-1 agonist → increased inotropy, modest chronotropy. Used in acute decompensated heart failure and stress testing. Risk of tachyarrhythmias.

Q: Nesiritide mechanism?
A: Recombinant BNP → vasodilation, natriuresis. Used acutely in decompensated heart failure. Limited by hypotension and questionable mortality benefit.

Q: ACE inhibitor — first-dose and renal effects?
A: 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%.

Q: Mechanism of ACE-inhibitor cough?
A: Increased bradykinin (normally degraded by ACE) accumulates in airways → dry, nonproductive cough. Switch to ARB.

Q: Mechanism of ACE-inhibitor angioedema?
A: 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).

Q: Aliskiren mechanism?
A: Direct renin inhibitor → decreased Angiotensinogen → AngI conversion. Used for HTN. Risk of hyperkalemia, renal dysfunction, angioedema (don't combine with ACE-I/ARB).

Q: Sacubitril/valsartan (Entresto) mechanism?
A: Sacubitril = neprilysin inhibitor → increased BNP, ANP, CNP (vasodilation, natriuresis). Combined with ARB for HFrEF. Do not combine with ACE-I (angioedema risk) — 36h washout.

Q: Beta-blocker benefit in heart failure?
A: Carvedilol, metoprolol succinate, bisoprolol reduce mortality in HFrEF by blocking chronic sympathetic-driven remodeling.

Q: Beta-blocker effect on lipid panel?
A: Non-selective beta-blockers increase triglycerides, decrease HDL. Cardioselective beta-blockers have less effect.

Q: Nitrate tolerance — cause and prevention?
A: Mechanism: depletion of sulfhydryl groups and increased oxidative stress with continuous exposure. Prevent with daily nitrate-free interval (e.g. remove patch at night).

Q: Calcium channel blockers — dihydropyridines vs non-DHPs?
A: Dihydropyridines (amlodipine, nifedipine) — vascular selective, cause reflex tachycardia, no negative inotropy. Non-DHPs (verapamil, diltiazem) — cardiac effects: negative inotropy/chronotropy/dromotropy, constipation (verapamil).

Q: Verapamil vs diltiazem differences?
A: Both non-DHP CCBs. Verapamil — more cardiac depression, more constipation, more negative inotropy. Diltiazem — intermediate; commonly used for rate control in AFib.

Q: Amiodarone — why caution with warfarin and digoxin?
A: CYP3A4 inhibitor + P-gp inhibitor → increased warfarin levels (bleed) and increased digoxin levels (toxicity). Also displaces digoxin from tissues.

Q: Amiodarone — pulmonary toxicity presentation?
A: Interstitial pneumonitis / pulmonary fibrosis — dry cough, dyspnea. Most dangerous non-cardiac toxicity. Get baseline CXR and PFTs; stop drug if suspected.

Q: Amiodarone — thyroid dysfunction?
A: Contains iodine (37% by weight) → inhibits 5'-deiodinase. Can cause both hyper- and hypothyroidism. Monitor TFTs.

Q: Sotalol class and key toxicity?
A: Class III K-blocker + non-selective beta-blocker. Used for AFib/flutter. Major risk: torsades de pointes from QT prolongation.

Q: Ibutilide mechanism and use?
A: Class III antiarrhythmic → increased K efflux → prolongs action potential. Used for pharmacologic cardioversion of atrial flutter/fibrillation. Risk of torsades.

Q: Adenosine mechanism and clinical pearls?
A: 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).

Q: Atropine mechanism and clinical uses?
A: Muscarinic antagonist → blocks parasympathetic (especially vagal) tone. Used for bradycardia (esp. symptomatic) and preop to dry secretions. Side: mydriasis, hyperthermia, dry mouth, urinary retention.

Q: Bethanechol mechanism and use?
A: Direct muscarinic agonist (resistant to AChE). Used for postoperative urinary retention and neurogenic ileus. Contraindicated in obstruction.

Q: Pilocarpine mechanism and use?
A: Direct muscarinic agonist. Used for open-angle and acute angle-closure glaucoma (after laser) — miosis opens trabecular meshwork.

Q: Pralidoxime (2-PAM) mechanism and use?
A: Regenerates AChE after organophosphate poisoning before aging occurs. Combined with atropine; doesn't reverse CNS effects.

Q: Organophosphate poisoning mechanism and signs?
A: Irreversible AChE inhibitor → increased ACh at NMJ and synapses → DUMBBBELS: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Salivation, Sweating. Treat with atropine + pralidoxime.

Q: Succinylcholine mechanism and key cautions?
A: Depolarizing NMJ blocker — Phase I block, ACh receptor agonist. Contraindicated in hyperkalemia, denervation injuries, burn patients, malignant hyperthermia history, muscular dystrophy (increased K+ release).

Q: Malignant hyperthermia trigger and treatment?
A: Triggered by succinylcholine / volatile anesthetics in RyR1 mutation → sustained Ca2+ release → hyperthermia, rigidity. Treat with dantrolene (blocks ryanodine receptor).

Q: Non-depolarizing NMJ blockers — example and reversal?
A: Vecuronium, rocuronium, cisatracurium. Reversal: sugammadex (cyclodextrin, binds rocuronium) or neostigmine + glycopyrrolate.

Q: Neostigmine mechanism and why combine with glycopyrrolate?
A: AChE inhibitor → increased ACh → useful in myasthenia gravis and reversing NMJ block. Glycopyrrolate is added to prevent muscarinic effects (bradycardia, GI cramps).

Q: Myasthenia gravis — diagnostic drug test and treatment?
A: Edrophonium (short-acting AChE inhibitor) historically for diagnosis; treat with pyridostigmine long-term, immunosuppressants, thymectomy.

Q: Lambert-Eaton syndrome — pharmacologic features?
A: 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.

Q: Dantrolene mechanism and main use?
A: Binds ryanodine receptor → decreased Ca2+ release from sarcoplasmic reticulum. Used for malignant hyperthermia and spasticity (esp. upper motor neuron).

Q: Botulinum toxin mechanism and clinical use?
A: Cleaves SNARE proteins → blocks ACh release at NMJ. Used for spasticity, blepharospasm, strabismus, migraine prophylaxis, cosmetics. Botulism food poisoning from C. botulinum.

Q: Tetrodotoxin mechanism and clinical effect?
A: Blocks voltage-gated Na+ channels on nerves (esp. from puffer fish). Causes ascending paralysis, paresthesias, respiratory failure — no antidote, supportive care.

Q: Local anesthetic mechanism and key property?
A: 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.

Q: Lidocaine — also antiarrhythmic use and key toxicity?
A: Class IB antiarrhythmic. Toxicity: CNS — perioral numbness, tinnitus, seizures, coma at high levels. Cardiac depression at very high levels.

Q: Bupivacaine — key clinical caution?
A: Long-acting amide local anesthetic. More cardiotoxic than lidocaine if intravascular — difficult-to-treat ventricular arrhythmias.

Q: Epinephrine added to local anesthetic — why and risk?
A: Causes vasoconstriction → prolongs anesthesia and reduces systemic absorption/bleeding. Risk: ischemia at end-arterial sites (fingers, toes, nose, penis) — avoid.

Q: Inhaled anesthetic potency vs speed of onset?
A: Potency = MAC (minimum alveolar concentration) — inverse to potency. Speed of onset governed by blood:gas partition coefficient (lower = faster, e.g. nitrous oxide).

Q: Methoxyflurane — main toxicity?
A: Nephrotoxic (fluoride release) — historical agent, rarely used now.

Q: Propofol mechanism and major adverse effect?
A: 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.

Q: Etomidate — distinctive adverse effect?
A: Adrenal suppression via 11beta-hydroxylase inhibition → decreased cortisol. Useful in hemodynamic instability but avoid in sepsis due to increased mortality.

Q: Ketamine mechanism and unique features?
A: NMDA antagonist. Dissociative anesthesia, bronchodilation, increased BP/HR (sympathomimetic), minimal respiratory depression. Causes emergence reactions / hallucinations; useful in pediatrics, trauma, field anesthesia.

Q: Barbiturates — examples and key feature?
A: Phenobarbital, thiopental — GABA-A agonists. CYP450 inducers; thiopental highly lipid-soluble → rapid CNS entry, redistribution. Overdose treated supportively.

Q: Benzodiazepine mechanism and key pharmacology?
A: GABA-A positive allosteric modulator → increased frequency of Cl- channel opening. Reversed by flumazenil. Long-acting vs short-acting (lorazepam vs midazolam).

Q: Flumazenil — clinical use and key risk?
A: Competitive benzodiazepine antagonist. Use: reverse benzodiazepine overdose. Risk: precipitates seizures in chronic users, especially with TCA co-ingestion.

Q: Benzodiazepine withdrawal management?
A: Long-acting benzo (diazepam, chlordiazepoxide) tapered slowly. Avoid abrupt discontinuation → seizures, delirium, death. Flumazenil contraindicated.

Q: Zolpidem mechanism and key features?
A: Non-benzodiazepine GABA-A agonist (BZ-1 selective) — minimal muscle relaxation, less dependence. Overdose reversed by flumazenil. Use short-term.

Q: Buspirone mechanism and use?
A: 5-HT1A partial agonist. Used for generalized anxiety disorder. No sedation, no dependence, no withdrawal, no respiratory depression. Takes 1-2 weeks for effect.

Q: TCA overdose — classic triad and treatment?
A: Anticholinergic (mydriasis, dry), cardiac (wide QRS, VT), CNS (seizures, coma). Treat QRS widening with sodium bicarbonate.

Q: TCA examples and side effect profile?
A: Amitriptyline, nortriptyline, imipramine, clomipramine, doxepin. Side: anticholinergic, orthostatic hypotension (alpha-1 block), sedation (H1), QT prolongation, weight gain.

Q: Bupropion mechanism and key contraindications?
A: NDRI (norepinephrine-dopamine reuptake inhibitor). Contraindicated in seizure disorders and eating disorders (anorexia/bulimia) — lowers seizure threshold. Useful for smoking cessation.

Q: Mirtazapine mechanism and side effect profile?
A: 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.

Q: Triptan — what to avoid combining and why?
A: Avoid with SSRIs/MAOIs/other serotonergic drugs → serotonin syndrome. Avoid in patients with CAD, stroke, PVD (vasoconstriction).

Q: Phenelzine / tranylcypromine — clinical use?
A: MAOI antidepressants (non-selective, irreversible). Used for refractory depression. Many drug and dietary interactions (tyramine).

Q: Phenoxybenzamine pre-op use?
A: Irreversible alpha-blocker given before pheochromocytoma surgery to control BP. Volume expansion then beta-blocker (never beta first — unopposed alpha → hypertensive crisis).

Q: Dantrolene vs baclofen for spasticity?
A: Dantrolene — direct muscle (RyR1). Baclofen — GABA-B receptor agonist in spinal cord. Both reduce spasticity; tizanidine (alpha-2 agonist) is another option.

Q: Tizanidine mechanism and main use?
A: Central alpha-2 agonist → increased presynaptic inhibition of motor neurons. Used for spasticity (esp. MS, spinal cord injury). Monitor LFTs.

Q: Hydroxychloroquine main toxicities?
A: Retinopathy (bull's-eye maculopathy), QT prolongation, hemolysis in G6PD deficiency, neuromyopathy. Used in SLE, RA. Get baseline and annual ophthalmology exam.

Q: Cyclophosphamide mechanism and main toxicities?
A: Alkylating agent — crosslinks DNA. Toxicities: hemorrhagic cystitis (give MESNA), SIADH, myelosuppression, secondary malignancies (bladder, leukemia).

Q: Methotrexate mechanism and key toxicities?
A: Inhibits dihydrofolate reductase → decreased purine/thymidylate synthesis. Leucovorin (folinic acid) rescue. Side: hepatotoxicity, pulmonary fibrosis, mucositis, myelosuppression, nephrotoxicity.

Q: 5-Fluorouracil mechanism and toxicities?
A: Pyrimidine analog → blocks thymidylate synthase → decreased dTMP. Toxicities: myelosuppression, mucositis, hand-foot syndrome, photosensitivity.

Q: 6-Mercaptopurine / azathioprine mechanism?
A: Purine analogs → decreased purine synthesis. 6-MP/azathioprine metabolized by xanthine oxidase — avoid with allopurinol (toxicity). Azathioprine is a prodrug → 6-MP.

Q: Bleomycin mechanism and key toxicity?
A: Generates free radicals → DNA strand breaks. Pulmonary fibrosis is dose-limiting toxicity; worsened by O2. Used in Hodgkin (ABVD), testicular cancer.

Q: Doxorubicin mechanism and dose-limiting toxicity?
A: Topoisomerase II inhibitor → DNA strand breaks. Cardiotoxicity — dose-dependent dilated cardiomyopathy. Prevent with dexrazoxane (iron chelator).

Q: Trastuzumab mechanism and key cardiotoxicity?
A: Monoclonal antibody against HER2. Causes reversible cardiomyopathy (not dose-dependent like doxorubicin) — monitor LVEF.

Q: Cisplatin mechanism and main toxicities?
A: Crosslinks DNA. Major toxicities: nephrotoxicity (give amifostine / aggressive hydration), ototoxicity, peripheral neuropathy, severe N/V (highly emetogenic).

Q: Carboplatin vs cisplatin?
A: Same mechanism; carboplatin — more myelosuppressive (esp. thrombocytopenia), less nephro/ototoxic. Dose by Calvert formula using GFR.

Q: Paclitaxel mechanism and main toxicity?
A: Stabilizes microtubules → prevents depolymerization → mitotic arrest. Major toxicity: peripheral neuropathy and myelosuppression; can cause hypersensitivity (give premeds).

Q: Vincristine / vinblastine mechanism?
A: Bind beta-tubulin → prevent microtubule polymerization → arrest mitosis. Vincristine — peripheral neuropathy dose-limiting. Vinblastine — bone marrow suppression.

Q: Etoposide mechanism and key toxicity?
A: Topoisomerase II inhibitor → DNA double-strand breaks. Toxicities: myelosuppression, secondary AML (with translocation t(15;17)), hypersensitivity.

Q: Imatinib mechanism and use?
A: BCR-ABL tyrosine kinase inhibitor → used in CML. Also c-KIT → GIST. Side: fluid retention, hepatotoxicity, myelosuppression.

Q: Rituximab mechanism?
A: Anti-CD20 monoclonal antibody → depletes B cells. Used in B-cell lymphomas, CLL, RA. Risk of PML (JC virus reactivation) and HBV reactivation.

Q: Bevacizumab mechanism and main toxicities?
A: Anti-VEGF monoclonal antibody. Used in many solid tumors. Side: HTN, proteinuria, poor wound healing, bleeding, thrombosis, GI perforation.

Q: Leuprolide mechanism and clinical uses?
A: GnRH analog — continuous dosing downregulates pituitary GnRH receptors → decreased LH/FSH. Used in prostate cancer, endometriosis, precocious puberty, fibroids.

Q: Finasteride mechanism and use?
A: 5alpha-reductase inhibitor → blocks conversion of testosterone to DHT. Used in BPH and male-pattern baldness. Side: decreased libido, gynecomastia. Pregnant women should not handle crushed tablets.

Q: Tamoxifen mechanism and risk?
A: Selective estrogen receptor modulator — antagonist in breast, agonist in endometrium/bone. Used in ER+ breast cancer. Risk: endometrial cancer and thromboembolism.

Q: Raloxifene mechanism and use?
A: SERM — agonist on bone (treats osteoporosis), antagonist on breast (BC chemoprevention), no endometrial stimulation. Risk: DVT.

Q: Aromatase inhibitors — examples and use?
A: Anastrozole, letrozole, exemestane — block conversion of androgens to estrogens. First-line for postmenopausal ER+ breast cancer. Side: osteoporosis, arthralgias.

Q: Sildenafil mechanism and major contraindication?
A: PDE5 inhibitor → increased cGMP → smooth muscle relaxation in corpus cavernosum. Contraindicated with nitrates → severe hypotension. Also can cause blue-tinted vision, hearing loss.

Q: Prostaglandin analogs for glaucoma?
A: Latanoprost (PGF2alpha analog) → increased uveoscleral outflow. Side: iris hyperpigmentation, eyelash growth, periorbital fat atrophy.