USMLE STEP 1 Pharmacology EXAM WITH COMPLETE SOLUTIONS 2023|2024 UPDATED RATED A+

What are the major functions of the α1 receptor? Correct Answer: Increase vascular smooth muscle contraction, increase pupillary dilator muscle contraction (mydriasis), increase intestinal and bladder sphincter muscle contraction What are the major functions of the α2 receptor? Correct Answer: Decrease sympathetic outflow, decrease insulin release, decrease lipolysis, increase platelet aggregation, decrease aqueous humor production What are the major functions of the β1 receptor? Correct Answer: Increase heart rate, increase contractility, increase renin release, increase lipolysis What are the major functions of the β2 receptor? Correct Answer: Vasodilation, bronchodilation, increase lipolysis, increase insulin release, decrease uterine tone (tocolysis), ciliary muscle relaxation, increase aqueous humor production What are the major functions of the M1 receptor? Correct Answer: CNS, enteric nervous system What are the major functions of the M2 receptor? Correct Answer: Decrease heart rate and contractility of atria What are the major functions of the M3 receptor? Correct Answer: Increase exocrine gland secretions (e.g., lacrimal, salivary, gastric acid), increase gut peristalsis, increase bladder contraction, increase bronchoconstriction, pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation) What are the major functions of the D1 receptor? Correct Answer: Relaxes renal vascular smooth muscle What are the major functions of the D2 receptor? Correct Answer: Modulates transmitter release, especially in the brain What are the major functions of the H1 receptor? Correct Answer: Increase nasal and bronchial mucus production, increase vascular permeability, contraction of bronchioles, pruritis, pain What are the major functions of the H2 receptor? Correct Answer: Increase gastric acid secretion What are the major functions of the V1 receptor? Correct Answer: Increase vascular smooth muscle contraction What are the major functions of the V2 receptor? Correct Answer: Increase H2O permeability and reabsorption in collecting tubules of kidney (V2 is found in the "2" kidneys) What receptors are associate with Gq? Correct Answer: H1, α1, V1, M1, and M3 What receptors are associated with Gs? Correct Answer: H2, B1, B2, V2, D1 What receptors are associated with Gi? Correct Answer: M2, α2, D2 Bethanechol Correct Answer: -Direct cholinergic agonist -Activates bowel and bladder smooth muscle -Used in postoperative and neurogenic ileus -Resistant to AChE Carbachol Correct Answer: -Direct cholinergic agonist -Carbon copy of acetylcholine -Constricts pupils and relieves intraocular pressure in glaucoma Methacholine Correct Answer: -Direct cholinergic agonist -Stimulates muscarinic receptors in airways when inhaled -Used as a challenge test for diagnosis of asthma Pilocarpine Correct Answer: -Direct cholinergic agonist -Contracts ciliary muscle of eye (open angle glaucoma), contracts pupillary sphincter (closed angle glaucoma) -Potent stimulator of sweat, tears and saliva -AChE resistant Donepezil Correct Answer: -Anticholinesterse - increases ACh -Alzheimer disease Galantamine Correct Answer: -Anticholinesterse - increases ACh -Alzheimer disease Rivastigmine Correct Answer: -Anticholinesterse - increases ACh -Alzheimer disease Edrophonium Correct Answer: -Anticholinesterse - increases ACh -Historically used to diagnose myasthenia gravis (MG is now diagnosed by anti-AChR Ab test. Neostigmine Correct Answer: -Anticholinesterse - increases ACh -Used in postoperative and neurogenic ileus and urinary retention, myasthenia gravis, and postoperative reversal of neuromuscular junction blockade Physostigmine Correct Answer: -Anticholinesterse - increases ACh -Used in anticholinergic toxicity -Crosses the blood-brain barrier (CNS) Pyridostigmine Correct Answer: -Anticholinesterse - increases ACh -Increases muscle strength -Used in myasthenia gravis (long acting) -Does not penetrate CNS Atropine Correct Answer: -Muscarinic antagonist -Used in bradycardia and for ophthalmic applications -Also used as antidote for cholinesterase inhibitor poisoning -Actions include increase pupil dilation, cycloplegia, decreased airway secretions, decreased acid secretions, decreased gut motility, decreased bladder urgency in cystitis -Toxicity: increased body temp (due to decreased sweating), rapid pulse, dry mouth, dry and flushed skin, cycloplegia, constipation, disorientation; -Can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants -See also homatropine and tropicamide Benztropine Correct Answer: -Muscarinic antagonist -Works in CNS -Used in Parkinson disease and acute dystonia Glycopyrrolate Correct Answer: -Muscarinic antagonist -Parental use: preoperative use to reduce airway secretions -Oral use: drooling, peptic ulcer Hyoscyamine Correct Answer: -Muscarinic antagonist -Antispasmodics for IBS Dicyclomide Correct Answer: -Muscarinic antagonist -Antispasmodics for IBS Ipratropium Correct Answer: -Muscarinic antagonist -Used in COPD and asthma Tiotropium Correct Answer: -Muscarinic antagonist -Used in COPD and asthma Oxybutynin Correct Answer: -Muscarinic antagonist -Reduced bladder spasms and urge urinary incontinence Solifenacin Correct Answer: -Muscarinic antagonist -Reduced bladder spasms and urge urinary incontinence Tolterodine Correct Answer: -Muscarinic antagonist -Reduced bladder spasms and urge urinary incontinence Scopalamine Correct Answer: -Muscarinic antagonist -Motion sickness Tetrodotoxin Correct Answer: -Poisoning can result from ingestion of poorly prepared puffer fish (exotic sushi) -Highly potent toxin that binds fast voltage-gated Na+ channels in cardiac and nerve tissue, preventing depolarization - blocks action potential without changing resting potential (same mechanism as Lidocaine) -Causes nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes. -Treatment is primarily supportive. Ciguatoxin Correct Answer: -Consumption of reef fish (e.g. barracuda, snapper, eel...) -Causes ciguatera fish poisoning. -Opens Na+ channels causing depolarization. Symptoms easily confused with cholinergic poisoning. -Temperature-related dysesthesia (e.g., "cold feels hot; hot feels cold") is regarded as a specific finding of ciguatera. -Treatment is primarily supportive. Scombroid poisoning Correct Answer: -Caused by consumption of dark-meat fish (e.g., bonito, mackerel, mahi-mahi, tuna) improperly stored at warm temperature. -Bacterial histidine decarboxylase converts histidine to histamine. Histamine is not degraded by cooking. -Acute-onset burning sensation of the mouth, flushing of face, erythema, urticaria, pruritus, headache. May cause anaphylaxis-like presentation (i.e., bronchospasm, angioedema, hypotension). -Frequently misdiagnosed as allergy to fish. -Treat supportively with antihistamines; if needed, antianaphylactics (e.g., bronchodilators, epinephrine). Albuterol Correct Answer: -β2 > β1 direct agonist -Acute asthma Salmterol Correct Answer: -β2 > β1 direct agonist -Long term asthma or COPD control Dobutamine Correct Answer: -β1 > β2, α direct agonist -Uses: heart failure (HF) (inotropic > chronotropic), cardiac stress testing. Dopamine Correct Answer: -D1 = D2 > β > α direct agonist -Uses: unstable bradycardia, HF, shock; inotropic and chronotropic α effects predominate at high doses. Epinephrine Correct Answer: -β > α direct agonist -Uses: anaphylaxis, asthma, open-angle glaucoma; α effects predominate at high doses. Significantly stronger effect at β2-receptor than norepinephrine. Isoprterenol Correct Answer: -β1 = β2 direct agonist -Uses: electrophysiologic evaluation of tachyarrhythmias. Can worsen ischemia Norepinephrine Correct Answer: -α1 > α2 > β1 direct agonist -Hypotension (butrenal perfusion). Significantly weaker effect at β2-receptor than epinephrine. Phenylephrine Correct Answer: -α1 > α2 direct agonist -Uses: hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant) Amphetamine Correct Answer: -Indirect general sympathetic agonist -reuptake inhibitor; also releases stored catecholamines -Narcolepsy, obesity, ADHD. Cocaine Correct Answer: -Indirect general sympathetic agonist -Reuptake inhibitor -Causes vasoconstriction and local anesthesia. -Never give β-blockers if cocaine intoxication is suspected (can lead to unopposed α1 activation and extreme hypertension). Ephedrine Correct Answer: -Indirect general sympathetic agonist -Releases stored catecholamines -Nasal decongestion, urinary incontinence, hypotension. Norepinephrine vs. isoproterenol Correct Answer: -Norepinephrine increases systolic and diastolic pressures as a result of α1-mediated vasoconstriction causing increased in mean arterial pressure and reflex bradycardia. -However, isoproterenol (no longer commonly used) has little α effect but causes β2-mediated vasodilation, resulting in decreased mean arterial pressure and increased heart rate through β1 and reflex activity. Clonidine Correct Answer: -α2-agonist -Uses: hypertensive urgency (limited situations); does not decrease renal blood flow; ADHD, Tourette syndrome -Toxicity: CNS depression, bradycardia, hypotension, respiratory depression, miosis α-methyldopa Correct Answer: -α2-agonist -Used for hypertension in pregnancy -Toxicity: Direct Coombs ⊕ hemolysis, SLE-like syndrome Phenoxybenzamine Correct Answer: -Nonselective α-blocker -Irreversible -Used preoperatively for pheochromocytoma to prevent catecholamine (hypertensive) crisis -Toxicity: orthostatic hypotension, reflex tachycardia Phentolamine Correct Answer: -Nonselective α-blocker -Give to patients on MAO inhibitors who eat tyramine containing foods -Toxicity: orthostatic hypotension, reflex tachycardia Prazosin Correct Answer: -Selective α1-blocker -Uses: urinary symptoms of BPH; PSTD -Hypertension -Toxicity: 1st-dose orthostatic hypotension, dizziness, headache Terazosin Correct Answer: -Selective α1-blocker -Uses: urinary symptoms of BPH; -Hypertension -Toxicity: 1st-dose orthostatic hypotension, dizziness, headache Doxazosin Correct Answer: -Selective α1-blocker -Uses: urinary symptoms of BPH; -Hypertension -Toxicity: 1st-dose orthostatic hypotension, dizziness, headache Tamsulosin Correct Answer: -Selective α1-blocker -Uses: urinary symptoms of BPH; -Toxicity: 1st-dose orthostatic hypotension, dizziness, headache Mirtazapine Correct Answer: -Selective α2-blocker -Used in depression -Toxicity: sedation, increased serum cholesterol, increased appetite α-blockade of epinephrine vs. phenylephrine Correct Answer: Shown in the picture are the effects of an α-blocker (e.g., phentolamine) on blood pressure responses to epinephrine and phenylephrine. The epinephrine response exhibits reversal of the mean blood pressure change, from a net increase (the α response) to a net decrease (the β2 response). The response to phenylephrine is suppressed but not reversed because phenylephrine is a "pure" α-agonist without β action. Effects of β-blockers Correct Answer: -Angina pectoris—decrease heart rate and contractility, resulting in decrease O2 consumption -MI—β-blockers (metoprolol, carvedilol, and bisoprolol) mortality -SVT (metoprolol, esmolol)—decrease AV conduction velocity (class II antiarrhythmic) -Hypertension—decrease cardiac output, decrease renin secretion (due to β1-receptor blockade on JGA cells) -HF—decrease mortality in chronic HF -Glaucoma (timolol)—decrease secretion of aqueous humor Nonselective β-blockers Correct Answer: -Nadolol, pindolol (partial agonist), propranolol, timolol -Mostly go from N to Z β1-selective antagonist Correct Answer: -acebutolol (partial agonist), atenolol, betaxolol, esmolol, metoprolol -Mostly go from A to M Nonselective α- and β-antagonists Correct Answer: -Carvedilol, labetalol Nebevolol Correct Answer: -Combines cardiac-selective β1-adrenergic blockade with stimulation of β3-receptors, which activate nitric oxide synthase in the vasculature Toxicity of β-blockers Correct Answer: -Impotence, cardiovascular adverse effects (bradycardia, AV block, HF), CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), and asthma/COPD exacerbations -Avoid in cocaine users due to risk of unopposed α-adrenergic receptor agonist activity -Despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweigh risks; not contraindicated Acetaminophen toxicity antidote Correct Answer: N-acetylcysteine (replenishes glutathione) AChE inhibitor/organophosphate toxicity antidote Correct Answer: Atropine > pralidoxime Amphetamines toxicity antidote Correct Answer: NH4Cl (acidify urine) Antimuscarinic, anticholinergic agents toxicity antidote Correct Answer: Physostigmine salicylate, control hyperthermia Benzodiasepines toxicity antidote Correct Answer: Flumazenil β-blocker toxicity antidote Correct Answer: Glucagon Carbon monoxide toxicity antidote Correct Answer: 100% O2, hyperbaric O2 Penicillamine Cyanide toxicity antidote Correct Answer: Nitrite + thiosulfate, hydroxocobalamin Digitalis toxicity antidote Correct Answer: Anti-dig Fab fragments Heparine toxicity antidote Correct Answer: Protamine sulfate Iron toxicity antidote Correct Answer: Deferoxamine, deferasirox Lead toxicity antidote Correct Answer: EDTA, dimercaprol, succimer, penicillamine Mercury, arsenic, gold toxicity antidote Correct Answer: Dimercaprol (BAL), succimer Copper, arsenic, gold toxicity antidote Correct Answer: Penicillamine Methanol, ethylene glycol (antifreeze) toxicity antidote Correct Answer: Fomepizole > ethanol, dialysis Methemoglobin toxicity antidote Correct Answer: Methylene blue, vitamin C Opioids toxicity antidote Correct Answer: Naloxone, naltrexone Salicylates toxicity antidote Correct Answer: NaHCO3 (alkalinize urine), dialysis TCAs toxicity antidote Correct Answer: NaHCO3 (plasma alkalinization) tPA, streptokinase, urokinase toxicity antidote Correct Answer: Aminocaproic acid Warfarin toxicity antidote Correct Answer: Vitamin K (delayed effect), fresh frozen plasma (immediate) Drugs that cause coronary vasospasm Correct Answer: Cocaine, sumatriptan, ergot alkaloids Drugs that cause cutaneous flushing Correct Answer: Vancomycin, Adenosine, Niacin, Ca2+ channel blockers (VANC) Drugs that cause dilated cardiomyopathy Correct Answer: Anthracyclines (e.g., doxorubicin, daunorubicin); prevent with dexrazoxane Drugs that cause Torsades de pointes Correct Answer: Class III (e.g., sotalol) and class IA (e.g., quinidine) antiarrhythmics, macrolide antibiotics, antipsychotics, TCAs Drugs that cause adrenocortical insufficiency Correct Answer: HPA suppression 2° to glucocorticoid withdrawal Drugs that cause hot flashes Correct Answer: Tamoxifen, clomiphene Drugs that cause hyperglycemia Correct Answer: Tacrolimus, Protease inhibitors, Niacin, HCTZ, Corticosteroids Drugs that cause hypothyroidism Correct Answer: Lithium, amiodarone, sulfonamides Drugs that cause acute cholestatic hepatitis, jaundice Correct Answer: Erythromycin Drugs that cause diarrhea Correct Answer: Metformin, Erythromycin, Colchicine, Orlistat, Acarbose Drugs that cause focal to massive hepatic necrosis Correct Answer: Halothane, Amanita phalloides (death cap mushroom), Valproic acid, Acetaminophen Drugs that cause hepatitis Correct Answer: Rifampin, isoniazid, pyrazinamide, statins, fibrates Drugs that cause pancreatitis Correct Answer: Didanosine, Corticosteroids, Alcohol, Valproicacid, Azathioprine, Diuretics (furosemide, HCTZ) Drugs that cause pseudomembranous colitis Correct Answer: Clindamycin, ampicillin, cephalosporins Drugs that cause agranulocytosis Correct Answer: Ganciclovir, Clozapine, Carbamazepine, Colchicine, Methimazole, Propylthiouracil Drugs that cause aplastic anemia Correct Answer: Carbamazepine, Methimazole, NSAIDs, Benzene, Chloramphenicol, Propylthiouracil Drugs that cause direct Coombs- positive hemolytic anemia Correct Answer: Methyldopa, penicillin Drugs that cause gray baby syndrome Correct Answer: Chloramphenicol Drugs that cause hemolysis in G6PD deficiency Correct Answer: Isoniazid, Sulfonamides, Dapsone, Primaquine, Aspirin, Ibuprofen, Nitrofurantoin Drugs that cause thrombocytopenia Correct Answer: Heparin Drugs that cause thrombotic complications Correct Answer: OCPs, hormone replacement therapy Drugs that cause Correct Answer: Protease inhibitors, Glucocorticoids Drugs that cause gingival hyperplasia Correct Answer: Phenytoin, Ca2+ channel blockers, cyclosporine Drugs that cause gout Correct Answer: Pyrazinamide, Thiazides, Furosemide, Niacin, Cyclosporine Drugs that cause myopathy Correct Answer: Fibrates, niacin, colchicine, hydroxychloroquine, interferon-α, penicillamine, statins, glucocorticoids Drugs that cause osteoporosis Correct Answer: Corticosteroids, heparin Drugs that cause photosensitivity Correct Answer: Sulfonamides, Amiodarone, Tetracyclines, 5-FU Drugs that cause Stevens-Johnson syndrome Correct Answer: Anti-epileptic drugs (especially lamotrigine), allopurinol, sulfa drugs, penicillin Drugs that cause SLE-like syndrome Correct Answer: Sulfa drugs, Hydralazine, Isoniazid, Procainamide, Phenytoin, Etanercept Drugs that cause teeth discoloration Correct Answer: Tetracyclines Drugs that cause tendonitis, tendon rupture, and cartilage damage Correct Answer: Fluoroquinolones Drugs that cause cinchonism (symptoms are tinnitus and slight deafness, photophobia and other visual disturbances, mental dullness, depression, confusion, headache, and nausea) Correct Answer: Quinidine, quinine Drugs that cause Parkinson-like syndrome Correct Answer: Antipsychotics, Reserpine, Metoclopramide Drugs that cause seizures Correct Answer: Isoniazid (vitamin B6 deficiency), Bupropion, Imipenem/cilastatin, Enflurane Drugs that cause tardive dyskinesia Correct Answer: Antipsychotics, metoclopramide Drugs that cause diabetes insipidus Correct Answer: Lithium, demeclocycline Drugs that cause fanconi syndrome Correct Answer: Expired tetracycline Drugs that cause hemorrhagic cystitis Correct Answer: Cyclophosphamide, ifosfamide Drugs that cause interstitial nephritis Correct Answer: Methicillin, NSAIDs, furosemide Drugs that cause SIADH Correct Answer: Carbamazepine, Cyclophosphamide, SSRIs Drugs that cause dry cough Correct Answer: ACE inhibitors Drugs that cause pulmonary fibrosis Correct Answer: Bleomycin, amiodarone, methotrexate, busulfan Drugs that cause antimuscarinic reaction Correct Answer: Atropine, TCAs, H1-blockers, antipsychotics Drugs that cause disulfiram-like reaction Correct Answer: Metronidazole, certain cephalosporins, griseofulvin, procarbazine, 1st-generation sulfonylureas Drugs that cause nephrotoxicity/ototoxicity Correct Answer: Aminoglycosides, vancomycin, loop diuretics, cisplatin. Cisplatin toxicity may respond to amifostine. Cytochrome P-450 inducers Correct Answer: Chronic alcohol use, St. John's wort, Phenytoin Phenobarbital, Nevirapine, Rifampin, Griseofulvin, Carbamazepine Cytochrome P-450 substrates Correct Answer: Anti-epileptics, Theophylline, Warfarin OCPs Cytochrome P-450 inhibitors Correct Answer: Acute alcohol abuse, Ritonavir, Amiodarone, Cimetidine, Ketoconazole, Sulfonamides, Isoniazid (INH), Grapefruit juice, Quinidine, Macrolides, (except azithromycin) Sulfa drugs Correct Answer: Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonamide antibiotics, Sulfasalazine, Sulfonylureas. Patients with sulfa allergies may develop fever, urinary tract infection, Stevens- Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives). Symptoms range from mild to life threatening. -azole Correct Answer: Ergosterol synthesis inhibitor -bendazole Correct Answer: Antiparasitic/antihelmintic -cillin Correct Answer: Peptidoglycan synthesis inhibitor -cycline Correct Answer: Protein synthesis inhibitor -ivir Correct Answer: Neuraminidase inhibitor -navir Correct Answer: Protease inhibitor -ovir Correct Answer: DNA polymerase inhibitor -thromycin Correct Answer: Macrolide antibiotic -ane Correct Answer: Inhalational general anesthetic -azine Correct Answer: Typical antipsychotic -barbital Correct Answer: Barbiturate -caine Correct Answer: Local anesthetic -etine Correct Answer: SSRI