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USMLE Pharmacology Syllabus

The Pharmacology syllabus for USMLE in full: 3 chapters and 9 topics, every one listed below, plus 50 Pharmacology flashcards with answers.

3Chapters
9Topics
50Flashcards

Pharmacology syllabus: all 3 chapters

Expand any chapter to see its topics and sub-topics.

  1. Pharmacokinetics

     3 topics
    • Drug absorption
    • Drug distribution
    • Drug metabolism

  2. Pharmacodynamics

     3 topics
    • Drug-receptor interaction
    • Dose-response relationship
    • Drug toxicity

  3. Autonomic Drugs

     3 topics
    • Sympathomimetics
    • Sympatholytics
    • Parasympathomimetics

USMLE Pharmacology flashcards — 50 questions with answers

  1. What is bioavailability (F), and what is its value for an intravenously administered drug?

    Bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation. $$F = \frac{\text{AUC}_{\text{oral}}}{\text{AUC}_{\text{IV}}}$$ For IV administration $F = 1$ (100%), because the drug bypasses first-pass metabolism and enters the blood directly.

  2. State the Henderson-Hasselbalch equation for a weak acid and explain how it predicts drug absorption across membranes.

    $$pH = pK_a + \log\frac{[A^{-}]}{[HA]}$$ Only the non-ionized (uncharged) form crosses lipid membranes. Weak acids are more non-ionized and absorbed in acidic environments; weak bases are more non-ionized and absorbed in basic environments ('acids in acid, bases in base').

  3. How does urinary ion trapping enhance elimination of a weak acid such as aspirin, and what agent is used?

    Alkalinizing the urine with sodium bicarbonate raises urine pH, ionizing the weak acid to $A^{-}$. The charged form cannot be reabsorbed across the tubular membrane and is trapped in the urine, increasing renal excretion. For a weak base overdose, acidify the urine instead.

  4. What is first-pass metabolism, and which routes of administration avoid it?

    First-pass metabolism is hepatic (and gut-wall) metabolism of an orally absorbed drug via the portal vein before it reaches systemic circulation, reducing bioavailability. It is bypassed by IV, sublingual, rectal (partially), inhalational, and transdermal routes.

  5. Contrast zero-order and first-order elimination kinetics, and give drug examples of each.

    Zero-order: a constant amount is eliminated per unit time regardless of concentration (straight line on a linear plot). First-order: a constant fraction is eliminated per unit time, rate proportional to concentration (straight line on a semilog plot). Zero-order: ethanol, high-dose phenytoin, high-dose aspirin. Most drugs are first-order.

  6. Define volume of distribution ($V_d$) and give its formula.

    $V_d$ is the theoretical volume needed to contain the total drug in the body at the plasma concentration. $$V_d = \frac{\text{amount of drug in body}}{\text{plasma drug concentration}}$$ Low $V_d$ suggests confinement to plasma (large/charged/protein-bound drugs); high $V_d$ suggests distribution into tissues/fat.

  7. How do plasma protein binding and tissue binding affect the volume of distribution?

    High plasma protein binding keeps drug in the vascular compartment, lowering $V_d$. High tissue binding pulls drug out of plasma, raising $V_d$ (often well above total body water). Only free (unbound) drug is pharmacologically active and available for elimination.

  8. Which drug property allows a drug to cross the blood-brain barrier and the placenta?

    High lipophilicity (non-ionized, uncharged, low molecular weight) allows passive diffusion across the blood-brain barrier and placenta. Charged/ionized and highly protein-bound drugs cross poorly.

  9. Define clearance (CL) and give the equation relating it to elimination rate and plasma concentration.

    Clearance is the volume of plasma cleared of drug per unit time. $$CL = \frac{\text{rate of elimination}}{C_p} = V_d \times k_e$$ where $k_e$ is the elimination rate constant and $C_p$ is plasma concentration.

  10. Give the formula for elimination half-life ($t_{1/2}$) in terms of $V_d$ and clearance.

    $$t_{1/2} = \frac{0.693 \times V_d}{CL}$$ In first-order kinetics it takes about $3.3$ half-lives to reach ~90% of steady state, and ~$4$–$5$ half-lives to reach steady state (or to be effectively eliminated).

  11. Write the equations for maintenance dose and loading dose.

    Maintenance dose: $$MD = \frac{C_{ss} \times CL \times \tau}{F}$$ Loading dose: $$LD = \frac{C_{ss} \times V_d}{F}$$ where $C_{ss}$ is target steady-state concentration, $\tau$ is the dosing interval, and $F$ is bioavailability. In renal/hepatic failure the loading dose is usually unchanged while the maintenance dose is reduced.

  12. What are Phase I versus Phase II drug metabolism reactions, and what is their general purpose?

    Phase I (oxidation, reduction, hydrolysis; mostly cytochrome P450) yields slightly polar, often still-active metabolites. Phase II (conjugation: glucuronidation, acetylation, sulfation, glutathione) yields very polar, usually inactive metabolites for excretion. Purpose: convert lipophilic drugs into water-soluble, excretable forms.

  13. Why do geriatric patients often lose Phase I metabolism before Phase II?

    With aging, cytochrome P450-dependent Phase I reactions decline first, while Phase II conjugation reactions are relatively preserved. This is why Phase II-dependent benzodiazepines (lorazepam, oxazepam, temazepam — 'LOT') are preferred in the elderly.

  14. Name three important cytochrome P450 inducers and three inhibitors relevant to drug interactions.

    Inducers (decrease drug levels): rifampin, phenytoin, carbamazepine, phenobarbital, griseofulvin, chronic alcohol, St. John's wort. Inhibitors (increase drug levels): cimetidine, ketoconazole, erythromycin/clarithromycin, grapefruit juice, isoniazid, ritonavir, acute alcohol, sulfonamides.

  15. Define an affinity constant and how affinity relates to $K_d$ in drug-receptor binding.

    Affinity is the tendency of a drug to bind its receptor. It is inversely related to the dissociation constant $K_d$: $$K_d = \frac{k_{off}}{k_{on}}$$ A lower $K_d$ means higher affinity. At equilibrium, $K_d$ equals the drug concentration that occupies 50% of receptors.

  16. Define potency versus efficacy in a dose-response relationship.

    Potency is the amount of drug needed to produce a given effect (reflected by $EC_{50}$/$ED_{50}$; leftward curve = more potent). Efficacy is the maximal effect a drug can produce ($E_{max}$; higher plateau = more efficacious). Potency depends on affinity; efficacy depends on intrinsic activity.

  17. Compare a full agonist, partial agonist, and inverse agonist.

    Full agonist: binds and produces the maximal response (intrinsic activity = 1). Partial agonist: binds but produces a submaximal response even at full occupancy (intrinsic activity between 0 and 1); acts as a partial antagonist in the presence of a full agonist. Inverse agonist: binds and produces the opposite effect (intrinsic activity < 0), reducing constitutive activity.

  18. How does a competitive antagonist alter an agonist dose-response curve, and how does this differ from a non-competitive antagonist?

    Competitive (reversible) antagonist: shifts the agonist curve rightward, decreasing potency but preserving $E_{max}$; effect is surmountable by more agonist. Non-competitive/irreversible antagonist: decreases $E_{max}$ (unsurmountable), reducing efficacy regardless of agonist concentration.

  19. Distinguish a pharmacologic antagonist, a physiologic antagonist, and a chemical antagonist.

    Pharmacologic antagonist binds the same receptor as the agonist and blocks it. Physiologic antagonist produces an opposing effect through a different receptor/pathway (e.g., epinephrine vs. histamine in anaphylaxis). Chemical antagonist inactivates the agonist by binding it directly (e.g., protamine binding heparin).

  20. Define the therapeutic index (TI) and write its formula.

    The therapeutic index measures drug safety: $$TI = \frac{TD_{50}}{ED_{50}}$$ (or $LD_{50}/ED_{50}$ in animals), the ratio of the dose toxic to 50% to the dose effective in 50%. A higher TI means a safer drug. Low-TI drugs (warfarin, digoxin, lithium, theophylline) need therapeutic monitoring.

Show the other 30 Pharmacology flashcards

  1. What does the $EC_{50}$ represent on a graded dose-response curve?

    The $EC_{50}$ is the concentration of drug that produces 50% of the maximal response ($E_{max}$). It reflects potency: a lower $EC_{50}$ indicates a more potent drug. On a quantal curve, the analogous term is $ED_{50}$, the dose effective in 50% of the population.

  2. Explain the concept of spare receptors and its effect on the $EC_{50}$ versus $K_d$.

    Spare receptors exist when a maximal response is achieved with less than full receptor occupancy. In this setting the $EC_{50}$ (50% of maximal effect) occurs at a concentration lower than $K_d$ (50% receptor occupancy), so $EC_{50} < K_d$.

  3. What is the mechanism and antidote for acetaminophen toxicity?

    Overdose depletes glutathione, allowing accumulation of the toxic Phase I metabolite NAPQI, which causes centrilobular hepatic necrosis. Antidote: N-acetylcysteine, which regenerates glutathione and provides sulfhydryl groups to detoxify NAPQI.

  4. Give the antidotes for: (a) opioid, (b) benzodiazepine, and (c) organophosphate poisoning.

    (a) Opioids: naloxone (or naltrexone). (b) Benzodiazepines: flumazenil (caution: can precipitate seizures). (c) Organophosphates (cholinesterase inhibitors): atropine plus pralidoxime (2-PAM), which regenerates acetylcholinesterase before aging.

  5. List the antidotes for warfarin, heparin, and direct thrombin inhibitor (dabigatran) toxicity.

    Warfarin: vitamin K (slow) plus fresh frozen plasma or PCC (rapid). Heparin: protamine sulfate. Dabigatran (direct thrombin inhibitor): idarucizumab. Factor Xa inhibitors (apixaban/rivaroxaban): andexanet alfa.

  6. What is the classic toxicity of aminoglycosides and how is it characterized?

    Aminoglycosides (gentamicin, tobramycin, amikacin) cause dose-dependent nephrotoxicity (acute tubular necrosis) and ototoxicity (cochlear and vestibular), the latter potentiated by loop diuretics. They can also cause neuromuscular blockade and are teratogenic.

  7. Identify the antidotes for iron poisoning, copper/Wilson disease, lead poisoning, and cyanide.

    Iron: deferoxamine or deferasirox. Copper/Wilson: penicillamine or trientine. Lead: EDTA, dimercaprol, succimer (DMSA for children). Cyanide: hydroxocobalamin, sodium thiosulfate, nitrites (induce methemoglobin).

  8. What receptors do sympathomimetics act on, and what are the second messengers for each adrenergic receptor subtype?

    $\alpha_1$: $G_q$ → increased IP3/DAG/$Ca^{2+}$. $\alpha_2$: $G_i$ → decreased cAMP. $\beta_1$, $\beta_2$, $\beta_3$: $G_s$ → increased cAMP. Sympathomimetics mimic the effects of endogenous catecholamines at these G-protein-coupled receptors.

  9. Compare the receptor selectivity and clinical use of epinephrine, norepinephrine, and isoproterenol.

    Epinephrine: $\alpha_1=\alpha_2$, $\beta_1=\beta_2$ (low dose $\beta$ predominates) — anaphylaxis, cardiac arrest. Norepinephrine: $\alpha_1 > \alpha_2 > \beta_1$ (minimal $\beta_2$) — septic shock/vasopressor. Isoproterenol: $\beta_1=\beta_2$ (no $\alpha$) — nonselective $\beta$-agonist, causes reflex tachycardia.

  10. Explain the 'epinephrine reversal' phenomenon caused by alpha-blockade.

    Normally epinephrine raises blood pressure via $\alpha_1$ vasoconstriction. After an $\alpha$-blocker (e.g., phentolamine), epinephrine's remaining $\beta_2$-mediated vasodilation dominates, so blood pressure paradoxically falls. Phenylephrine (pure $\alpha_1$) shows only a blunted response, not reversal.

  11. What is the mechanism and clinical use of dobutamine?

    Dobutamine is a predominantly $\beta_1$-selective agonist ($\beta_1 > \beta_2$) that increases myocardial contractility (positive inotrope) and heart rate. It is used in acute decompensated heart failure and cardiogenic shock, and as a pharmacologic cardiac stress test.

  12. Compare the actions of low-dose versus high-dose dopamine.

    Low dose: activates $D_1$ receptors (renal/mesenteric vasodilation, increased renal blood flow). Medium dose: activates $\beta_1$ (increased contractility and heart rate). High dose: activates $\alpha_1$ (vasoconstriction, increased blood pressure). Used in shock and heart failure.

  13. What are the clinical uses of the selective $\beta_2$-agonists albuterol and terbutaline?

    Albuterol (short-acting) and salmeterol/formoterol (long-acting) cause bronchodilation for acute asthma/COPD. Terbutaline and ritodrine relax the uterus (tocolysis) to delay preterm labor. $\beta_2$ agonism also shifts $K^{+}$ intracellularly, useful in hyperkalemia.

  14. How do amphetamine, ephedrine, and cocaine act as indirect sympathomimetics?

    Amphetamine releases stored catecholamines and reverses the reuptake transporter. Ephedrine releases stored norepinephrine (and has direct action). Cocaine blocks presynaptic reuptake of norepinephrine/dopamine. All increase synaptic catecholamine levels indirectly rather than binding receptors directly.

  15. What is the mechanism and primary use of phenylephrine?

    Phenylephrine is a selective $\alpha_1$-agonist causing vasoconstriction (raises blood pressure, causes reflex bradycardia), mydriasis without cycloplegia, and nasal decongestion. Used for hypotension, as a decongestant, and to dilate the pupil for eye exams.

  16. Describe the mechanism and uses of the $\alpha_2$-agonist clonidine.

    Clonidine is a central $\alpha_2$-agonist that reduces central sympathetic outflow, lowering blood pressure. Uses: hypertension (especially with renal disease), ADHD, Tourette syndrome, and to blunt opioid/alcohol withdrawal. Abrupt cessation causes rebound hypertension.

  17. How do non-selective ($\alpha_1 = \alpha_2$) alpha-blockers phentolamine and phenoxybenzamine differ?

    Phentolamine is a reversible/competitive non-selective $\alpha$-blocker (short-acting). Phenoxybenzamine is an irreversible non-selective $\alpha$-blocker (long-acting). Phenoxybenzamine is used preoperatively for pheochromocytoma; phentolamine treats catecholamine/tyramine-induced hypertensive crisis. Both cause reflex tachycardia and orthostatic hypotension.

  18. What are the clinical uses of the selective $\alpha_1$-blockers ('-osin' drugs) and their key side effect?

    Prazosin, terazosin, doxazosin, and tamsulosin block $\alpha_1$ to relax vascular and prostatic/bladder-neck smooth muscle. Uses: BPH (urinary symptoms) and hypertension; prazosin also treats PTSD nightmares. Key side effect: first-dose orthostatic hypotension. Tamsulosin is uroselective.

  19. Distinguish cardioselective from non-selective beta-blockers, and name the '-olol' mnemonic split.

    Cardioselective ($\beta_1$) blockers (A–M): atenolol, betaxolol, esmolol, metoprolol, acebutolol — safer in asthma/COPD. Non-selective ($\beta_1 = \beta_2$) blockers (N–Z): nadolol, propranolol, timolol, pindolol. Labetalol and carvedilol also block $\alpha_1$.

  20. List the major clinical uses and mechanisms by which beta-blockers help in cardiovascular disease.

    Beta-blockers reduce heart rate, contractility, and renin release (decreasing cAMP). Uses: angina, hypertension, post-MI/heart failure (reduce mortality), arrhythmias (SVT rate control), thyroid storm symptom control, glaucoma (timolol reduces aqueous humor), and migraine prophylaxis.

  21. Why must beta-blockers be avoided or used cautiously in a patient with a pheochromocytoma before alpha-blockade?

    Giving a beta-blocker first blocks $\beta_2$-mediated vasodilation while leaving $\alpha_1$-mediated vasoconstriction unopposed, causing a hypertensive crisis (unopposed alpha stimulation). Alpha-blockade (e.g., phenoxybenzamine) must be established before adding a beta-blocker. The same caution applies to cocaine-induced hypertension.

  22. What is the effect of beta-blockers in a diabetic patient regarding hypoglycemia?

    Non-selective beta-blockers mask the adrenergic warning symptoms of hypoglycemia (tremor, tachycardia, palpitations), leaving sweating intact, and can blunt glycogenolysis-mediated recovery. This masking effect can delay recognition of hypoglycemia.

  23. Compare the muscarinic and nicotinic acetylcholine receptors, including their signaling.

    Muscarinic ($M_1$–$M_5$) are G-protein-coupled: $M_1, M_3, M_5$ use $G_q$ (IP3/DAG); $M_2$ uses $G_i$ (decreased cAMP, slows heart). Nicotinic ($N_N$ ganglia/CNS, $N_M$ neuromuscular junction) are ligand-gated $Na^{+}/K^{+}$ ion channels causing fast depolarization.

  24. What is the mechanism and clinical use of bethanechol?

    Bethanechol is a direct muscarinic agonist resistant to acetylcholinesterase. It activates the bowel and bladder (increased motility/tone) and is used for postoperative ileus and urinary retention (non-obstructive, e.g., neurogenic bladder). 'Bethanechol activates the Bowel and Bladder.'

  25. Describe the mechanism and clinical uses of pilocarpine.

    Pilocarpine is a direct muscarinic agonist resistant to cholinesterase that contracts the ciliary muscle (open-angle glaucoma) and pupillary sphincter (closed-angle glaucoma), and stimulates secretions. Used for glaucoma (potent, enters eye) and for xerostomia/dry mouth in Sjögren syndrome.

  26. How does neostigmine differ from physostigmine, and give a clinical use of each.

    Both are reversible acetylcholinesterase inhibitors that increase acetylcholine. Neostigmine is charged and does NOT cross the blood-brain barrier — used for myasthenia gravis, postoperative ileus/urinary retention, and reversal of neuromuscular blockade. Physostigmine is uncharged and crosses into the CNS — used for anticholinergic (atropine) toxicity.

  27. What are the signs of cholinergic (muscarinic) excess, and give a mnemonic.

    DUMBBELSS / SLUDGE: Diarrhea, Urination, Miosis, Bradycardia/Bronchospasm, Emesis, Lacrimation, Salivation, Sweating (or Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis). Caused by organophosphates or cholinergic overdose; treat with atropine (+ pralidoxime for organophosphates).

  28. What is edrophonium and how was it historically used in myasthenia gravis?

    Edrophonium is a very short-acting acetylcholinesterase inhibitor. In the historical Tensilon test, it transiently improved muscle strength in myasthenia gravis (diagnostic); it also distinguished myasthenic crisis (improves) from cholinergic crisis (worsens). Largely replaced by antibody testing today.

  29. What is the mechanism of botulinum toxin, and how does it relate to the cholinergic system?

    Botulinum toxin is an indirect anticholinergic that cleaves SNARE proteins, preventing presynaptic release of acetylcholine at the neuromuscular junction and cholinergic terminals. This causes flaccid paralysis. Clinically used for dystonias, spasticity, blepharospasm, hyperhidrosis, chronic migraine, and cosmesis.

  30. Summarize the direct-acting cholinergic agonists and their target-organ mnemonic ('Bethanechol, Carbachol, Methacholine, Pilocarpine').

    Bethanechol → bladder and bowel (urinary retention, ileus). Carbachol → eye (glaucoma, constricts pupil, resistant to cholinesterase). Methacholine → challenge test for bronchial hyperreactivity (asthma diagnosis). Pilocarpine → glaucoma and dry mouth (potent, crosses into eye, stimulates secretions/sweat).

USMLE Pharmacology FAQ

What is in the USMLE Pharmacology syllabus?

USMLE Pharmacology is split into 3 chapters: Pharmacokinetics, Pharmacodynamics and Autonomic Drugs. Together they contain 9 topics.

How many chapters are in USMLE Pharmacology?

3 chapters, containing 9 topics. The largest chapter is Pharmacokinetics, with 3 topics.

Are there flashcards for USMLE Pharmacology?

Yes — a 50-card Pharmacology deck, printed in full in the flashcards section of this page and available in the Examius app with spaced repetition. The free plan covers one exam of your choice, including its flashcards; Examius Pro, a one-time purchase, unlocks every other exam and deck.