USMLE Step 1 Pharmacology 2025 — 55 Q&A High-Yield Practice
Questions Verified
Series:
CrashCourses Professional Study Series
Author:
Dr Z. Moomba, MBChB, MRCPsych | BethelWellness Ltd
Exam Target:
USMLE Step 1
Year:
2025/2026
Format:
55 Questions with Verified Answers and Rationales
>
Author's Note:
This document is an original work produced for the CrashCourses Professional Study Series.
Clinical questions and professional scenarios were composed by Dr Z. Moomba based on current
exam objectives, published guidelines, and evidence-based sources (2024–2025). All patient
names, ages, and case details are fictional. Any resemblance to existing published Q&A banks is
coincidental. For personal study use only — not for reproduction or redistribution.
SECTION A — FOUNDATIONS
Question 1
A 45-year-old man with a seizure disorder presents to the emergency department after ingesting a
large amount of his anti-seizure medication in a suicide attempt. Toxicological screening confirms
massive phenytoin overdose. Which of the following pharmacokinetic principles best explains the
delayed clearance of the drug in this patient?
A) First-pass metabolism saturation
B) High volume of distribution into adipose tissue
C) Zero-order elimination kinetics
D) Irreversible binding to plasma proteins
,Answer: C
Rationale:
a) Phenytoin is a classic example of a drug that exhibits zero-order elimination kinetics at high,
toxic concentrations due to the saturation of hepatic metabolising enzymes.
b) The key feature is the massive overdose; at therapeutic doses, phenytoin follows first-order
kinetics, but at high doses, a constant amount of drug is eliminated per unit time, leading to rapid,
unpredictable accumulation and delayed clearance.
c) First-pass metabolism saturation (Option A) would increase oral bioavailability but does not
explain the delayed elimination phase seen in overdose.
d)
High-Yield Pearl:
The "PEA" drugs exhibit zero-order kinetics at high doses: Phenytoin, Ethanol, and Aspirin.
[Katzung Basic & Clinical Pharmacology 2024]
Question 2
A 60-year-old woman is prescribed an oral medication with a high degree of lipophilicity and a
volume of distribution (Vd) of 500 L. She has normal renal and hepatic function. Which of the
following characteristics is most likely associated with this drug?
A) It is primarily confined to the intravascular compartment.
B) It requires a loading dose to rapidly achieve therapeutic plasma concentrations.
C) It is highly bound to plasma albumin.
D) It is cleared entirely unchanged by the kidneys.
Answer: B
Rationale:
a) Drugs with a very high volume of distribution (Vd) distribute extensively into extravascular
tissues, including adipose tissue, meaning plasma concentrations will initially be low.
b) To quickly achieve a target therapeutic plasma concentration for a drug with a high Vd, a
loading dose is necessary.
c) Highly bound to plasma albumin (Option C) would result in a low Vd (e.g., 3-5 L), as the drug
remains trapped in the intravascular space.
d)
,High-Yield Pearl:
Loading Dose = (Cp × Vd) / F. Maintenance dose depends on clearance, but loading dose
depends on Vd. [USMLE Step 1 First Aid 2025]
Question 3
A 55-year-old man with non-obstructive urinary retention post-surgery is administered
bethanechol. Shortly after, he experiences sweating, salivation, and abdominal cramps. The
intended therapeutic effect of this drug is mediated by which of the following mechanisms?
A) Inhibition of acetylcholinesterase
B) Direct agonism of muscarinic receptors
C) Blockade of presynaptic alpha-2 receptors
D) Direct agonism of nicotinic receptors
Answer: B
Rationale:
a) Bethanechol is a direct-acting muscarinic cholinergic agonist that stimulates the detrusor
muscle of the bladder and relaxes the trigone/sphincter, promoting voiding.
b) The adverse effects (sweating, salivation) are classic signs of systemic muscarinic
overstimulation, confirming its direct mechanism at muscarinic sites.
c) Inhibition of acetylcholinesterase (Option A) describes drugs like neostigmine; while they also
treat urinary retention, bethanechol acts directly on the receptor, not the enzyme.
d)
High-Yield Pearl:
"Bethany, call (bethanechol) me to empty my bladder and bowels." It treats post-operative ileus
and urinary retention. [Goodman & Gilman's 2024]
Question 4
A 32-year-old woman presents to the clinic complaining of severe dry mouth, blurry vision, and
constipation. She recently started taking a new medication for motion sickness. Which of the
following drugs is most likely responsible for her symptoms?
A) Scopolamine
B) Pilocarpine
C) Physostigmine
D) Pralidoxime
, Answer: A
Rationale:
a) Scopolamine is a muscarinic antagonist (anticholinergic) that readily crosses the blood-brain
barrier to prevent motion sickness.
b) The patient's symptoms (dry mouth, blurry vision due to cycloplegia, constipation) represent a
classic anticholinergic side effect profile.
c) Pilocarpine (Option B) is a muscarinic agonist and would cause the opposite effects (salivation,
miosis, diarrhoea).
d)
High-Yield Pearl:
Anticholinergic toxidrome: "Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a
bone, the bowel and bladder lose their tone, and the heart runs alone." [Goldfrank's Toxicologic
Emergencies]
Question 5
During a minor surgical procedure, a patient experiences acute, severe hypotension. The
anaesthesiologist administers a bolus of phenylephrine. Which of the following haemodynamic
responses is most likely to occur immediately following this administration?
A) Increased heart rate and decreased systemic vascular resistance
B) Increased heart rate and increased systemic vascular resistance
C) Decreased heart rate and increased systemic vascular resistance
D) Decreased heart rate and decreased systemic vascular resistance
Answer: C
Rationale:
a) Phenylephrine is a pure alpha-1 adrenergic agonist. It causes profound vasoconstriction,
increasing systemic vascular resistance (SVR) and blood pressure.
b) The sudden rise in blood pressure triggers a baroreceptor reflex, leading to increased vagal
tone and a subsequent decrease in heart rate (reflex bradycardia).
c) Increased heart rate (Option B) would be expected with a drug that also has beta-1 activity (like
norepinephrine) or a pure beta-1 agonist, which phenylephrine lacks.
d)
Questions Verified
Series:
CrashCourses Professional Study Series
Author:
Dr Z. Moomba, MBChB, MRCPsych | BethelWellness Ltd
Exam Target:
USMLE Step 1
Year:
2025/2026
Format:
55 Questions with Verified Answers and Rationales
>
Author's Note:
This document is an original work produced for the CrashCourses Professional Study Series.
Clinical questions and professional scenarios were composed by Dr Z. Moomba based on current
exam objectives, published guidelines, and evidence-based sources (2024–2025). All patient
names, ages, and case details are fictional. Any resemblance to existing published Q&A banks is
coincidental. For personal study use only — not for reproduction or redistribution.
SECTION A — FOUNDATIONS
Question 1
A 45-year-old man with a seizure disorder presents to the emergency department after ingesting a
large amount of his anti-seizure medication in a suicide attempt. Toxicological screening confirms
massive phenytoin overdose. Which of the following pharmacokinetic principles best explains the
delayed clearance of the drug in this patient?
A) First-pass metabolism saturation
B) High volume of distribution into adipose tissue
C) Zero-order elimination kinetics
D) Irreversible binding to plasma proteins
,Answer: C
Rationale:
a) Phenytoin is a classic example of a drug that exhibits zero-order elimination kinetics at high,
toxic concentrations due to the saturation of hepatic metabolising enzymes.
b) The key feature is the massive overdose; at therapeutic doses, phenytoin follows first-order
kinetics, but at high doses, a constant amount of drug is eliminated per unit time, leading to rapid,
unpredictable accumulation and delayed clearance.
c) First-pass metabolism saturation (Option A) would increase oral bioavailability but does not
explain the delayed elimination phase seen in overdose.
d)
High-Yield Pearl:
The "PEA" drugs exhibit zero-order kinetics at high doses: Phenytoin, Ethanol, and Aspirin.
[Katzung Basic & Clinical Pharmacology 2024]
Question 2
A 60-year-old woman is prescribed an oral medication with a high degree of lipophilicity and a
volume of distribution (Vd) of 500 L. She has normal renal and hepatic function. Which of the
following characteristics is most likely associated with this drug?
A) It is primarily confined to the intravascular compartment.
B) It requires a loading dose to rapidly achieve therapeutic plasma concentrations.
C) It is highly bound to plasma albumin.
D) It is cleared entirely unchanged by the kidneys.
Answer: B
Rationale:
a) Drugs with a very high volume of distribution (Vd) distribute extensively into extravascular
tissues, including adipose tissue, meaning plasma concentrations will initially be low.
b) To quickly achieve a target therapeutic plasma concentration for a drug with a high Vd, a
loading dose is necessary.
c) Highly bound to plasma albumin (Option C) would result in a low Vd (e.g., 3-5 L), as the drug
remains trapped in the intravascular space.
d)
,High-Yield Pearl:
Loading Dose = (Cp × Vd) / F. Maintenance dose depends on clearance, but loading dose
depends on Vd. [USMLE Step 1 First Aid 2025]
Question 3
A 55-year-old man with non-obstructive urinary retention post-surgery is administered
bethanechol. Shortly after, he experiences sweating, salivation, and abdominal cramps. The
intended therapeutic effect of this drug is mediated by which of the following mechanisms?
A) Inhibition of acetylcholinesterase
B) Direct agonism of muscarinic receptors
C) Blockade of presynaptic alpha-2 receptors
D) Direct agonism of nicotinic receptors
Answer: B
Rationale:
a) Bethanechol is a direct-acting muscarinic cholinergic agonist that stimulates the detrusor
muscle of the bladder and relaxes the trigone/sphincter, promoting voiding.
b) The adverse effects (sweating, salivation) are classic signs of systemic muscarinic
overstimulation, confirming its direct mechanism at muscarinic sites.
c) Inhibition of acetylcholinesterase (Option A) describes drugs like neostigmine; while they also
treat urinary retention, bethanechol acts directly on the receptor, not the enzyme.
d)
High-Yield Pearl:
"Bethany, call (bethanechol) me to empty my bladder and bowels." It treats post-operative ileus
and urinary retention. [Goodman & Gilman's 2024]
Question 4
A 32-year-old woman presents to the clinic complaining of severe dry mouth, blurry vision, and
constipation. She recently started taking a new medication for motion sickness. Which of the
following drugs is most likely responsible for her symptoms?
A) Scopolamine
B) Pilocarpine
C) Physostigmine
D) Pralidoxime
, Answer: A
Rationale:
a) Scopolamine is a muscarinic antagonist (anticholinergic) that readily crosses the blood-brain
barrier to prevent motion sickness.
b) The patient's symptoms (dry mouth, blurry vision due to cycloplegia, constipation) represent a
classic anticholinergic side effect profile.
c) Pilocarpine (Option B) is a muscarinic agonist and would cause the opposite effects (salivation,
miosis, diarrhoea).
d)
High-Yield Pearl:
Anticholinergic toxidrome: "Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a
bone, the bowel and bladder lose their tone, and the heart runs alone." [Goldfrank's Toxicologic
Emergencies]
Question 5
During a minor surgical procedure, a patient experiences acute, severe hypotension. The
anaesthesiologist administers a bolus of phenylephrine. Which of the following haemodynamic
responses is most likely to occur immediately following this administration?
A) Increased heart rate and decreased systemic vascular resistance
B) Increased heart rate and increased systemic vascular resistance
C) Decreased heart rate and increased systemic vascular resistance
D) Decreased heart rate and decreased systemic vascular resistance
Answer: C
Rationale:
a) Phenylephrine is a pure alpha-1 adrenergic agonist. It causes profound vasoconstriction,
increasing systemic vascular resistance (SVR) and blood pressure.
b) The sudden rise in blood pressure triggers a baroreceptor reflex, leading to increased vagal
tone and a subsequent decrease in heart rate (reflex bradycardia).
c) Increased heart rate (Option B) would be expected with a drug that also has beta-1 activity (like
norepinephrine) or a pure beta-1 agonist, which phenylephrine lacks.
d)
