, HESI Pharmacology V2 Exam 2026/2027: Elsevier Evolve
NCSBN Clinical Judgment Model-Aligned Study Set with
Questions & Rationales - 127 Questions
Section 1: Pharmacokinetics and Pharmacodynamics (Questions 1-3)
1 A drug exhibits a volume of distribution (Vd) of 0.5 L/kg and a clearance (Cl) of 0.1 L/hr/kg. Which of the
following best describes the expected half-life (t½) of this drug?
A) Approximately 3.5 hours
B) Approximately 6.9 hours
C) Approximately 10.4 hours
D) Approximately 13.9 hours
Answer: A
Rationale: Half-life is calculated as t½ = (0.693 × Vd) / Cl. Substituting: (0.693 × 0.5) / 0.1 = 0..1 = 3.465
hours 3.5 hours. Option B (6.9 hours) would result from using Vd = 1 L/kg. Option C (10.4 hours) uses Cl = 0.05
L/hr/kg. Option D (13.9 hours) corresponds to Vd = 2 L/kg with Cl = 0.1 L/hr/kg.
2 A drug is administered as a continuous intravenous infusion. At steady state, the plasma concentration is 10
mg/L. The infusion rate is 50 mg/hr. The drug is known to be eliminated by first-order kinetics and has a
volume of distribution of 20 L. Which of the following is the elimination rate constant (ke) of the drug?
A) 0.25 hr¹
B) 0.5 hr¹
C) 0.75 hr¹
D) 1.0 hr¹
Answer: A
Rationale: At steady state, infusion rate (R) = clearance (Cl) × Css. Cl = R / Css = 50 mg/hr / 10 mg/L = 5 L/hr.
Clearance also equals ke × Vd, so ke = Cl / Vd = 5 L/hr / 20 L = 0.25 hr¹. Option B (0.5 hr¹) would result if Vd =
10 L. Option C (0.75 hr¹) and D (1.0 hr¹) correspond to incorrect calculations (e.g., using Css in denominator
without converting units).
3 A drug is a weak acid with pKa = 4.5. After oral administration, it is absorbed in the stomach (pH 1.5) and then
enters the bloodstream (pH 7.4). Which of the following best describes the predominant form of the drug in the
stomach and in the blood, respectively?
A) Stomach: unionized; Blood: ionized
B) Stomach: ionized; Blood: unionized
C) Stomach: unionized; Blood: unionized
D) Stomach: ionized; Blood: ionized
Answer: A
Rationale: For a weak acid, the Henderson-Hasselbalch equation is pH = pKa + log([A {]/[HA]). In the stomach (pH
1.5), pH < pKa, so [HA] > [A], thus the unionized form predominates, favoring absorption. In blood (pH 7.4), pH >
pKa, so [A] > [HA], thus the ionized form predominates, trapping the drug in the blood. Option B reverses the
forms. Options C and D are incorrect because the ratio changes with pH.
,Section 2: Autonomic Nervous System Drugs (Questions 4-16)
4 A patient with a history of hypertension and type 2 diabetes is prescribed a non-selective beta-blocker for
migraine prophylaxis. Which of the following physiological responses is most likely to occur in this patient due
to the drug's mechanism of action?
A) Increased heart rate due to reflex sympathetic activation
B) Masking of tachycardia as a sign of hypoglycemia
C) Enhanced lipolysis in adipose tissue
D) Bronchodilation from beta-2 receptor blockade
Answer: B
Rationale: Non-selective beta-blockers block both beta-1 and beta-2 receptors. Blocking beta-2 receptors can mask
the adrenergic symptoms of hypoglycemia (e.g., tachycardia, palpitations), which is dangerous in diabetic patients.
Option A is incorrect because beta-blockade decreases heart rate, not increases. Option C is wrong because
beta-blockade inhibits lipolysis. Option D is incorrect; beta-2 blockade causes bronchoconstriction, not
bronchodilation.
5 A patient receiving an intravenous infusion of norepinephrine develops a sudden drop in blood pressure upon
accidental extravasation. The nurse administers phentolamine locally. Which pharmacological principle best
explains the therapeutic effect of phentolamine in this scenario?
A) Competitive antagonism at alpha-1 adrenergic receptors causing vasodilation
B) Partial agonist activity at beta-2 receptors leading to smooth muscle relaxation
C) Inhibition of neuronal reuptake of norepinephrine, reducing local concentration
D) Direct vasoconstriction via alpha-2 receptor activation to counteract extravasation
Answer: A
Rationale: Phentolamine is a non-selective alpha-adrenergic antagonist that competitively blocks alpha-1 receptors
on vascular smooth muscle, causing vasodilation and reversing the vasoconstriction caused by norepinephrine
extravasation. Option B is incorrect as phentolamine does not act on beta receptors. Option C is wrong;
phentolamine does not inhibit reuptake. Option D is opposite; phentolamine causes vasodilation, not
vasoconstriction.
6 Which of the following best describes the effect of a selective beta-1 adrenergic antagonist on cardiac output in
a patient with compensated heart failure?
A) Immediate increase in cardiac output due to reflex sympathetic activation
B) Reduction in cardiac output primarily by decreasing heart rate and contractility
C) No change in cardiac output because beta-1 receptors are not involved
D) Increase in cardiac output due to unopposed alpha-mediated vasoconstriction
Answer: B
Rationale: Beta-1 selective antagonists (e.g., metoprolol) decrease heart rate and myocardial contractility by
blocking beta-1 receptors in the heart, leading to reduced cardiac output. In compensated heart failure, this
reduction is initially present but may improve long-term outcomes. Option A is incorrect because beta-blockade
does not increase heart rate. Option C is false; beta-1 receptors are the predominant cardiac subtype. Option D is
incorrect; unopposed alpha activity would increase afterload, not cardiac output.
7 A patient with glaucoma is treated with pilocarpine. Which of the following best describes the mechanism by
which pilocarpine reduces intraocular pressure?
A) Activation of muscarinic receptors on the ciliary muscle, increasing aqueous humor outflow
B) Blockade of beta-adrenergic receptors in the ciliary body, reducing aqueous humor production
, C) Stimulation of alpha-2 adrenergic receptors, decreasing aqueous humor formation
D) Inhibition of carbonic anhydrase, reducing sodium and water transport in the ciliary epithelium
Answer: A
Rationale: Pilocarpine is a direct-acting muscarinic agonist that contracts the ciliary muscle and opens the trabecular
meshwork, facilitating aqueous humor outflow and lowering intraocular pressure. Option B describes beta-blockers
like timolol. Option C describes alpha-2 agonists like brimonidine. Option D describes carbonic anhydrase
inhibitors like acetazolamide.
8 Which of the following statements accurately compares the effects of atropine and glycopyrrolate on the
autonomic nervous system?
A) Both drugs are non-selective muscarinic antagonists, but glycopyrrolate has a longer duration of action and
does not cross the blood-brain barrier.
B) Atropine is a selective M1 antagonist, while glycopyrrolate is a non-selective antagonist with greater central
nervous system penetration.
C) Both drugs are quaternary ammonium compounds that poorly penetrate the CNS, but atropine causes more
pronounced tachycardia.
D) Glycopyrrolate is a beta-2 agonist, while atropine is a muscarinic antagonist with similar peripheral effects.
Answer: A
Rationale: Both atropine and glycopyrrolate are non-selective muscarinic antagonists. Glycopyrrolate is a quaternary
ammonium compound that does not cross the blood-brain barrier, minimizing CNS effects, and has a longer
duration. Atropine is a tertiary amine that can enter the CNS. Option B is incorrect; atropine is non-selective.
Option C is wrong because atropine is not quaternary. Option D is incorrect; glycopyrrolate is not a beta-2 agonist.
9 A patient with myasthenia gravis is being treated with neostigmine. Which of the following best explains why
neostigmine is preferred over physostigmine for chronic management of this condition?
A) Neostigmine has a longer half-life and produces fewer muscarinic side effects due to its quaternary structure.
B) Physostigmine penetrates the blood-brain barrier, causing unacceptable central cholinergic side effects.
C) Neostigmine directly activates nicotinic receptors at the neuromuscular junction, while physostigmine does
not.
D) Physostigmine is more potent at inhibiting acetylcholinesterase, leading to excessive cholinergic crisis.
Answer: B
Rationale: Physostigmine is a tertiary amine that crosses the blood-brain barrier, causing CNS side effects (e.g.,
seizures, confusion), making it unsuitable for chronic use in myasthenia gravis. Neostigmine, a quaternary amine,
does not cross the BBB and thus avoids central effects. Option A is incorrect; neostigmine has a shorter half-life.
Option C is false; both drugs inhibit acetylcholinesterase, not directly activate receptors. Option D is not the
primary reason; both can cause cholinergic crisis.
10 A researcher is studying a novel compound that selectively activates alpha-2 adrenergic receptors in the central
nervous system. Which of the following physiological effects would most likely be observed upon
administration of this compound?
A) Increased heart rate and contractility due to sympathetic outflow
B) Reduction in blood pressure and sedation due to decreased sympathetic outflow
C) Bronchoconstriction and mydriasis due to peripheral alpha-2 activation
D) Enhanced release of norepinephrine from presynaptic terminals
Answer: B
Rationale: Central alpha-2 receptor activation (e.g., by clonidine) reduces sympathetic outflow from the vasomotor
center, leading to decreased blood pressure, heart rate, and sedation. Option A is opposite; sympathetic outflow is
NCSBN Clinical Judgment Model-Aligned Study Set with
Questions & Rationales - 127 Questions
Section 1: Pharmacokinetics and Pharmacodynamics (Questions 1-3)
1 A drug exhibits a volume of distribution (Vd) of 0.5 L/kg and a clearance (Cl) of 0.1 L/hr/kg. Which of the
following best describes the expected half-life (t½) of this drug?
A) Approximately 3.5 hours
B) Approximately 6.9 hours
C) Approximately 10.4 hours
D) Approximately 13.9 hours
Answer: A
Rationale: Half-life is calculated as t½ = (0.693 × Vd) / Cl. Substituting: (0.693 × 0.5) / 0.1 = 0..1 = 3.465
hours 3.5 hours. Option B (6.9 hours) would result from using Vd = 1 L/kg. Option C (10.4 hours) uses Cl = 0.05
L/hr/kg. Option D (13.9 hours) corresponds to Vd = 2 L/kg with Cl = 0.1 L/hr/kg.
2 A drug is administered as a continuous intravenous infusion. At steady state, the plasma concentration is 10
mg/L. The infusion rate is 50 mg/hr. The drug is known to be eliminated by first-order kinetics and has a
volume of distribution of 20 L. Which of the following is the elimination rate constant (ke) of the drug?
A) 0.25 hr¹
B) 0.5 hr¹
C) 0.75 hr¹
D) 1.0 hr¹
Answer: A
Rationale: At steady state, infusion rate (R) = clearance (Cl) × Css. Cl = R / Css = 50 mg/hr / 10 mg/L = 5 L/hr.
Clearance also equals ke × Vd, so ke = Cl / Vd = 5 L/hr / 20 L = 0.25 hr¹. Option B (0.5 hr¹) would result if Vd =
10 L. Option C (0.75 hr¹) and D (1.0 hr¹) correspond to incorrect calculations (e.g., using Css in denominator
without converting units).
3 A drug is a weak acid with pKa = 4.5. After oral administration, it is absorbed in the stomach (pH 1.5) and then
enters the bloodstream (pH 7.4). Which of the following best describes the predominant form of the drug in the
stomach and in the blood, respectively?
A) Stomach: unionized; Blood: ionized
B) Stomach: ionized; Blood: unionized
C) Stomach: unionized; Blood: unionized
D) Stomach: ionized; Blood: ionized
Answer: A
Rationale: For a weak acid, the Henderson-Hasselbalch equation is pH = pKa + log([A {]/[HA]). In the stomach (pH
1.5), pH < pKa, so [HA] > [A], thus the unionized form predominates, favoring absorption. In blood (pH 7.4), pH >
pKa, so [A] > [HA], thus the ionized form predominates, trapping the drug in the blood. Option B reverses the
forms. Options C and D are incorrect because the ratio changes with pH.
,Section 2: Autonomic Nervous System Drugs (Questions 4-16)
4 A patient with a history of hypertension and type 2 diabetes is prescribed a non-selective beta-blocker for
migraine prophylaxis. Which of the following physiological responses is most likely to occur in this patient due
to the drug's mechanism of action?
A) Increased heart rate due to reflex sympathetic activation
B) Masking of tachycardia as a sign of hypoglycemia
C) Enhanced lipolysis in adipose tissue
D) Bronchodilation from beta-2 receptor blockade
Answer: B
Rationale: Non-selective beta-blockers block both beta-1 and beta-2 receptors. Blocking beta-2 receptors can mask
the adrenergic symptoms of hypoglycemia (e.g., tachycardia, palpitations), which is dangerous in diabetic patients.
Option A is incorrect because beta-blockade decreases heart rate, not increases. Option C is wrong because
beta-blockade inhibits lipolysis. Option D is incorrect; beta-2 blockade causes bronchoconstriction, not
bronchodilation.
5 A patient receiving an intravenous infusion of norepinephrine develops a sudden drop in blood pressure upon
accidental extravasation. The nurse administers phentolamine locally. Which pharmacological principle best
explains the therapeutic effect of phentolamine in this scenario?
A) Competitive antagonism at alpha-1 adrenergic receptors causing vasodilation
B) Partial agonist activity at beta-2 receptors leading to smooth muscle relaxation
C) Inhibition of neuronal reuptake of norepinephrine, reducing local concentration
D) Direct vasoconstriction via alpha-2 receptor activation to counteract extravasation
Answer: A
Rationale: Phentolamine is a non-selective alpha-adrenergic antagonist that competitively blocks alpha-1 receptors
on vascular smooth muscle, causing vasodilation and reversing the vasoconstriction caused by norepinephrine
extravasation. Option B is incorrect as phentolamine does not act on beta receptors. Option C is wrong;
phentolamine does not inhibit reuptake. Option D is opposite; phentolamine causes vasodilation, not
vasoconstriction.
6 Which of the following best describes the effect of a selective beta-1 adrenergic antagonist on cardiac output in
a patient with compensated heart failure?
A) Immediate increase in cardiac output due to reflex sympathetic activation
B) Reduction in cardiac output primarily by decreasing heart rate and contractility
C) No change in cardiac output because beta-1 receptors are not involved
D) Increase in cardiac output due to unopposed alpha-mediated vasoconstriction
Answer: B
Rationale: Beta-1 selective antagonists (e.g., metoprolol) decrease heart rate and myocardial contractility by
blocking beta-1 receptors in the heart, leading to reduced cardiac output. In compensated heart failure, this
reduction is initially present but may improve long-term outcomes. Option A is incorrect because beta-blockade
does not increase heart rate. Option C is false; beta-1 receptors are the predominant cardiac subtype. Option D is
incorrect; unopposed alpha activity would increase afterload, not cardiac output.
7 A patient with glaucoma is treated with pilocarpine. Which of the following best describes the mechanism by
which pilocarpine reduces intraocular pressure?
A) Activation of muscarinic receptors on the ciliary muscle, increasing aqueous humor outflow
B) Blockade of beta-adrenergic receptors in the ciliary body, reducing aqueous humor production
, C) Stimulation of alpha-2 adrenergic receptors, decreasing aqueous humor formation
D) Inhibition of carbonic anhydrase, reducing sodium and water transport in the ciliary epithelium
Answer: A
Rationale: Pilocarpine is a direct-acting muscarinic agonist that contracts the ciliary muscle and opens the trabecular
meshwork, facilitating aqueous humor outflow and lowering intraocular pressure. Option B describes beta-blockers
like timolol. Option C describes alpha-2 agonists like brimonidine. Option D describes carbonic anhydrase
inhibitors like acetazolamide.
8 Which of the following statements accurately compares the effects of atropine and glycopyrrolate on the
autonomic nervous system?
A) Both drugs are non-selective muscarinic antagonists, but glycopyrrolate has a longer duration of action and
does not cross the blood-brain barrier.
B) Atropine is a selective M1 antagonist, while glycopyrrolate is a non-selective antagonist with greater central
nervous system penetration.
C) Both drugs are quaternary ammonium compounds that poorly penetrate the CNS, but atropine causes more
pronounced tachycardia.
D) Glycopyrrolate is a beta-2 agonist, while atropine is a muscarinic antagonist with similar peripheral effects.
Answer: A
Rationale: Both atropine and glycopyrrolate are non-selective muscarinic antagonists. Glycopyrrolate is a quaternary
ammonium compound that does not cross the blood-brain barrier, minimizing CNS effects, and has a longer
duration. Atropine is a tertiary amine that can enter the CNS. Option B is incorrect; atropine is non-selective.
Option C is wrong because atropine is not quaternary. Option D is incorrect; glycopyrrolate is not a beta-2 agonist.
9 A patient with myasthenia gravis is being treated with neostigmine. Which of the following best explains why
neostigmine is preferred over physostigmine for chronic management of this condition?
A) Neostigmine has a longer half-life and produces fewer muscarinic side effects due to its quaternary structure.
B) Physostigmine penetrates the blood-brain barrier, causing unacceptable central cholinergic side effects.
C) Neostigmine directly activates nicotinic receptors at the neuromuscular junction, while physostigmine does
not.
D) Physostigmine is more potent at inhibiting acetylcholinesterase, leading to excessive cholinergic crisis.
Answer: B
Rationale: Physostigmine is a tertiary amine that crosses the blood-brain barrier, causing CNS side effects (e.g.,
seizures, confusion), making it unsuitable for chronic use in myasthenia gravis. Neostigmine, a quaternary amine,
does not cross the BBB and thus avoids central effects. Option A is incorrect; neostigmine has a shorter half-life.
Option C is false; both drugs inhibit acetylcholinesterase, not directly activate receptors. Option D is not the
primary reason; both can cause cholinergic crisis.
10 A researcher is studying a novel compound that selectively activates alpha-2 adrenergic receptors in the central
nervous system. Which of the following physiological effects would most likely be observed upon
administration of this compound?
A) Increased heart rate and contractility due to sympathetic outflow
B) Reduction in blood pressure and sedation due to decreased sympathetic outflow
C) Bronchoconstriction and mydriasis due to peripheral alpha-2 activation
D) Enhanced release of norepinephrine from presynaptic terminals
Answer: B
Rationale: Central alpha-2 receptor activation (e.g., by clonidine) reduces sympathetic outflow from the vasomotor
center, leading to decreased blood pressure, heart rate, and sedation. Option A is opposite; sympathetic outflow is
