NU553 Unit 1 Principles of Therapeutics Exam 1
Advanced Pharmacology and
Pharmacotherapeutics 2026
1. A patient with acute heart failure is administered intravenous furosemide
rather than oral. This route is chosen primarily because:
A. It avoids first-pass metabolism, ensuring 100% bioavailability
B. It has a slower onset of action, reducing adverse effects
C. It requires a higher total dose to achieve therapeutic effect
D. It distributes only to the intravascular space
Answer: A. It avoids first-pass metabolism, ensuring 100% bioavailability
*Rationale: IV administration bypasses absorption and first-pass hepatic
metabolism, delivering the drug directly into systemic circulation with 100%
bioavailability. Option C is incorrect because IV often requires lower doses.
Option D is false as IV drugs still distribute to tissues.*
2. A drug has a high volume of distribution (Vd > 40 L). This suggests the
drug:
A. Is primarily confined to the plasma compartment
B. Is highly bound to plasma albumin
C. Is extensively distributed into peripheral tissues
D. Has poor lipid solubility
Answer: C. Is extensively distributed into peripheral tissues
Rationale: High Vd indicates extensive tissue distribution (e.g., lipophilic drugs
like digoxin). Low Vd (e.g., warfarin) suggests confinement to plasma. High
plasma protein binding typically reduces Vd.
3. A patient with hepatic cirrhosis has reduced cytochrome P450 enzyme
activity. The nurse expects the half-life of a drug metabolized by CYP3A4 to:
A. Decrease, requiring higher doses
B. Remain unchanged due to renal compensation
C. Increase, requiring lower doses or longer intervals
D. Fluctuate unpredictably
,Answer: C. Increase, requiring lower doses or longer intervals
*Rationale: Reduced hepatic metabolism prolongs half-life (t1/2 = 0.693 *
Vd/CL). Doses must be reduced or intervals extended to avoid toxicity. Renal
compensation does not apply here.*
4. Which of the following drug characteristics most favors passive diffusion
across the blood-brain barrier?
A. High polarity and ionization at physiologic pH
B. Low molecular weight and high lipophilicity
C. High protein binding and large molecular size
D. Active transport via P-glycoprotein
Answer: B. Low molecular weight and high lipophilicity
Rationale: The BBB is lipophilic. Small, nonpolar, unionized drugs cross easily. P-
glycoprotein actively excludes many drugs.
5. A drug follows zero-order kinetics. Which statement accurately describes
its elimination?
A. A constant fraction of the drug is eliminated per unit time
B. Half-life remains constant regardless of dose
C. A constant amount of the drug is eliminated per unit time
D. Elimination rate is directly proportional to drug concentration
Answer: C. A constant amount of the drug is eliminated per unit time
Rationale: Zero-order (e.g., phenytoin, ethanol) means
constant amount eliminated/time. First-order (most drugs) means
constant fraction eliminated/time. Zero-order kinetics lead to a non-constant half-
life.
6. Grapefruit juice inhibits CYP3A4 in the gut wall. A patient taking
simvastatin (CYP3A4 substrate) drinks a large glass of grapefruit juice daily.
The expected outcome is:
A. Reduced simvastatin effect and lower LDL reduction
B. Increased simvastatin concentration and risk of myopathy
C. No change due to first-pass metabolism in the liver
D. Accelerated simvastatin clearance by P-glycoprotein
Answer: B. Increased simvastatin concentration and risk of myopathy
*Rationale: CYP3A4 inhibition decreases presystemic metabolism, raising
,simvastatin levels, increasing risk of myopathy/rhabdomyolysis. Patients should
avoid grapefruit.*
7. A patient is receiving digoxin. Which concurrent medication would most
likely increase digoxin toxicity by displacing it from plasma protein binding
sites?
A. Metoprolol
B. Lisinopril
C. Warfarin
D. Furosemide
Answer: C. Warfarin
Rationale: Digoxin is not highly protein bound (25%). However, warfarin is highly
bound and could displace other drugs, but more clinically relevant: furosemide
can cause hypokalemia, increasing digoxin toxicity. The best answer here is
warfarin for displacement (though digoxin's low binding makes displacement less
significant than electrolyte effects). A better classic example is phenytoin
displacing warfarin. Given options, warfarin is the only highly bound drug that
might compete, but the rationale notes furosemide's hypokalemia is a greater risk.
(In advanced questions, always consider electrolyte effects for digoxin).
8. A renally cleared drug has an elimination half-life of 8 hours in a healthy
young adult. In an 85-year-old patient with an estimated creatinine clearance
of 30 mL/min, the expected half-life would be approximately:
A. 2 hours
B. 8 hours
C. 16 hours
D. 32 hours
Answer: C. 16 hours
*Rationale: Half-life is inversely related to clearance. Reduced renal function
prolongs half-life. With CrCl ~30 (moderate impairment), half-life roughly doubles
to ~16 hours. Dose adjustment is required.*
9. A drug administered orally has an absolute bioavailability of 0.5 (50%).
This means:
A. 50% of the drug is excreted unchanged in urine
B. 50% of the drug reaches systemic circulation compared to IV dose
, C. 50% of the drug is metabolized by the liver
D. 50% of the drug is absorbed from the gut but then redistributed
Answer: B. 50% of the drug reaches systemic circulation compared to IV dose
*Rationale: Absolute bioavailability (F) = (AUC oral / AUC IV) x 100%. It
accounts for absorption and first-pass loss.*
10. Which transporter is responsible for the biliary excretion of many drugs
and is a common site of drug-drug interactions?
A. Organic anion transporting polypeptide (OATP)
B. P-glycoprotein (P-gp)
C. Glucose transporter (GLUT)
D. Sodium-potassium ATPase
Answer: B. P-glycoprotein (P-gp)
Rationale: P-gp is an efflux transporter in the liver (canalicular membrane),
kidneys, and intestine. It pumps drugs into bile and urine. OATP is an uptake
transporter.
11. A patient is started on a drug that is a weak acid with a pKa of 4.4. In the
stomach (pH 1.4), the drug will primarily be:
A. Ionized and lipid-soluble, favoring absorption
B. Non-ionized and lipid-soluble, favoring absorption
C. Ionized and water-soluble, hindering absorption
D. Non-ionized and water-soluble, hindering absorption
Answer: B. Non-ionized and lipid-soluble, favoring absorption
Rationale: For a weak acid, pH < pKa favors non-ionized form. Non-ionized =
lipophilic = crosses membranes. Weak acids absorb well in acidic stomach.
12. The rate of drug elimination is directly proportional to plasma
concentration in which type of kinetics?
A. Zero-order
B. First-order
C. Michaelis-Menten saturation
D. Nonlinear kinetics
Answer: B. First-order
Rationale: First-order: Rate = k × C (constant fraction). Zero-order: Rate = k
(constant amount, independent of C).
Advanced Pharmacology and
Pharmacotherapeutics 2026
1. A patient with acute heart failure is administered intravenous furosemide
rather than oral. This route is chosen primarily because:
A. It avoids first-pass metabolism, ensuring 100% bioavailability
B. It has a slower onset of action, reducing adverse effects
C. It requires a higher total dose to achieve therapeutic effect
D. It distributes only to the intravascular space
Answer: A. It avoids first-pass metabolism, ensuring 100% bioavailability
*Rationale: IV administration bypasses absorption and first-pass hepatic
metabolism, delivering the drug directly into systemic circulation with 100%
bioavailability. Option C is incorrect because IV often requires lower doses.
Option D is false as IV drugs still distribute to tissues.*
2. A drug has a high volume of distribution (Vd > 40 L). This suggests the
drug:
A. Is primarily confined to the plasma compartment
B. Is highly bound to plasma albumin
C. Is extensively distributed into peripheral tissues
D. Has poor lipid solubility
Answer: C. Is extensively distributed into peripheral tissues
Rationale: High Vd indicates extensive tissue distribution (e.g., lipophilic drugs
like digoxin). Low Vd (e.g., warfarin) suggests confinement to plasma. High
plasma protein binding typically reduces Vd.
3. A patient with hepatic cirrhosis has reduced cytochrome P450 enzyme
activity. The nurse expects the half-life of a drug metabolized by CYP3A4 to:
A. Decrease, requiring higher doses
B. Remain unchanged due to renal compensation
C. Increase, requiring lower doses or longer intervals
D. Fluctuate unpredictably
,Answer: C. Increase, requiring lower doses or longer intervals
*Rationale: Reduced hepatic metabolism prolongs half-life (t1/2 = 0.693 *
Vd/CL). Doses must be reduced or intervals extended to avoid toxicity. Renal
compensation does not apply here.*
4. Which of the following drug characteristics most favors passive diffusion
across the blood-brain barrier?
A. High polarity and ionization at physiologic pH
B. Low molecular weight and high lipophilicity
C. High protein binding and large molecular size
D. Active transport via P-glycoprotein
Answer: B. Low molecular weight and high lipophilicity
Rationale: The BBB is lipophilic. Small, nonpolar, unionized drugs cross easily. P-
glycoprotein actively excludes many drugs.
5. A drug follows zero-order kinetics. Which statement accurately describes
its elimination?
A. A constant fraction of the drug is eliminated per unit time
B. Half-life remains constant regardless of dose
C. A constant amount of the drug is eliminated per unit time
D. Elimination rate is directly proportional to drug concentration
Answer: C. A constant amount of the drug is eliminated per unit time
Rationale: Zero-order (e.g., phenytoin, ethanol) means
constant amount eliminated/time. First-order (most drugs) means
constant fraction eliminated/time. Zero-order kinetics lead to a non-constant half-
life.
6. Grapefruit juice inhibits CYP3A4 in the gut wall. A patient taking
simvastatin (CYP3A4 substrate) drinks a large glass of grapefruit juice daily.
The expected outcome is:
A. Reduced simvastatin effect and lower LDL reduction
B. Increased simvastatin concentration and risk of myopathy
C. No change due to first-pass metabolism in the liver
D. Accelerated simvastatin clearance by P-glycoprotein
Answer: B. Increased simvastatin concentration and risk of myopathy
*Rationale: CYP3A4 inhibition decreases presystemic metabolism, raising
,simvastatin levels, increasing risk of myopathy/rhabdomyolysis. Patients should
avoid grapefruit.*
7. A patient is receiving digoxin. Which concurrent medication would most
likely increase digoxin toxicity by displacing it from plasma protein binding
sites?
A. Metoprolol
B. Lisinopril
C. Warfarin
D. Furosemide
Answer: C. Warfarin
Rationale: Digoxin is not highly protein bound (25%). However, warfarin is highly
bound and could displace other drugs, but more clinically relevant: furosemide
can cause hypokalemia, increasing digoxin toxicity. The best answer here is
warfarin for displacement (though digoxin's low binding makes displacement less
significant than electrolyte effects). A better classic example is phenytoin
displacing warfarin. Given options, warfarin is the only highly bound drug that
might compete, but the rationale notes furosemide's hypokalemia is a greater risk.
(In advanced questions, always consider electrolyte effects for digoxin).
8. A renally cleared drug has an elimination half-life of 8 hours in a healthy
young adult. In an 85-year-old patient with an estimated creatinine clearance
of 30 mL/min, the expected half-life would be approximately:
A. 2 hours
B. 8 hours
C. 16 hours
D. 32 hours
Answer: C. 16 hours
*Rationale: Half-life is inversely related to clearance. Reduced renal function
prolongs half-life. With CrCl ~30 (moderate impairment), half-life roughly doubles
to ~16 hours. Dose adjustment is required.*
9. A drug administered orally has an absolute bioavailability of 0.5 (50%).
This means:
A. 50% of the drug is excreted unchanged in urine
B. 50% of the drug reaches systemic circulation compared to IV dose
, C. 50% of the drug is metabolized by the liver
D. 50% of the drug is absorbed from the gut but then redistributed
Answer: B. 50% of the drug reaches systemic circulation compared to IV dose
*Rationale: Absolute bioavailability (F) = (AUC oral / AUC IV) x 100%. It
accounts for absorption and first-pass loss.*
10. Which transporter is responsible for the biliary excretion of many drugs
and is a common site of drug-drug interactions?
A. Organic anion transporting polypeptide (OATP)
B. P-glycoprotein (P-gp)
C. Glucose transporter (GLUT)
D. Sodium-potassium ATPase
Answer: B. P-glycoprotein (P-gp)
Rationale: P-gp is an efflux transporter in the liver (canalicular membrane),
kidneys, and intestine. It pumps drugs into bile and urine. OATP is an uptake
transporter.
11. A patient is started on a drug that is a weak acid with a pKa of 4.4. In the
stomach (pH 1.4), the drug will primarily be:
A. Ionized and lipid-soluble, favoring absorption
B. Non-ionized and lipid-soluble, favoring absorption
C. Ionized and water-soluble, hindering absorption
D. Non-ionized and water-soluble, hindering absorption
Answer: B. Non-ionized and lipid-soluble, favoring absorption
Rationale: For a weak acid, pH < pKa favors non-ionized form. Non-ionized =
lipophilic = crosses membranes. Weak acids absorb well in acidic stomach.
12. The rate of drug elimination is directly proportional to plasma
concentration in which type of kinetics?
A. Zero-order
B. First-order
C. Michaelis-Menten saturation
D. Nonlinear kinetics
Answer: B. First-order
Rationale: First-order: Rate = k × C (constant fraction). Zero-order: Rate = k
(constant amount, independent of C).
