NURS 6521 ADVANCED PHARMACOLOGY:
200-QUESTION MIDTERM
COMPREHENSIVE EXAMINATION WITH
VERIFIED ANSWERS AND CLINICAL
RATIONALES
SECTION 1: PHARMACOKINETICS &
PHARMACODYNAMICS
Question 1
First-pass metabolism occurs primarily in which organ?
A) Kidneys
B) Lungs
C) Liver
D) Intestines
Correct Answer: C
Rationale: First-pass metabolism occurs when a drug is metabolized in the liver
before reaching systemic circulation, reducing its bioavailability. Drugs administered
orally pass through the hepatic portal system and undergo metabolism by hepatic
enzymes, particularly the CYP450 system. This is why some drugs require higher oral
doses than intravenous doses to achieve therapeutic effects. The kidneys are
responsible for drug excretion, not first-pass metabolism. The lungs are involved in
elimination of volatile drugs but are not the primary site. Intestinal metabolism
occurs to a lesser extent through enteric enzymes and the gut microbiome .
Question 2
Bioavailability refers to:
,A) The distribution of a drug to target tissues
B) The amount of active drug that reaches systemic circulation
C) The rate at which a drug is metabolized
D) The time required for drug excretion
Correct Answer: B
Rationale: Bioavailability is the fraction of the administered drug dose that reaches
systemic circulation in its unchanged, active form. Intravenous administration has
100% bioavailability because the drug bypasses absorption barriers. Oral
bioavailability is affected by first-pass metabolism, drug solubility, and formulation
factors. Distribution describes drug movement from blood to tissues; metabolism
describes drug biotransformation; excretion describes drug elimination from the
body .
Question 3
A drug's half-life determines:
A) Its potency at receptor sites
B) Its duration of action and dosing interval
C) The rate of drug absorption
D) The extent of protein binding
Correct Answer: B
Rationale: Half-life (t½) is the time required for plasma concentration to decrease by
50%. It determines dosing frequency and time to reach steady state. Drugs with
shorter half-lives require more frequent dosing, while longer half-lives allow once-
daily or extended-interval dosing. Potency is determined by receptor affinity, not
half-life. Absorption rate is determined by drug formulation and route. Protein
binding influences distribution and free drug concentration .
Question 4
A drug is 95% protein bound. If a second drug displaces it from protein binding sites,
what happens to the free drug concentration?
,A) Increases by 5%
B) Approximately doubles
C) Remains unchanged
D) Decreases by half
Correct Answer: B
Rationale: The free fraction changes from 5% to 10% — effectively doubling the free
drug concentration. Highly bound drugs (>90%) are most susceptible to clinically
significant displacement interactions, which can lead to increased drug effects and
toxicity. This principle is particularly important for drugs like warfarin and phenytoin .
Question 5
Steady state is typically achieved after approximately how many half-lives?
A) 2
B) 3
C) 4-5
D) 10
Correct Answer: C
Rationale: Steady state is achieved after approximately 4-5 half-lives of regular
dosing. For example, a drug with a 12-hour half-life would reach steady state in
about 60 hours (12 hours × 5). This principle guides dosing interval decisions to
ensure therapeutic drug levels are maintained .
SECTION 2: PHARMACOGENOMICS & SPECIAL
POPULATIONS
Question 6
A patient is a poor metabolizer of CYP2D6. Which drug is MOST likely to cause
toxicity at standard doses?
, A) Codeine
B) Tamoxifen
C) Metoprolol
D) Clopidogrel
Correct Answer: C
Rationale: Metoprolol is metabolized by CYP2D6; poor metabolizers have higher
plasma levels, leading to excessive beta-blockade (bradycardia, hypotension).
Codeine and tamoxifen are prodrugs requiring CYP2D6 activation, so poor
metabolizers would have reduced effects (less pain relief, less therapeutic effect for
breast cancer). Clopidogrel is a prodrug activated by CYP2C19, not CYP2D6 .
Question 7
Before starting carbamazepine in an Asian patient, which test is most important to
reduce serious dermatologic risk?
A) HLA-B*1502 genotyping
B) CYP3A5 genotype
C) CYP2C9 genotype
D) G6PD activity
Correct Answer: A
Rationale: HLA-B*1502 strongly predicts Stevens-Johnson syndrome/toxic epidermal
necrolysis in Asian patients. The FDA has issued a boxed warning recommending
screening in patients of Asian ancestry before starting carbamazepine. If positive,
carbamazepine should be avoided .
Question 8
A 60-year-old African-American man lives with several chronic health problems.
Genetic factors are likely to influence his etiology and/or treatment of:
A) Hypertension
B) Diabetes mellitus
C) COPD
D) Osteoarthritis
200-QUESTION MIDTERM
COMPREHENSIVE EXAMINATION WITH
VERIFIED ANSWERS AND CLINICAL
RATIONALES
SECTION 1: PHARMACOKINETICS &
PHARMACODYNAMICS
Question 1
First-pass metabolism occurs primarily in which organ?
A) Kidneys
B) Lungs
C) Liver
D) Intestines
Correct Answer: C
Rationale: First-pass metabolism occurs when a drug is metabolized in the liver
before reaching systemic circulation, reducing its bioavailability. Drugs administered
orally pass through the hepatic portal system and undergo metabolism by hepatic
enzymes, particularly the CYP450 system. This is why some drugs require higher oral
doses than intravenous doses to achieve therapeutic effects. The kidneys are
responsible for drug excretion, not first-pass metabolism. The lungs are involved in
elimination of volatile drugs but are not the primary site. Intestinal metabolism
occurs to a lesser extent through enteric enzymes and the gut microbiome .
Question 2
Bioavailability refers to:
,A) The distribution of a drug to target tissues
B) The amount of active drug that reaches systemic circulation
C) The rate at which a drug is metabolized
D) The time required for drug excretion
Correct Answer: B
Rationale: Bioavailability is the fraction of the administered drug dose that reaches
systemic circulation in its unchanged, active form. Intravenous administration has
100% bioavailability because the drug bypasses absorption barriers. Oral
bioavailability is affected by first-pass metabolism, drug solubility, and formulation
factors. Distribution describes drug movement from blood to tissues; metabolism
describes drug biotransformation; excretion describes drug elimination from the
body .
Question 3
A drug's half-life determines:
A) Its potency at receptor sites
B) Its duration of action and dosing interval
C) The rate of drug absorption
D) The extent of protein binding
Correct Answer: B
Rationale: Half-life (t½) is the time required for plasma concentration to decrease by
50%. It determines dosing frequency and time to reach steady state. Drugs with
shorter half-lives require more frequent dosing, while longer half-lives allow once-
daily or extended-interval dosing. Potency is determined by receptor affinity, not
half-life. Absorption rate is determined by drug formulation and route. Protein
binding influences distribution and free drug concentration .
Question 4
A drug is 95% protein bound. If a second drug displaces it from protein binding sites,
what happens to the free drug concentration?
,A) Increases by 5%
B) Approximately doubles
C) Remains unchanged
D) Decreases by half
Correct Answer: B
Rationale: The free fraction changes from 5% to 10% — effectively doubling the free
drug concentration. Highly bound drugs (>90%) are most susceptible to clinically
significant displacement interactions, which can lead to increased drug effects and
toxicity. This principle is particularly important for drugs like warfarin and phenytoin .
Question 5
Steady state is typically achieved after approximately how many half-lives?
A) 2
B) 3
C) 4-5
D) 10
Correct Answer: C
Rationale: Steady state is achieved after approximately 4-5 half-lives of regular
dosing. For example, a drug with a 12-hour half-life would reach steady state in
about 60 hours (12 hours × 5). This principle guides dosing interval decisions to
ensure therapeutic drug levels are maintained .
SECTION 2: PHARMACOGENOMICS & SPECIAL
POPULATIONS
Question 6
A patient is a poor metabolizer of CYP2D6. Which drug is MOST likely to cause
toxicity at standard doses?
, A) Codeine
B) Tamoxifen
C) Metoprolol
D) Clopidogrel
Correct Answer: C
Rationale: Metoprolol is metabolized by CYP2D6; poor metabolizers have higher
plasma levels, leading to excessive beta-blockade (bradycardia, hypotension).
Codeine and tamoxifen are prodrugs requiring CYP2D6 activation, so poor
metabolizers would have reduced effects (less pain relief, less therapeutic effect for
breast cancer). Clopidogrel is a prodrug activated by CYP2C19, not CYP2D6 .
Question 7
Before starting carbamazepine in an Asian patient, which test is most important to
reduce serious dermatologic risk?
A) HLA-B*1502 genotyping
B) CYP3A5 genotype
C) CYP2C9 genotype
D) G6PD activity
Correct Answer: A
Rationale: HLA-B*1502 strongly predicts Stevens-Johnson syndrome/toxic epidermal
necrolysis in Asian patients. The FDA has issued a boxed warning recommending
screening in patients of Asian ancestry before starting carbamazepine. If positive,
carbamazepine should be avoided .
Question 8
A 60-year-old African-American man lives with several chronic health problems.
Genetic factors are likely to influence his etiology and/or treatment of:
A) Hypertension
B) Diabetes mellitus
C) COPD
D) Osteoarthritis
