Pharmacology Pharmacokinetics and Drug Metabolism 3 — Questions and Answers
Question 1: Which factor most directly determines whether a drug undergoes glomerular filtration in the kidney?
- Lipid solubility
- pKa of the drug
- Degree of plasma protein binding (Correct answer)
- Hepatic extraction ratio
Correct answer: Degree of plasma protein binding
Only the free (unbound) fraction of a drug is filtered at the glomerulus; protein-bound drug cannot pass through the filtration barrier.
Question 2: A weakly acidic drug (pKa 4.5) is in an alkaline urine environment (pH 8). What happens to its renal excretion?
- Decreased, because the drug is more lipid-soluble at high pH
- Increased, because the ionized form is trapped in tubular urine (Correct answer)
- Decreased, because the drug is more protein-bound at high pH
- Unchanged, because pKa is fixed
Correct answer: Increased, because the ionized form is trapped in tubular urine
In alkaline urine, weak acids are predominantly ionized, preventing tubular reabsorption and increasing urinary excretion (ion trapping).
Question 3: What is the primary consequence of inhibiting CYP2D6 with fluoxetine in a patient taking codeine?
- Increased conversion of codeine to morphine
- Decreased conversion of codeine to morphine (Correct answer)
- Increased renal clearance of codeine
- Decreased protein binding of codeine
Correct answer: Decreased conversion of codeine to morphine
CYP2D6 converts codeine to its active metabolite morphine; inhibition by fluoxetine reduces morphine formation, decreasing analgesic efficacy.
Question 4: During pregnancy, increased plasma volume and renal blood flow alter drug pharmacokinetics. Which parameter is most likely to increase for a renally cleared drug?
- Half-life
- Volume of distribution
- Renal clearance (Correct answer)
- Protein binding
Correct answer: Renal clearance
Increased GFR and renal blood flow during pregnancy enhance renal clearance of drugs eliminated by the kidneys.
Question 5: An elderly patient has reduced hepatic blood flow. Which class of drugs will show the greatest increase in bioavailability when given orally?
- Low-extraction-ratio drugs
- High-extraction-ratio drugs (Correct answer)
- Renally cleared drugs
- Drugs with zero-order kinetics
Correct answer: High-extraction-ratio drugs
High-extraction drugs depend on hepatic blood flow for clearance; reduced flow decreases first-pass metabolism and increases oral bioavailability.
Question 6: A loading dose is calculated primarily based on which pharmacokinetic parameter?
- Clearance
- Half-life
- Volume of distribution (Correct answer)
- Bioavailability
Correct answer: Volume of distribution
Loading dose = target concentration × volume of distribution; Vd determines how much drug is needed to achieve the desired plasma level quickly.
Question 7: Which metabolic reaction converts prodrug enalapril to its active form enalaprilat?
- Glucuronidation
- Hydrolysis (Correct answer)
- Oxidation by CYP3A4
- N-acetylation
Correct answer: Hydrolysis
Enalapril is hydrolyzed (an ester bond is cleaved) by intestinal and hepatic esterases to produce the active ACE inhibitor enalaprilat.
Pharmacology Pharmacokinetics and Drug Metabolism 3
Which factor most directly determines whether a drug undergoes glomerular filtration in the kidney?