MPharm Master of Pharmacy Master of Pharmacy: Pharmacokinetics and Pharmacodynamics 3 — Questions and Answers
Question 1: For a drug following two-compartment pharmacokinetics, the terminal elimination phase primarily reflects:
- Absorption from the GI tract
- Distribution from central to peripheral compartment
- Redistribution from peripheral back to central compartment followed by elimination (Correct answer)
- Hepatic first-pass metabolism
Correct answer: Redistribution from peripheral back to central compartment followed by elimination
In two-compartment models, the terminal beta phase represents slow redistribution of drug from peripheral tissues back to the central compartment, then elimination.
Question 2: Which enzyme system is primarily responsible for Phase I oxidative metabolism of most drugs in the liver?
- Glucuronosyltransferases (UGT)
- Sulfotransferases (SULT)
- Cytochrome P450 (CYP) enzymes (Correct answer)
- N-acetyltransferases (NAT)
Correct answer: Cytochrome P450 (CYP) enzymes
Cytochrome P450 enzymes are the major Phase I metabolizing enzymes responsible for oxidation, reduction, and hydrolysis of most drugs.
Question 3: Apparent clearance (CL/F) differs from true systemic clearance because it accounts for:
- Renal versus hepatic clearance ratio
- Incomplete bioavailability (F) after oral dosing (Correct answer)
- Protein binding in plasma
- First-order versus zero-order elimination
Correct answer: Incomplete bioavailability (F) after oral dosing
CL/F is apparent clearance calculated from oral dose data; dividing by F corrects for the fraction of dose that actually reaches systemic circulation.
Question 4: A drug that acts as a partial agonist at a receptor will:
- Always produce less effect than a full agonist at any concentration
- Produce the same maximum effect as a full agonist given sufficient dose
- Activate the receptor but with lower intrinsic efficacy than a full agonist (Correct answer)
- Block the receptor without producing any biological effect
Correct answer: Activate the receptor but with lower intrinsic efficacy than a full agonist
Partial agonists bind and activate receptors but have lower intrinsic efficacy, producing a submaximal response even at receptor saturation.
Question 5: Renal clearance of a drug exceeding glomerular filtration rate (GFR) suggests:
- Extensive tubular reabsorption
- Active tubular secretion in addition to filtration (Correct answer)
- Plasma protein binding reducing free drug
- Hepatic elimination contributing to renal clearance
Correct answer: Active tubular secretion in addition to filtration
If CLrenal > GFR × fu, active tubular secretion must be occurring to add drug to the filtrate beyond what was filtered.
Question 6: The Michaelis-Menten constant (Km) in drug metabolism represents:
- The maximum rate of metabolic reaction
- The drug concentration at which metabolism rate is half of Vmax (Correct answer)
- The total enzyme concentration in the liver
- The intrinsic hepatic clearance
Correct answer: The drug concentration at which metabolism rate is half of Vmax
Km is the substrate concentration at which the enzymatic reaction proceeds at half its maximum velocity (Vmax), reflecting enzyme-substrate affinity.
Question 7: Tachyphylaxis is best described as:
- Increased drug response after repeated dosing due to receptor sensitization
- Rapid decrease in response following repeated doses in a short time period (Correct answer)
- Permanent loss of receptor function due to prolonged agonist exposure
- Cross-tolerance between two different drug classes
Correct answer: Rapid decrease in response following repeated doses in a short time period
Tachyphylaxis is a rapid, short-term decrease in response to a drug after repeated administration, often due to receptor desensitization or depletion of mediators.
MPharm Master of Pharmacy Master of Pharmacy: Pharmacokinetics and Pharmacodynamics 3
For a drug following two-compartment pharmacokinetics, the terminal elimination phase primarily reflects: