MPharm Master of Pharmacy Master of Pharmacy: Pharmacokinetics and Pharmacodynamics 5 — Questions and Answers
Question 1: The Emax model in pharmacodynamics relates drug effect to concentration. At concentrations much lower than EC50, the relationship approximates:
- Zero-order kinetics
- A linear relationship between concentration and effect (Correct answer)
- Maximum effect plateau
- Inverse dose-response
Correct answer: A linear relationship between concentration and effect
When C << EC50, the Emax equation simplifies to E ≈ Emax × C/EC50, which is a linear approximation.
Question 2: Population pharmacokinetics differs from classical PK analysis primarily in that it:
- Uses in vitro data exclusively to predict in vivo behavior
- Quantifies between-subject variability and identifies covariates explaining it (Correct answer)
- Requires rich sampling from each individual
- Only applies to single-dose studies
Correct answer: Quantifies between-subject variability and identifies covariates explaining it
Population PK uses nonlinear mixed-effects modeling (e.g., NONMEM) to characterize PK parameters and their variability across a patient population with sparse sampling.
Question 3: Which statement about drug protein binding is correct regarding pharmacokinetic implications?
- Only bound drug is pharmacologically active
- Changes in protein binding always significantly alter total drug clearance
- Only the unbound fraction is available for distribution, metabolism, and receptor interaction (Correct answer)
- Protein binding does not affect volume of distribution
Correct answer: Only the unbound fraction is available for distribution, metabolism, and receptor interaction
Only free (unbound) drug crosses membranes, interacts with receptors, and is available for metabolism and elimination.
Question 4: A patient with chronic kidney disease (CKD) stage 4 is prescribed a drug that is 80% renally eliminated unchanged. The expected outcome without dose adjustment is:
- Increased first-pass metabolism compensating for reduced clearance
- Drug accumulation and potential toxicity due to reduced elimination (Correct answer)
- Enhanced therapeutic effect with no risk of toxicity
- Increased volume of distribution reducing plasma concentrations
Correct answer: Drug accumulation and potential toxicity due to reduced elimination
CKD severely reduces renal clearance of drugs eliminated unchanged, causing accumulation and elevated plasma concentrations that may lead to toxicity.
Question 5: Mechanism-based (irreversible) enzyme inhibition differs from reversible inhibition because it:
- Can be overcome by increasing substrate concentration
- Requires new enzyme synthesis for recovery of metabolic capacity (Correct answer)
- Only affects non-CYP enzymes
- Has no clinical significance for drug interactions
Correct answer: Requires new enzyme synthesis for recovery of metabolic capacity
Mechanism-based inhibitors covalently inactivate the enzyme, so metabolic function is only restored when new enzyme protein is synthesized.
Question 6: The concept of therapeutic index (TI) is best defined as:
- The ratio of the dose producing a therapeutic effect to the minimum effective dose
- The ratio of the median toxic dose (TD50) to the median effective dose (ED50) (Correct answer)
- The plasma concentration range associated with efficacy
- The difference between Emax and EC50
Correct answer: The ratio of the median toxic dose (TD50) to the median effective dose (ED50)
The therapeutic index is TD50/ED50; drugs with a narrow TI require careful monitoring because toxic and therapeutic doses are close.
Question 7: Pharmacodynamic tolerance that develops due to reduced receptor density following prolonged agonist exposure is specifically called:
- Metabolic tolerance
- Pharmacokinetic tolerance
- Down-regulation (receptor desensitization) (Correct answer)
- Cross-tolerance
Correct answer: Down-regulation (receptor desensitization)
Prolonged agonist stimulation causes receptor internalization and degradation (down-regulation), reducing receptor number and attenuating drug response.
MPharm Master of Pharmacy Master of Pharmacy: Pharmacokinetics and Pharmacodynamics 5
The Emax model in pharmacodynamics relates drug effect to concentration.
At concentrations much lower than EC50, the relationship approximates: