DHA Pharmacist Pharmacokinetics and Pharmacodynamics — Questions and Answers
Question 1: A drug has a volume of distribution (Vd) of 700 L in a 70 kg patient. What does this suggest?
- The drug is largely confined to plasma
- The drug is extensively distributed into tissues (Correct answer)
- The drug has poor oral bioavailability
- The drug undergoes significant first-pass metabolism
Correct answer: The drug is extensively distributed into tissues
A large Vd (much greater than total body water ~42 L) indicates the drug distributes extensively into peripheral tissues rather than remaining in plasma.
Question 2: A drug has a half-life of 8 hours. Approximately how long will it take to reach steady-state plasma concentration with regular dosing?
- 8 hours
- 16 hours
- 40 hours (Correct answer)
- 80 hours
Correct answer: 40 hours
Steady-state is reached after approximately 4–5 half-lives; 5 × 8 hours = 40 hours.
Question 3: Which route of administration completely bypasses first-pass hepatic metabolism?
- Oral
- Rectal (proximal)
- Intravenous (Correct answer)
- Sublingual and intravenous only
Correct answer: Intravenous
Intravenous administration delivers the drug directly into systemic circulation, completely bypassing hepatic first-pass metabolism.
Question 4: The bioavailability of an oral drug is 25%. If the IV dose producing the desired effect is 20 mg, what oral dose is required to achieve the same effect?
- 5 mg
- 20 mg
- 40 mg
- 80 mg (Correct answer)
Correct answer: 80 mg
Oral dose = IV dose / bioavailability = 20 mg / 0.25 = 80 mg to achieve equivalent systemic exposure.
Question 5: Hepatic clearance of a high-extraction drug (extraction ratio > 0.7) is primarily dependent on:
- Plasma protein binding
- Hepatic blood flow (Correct answer)
- Renal function
- Glomerular filtration rate
Correct answer: Hepatic blood flow
High-extraction drugs are efficiently cleared by the liver on first pass, so their clearance is limited by hepatic blood flow, not enzyme capacity.
Question 6: A drug follows first-order kinetics. Which of the following statements is TRUE?
- A constant amount of drug is eliminated per unit time
- The rate of elimination is proportional to drug concentration (Correct answer)
- Elimination pathways become saturated at therapeutic doses
- Half-life increases as plasma concentration increases
Correct answer: The rate of elimination is proportional to drug concentration
In first-order kinetics, a constant fraction (not amount) of drug is eliminated per unit time, meaning the rate is proportional to concentration.
Question 7: Which pharmacokinetic parameter is most useful when calculating a maintenance dose to maintain a target steady-state plasma concentration?
- Volume of distribution (Vd)
- Half-life (t½)
- Total body clearance (CL) (Correct answer)
- Peak plasma concentration (Cmax)
Correct answer: Total body clearance (CL)
Maintenance dose rate = CL × target Css; clearance determines how much drug must be given per unit time to replace what is eliminated.
Question 8: On a dose-response curve, potency refers to:
- The maximum effect a drug can produce
- The dose required to produce 50% of the maximum effect (ED50) (Correct answer)
- The slope of the dose-response curve
- The difference between ED50 and LD50
Correct answer: The dose required to produce 50% of the maximum effect (ED50)
Potency is indicated by the ED50 — a more potent drug requires a lower dose to produce 50% of maximal effect; it does not describe the magnitude of effect.
Question 9: A full agonist differs from a partial agonist in that a full agonist:
- Binds to a different receptor subtype
- Produces maximal receptor activation (efficacy = 1) (Correct answer)
- Has a lower affinity for the receptor
- Blocks receptor activation by antagonists
Correct answer: Produces maximal receptor activation (efficacy = 1)
A full agonist has intrinsic efficacy of 1, producing the maximum possible response; a partial agonist has intrinsic efficacy between 0 and 1, producing submaximal response even at full receptor occupancy.
Question 10: The therapeutic index (TI) of a drug is calculated as:
- ED50 / LD50
- LD50 / ED50 (Correct answer)
- Cmax / MEC
- Vd / CL
Correct answer: LD50 / ED50
TI = LD50 / ED50; a higher TI indicates a wider margin between effective and lethal doses, meaning a safer drug.
Question 11: A competitive antagonist differs from a non-competitive antagonist because a competitive antagonist:
- Cannot be overcome by increasing agonist concentration
- Permanently binds to the receptor
- Can be displaced by increasing agonist concentration, shifting the curve right (Correct answer)
- Decreases the maximum effect of the agonist
Correct answer: Can be displaced by increasing agonist concentration, shifting the curve right
Competitive antagonists reversibly bind at the same site as the agonist; adding more agonist can displace them, restoring maximal effect but requiring higher doses.
Question 12: Drug tolerance is best described as:
- An immune-mediated hypersensitivity reaction to a drug
- A decreased response to a drug after repeated administration requiring higher doses for the same effect (Correct answer)
- An increased sensitivity to a drug after initial exposure
- The inability to metabolize a drug due to genetic polymorphism
Correct answer: A decreased response to a drug after repeated administration requiring higher doses for the same effect
Tolerance is a pharmacological adaptation where repeated drug exposure causes diminished response, necessitating dose escalation to achieve the original effect.
Question 13: Which of the following best describes the Emax model in pharmacodynamics?
- Drug effect increases linearly with dose without a maximum
- Drug effect follows a sigmoidal curve and reaches a maximum ceiling effect (Correct answer)
- Drug effect is proportional only to free drug concentration
- Drug effect depends solely on the route of administration
Correct answer: Drug effect follows a sigmoidal curve and reaches a maximum ceiling effect
The Emax model describes a sigmoidal concentration-effect relationship where effect increases with concentration but plateaus at Emax when all receptors are occupied.
Question 14: A patient on warfarin is started on rifampicin. Rifampicin is a potent CYP2C9 inducer. What pharmacokinetic change is expected and what clinical action is required?
- Warfarin levels increase; reduce warfarin dose
- Warfarin metabolism increases; increase warfarin dose to maintain anticoagulation (Correct answer)
- Warfarin absorption decreases; switch to parenteral warfarin
- Rifampicin inhibits warfarin; monitor for bleeding and reduce dose
Correct answer: Warfarin metabolism increases; increase warfarin dose to maintain anticoagulation
Rifampicin induces CYP2C9, accelerating warfarin metabolism and lowering plasma levels, which reduces anticoagulant effect and increases thrombosis risk; the warfarin dose must be increased.
