GAMSAT Pharmacology Fundamentals 2 — Questions and Answers
Question 1: A drug has a therapeutic index (TI) of 2. Which statement best describes this drug?
- It has a wide margin between therapeutic and toxic doses
- The toxic dose is twice the effective dose, indicating a narrow safety margin (Correct answer)
- It requires twice-daily dosing to maintain efficacy
- It has two distinct therapeutic mechanisms
Correct answer: The toxic dose is twice the effective dose, indicating a narrow safety margin
A TI of 2 means the toxic dose (TD50) is only twice the effective dose (ED50), indicating a narrow safety window and higher risk of toxicity.
Question 2: Which pharmacokinetic process is primarily responsible for the first-pass effect?
- Renal filtration before systemic circulation
- Hepatic metabolism of orally absorbed drug before it reaches systemic circulation (Correct answer)
- Protein binding in plasma reducing free drug levels
- Pulmonary metabolism during the first breath cycle
Correct answer: Hepatic metabolism of orally absorbed drug before it reaches systemic circulation
The first-pass effect occurs when orally absorbed drugs pass through the portal circulation to the liver, where hepatic enzymes metabolise a significant fraction before the drug reaches systemic circulation.
Question 3: An antagonist is described as 'competitive' and 'surmountable.' What does this mean?
- It cannot be displaced regardless of agonist concentration
- Increasing agonist concentration can overcome the blockade and restore the maximal response (Correct answer)
- It permanently binds to the receptor, reducing efficacy
- It acts at a different receptor to indirectly reduce the agonist's effect
Correct answer: Increasing agonist concentration can overcome the blockade and restore the maximal response
A competitive surmountable antagonist reversibly binds the same receptor site as the agonist; increasing agonist concentration shifts the dose-response curve right but the same Emax is achievable.
Question 4: Which cytochrome P450 enzyme is most commonly responsible for drug-drug interactions in clinical practice?
- CYP2E1
- CYP1A2
- CYP3A4 (Correct answer)
- CYP2C9
Correct answer: CYP3A4
CYP3A4 metabolises approximately 50% of all marketed drugs, making it the most clinically significant isoenzyme for drug-drug interactions.
Question 5: A patient takes Drug X (a CYP2D6 substrate) with Drug Y (a potent CYP2D6 inhibitor). What is the most likely outcome?
- Reduced plasma levels of Drug X due to increased clearance
- Elevated plasma levels of Drug X due to decreased metabolism (Correct answer)
- Decreased therapeutic effect of Drug Y
- Increased renal excretion of Drug X compensating for reduced hepatic metabolism
Correct answer: Elevated plasma levels of Drug X due to decreased metabolism
Inhibiting CYP2D6 reduces the metabolism of Drug X, leading to higher plasma concentrations and potential toxicity.
Question 6: The volume of distribution (Vd) of a drug is 350 L in a 70 kg adult. What does this suggest?
- The drug is confined largely to the plasma compartment
- The drug distributes extensively into peripheral tissues (Correct answer)
- The drug is primarily bound to plasma proteins
- The drug has poor oral bioavailability
Correct answer: The drug distributes extensively into peripheral tissues
A Vd of 350 L far exceeds total body water (~42 L), indicating extensive sequestration in peripheral tissues such as fat or muscle.
Question 7: Which statement accurately describes zero-order kinetics?
- A constant fraction of drug is eliminated per unit time
- A constant amount of drug is eliminated per unit time regardless of concentration (Correct answer)
- Elimination rate doubles as plasma concentration doubles
- The half-life shortens as plasma concentration decreases
Correct answer: A constant amount of drug is eliminated per unit time regardless of concentration
Zero-order kinetics occurs when elimination pathways are saturated, so a fixed amount (not fraction) of drug is removed per unit time, leading to linear accumulation.
GAMSAT Pharmacology Fundamentals 2
A drug has a therapeutic index (TI) of 2.
Which statement best describes this drug?