PSA Pharmacology Principles 2 — Questions and Answers
Question 1: A drug with a half-life of 6 hours is started at regular dosing intervals. Approximately when will it reach steady-state plasma concentration?
- After 1-2 half-lives (6-12 hours)
- After 2-3 half-lives (12-18 hours)
- After 4-5 half-lives (24-30 hours) (Correct answer)
- After 10 half-lives (60 hours)
Correct answer: After 4-5 half-lives (24-30 hours)
Steady state is reached after approximately 4-5 half-lives, regardless of the dosing interval or dose size.
Question 2: Which route of administration most reliably bypasses hepatic first-pass metabolism?
- Oral tablet
- Enteric-coated capsule
- Sublingual tablet (Correct answer)
- Modified-release oral formulation
Correct answer: Sublingual tablet
Sublingual administration allows drug absorption directly into systemic circulation via the sublingual veins, bypassing the portal circulation and hepatic first-pass effect.
Question 3: A drug has a volume of distribution (Vd) of 700 L. What does this indicate about the drug?
- It is confined mainly to the plasma compartment
- It distributes equally between plasma and interstitial fluid
- It is extensively distributed into peripheral tissues or fat (Correct answer)
- It has very high plasma protein binding
Correct answer: It is extensively distributed into peripheral tissues or fat
A large Vd (>100 L) indicates the drug distributes extensively into peripheral tissues or adipose tissue, with low plasma concentrations relative to total body drug.
Question 4: Creatinine clearance (CrCl) is primarily used to guide dose adjustment for which category of drugs?
- Drugs with high hepatic extraction ratios
- Drugs that are predominantly renally excreted unchanged (Correct answer)
- Highly lipophilic drugs with large volumes of distribution
- Drugs that undergo extensive plasma protein binding
Correct answer: Drugs that are predominantly renally excreted unchanged
CrCl estimates glomerular filtration rate and is used to adjust doses of renally excreted drugs (e.g., gentamicin, metformin) to prevent accumulation and toxicity.
Question 5: Why is a loading dose used when initiating therapy with certain drugs?
- To reduce the risk of adverse effects during initiation
- To rapidly achieve therapeutic plasma concentrations (Correct answer)
- To prolong the drug's effective half-life
- To saturate plasma protein binding sites
Correct answer: To rapidly achieve therapeutic plasma concentrations
A loading dose rapidly achieves therapeutic drug levels by filling the volume of distribution, which is particularly important for drugs with long half-lives where waiting for steady state would be clinically unacceptable.
Question 6: A drug undergoes Phase I metabolism primarily via CYP3A4. Which Phase I reaction is most commonly catalysed by CYP enzymes?
- Glucuronidation
- Sulfation
- Oxidation (Correct answer)
- Acetylation
Correct answer: Oxidation
CYP450 enzymes primarily catalyse oxidation reactions as Phase I metabolism, introducing or unmasking polar functional groups to facilitate drug elimination.
Question 7: A patient has eGFR of 20 mL/min/1.73m². Which pharmacokinetic parameter is most directly altered for a drug that is 90% renally excreted?
- Volume of distribution
- Oral bioavailability
- Total drug clearance (Correct answer)
- Plasma protein binding
Correct answer: Total drug clearance
Renal impairment reduces total drug clearance for renally excreted drugs, prolonging their half-life and increasing accumulation risk with standard dosing.
PSA Pharmacology Principles 2
A drug with a half-life of 6 hours is started at regular dosing intervals.
Approximately when will it reach steady-state plasma concentration?