Wattle Pharmacy Prep

Distribution and protein binding
Practice questions with explanations

Distribution and protein binding belongs to Pharmacokinetics and pharmacodynamics, which makes up about 10% of the Overseas Pharmacist Readiness Assessment (OPRA®). Answer each question yourself before opening the explanation.

1. Which situation makes a protein-binding displacement interaction clinically significant?

  1. A drug with a very large volume of distribution
  2. A drug with low protein binding
  3. Any two drugs that are protein bound
  4. A highly bound drug with a narrow therapeutic index and a small volume of distribution, particularly when its clearance is also impaired
Show answer

D. A highly bound drug with a narrow therapeutic index and a small volume of distribution, particularly when its clearance is also impaired

Displacement usually produces a transient rise in free concentration that is corrected as the newly free drug is cleared, so the total falls to a new steady state and nothing happens clinically. It matters when clearance cannot rise to compensate, or when the drug is confined to plasma, which is why the classic warfarin and phenytoin interactions usually involve metabolic inhibition as well.

2. How does the placenta affect drug distribution in pregnancy?

  1. Most small lipophilic unbound drugs cross readily, so fetal exposure should be assumed unless the molecule is large or highly polar
  2. Only drugs given intravenously cross
  3. Drug transfer occurs only in the third trimester
  4. The placenta blocks all drugs from reaching the fetus
Show answer

A. Most small lipophilic unbound drugs cross readily, so fetal exposure should be assumed unless the molecule is large or highly polar

The placenta is a lipid membrane with transporters, not a barrier, so the same properties that govern any membrane apply. Large molecules such as heparin and insulin do not cross meaningfully, which is why they are used in pregnancy, while warfarin does and is teratogenic. Efflux transporters provide partial protection against some substrates.

3. Which sequestration explains the very long half-life of amiodarone?

  1. Storage in the gallbladder
  2. Very slow renal excretion of unchanged drug
  3. Irreversible binding to plasma albumin
  4. Extensive accumulation in adipose tissue and other organs, giving a volume of distribution of thousands of litres
Show answer

D. Extensive accumulation in adipose tissue and other organs, giving a volume of distribution of thousands of litres

Amiodarone loads into fat, liver, lung, skin and other tissue over weeks, which is why a loading regimen is needed to fill the reservoir and why effects and adverse effects persist for months after stopping. Interactions such as the doubling of digoxin concentration therefore continue long after the drug is ceased, which is easily forgotten.

These are 3 of the 20 questions on distribution and protein binding in the app.

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More topics in Pharmacokinetics and pharmacodynamics

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