MRCP Part 1

Sample

1. Which of the following drugs is most typically eliminated by zero-order (saturable) kinetics at therapeutic doses?

Phenytoin, ethanol and high-dose salicylate show zero-order kinetics because their metabolising enzymes become saturated. A constant amount rather than a constant fraction is eliminated per unit time, so small dose increases can cause disproportionate rises in plasma concentration.

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2. Which drug property is most likely to produce a large apparent volume of distribution?

Lipophilic drugs distribute extensively into tissues and fat, giving a large apparent volume of distribution. Drugs that are highly protein bound or confined to plasma water tend to have a small volume of distribution.

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3. A drug is administered by the intravenous route. What is its bioavailability?

Bioavailability is the fraction of an administered dose reaching the systemic circulation. By definition an intravenous dose has a bioavailability of 100%, as it bypasses absorption and first-pass metabolism.

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4. At which site does first-pass metabolism predominantly occur for orally administered drugs?

After absorption from the gut, drugs pass via the portal vein to the liver, where first-pass (pre-systemic) metabolism can substantially reduce the amount reaching the systemic circulation. The gut wall also contributes to a lesser extent.

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5. Approximately how many half-lives are required for a drug given at a constant maintenance dose to reach steady state?

Steady state is reached after approximately four to five half-lives, when the rate of drug administration equals the rate of elimination. The same rule applies to the time taken to fully eliminate a drug after stopping it.

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6. When rapid therapeutic effect is required, the loading dose of a drug is determined principally by which pharmacokinetic parameter?

The loading dose is calculated from the target plasma concentration multiplied by the volume of distribution. Clearance determines the maintenance dose rather than the loading dose.

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7. The maintenance dose of a drug at steady state is determined principally by which pharmacokinetic parameter?

At steady state the maintenance dosing rate equals clearance multiplied by the target plasma concentration. Volume of distribution governs the loading dose rather than the maintenance dose.

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8. Which statement best defines drug clearance?

Clearance is the volume of plasma from which drug is completely removed per unit time and reflects the efficiency of elimination. Together with volume of distribution it determines the elimination half-life.

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9. Which statement correctly describes first-order elimination kinetics?

In first-order kinetics a constant fraction of drug is eliminated per unit time, so the rate of elimination is proportional to the plasma concentration. Most drugs at therapeutic concentrations follow first-order kinetics.

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10. For a drug with a high hepatic extraction ratio, clearance is most dependent on which factor?

Drugs with a high hepatic extraction ratio are efficiently removed on each pass through the liver, so their clearance is limited by, and sensitive to changes in, hepatic blood flow. Low-extraction drugs are more dependent on intrinsic enzyme activity and protein binding.