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Therapeutic drug monitoring: pharmacokinetics

9 ASCP MLS practice questions on Therapeutic drug monitoring: pharmacokinetics, part of Chemistry. The first 9 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

  1. Question 1 · Medium

    A patient with an albumin of 2.0 g/dL [20 g/L] takes a drug that is normally 90% bound to albumin. The total drug level is in the therapeutic range, but signs of toxicity appear. The most likely reason is:

    1. AThe free fraction is raised
    2. BThe drug is bound more tightly
    3. CElimination has become zero-order
    4. DThe total level is falsely low
    Show answer

    Answer: A · The free fraction is raised

    Only unbound (free) drug crosses membranes and acts on its target. With low albumin, fewer binding sites are available, so a larger share of the drug is free even when the total level looks acceptable. If binding falls from 90% to 80%, the free fraction doubles from 10% to 20%. Measuring the free drug level is the best guide for highly bound drugs in hypoalbuminemia, uremia or late pregnancy.

    • B: Low albumin means less binding, not tighter binding.
    • C: A therapeutic total level does not suggest saturated elimination.
    • D: The total measurement is accurate; the problem is how much is unbound.

  2. Question 2 · Easy

    In first-order elimination, the body removes per hour:

    1. AA fixed amount, whatever the level
    2. BA constant fraction of drug present
    3. CA larger fraction as the level falls
    4. DHalf the dose every dosing interval
    Show answer

    Answer: B · A constant fraction of drug present

    Most drugs follow first-order kinetics at therapeutic doses: the elimination rate is proportional to the concentration, so a constant fraction is removed per unit of time. This gives a fixed half-life, whatever the starting level, and a straight line when log concentration is plotted against time. When elimination enzymes become saturated, as with ethanol or high phenytoin levels, elimination becomes zero-order and a fixed amount is removed per hour. Small dose increases can then cause large rises in level.

    • A: A fixed amount per hour describes zero-order (saturated) elimination.
    • C: In first-order elimination the fraction removed stays constant.
    • D: The half-life is a property of the drug and need not match the dosing interval.

  3. Question 3 · Hard

    An oral drug with a half-life of 24 hours was started 2 days ago at a standard daily dose, with no loading dose. A level drawn today is below the therapeutic range. The best interpretation is:

    1. AThe patient is a rapid metabolizer
    2. BThe dose should be doubled at once
    3. CSteady state has not yet been reached
    4. DThe drug is not being absorbed
    Show answer

    Answer: C · Steady state has not yet been reached

    With regular dosing and no loading dose, a drug takes about 5 half-lives to reach steady state, about 97% of its final level. With a 24-hour half-life that is about 5 days, so after 2 days the level is only about 75% of where it will settle. A trough sample should be taken after steady state is reached, before the dose is changed. A loading dose is used when therapeutic levels are needed sooner.

    • A: Nothing yet suggests fast metabolism; the level is still rising.
    • B: Raising the dose before steady state risks toxicity once levels settle.
    • D: Poor absorption cannot be judged until steady state is reached.

  4. Question 4 · Medium

    Why are peak samples for many intravenous drugs collected after the infusion ends and the drug has had time to distribute?

    1. AElimination has not yet started
    2. BEarly levels overstate tissue exposure
    3. CThe IV line contaminates the sample
    4. DIV drugs need time to be absorbed
    Show answer

    Answer: B · Early levels overstate tissue exposure

    After an IV dose, the drug is first concentrated in the blood and then moves into the tissues during the distribution phase. A sample taken during this phase is falsely high compared with the concentration that matches the drug's effect. Peaks are therefore timed after distribution, for example about 30 minutes after a 30-minute aminoglycoside infusion ends. Oral drugs peak later, after absorption, at a time that depends on the drug and its formulation.

    • A: Elimination begins as soon as the drug enters the blood.
    • C: Contamination is avoided by drawing from the other arm, not by waiting.
    • D: IV drugs enter the blood directly and need no absorption.

  5. Question 5 · Hard

    A drug follows first-order kinetics. After a dose, the level is 16 µg/mL at 1 hour and 4 µg/mL at 9 hours. What is the half-life?

    1. A4 hours
    2. B8 hours
    3. C2 hours
    4. D5.3 hours
    Show answer

    Answer: A · 4 hours

    The level fell fourfold, from 16 to 4 µg/mL, which is two halvings (16 to 8 to 4). Two half-lives took 9 - 1 = 8 hours, so one half-life is 8 / 2 = 4 hours. The formula gives the same answer: t1/2 = 0.693 x 8 / ln(16/4) = 0.693 x 8 / 1.386 = 4 hours. Treating the fall as a straight line (zero-order) gives the wrong answer of about 5.3 hours.

    • B: 8 hours treats the whole interval as one half-life.
    • C: 2 hours divides the interval by the fourfold fall instead of by two half-lives.
    • D: 5.3 hours assumes a straight-line (zero-order) fall.

  6. Question 6 · Easy

    When should a trough sample for therapeutic drug monitoring be collected?

    1. AAt any time on the same day
    2. BJust before the next dose
    3. CRight after the dose is given
    4. DMidway through the dosing interval

    Answer and explanation in LearnFree account

  7. Question 7 · Easy

    The concentration-time curve shown is for a drug given intravenously every 8 hours with no loading dose. About how long after the first dose did it reach steady state?

    Figure: MedExams
    Concentration-time curve over 96 hours for intravenous doses every 8 hours: each dose raises the level by 10 mg/L and the level halves before the next dose. Peaks rise from 10 to 15, 17.5 and 18.8 mg/L and then level off near 20 mg/L, with troughs near 10 mg/L.
    1. AAbout 16 hours
    2. BAbout 40 hours
    3. CAbout 8 hours
    4. DAbout 80 hours

    Answer and explanation in LearnFree account

  8. Question 8 · Medium

    The same intravenous dose of a drug was given to patients A and B, and their levels are shown. Compared with patient A, patient B has:

    Figure: MedExams
    Concentration-time curves for patients A (solid) and B (dashed) over 24 hours after the same intravenous dose. Both start at 20 mg/L; A falls to 10 mg/L at 4 hours and 5 mg/L at 8 hours, while B falls to 10 mg/L only at 12 hours.
    1. AA smaller volume of distribution
    2. BA larger volume of distribution
    3. CFaster elimination of the drug
    4. DSlower elimination of the drug

    Answer and explanation in LearnFree account

  9. Question 9 · Medium

    At steady state, a patient's drug levels follow the curve shown, with the therapeutic range shaded. Which dosing change best corrects the pattern?

    Figure: MedExams
    Steady-state concentration-time curve over 36 hours with doses every 12 hours and a shaded therapeutic range of 8-18 mg/L. Each peak reaches about 24 mg/L and each trough falls to about 3.6 mg/L.
    1. ALarger doses at the same interval
    2. BThe same dose at longer intervals
    3. CSmaller doses given at shorter intervals
    4. DThe same dose at shorter intervals

    Answer and explanation in LearnFree account

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