A 63-year-old man with epilepsy has been stable for years on valproate 1,000 mg twice daily, with trough levels of 70-85 mg/L (target 50-100 mg/L). He is admitted with ESBL-producing Escherichia coli bacteremia. Nurses give every dose, and trough samples are drawn just before the morning dose. On day 3 of intravenous meropenem his trough valproate is 14 mg/L, and he has a seizure. Albumin is 36 g/L (reference 35-50), creatinine and liver tests are normal, and the sample is not hemolyzed. The most likely cause of the low level is:

Meropenem lowering the valproate level

Nonadherence to the prescribed doses

Valproate inducing its own metabolism

Low albumin reducing total valproate

Why is a loading dose often given when starting a drug with a long half-life, such as digoxin or amiodarone?

To reach target levels without a long delay

To shorten the drug's elimination half-life

To saturate the liver enzymes that clear it

To fill the plasma protein binding sites first

A 72-year-old man on digoxin has no nausea, visual change or arrhythmia. His digoxin is 3.6 nmol/L [2.8 ng/mL] (heart failure target 0.6-1.2 nmol/L [0.5-0.9 ng/mL]), with normal potassium and creatinine. The request shows the sample was drawn 90 minutes after his morning dose. What should be done next?

Repeat the level at least 6 hours after a dose

Check for digoxin-like immunoreactive substances

Halve the digoxin dose from today

Give digoxin-specific antibody fragments

After high-dose methotrexate, serial serum methotrexate levels are measured mainly to:

Guide how long leucovorin rescue must continue

Find the time of the peak level for the next dose

Check that enough drug reached the cerebrospinal fluid

Confirm that the tumor has responded to treatment

Therapeutic drug monitoring

16 DOH Abu Dhabi (HAAD) lab licensing practice questions on Therapeutic drug monitoring, part of Clinical Chemistry. The first 16 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 63-year-old man with epilepsy has been stable for years on valproate 1,000 mg twice daily, with trough levels of 70-85 mg/L (target 50-100 mg/L). He is admitted with ESBL-producing Escherichia coli bacteremia. Nurses give every dose, and trough samples are drawn just before the morning dose. On day 3 of intravenous meropenem his trough valproate is 14 mg/L, and he has a seizure. Albumin is 36 g/L (reference 35-50), creatinine and liver tests are normal, and the sample is not hemolyzed. The most likely cause of the low level is:
1. AMeropenem lowering the valproate level
2. BNonadherence to the prescribed doses
3. CValproate inducing its own metabolism
4. DLow albumin reducing total valproate
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Answer: A · Meropenem lowering the valproate level
Carbapenems such as meropenem, ertapenem and imipenem lower valproate concentrations by more than half, often by 60-90%, within about a day. The main mechanism is inhibition of the liver enzyme that hydrolyzes valproate glucuronide back to valproate, so more of the drug is lost as the glucuronide. Raising the valproate dose does not overcome the effect, so another antibiotic or an additional antiseizure drug is usually needed, and the effect can last a week or more after the carbapenem is stopped. Supervised dosing, correct trough timing and a normal albumin exclude the other explanations. Valproate inhibits drug-metabolizing enzymes rather than inducing them.
- B: Nurses gave every dose, so missed doses are excluded.
- C: Valproate inhibits drug metabolism; autoinduction is a feature of carbamazepine.
- D: Albumin is normal, so protein binding has not changed.
Question 2 · Hard
After a vancomycin dose, a man with kidney impairment has a level of 32 mg/L. His elimination half-life is 12 hours. Assuming first-order elimination, about how long will the level take to fall to 8 mg/L?
1. A48 hours
2. B12 hours
3. C24 hours
4. D36 hours
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Answer: C · 24 hours
In first-order elimination the level halves every half-life: 32 to 16 mg/L takes 12 hours, and 16 to 8 mg/L takes another 12 hours. Two half-lives therefore take 24 hours. A common mistake is to treat the fourfold fall as four half-lives, which gives 48 hours. Estimates like this help decide when to re-dose a patient whose clearance is reduced.
- A: 48 hours treats a fourfold fall as four half-lives; it is two.
- B: 12 hours is one half-life, which only brings the level to 16 mg/L.
- D: 36 hours is three half-lives, which brings the level to 4 mg/L.
Question 3 · Medium
Why is a loading dose often given when starting a drug with a long half-life, such as digoxin or amiodarone?
1. ATo shorten the drug's elimination half-life
2. BTo saturate the liver enzymes that clear it
3. CTo fill the plasma protein binding sites first
4. DTo reach target levels without a long delay
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Answer: D · To reach target levels without a long delay
Without a loading dose, a drug given at a constant rate takes about 4 to 5 half-lives to reach steady state, which for a drug with a long half-life means days or weeks. A loading dose fills the volume of distribution quickly, and maintenance doses then replace what is eliminated. The loading dose depends on the volume of distribution, while the maintenance dose depends on clearance. Levels should still be checked once steady state is expected.
- A: Half-life is a property of the drug and the patient; dosing does not change it.
- B: Saturating the clearing enzymes would cause toxicity and is not the aim.
- C: A loading dose does not change protein binding.
Question 4 · Hard
A 72-year-old man on digoxin has no nausea, visual change or arrhythmia. His digoxin is 3.6 nmol/L [2.8 ng/mL] (heart failure target 0.6-1.2 nmol/L [0.5-0.9 ng/mL]), with normal potassium and creatinine. The request shows the sample was drawn 90 minutes after his morning dose. What should be done next?
1. ACheck for digoxin-like immunoreactive substances
2. BHalve the digoxin dose from today
3. CRepeat the level at least 6 hours after a dose
4. DGive digoxin-specific antibody fragments
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Answer: C · Repeat the level at least 6 hours after a dose
Digoxin distributes slowly from blood into tissues, including the heart, so for the first 6 to 8 hours after a dose the serum level is high and does not reflect the level at its site of action. A sample taken 90 minutes after a dose falls in this distribution phase, which explains a high level in a well patient. The level should be repeated at least 6 hours after a dose, ideally just before the next one, before the dose is changed. Antibody fragments are kept for true, symptomatic toxicity.
- A: Digoxin-like substances matter mainly in neonates, pregnancy and kidney or liver failure.
- B: Changing the dose on a sample from the distribution phase may leave him under-treated.
- D: Antibody fragments are for true toxicity, and this patient has no signs of it.
Question 5 · Medium
After high-dose methotrexate, serial serum methotrexate levels are measured mainly to:
1. AFind the time of the peak level for the next dose
2. BCheck that enough drug reached the cerebrospinal fluid
3. CConfirm that the tumor has responded to treatment
4. DGuide how long leucovorin rescue must continue
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Answer: D · Guide how long leucovorin rescue must continue
High-dose methotrexate is given with leucovorin (folinic acid) rescue, which bypasses the blocked folate pathway in normal cells. Levels are measured at set times, such as 24, 48 and 72 hours, and rescue continues until methotrexate falls below a protocol threshold, often around 0.1 µmol/L or lower. Delayed clearance, usually from kidney injury, calls for more leucovorin, hydration and urine alkalinization, and sometimes glucarpidase. After glucarpidase, a metabolite (DAMPA) cross-reacts in immunoassays, so LC-MS/MS is preferred.
- A: The peak is not the target; the falling levels decide the rescue.
- B: Serum levels do not measure the amount that reached the cerebrospinal fluid.
- C: Tumor response is judged clinically and by imaging, not by drug levels.
Question 6 · Easy
The preferred specimen for tacrolimus monitoring is:
1. ASodium citrate plasma
2. BLithium heparin plasma
3. CEDTA whole blood
4. DSerum from a gel separator tube
Answer and explanation in LearnFree account
Question 7 · Hard
A patient on gentamicin every 8 hours (traditional dosing) has a peak of 7.0 mg/L (target 5-10 mg/L) and a trough of 3.5 mg/L (target below 2 mg/L). Which dosing change is most appropriate?
1. AKeep the dose and lengthen the interval
2. BIncrease the dose and keep the interval
3. CKeep the dose and shorten the interval
4. DMake no change; the peak is in range
Answer and explanation in LearnFree account
Question 8 · Medium
For a serious MRSA infection, what do the 2020 ASHP/IDSA consensus guidelines recommend for guiding vancomycin dosing?
1. AA trough level kept between 15 and 20 mg/L
2. BThe 24-hour area under the curve (AUC)
3. CThe serum creatinine alone, without drug levels
4. DA single peak level 1 hour after the infusion
Answer and explanation in LearnFree account
Question 9 · Easy
When should routine serum lithium samples be taken?
1. A24 hours after stopping lithium
2. B2 hours after the last dose
3. C12 hours after the last dose
4. DAt any time of day
Answer and explanation in LearnFree account
Question 10 · Hard
A 70-kg patient needs an intravenous loading dose of a drug with a volume of distribution of 0.5 L/kg, to reach a plasma level of 12 mg/L. What dose is needed?
1. A1,680 mg
2. B840 mg
3. C6 mg
4. D420 mg
Answer and explanation in LearnFree account
Question 11 · Hard
A 60-year-old man has taken the same dose of theophylline for years. Three weeks after he stops smoking he has nausea, palpitations and tremor, and his theophylline is 28 mg/L [155 µmol/L] (target 10-20 mg/L [55-110 µmol/L]). The most likely reason for the rise is:
1. ALower protein binding raising the free drug
2. BLoss of liver enzyme induction from smoke
3. CReduced kidney excretion of theophylline
4. DEnzyme inhibition by nicotine replacement
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Question 12 · Medium
Aminoglycosides such as gentamicin are often given once daily in a large dose because their bacterial killing is:
1. AConcentration-dependent, with a post-antibiotic effect
2. BTime-dependent, so levels must stay above the MIC all day
3. CStrongest when the trough stays above the MIC
4. DUnrelated to the drug concentration achieved
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Question 13 · Medium
A woman stable on lithium for years has no symptoms, but today's lithium is 4.6 mmol/L (target 0.4-1.0 mmol/L). Her sodium, creatinine and thyroid tests are normal. Which error most likely explains the result?
1. ADelay before separating the serum
2. BHemolysis during venipuncture
3. CCollection into a lithium heparin tube
4. DSampling 2 hours after the dose
Answer and explanation in LearnFree account
Question 14 · Easy
The curve shows plasma levels of a drug given by mouth every 12 hours, with four sampling times marked. The correct time to collect a routine trough sample is:
Figure: MedExams
1. APoint B
2. BPoint D
3. CPoint C
4. DPoint A
Answer and explanation in LearnFree account
Question 15 · Medium
Serial vancomycin levels after an intravenous dose are plotted on a log scale. The elimination half-life is:
Figure: MedExams
1. A4 hours
2. B12 hours
3. C3 hours
4. D6 hours
Answer and explanation in LearnFree account
Question 16 · Medium
A 78-year-old woman's digoxin sample was drawn soon after her morning tablet. The typical concentration curve after an oral dose is shown, with her result marked. What should the laboratory advise?
Figure: MedExams
1. AReport the level as a valid peak
2. BReduce the dose, as the level is toxic
3. CRedraw 1 hour after the next dose
4. DRedraw at least 6 hours after a dose
Answer and explanation in LearnFree account

Therapeutic drug monitoring

After a vancomycin dose, a man with kidney impairment has a level of 32 mg/L. His elimination half-life is 12 hours. Assuming first-order elimination, about how long will the level take to fall to 8 mg/L?

Why is a loading dose often given when starting a drug with a long half-life, such as digoxin or amiodarone?

After high-dose methotrexate, serial serum methotrexate levels are measured mainly to:

The preferred specimen for tacrolimus monitoring is:

A patient on gentamicin every 8 hours (traditional dosing) has a peak of 7.0 mg/L (target 5-10 mg/L) and a trough of 3.5 mg/L (target below 2 mg/L). Which dosing change is most appropriate?

For a serious MRSA infection, what do the 2020 ASHP/IDSA consensus guidelines recommend for guiding vancomycin dosing?

When should routine serum lithium samples be taken?

A 70-kg patient needs an intravenous loading dose of a drug with a volume of distribution of 0.5 L/kg, to reach a plasma level of 12 mg/L. What dose is needed?

A 60-year-old man has taken the same dose of theophylline for years. Three weeks after he stops smoking he has nausea, palpitations and tremor, and his theophylline is 28 mg/L [155 µmol/L] (target 10-20 mg/L [55-110 µmol/L]). The most likely reason for the rise is:

Aminoglycosides such as gentamicin are often given once daily in a large dose because their bacterial killing is:

A woman stable on lithium for years has no symptoms, but today's lithium is 4.6 mmol/L (target 0.4-1.0 mmol/L). Her sodium, creatinine and thyroid tests are normal. Which error most likely explains the result?

The curve shows plasma levels of a drug given by mouth every 12 hours, with four sampling times marked. The correct time to collect a routine trough sample is:

Serial vancomycin levels after an intravenous dose are plotted on a log scale. The elimination half-life is:

A 78-year-old woman's digoxin sample was drawn soon after her morning tablet. The typical concentration curve after an oral dose is shown, with her result marked. What should the laboratory advise?