Toxicology and drugs of abuse

13 DOH Abu Dhabi (HAAD) lab licensing practice questions on Toxicology and drugs of abuse, part of Clinical Chemistry. The first 13 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 · Hard

   A 34-year-old man is brought in drowsy about 8 hours after drinking an unknown liquid in a garage. An arterial blood gas shows pH 7.09, bicarbonate 7 mmol/L and lactate 13.6 mmol/L on the blood gas analyzer. Plasma drawn at the same time gives lactate 2.3 mmol/L on the chemistry analyzer (reference 0.5-2.2), anion gap 31 mmol/L (reference 8-16), osmolal gap 24 mOsm/kg (reference < 10), no ethanol and a normal beta-hydroxybutyrate. Both samples were analyzed within 15 minutes. The manufacturer lists the gas analyzer's lactate oxidase sensor as cross-reacting with glycolate; the chemistry method does not. The most likely cause is:

   1. AMethanol ingestion
   2. BMetformin lactic acidosis
   3. CIsopropanol ingestion
   4. DEthylene glycol ingestion

   Show answerHide answer

   Answer: D · Ethylene glycol ingestion

   Two lactate results that differ by more than 11 mmol/L on samples taken together point to an interfering substance rather than true lactic acidosis. Ethylene glycol is metabolized to glycolate, which accumulates and is oxidized by some lactate oxidase sensors, so the blood gas analyzer reads it as lactate. Glycolate and oxalate also explain the high anion gap acidosis, and the raised osmolal gap shows that unmetabolized glycol is still present. Methanol forms formate, which does not create a lactate gap, and in metformin toxicity both methods would show a high lactate. Isopropanol raises the osmolal gap without acidosis. A lactate gap should prompt an urgent ethylene glycol level and early fomepizole.

   • A: Methanol produces formate, which does not interfere with lactate methods, so there would be no lactate gap.
   • B: True lactic acidosis would give a high lactate by both methods.
   • C: Isopropanol raises the osmolal gap and acetone but does not cause a high anion gap acidosis.

2. Question 2 · Hard

   An adult took an aspirin overdose 6 hours ago and is breathing fast. Results: pH 7.48, pCO2 2.9 kPa (22 mm Hg), bicarbonate 16 mmol/L, anion gap 22 mmol/L (reference 8-16). How is this acid-base picture best described?

   1. AMetabolic alkalosis with respiratory acidosis
   2. BMetabolic acidosis with respiratory compensation only
   3. CRespiratory alkalosis with high anion gap metabolic acidosis
   4. DRespiratory alkalosis with metabolic compensation only

   Show answerHide answer

   Answer: C · Respiratory alkalosis with high anion gap metabolic acidosis

   The pH is alkaline and the pCO2 is low, so the primary disorder is respiratory alkalosis, caused by salicylate stimulating the respiratory centre. In acute respiratory alkalosis bicarbonate falls only about 2 mmol/L for each 10 mm Hg fall in pCO2, to about 20 mmol/L here; a bicarbonate of 16 with a raised anion gap shows a second, metabolic acidosis. Salicylate uncouples oxidative phosphorylation, so lactate and ketoacids accumulate. Adults usually show this mixed picture, while young children more often present with metabolic acidosis alone.

   • A: A low pCO2 and a low bicarbonate rule out both metabolic alkalosis and respiratory acidosis.
   • B: With an alkaline pH, metabolic acidosis cannot be the only primary disorder.
   • D: Compensation alone would leave the anion gap normal and bicarbonate near 20 mmol/L.

3. Question 3 · Medium

   A 40-year-old man is drowsy after drinking hand sanitizer. Results: pH 7.39, anion gap 12 mmol/L (reference 8-16), osmolal gap 32 mOsm/kg (reference < 10), glucose 5.6 mmol/L (101 mg/dL), serum acetone raised, beta-hydroxybutyrate normal, ethanol not detected. Which alcohol did he most likely drink?

   1. APropylene glycol
   2. BIsopropanol
   3. CMethanol
   4. DEthylene glycol

   Show answerHide answer

   Answer: B · Isopropanol

   Alcohol dehydrogenase converts isopropanol to acetone, a ketone that is not an acid. The patient therefore has a raised osmolal gap and ketosis without metabolic acidosis. A normal beta-hydroxybutyrate and glucose rule out diabetic or alcoholic ketoacidosis as the source of the acetone. Acetone with a normal anion gap is the classic pattern of isopropanol poisoning.

   • A: Propylene glycol is metabolized to lactate and does not form acetone.
   • C: Methanol is converted to formic acid and gives a high anion gap acidosis, not acetone.
   • D: Ethylene glycol forms glycolic and oxalic acids and gives a high anion gap acidosis.

4. Question 4 · Easy

   Most automated serum ethanol methods use alcohol dehydrogenase and follow:

   1. AThe rise in NADH absorbance at 340 nm
   2. BA colored acetaldehyde product at 540 nm
   3. CThe oxygen used up at an electrode
   4. DThe fall in NADH absorbance at 340 nm

   Show answerHide answer

   Answer: A · The rise in NADH absorbance at 340 nm

   Alcohol dehydrogenase oxidizes ethanol to acetaldehyde and reduces NAD+ to NADH in the same step. NADH absorbs at 340 nm and NAD+ does not, so the absorbance rises in proportion to the ethanol present. An alkaline pH and a reagent that traps acetaldehyde push the reaction to completion. Serum and plasma give higher ethanol values than whole blood, so the specimen type must be stated when a result may be used for legal purposes.

   • B: The dehydrogenase method follows NADH at 340 nm, not a colored acetaldehyde product.
   • C: Oxygen-electrode methods use alcohol oxidase, not alcohol dehydrogenase.
   • D: NADH is formed, not used, so absorbance rises rather than falls.

5. Question 5 · Medium

   Confirmation cutoffs for drugs of abuse are usually lower than the matching screening cutoffs. Why?

   1. AMass spectrometry measures one compound, the screen many
   2. BConfirmation is done on a more diluted specimen
   3. CScreening cutoffs include an allowance for adulteration
   4. DMass spectrometry is less sensitive than immunoassay

   Show answerHide answer

   Answer: A · Mass spectrometry measures one compound, the screen many

   An immunoassay signal is the sum of everything the antibody binds: the target, its metabolites and cross-reacting compounds, all expressed as equivalents of the calibrator. Mass spectrometry measures one named compound, so its amount in a true positive is often lower than the screen value. A lower confirmation cutoff avoids missing true positives. US federal workplace programs, for example, screen cocaine metabolites at 150 ng/mL and confirm benzoylecgonine at 100 ng/mL.

   • B: Confirmation uses the same specimen; it is not diluted further.
   • C: Adulteration is checked with specimen validity tests, not by the choice of cutoff.
   • D: Mass spectrometry is more specific and usually at least as sensitive as immunoassay.

6. Question 6 · Hard

   A patient who takes clonazepam daily, as prescribed, has a negative urine benzodiazepine immunoassay. Urine creatinine is 9.7 mmol/L (110 mg/dL), and pill counts suggest good adherence. What is the best explanation and next step?

   1. AThe urine is too dilute; collect a new specimen
   2. BClonazepam is not excreted in urine; test serum instead
   3. CNonadherence is confirmed; report this to the prescriber
   4. DThe assay detects 7-aminoclonazepam poorly; use LC-MS/MS

   Answer and explanation in LearnFree account

7. Question 7 · Medium

   After a large acetaminophen (paracetamol) overdose, serum ALT and AST usually reach their peak:

   1. AWithin 4 hours of ingestion
   2. BAbout 3 to 4 days after ingestion
   3. CAbout 2 to 3 weeks after ingestion
   4. DAbout 12 hours after ingestion

   Answer and explanation in LearnFree account

8. Question 8 · Hard

   A man arrives about 30 hours after drinking an unknown liquid. Results: pH 7.06, bicarbonate 5 mmol/L, anion gap 31 mmol/L (reference 8-16), lactate 2.4 mmol/L (reference 0.5-2.2), beta-hydroxybutyrate normal, creatinine 88 µmol/L (1.0 mg/dL), salicylate and ethanol not detected, osmolal gap 7 mOsm/kg (reference < 10). How should the normal osmolal gap be interpreted?

   1. AToxic alcohol is still likely, already metabolized to acids
   2. BToxic alcohol is excluded, so another cause must be found
   3. CLactic acidosis fully explains the high anion gap
   4. DIsopropanol is likely, because the osmolal gap is normal

   Answer and explanation in LearnFree account

9. Question 9 · Medium

   Why is a positive urine drug immunoassay reported only as presumptive until mass spectrometry confirms it?

   1. AImmunoassays cannot be calibrated at the cutoff
   2. BUrine pH alters the antibody binding
   3. CImmunoassays detect only the parent drug
   4. DAntibodies may cross-react with other compounds

   Answer and explanation in LearnFree account

10. Question 10 · Easy

    Fomepizole is started early when methanol or ethylene glycol poisoning is suspected. Which enzyme does it block?

    1. AAlcohol dehydrogenase
    2. BGlycolate oxidase
    3. CCytochrome P450 2E1
    4. DAldehyde dehydrogenase

    Answer and explanation in LearnFree account

11. Question 11 · Hard

    A 52-year-old woman with decompensated cirrhosis denies taking acetaminophen. Total bilirubin is 510 µmol/L (30 mg/dL). An enzymatic (arylacylamidase) acetaminophen assay gives 18 mg/L (119 µmol/L), but LC-MS/MS on the same sample finds none. The most likely explanation is:

    1. ABilirubin interference in the enzymatic assay
    2. BLC-MS/MS is not sensitive enough at this level
    3. CHemolysis released acetaminophen from red cells
    4. DAcetaminophen cleared after the sample was drawn

    Answer and explanation in LearnFree account

12. Question 12 · Hard

    A workplace urine drug screen is negative for all drugs. Creatinine is 0.88 mmol/L (10 mg/dL) and specific gravity 1.0020. The laboratory follows US federal criteria: dilute if creatinine is 0.18-1.77 mmol/L (2-20 mg/dL) with specific gravity above 1.0010 and below 1.0030; substituted if creatinine is below 0.18 mmol/L with specific gravity 1.0010 or less, or 1.0200 or more. How should the result be reported?

    1. AAs a valid negative with no comment
    2. BAs adulterated with an oxidizing agent
    3. CAs substituted; the specimen is not urine
    4. DAs negative-dilute; drugs may have been missed

    Answer and explanation in LearnFree account

13. Question 13 · Medium

    After a paracetamol (acetaminophen) overdose, when should the level first be measured for interpretation on the treatment nomogram?

    1. AOnly at 24 hours
    2. BAt least 4 hours after ingestion
    3. CAt any time, without regard to timing
    4. D30 minutes after ingestion

    Answer and explanation in LearnFree account