View Case

Back

Questions
Discussion
References

237) A 45-year-old woman with manic depression has been receiving haloperidol 5 mg daily, lithium carbonate 800 mg daily, and oxazepam 10 mg twice daily. Several days into a heat wave, her psychiatrist decides to add carbamazepine 200 mg twice daily as a mood stabilizer. Two days later, the patient develops drowsiness, tremors, and muscle weakness. Serum chemistry results:

Result Reference Range Units

Na 151 136-146 mmol/L

K 4.0 3.5-5.0 mmol/L

Cl 105 102-109 mmol/L

HCO₃ 25 32-45 mmol/L

Creatinine 1.0 0.6-1.2 mg/dL

BUN 12 7-20 mg/dL

Glu 90 75-115 mg/dL

ALT 25 0-35 U/L

AST 24 0-35 U/L

Carbamazepine = 8 mg/L by immunoassay (therapeutic range, 6 to 12 mg/L), lithium = 1.6 mmol/L by atomic absorption spectroscopy (therapeutic range, 0.6 to 1.2 mmol/L), haloperidol = 10 ng/mL by liquid chromatography–tandem mass spectrometry (AAS, therapeutic range, 2.0 to 15 ng/mL). Which one of the following answers best explains the patient’s symptoms and represents the most appropriate therapeutic intervention?

	Result	Reference Range	Units
Na	151	136-146	mmol/L
K	4.0	3.5-5.0	mmol/L
Cl	105	102-109	mmol/L
HCO₃	25	32-45	mmol/L
Creatinine	1.0	0.6-1.2	mg/dL
BUN	12	7-20	mg/dL
Glu	90	75-115	mg/dL
ALT	25	0-35	U/L
AST	24	0-35	U/L

The patient is a slow metabolizer of carbamazepine. The carbamazepine dose should be reduced. The patient is dehydrated, leading to toxic lithium levels. The lithium dose should be reduced. Carbamazepine induces the metabolism of haloperidol. The haloperidol dose should be reduced. Oxazepam inhibits the metabolism of carbamazepine. The carbamazepine dose should be reduced. Carbamazepine inhibits the metabolism of lithium. The lithium dose should be reduced.

Show Diagnosis/Topic

• Carbamazepine and haloperidol are metabolized by the CYP3A4 isoenzyme, which has genetic polymorphisms in humans.

• Lithium excretion parallels that of sodium. In dehydration, the proximal tubular reabsorption of sodium (and lithium) is increased, leading to decreased clearance of lithium and increased blood levels.

• Lithium can be measured in serum, plasma, and urine by ion-selective electrode, flame emission photometry, atomic absorption spectrometry, or inductively coupled plasma mass spectrometry (ICP-MS).

• Therapeutic 12-hour serum levels of lithium are 0.6 to 1.2 mmol/L. Higher levels, especially more than 1.5 mmol/L, are associated with a significant risk for intoxication.

• There are three types of lithium poisoning: acute, acute on chronic, and chronic.

• Symptoms of mild lithium poisoning include lethargy, drowsiness, coarse hand tremor, muscle weakness, nausea, vomiting, and diarrhea. Moderate toxicity is associated with confusion, dysarthria, nystagmus, ataxia, myoclonic twitches, and electrocardiographic changes. Severe, life-threatening toxicity is associated with grossly impaired consciousness, increased deep tendon reflexes, seizures, syncope, renal insufficiency, coma, and death.

Timmer, RT, Sands JM: Lithium Intoxication. J Am Soc Nephrol 1999;10:666–674.

Clinical toxicology.In: Burtis CA, Ashwood ER, Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnosis. 4th ed. St. Louis: Saunders, 2005.: 1287–1369.

Back

Clinical Pathology: Clinical Chemistry

View Notes

Add a Note