A 39-year-old woman is brought to the emergency department after her husband found her confused. The patient was unable to answer questions about why she did not go to work that day and could not remember the day of the week. She has a history of bipolar disorder and has taken the same dose of lithium for the past 10 years. Over the past week, the patient started taking several daily doses of a new medication following a dental extraction. Yesterday, she felt nauseated and vomited twice, and earlier today, she started having diarrhea. Vital signs are within normal limits. The patient is alert and oriented to self only. The abdomen is soft and nontender with increased bowel sounds. Coarse tremors are noted in the upper extremities. Deep tendon reflexes are 2+ in the bilateral extremities. Gait is mildly ataxic. A drug interaction involving which of the following medications is most likely causing this patient's symptoms?
Lithium toxicity | |
Etiology | Acute toxicity
Chronic toxicity
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Clinical features | Acute toxicity
Chronic toxicity (neurologic)
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Treatment |
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NSAID = nonsteroidal anti-inflammatory drug. | |
Lithium, a mood stabilizer used to treat bipolar disorder, has a narrow therapeutic index and is excreted by the kidneys. As a result, drugs or medical conditions that affect kidney function or compete with lithium for clearance may interfere with lithium excretion and lead to toxicity. This patient's acute gastrointestinal upset followed by the development of neurologic symptoms (ie, confusion, coarse tremors, ataxia) is consistent with lithium toxicity.
The most likely cause of lithium toxicity in this patient is a drug interaction with a nonsteroidal anti-inflammatory drug (NSAID), such as ibuprofen. NSAIDs decrease renal blood flow and lithium clearance, increasing serum lithium levels. Other drugs that increase lithium levels and the risk for toxicity include thiazide diuretics, ACE inhibitors, tetracyclines, and metronidazole. Lithium levels should be monitored closely in patients taking these medications.
(Choices A, C, and E) Acetaminophen, ondansetron (5-HT3 antagonist), and tramadol (opioid agonist) do not impair renal clearance of lithium and therefore are not associated with an increased risk for lithium toxicity.
(Choice D) Although prednisone can precipitate neuropsychiatric symptoms (eg, confusion, emotional lability, akathisia), it does not increase the risk for lithium toxicity because it does not interfere with kidney function or lithium clearance.
Educational objective:
Lithium toxicity can be caused by drug interactions with nonsteroidal anti-inflammatory drugs, thiazide diuretics, ACE inhibitors, tetracyclines, and metronidazole. Signs of lithium toxicity include confusion, ataxia, and tremor.