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Difficulty: MediumPsychopharmacology and Psychological Therapies

A 42-year-old woman is brought to the emergency department by her husband due to a 2-day history of worsening confusion, slurred speech, and an unsteady gait. She also reports several episodes of severe nausea and vomiting. Her medical history is significant for bipolar I disorder, which has been well-controlled on a stable dose of lithium carbonate for the past 4 years. Two weeks ago, she was evaluated by her primary care physician for newly diagnosed essential hypertension, and a daily medication was added to her regimen. Her temperature is 37.1°C (98.8°F), blood pressure is 128/82 mmHg, and pulse is 84/min. On physical examination, the patient appears lethargic. Neurological examination reveals a coarse, irregular resting tremor in both hands and truncal ataxia. Which of the following medications was most likely recently prescribed to this patient?

  1. HydrochlorothiazideAnswer
  2. B
    Amlodipine
  3. C
    Furosemide
  4. D
    Metoprolol
  5. E
    Clonidine

Answer

Hydrochlorothiazide
The patient is presenting with classic signs of severe lithium toxicity, which include altered mental status, coarse tremors, ataxia, and gastrointestinal distress. Lithium has a narrow therapeutic index and is primarily cleared by the kidneys, where it is handled similarly to sodium. Thiazide diuretics, such as hydrochlorothiazide, inhibit the Na+/Cl- cotransporter in the distal convoluted tubule. The resulting mild volume depletion triggers a compensatory increase in the reabsorption of both sodium and lithium in the proximal convoluted tubule. This significantly decreases lithium clearance and rapidly leads to toxicity. Other common medications that increase lithium levels include NSAIDs (except aspirin), ACE inhibitors, and ARBs.

Step-by-Step Solution

1
Identify the patient's acute clinical syndrome based on the presentation.
The patient has acute-on-chronic lithium toxicity, characterized by gastrointestinal symptoms (nausea, vomiting) and severe neurologic signs (lethargy, confusion, ataxia, slurred speech, coarse tremors).
Recognizing the toxicity syndrome is required to determine which recent medication change precipitated the adverse event.
2
Determine the pharmacokinetic relationship between the new hypertension diagnosis and lithium clearance.
Lithium has a narrow therapeutic index and is cleared almost entirely by the kidneys. Its reabsorption in the proximal convoluted tubule is closely coupled with sodium.
Understanding lithium's renal handling allows the identification of drug classes that alter its excretion.
3
Select the antihypertensive medication that most significantly impairs lithium clearance.
Hydrochlorothiazide causes volume depletion, which triggers a compensatory increase in the reabsorption of both sodium and lithium in the proximal tubule, leading to systemic toxicity.
Thiazide diuretics are a classic and highly tested cause of drug-induced lithium toxicity.

Key Concept

Lithium toxicity can be precipitated by medications that decrease its renal clearance, most notably thiazide diuretics, NSAIDs, ACE inhibitors, and angiotensin II receptor blockers (ARBs).
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Topics

Psychopharmacology and Psychological Therapies

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