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Zorluk: KolayPsychopharmacology and Psychological Therapies

A 42-year-old woman is brought to the emergency department by her husband due to worsening confusion, severe nausea, vomiting, and a prominent hand tremor. Her husband reports that she has been unusually unsteady on her feet for the past three days. Her medical history is significant for bipolar disorder, which has been well-controlled on a stable dose of lithium for the past five years. Three weeks ago, she was diagnosed with essential hypertension by her primary care provider and was started on a new daily medication. On physical examination, the patient is lethargic and exhibits a coarse resting tremor, hyperreflexia, and ataxia. Her serum lithium level is 2.1 mEq/L (therapeutic range: 0.6-1.2 mEq/L). Which of the following antihypertensive medications was most likely prescribed to this patient?

  1. HydrochlorothiazideCevap
  2. B
    Amlodipine
  3. C
    Metoprolol
  4. D
    Clonidine
  5. E
    Prazosin

Cevap

Hydrochlorothiazide
The correct answer is hydrochlorothiazide. This patient is experiencing acute lithium toxicity, characterized by gastrointestinal symptoms, coarse tremor, ataxia, and confusion, confirmed by an elevated serum lithium level. Lithium is almost entirely excreted by the kidneys. Thiazide diuretics (such as hydrochlorothiazide) inhibit sodium reabsorption in the distal convoluted tubule, leading to mild hypovolemia. This volume depletion stimulates the kidneys to increase sodium reabsorption in the proximal convoluted tubule. Because lithium is handled similarly to sodium by the kidneys, lithium reabsorption is concurrently increased in the proximal tubule. This leads to decreased lithium clearance and a rapid accumulation of the drug to toxic levels. Other common medications that precipitate lithium toxicity include NSAIDs, ACE inhibitors, and ARBs.

Adım Adım Çözüm

1
Identify the patient's acute clinical presentation.
The patient presents with confusion, ataxia, coarse tremor, and gastrointestinal distress, confirmed by an elevated serum lithium level of 2.1 mEq/L.
Recognizing the clinical syndrome of lithium toxicity is the essential first step in determining its underlying cause.
2
Correlate the toxicity with recent changes in medical management.
The toxicity began shortly after starting a new antihypertensive medication three weeks ago.
Lithium has a narrow therapeutic index, and its serum levels are highly sensitive to concurrent medications that alter renal function.
3
Determine which class of antihypertensives decreases lithium clearance.
Thiazide diuretics (like hydrochlorothiazide) are classic agents that decrease renal lithium clearance and precipitate toxicity.
Thiazides cause mild volume depletion, triggering a compensatory increase in proximal tubular reabsorption of sodium and lithium.

Anahtar Kavram

Lithium has a narrow therapeutic index and is almost exclusively cleared by the kidneys. Its renal clearance is significantly decreased by concurrent use of thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and angiotensin-converting enzyme (ACE) inhibitors, which can rapidly lead to potentially fatal toxicity.
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