What medication's long-term administration effects are most similar to those of a condition characterized by metabolic alkalosis, polyuria, and failure to thrive in a neonate?

From the Guidelines

The answer is F. Acetazolamide. This newborn presents with symptoms consistent with Bartter syndrome, a rare genetic disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis, and normal blood pressure. The clinical presentation includes polyhydramnios during pregnancy, failure to thrive, frequent urination, and distinctive facial features. Laboratory findings would typically show hypokalemia, metabolic alkalosis (elevated pH), and possibly hypochloremia.

Key Features of the Condition

• Polyhydramnios during pregnancy
• Failure to thrive
• Frequent urination
• Distinctive facial features
• Hypokalemia
• Metabolic alkalosis (elevated pH)
• Possibly hypochloremia

Acetazolamide, a carbonic anhydrase inhibitor, produces effects most similar to Bartter syndrome because it causes bicarbonate diuresis, leading to metabolic alkalosis, hypokalemia, and salt wasting. The drug inhibits proximal tubule sodium reabsorption and increases urinary bicarbonate excretion, mimicking the electrolyte abnormalities seen in this condition 1. Other medications listed would produce different electrolyte patterns - for example, hydrochlorothiazide causes hypokalemia but with metabolic alkalosis, while triamterene is potassium-sparing and would cause hyperkalemia rather than the hypokalemia seen in this patient.

Comparison with Other Medications

• Hydrochlorothiazide: causes hypokalemia with metabolic alkalosis
• Triamterene: potassium-sparing, causes hyperkalemia
• Fludrocortisone: increases K+ excretion but associated with fluid retention, hypertension, and vascular injury 1 The effects of this patient's condition are most similar to the long-term administration of acetazolamide, as it mimics the electrolyte abnormalities and clinical presentation of Bartter syndrome.

From the FDA Drug Label

e. hyponatremia, hypochloremic alkalosis, and hypokalemia and hypomagnesemia. Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting The effects of this patient's condition are most similar to the long-term administration of Hydrochlorothiazide 2.

• The patient's symptoms of persistent irritability and crying, along with the physical examination findings and serum studies, suggest a condition characterized by hypokalemia, hypochloremic alkalosis, and dehydration.
• These symptoms are consistent with the side effects of hydrochlorothiazide, a thiazide diuretic that can cause electrolyte depletion and dehydration.
• The patient's condition is likely related to an underlying condition that affects electrolyte balance, and the use of hydrochlorothiazide would exacerbate these effects.

From the Research

Patient's Condition and Similar Effects

The patient's condition, characterized by persistent irritability and crying, triangular face, prominent forehead, large protruding ears, and serum studies showing a pH of 7.51, suggests a metabolic alkalosis. The effects of this patient's condition are most similar to the long-term administration of a drug that causes hypokalemia, metabolic alkalosis, and increased urine production.

Similar Drug Effects

• The long-term administration of Hydrochlorothiazide (HCTZ), a thiazide diuretic, can cause hypokalemia, metabolic alkalosis, and increased urine production, similar to the patient's condition 3, 4, 5, 6.
• Thiazide diuretics, such as HCTZ, can lead to hypokalemia, which can cause muscle weakness, fatigue, and cardiac arrhythmias 3, 4, 7.
• The combination of loop diuretics with thiazide-type diuretics can produce diuretic synergy, leading to increased urine production and potential hypokalemia 4, 5, 6.

Relevant Studies

• Studies have shown that thiazide diuretics, such as HCTZ, are effective in treating hypertension and heart failure, but can cause hypokalemia and metabolic alkalosis 3, 4, 7.
• The CLOROTIC trial demonstrated that the addition of HCTZ to loop diuretic therapy improved diuretic response in patients with acute heart failure, but also increased the risk of impaired renal function 5, 6.