HCO3 depletion leads to enhanced NaCl reabsorption by the so prolonged therapy requires oral HCO3−. As a result, these agents remainder of the nephron, the diuretic efficacy of acetazolamide have proved to be of limited utility for this indication.
decreases significantly with use over several days. At present, the major clinical applications of acetazolamide
C. Metabolic Alkalosis involve carbonic anhydrase–dependent HCO3− and fluid transport Metabolic alkalosis is generally treated by correction of abnormalities in total body K+, intravascular volume, or mineralocorticoid TABLE 15–2 Changes in urinary electrolyte patterns levels. However, when the alkalosis is due to excessive use of diuretand body pH in response to diuretic ics in patients with severe heart failure, replacement of intravascular drugs. volume may be contraindicated. In these cases, acetazolamide can be useful in correcting the alkalosis as well as producing a small additional diuresis for correction of volume overload. Acetazolamide can also be used to rapidly correct the metabolic alkalosis that may appear following the correction of respiratory acidosis.
D. Acute Mountain Sickness
Weakness, dizziness, insomnia, headache, and nausea can occur in mountain travelers who rapidly ascend above 3000 m. The symptoms are usually mild and last for a few days. In more seri ous cases, rapidly progressing pulmonary or cerebral edema can be life-threatening. By decreasing CSF formation and by decreas+, increase; −, decrease; 0, no change; ↓, acidosis; ↑, alkalosis. ing the pH of the CSF and brain, acetazolamide can increase ventilation and diminish symptoms of mountain sickness. This mild metabolic central and CSF acidosis is also useful in the treatment of sleep apnea.
E. Other Uses
Carbonic anhydrase inhibitors have been used as adjuvants in the treatment of epilepsy and in some forms of hypokalemic periodic paralysis. They are also useful in treating patients with CSF leakage (usually caused by tumor or head trauma, but often idiopathic). By reducing the rate of CSF formation and intracranial pressure, carbonic anhydrase inhibitors can significantly slow the rate of CSF leakage. They also increase urinary phosphate excretion during severe hyperphosphatemia. Finally, acetazolamide may have a role in the treatment of Meniere’s disease, nephrogenic diabetes insipidus, idiopathic intracranial hypertension, and Kleine-Levin syndrome (episodes of hypersomnia and cognitive and behavioral abnormalities).
A. Hyperchloremic Metabolic Acidosis
Acidosis predictably results from chronic reduction of body HCO3− stores by carbonic anhydrase inhibitors (Table 15–2) and limits the diuretic efficacy of these drugs to 2 or 3 days. Unlike the diuretic effect, acidosis persists as long as the drug is continued.
B. Renal Stones
Phosphaturia and hypercalciuria occur during the bicarbonaturic response to inhibitors of carbonic anhydrase. Renal excretion of solubilizing factors (eg, citrate) may also decline with chronic use. Calcium phosphate salts are relatively insoluble at alkaline pH, which means that the potential for renal stone formation from these salts is enhanced.
C. Renal Potassium Wasting
Potassium wasting can occur because the increased Na+ presented to the collecting tubule (with HCO3−) is partially reabsorbed, increasing the lumen-negative electrical potential in that segment and enhancing K+ secretion. This effect can be counteracted by simultaneous administration of potassium chloride or a K+-sparing diuretic. Potassium wasting is theoretically a problem with any diuretic that increases Na+ delivery to the collecting tubule.