Diuretics are a class of medications that increase urine output by decreasing the reabsorption of water and sodium. They are used to treat conditions of intravascular volume overload, particularly in those patients refractory to fluid and salt restriction. Common indications include hypertension, congestive heart failure, pulmonary edema, and cerebral edema. Diuretics target receptors on cell membranes within the renal tubule. They are typically categorized by their primary site of action in the nephron (Figure 178-1).
Diuretics—tubular sites of action. (Reproduced with permission from Fuster V, Hurst’s The Heart, 13th ed. New York: McGraw-Hill; 2011.)
CARBONIC ANHYDRASE INHIBITORS
In the lumen of the proximal convoluted tubule, secreted protons (H+) combine with bicarbonate (HCO3−) to form carbonic acid (H2CO3). Catalyzed by the enzyme carbonic anhydrase, H2CO3 breaks down to form water (H2O) and carbon dioxide (CO2).
When carbonic anhydrase is inhibited, H2CO3 is unable to form into H2O and CO2, so H2CO3 is converted back into H+ and HCO3−.
H+ ions that accumulate in the tubule are then reabsorbed in exchange for Na+ ions. H2O follows Na+, enabling diuresis. Accumulation and excretion of bicarbonate, plus H+ reabsorption, results in alkaline urine.
Acetazolamide and methazolamide are the most commonly prescribed carbonic anhydrase inhibitors. Despite blocking sodium reabsorption, carbonic anhydrase inhibitors are considered weak diuretics. Subsequent reabsorption of sodium distally in the nephron limits their effectiveness. These drugs are often used to improve excretion of acidic substances (eg, salicylate overdose) through urine alkalinization. Inhibition of carbonic anhydrase in the ciliary body decreases intraocular pressure in open-angle glaucoma by decreasing aqueous humor production. Other indications include increasing respiratory drive in patients who suffer from central sleep apnea and treating altitude sickness. Hyperchloremic metabolic acidosis and possible sedation are possible side effects of carbonic anhydrase inhibitors.
Once filtered through the renal glomerulus, osmotic diuretics enter the proximal convoluted tubule where they are either poorly reabsorbed or not absorbed at all. The presence of the diuretic increases intraluminal oncotic pressure, thereby decreasing passive water reabsorption and leading to increased urinary excretion of water. In higher doses, osmotic diuretics may increase excretion of sodium, potassium, and magnesium. Massive diuresis can result in hypovolemia and hypernatremia (due to greater water loss relative to sodium).
Mannitol, a sugar with six carbons, is the most commonly used osmotic diuretic. The usual dose is 0.25-1 mg/kg IV given over 30 minutes. In patients with elevated intracranial pressure from cerebral edema, mannitol decreases intracranial volume within ...