Chapter 187: Diuretics

INTRODUCTION

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 187-1).

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 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.

OSMOTIC DIURETICS

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 ...