Metabolic and adverse effects of diuretics

Diuretics are among the most frequently prescribed drugs. They enjoy a very high clinical reputation for safety and efficacy. However, more than 3 decades of clinical investigation have disclosed a number of abnormalities in fluid electrolyte handling, metabolism, and other adverse effects that can complicate therapy with diuretic drugs. Some of these complications are a direct extension of the wanted action of the drug. These include extracellular fluid volume depletion, associated orthostatic hypotension, and prerenal azotemia. Others are not a direct action of the diuretic, but can be explained as an intranephronal compensation to the diuretic action. These include hypokalemia, in part to increased potassium secretion secondary to the enhanced tubular fluid flow and aldosterone secretion induced by diuretic administration. Metabolic abnormalities are usually mild. Hyperglycemia and carbohydrate intolerance have been related to diuretic-induced hypokalemia, which inhibits insulin secretion by the beta cells, and reductions in extracellular fluid volume and cardiac output. This is compounded by increases in catecholamines from sympathetic nerve activity which decrease peripheral glucose utilization. A mild increase in serum cholesterol concentration is seen frequently during initiation of diuretic therapy, but during steady state therapy after 6 to 12 months, values usually return to baseline. Knowledge of the more common adverse effects induced by diuretics helps the physician in predicting patients at risk and taking effective steps to anticipate or treat adverse responses.