Some wrong-way chemical changes during antihypertensive treatment: comparison of indapamide and related agents

Despite the beneficial therapeutic effects of antihypertensive drugs, some agents--particularly diuretics--seem to go in the "wrong direction" chemically. In fact, these changes could counteract some of the benefits resulting from lowering a patient's blood pressure. In the absence of hard evidence of the efficacy of long-term diuretic treatment of mild hypertension, we must be maximally sure that such therapy causes no harm. Thiazide and related diuretics have been associated with four distinct wrong-way chemical changes: increases in plasma concentrations of cholesterol, glucose, and uric acid, and a decrease in plasma potassium levels. The potential ramifications of such changes are well understood. The increase in circulating cholesterol, an established risk factor of myocardial infarction and stroke, is of particular concern--each year approximately one million hypertensive patients have myocardial infarctions. As a result, the search for safer and more effective diuretics must continue. Indapamide, a new antihypertensive drug, appears to meet these criteria. It is an effective diuretic with a considerable peripheral vasodilatory effect. Additionally, it does not appear to induce any significant change in circulating cholesterol, whereas chlorthalidone has been found to increase total cholesterol by 5%. Hydralazine is the only antihypertensive agent that seems to lower total cholesterol levels significantly. Neither indapamide nor hydralazine appears to affect plasma glucose levels; benzothiadiazines, however, have been found to induce an increase in circulating glucose.