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Metabolic Effects

Chlorthalidone represents one of three different types of diuretics. Each type works in a slightly different way, but all diuretics lower the amount of salt and water in the body, thereby helping to reduce blood pressure. Diuretic treatments are not benign, and not every patient can tolerate them. As a class of drugs, diuretics have been shown to contribute to heart enlargement, increase the risk of type-2 diabetes, and worsen blood lipid (cholesterol) profiles.

In ridding the body of excess water through increased urinary excretion, diuretics can also deplete the body of some essential elements and cause imbalances in metabolism. They cause patients to excrete excessive amounts of potassium and bicarbonate, necessitating supplements to replace these essential elements. Conversely, they may cause excessive retention of calcium and uric acid, which can lead to gout. Patients taking diuretics require careful monitoring by physicians, along with the possible addition of drugs (e.g., potassium supplements and gout medications), and frequent blood tests to assess glucose tolerance and lipid profiles.

Variations in Effectiveness

Diuretics and the other classes of antihypertensive drugs vary in their efficacy, particularly among African-Americans, older adults, and diabetic patients.


Hypertension is more prevalent and is associated with worse outcomes in African-Americans patients. Although these patients respond well to diuretics, most require two or more antihypertension drugs to control their blood pressure by current standards.8,14,15 Longer-acting calcium-channel blockers are effective in reducing stroke and coronary artery disease in this population, and calcium-channel antagonists and ACE-inhibitors are effective in slowing the chronic progression of kidney disease in African-Americans with type-2 diabetic kidney disease.

Angiotensin-receptor blockers (ARBs) have been effective in type-2 diabetes for renoprotection. In its recent consensus statement, the International Society on Hypertension in Blacks (ISHIB) recommended initiating treatment with two drugs from different classes if blood pressure readings exceeded targets for control. The ISHIB considers ACE-inhibitors, calcium-channel blockers, and diuretics—as well as other classes of antihypertensive agents—to be appropriate in combination for treatment but suggests that diuretics coupled with calcium channel-blockers may be the most effective in this population.
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Older Patients (Aged 60 to 79)

Individual physical and medical differences increase as people age, making multiple treatment options necessary for safe and effective therapy. In addition to variations in action and side-effect patterns, different classes of medications—and different options within the same class—offer elderly patients choices among dosage forms and duration.

In the Systolic Hypertension in the Elderly Program (SHEP) trials, which used primarily diuretics and beta block-ers, drug therapy decreased stroke risk by an average of 32% and cardiac events by 14%. More recently, a large-scale, prospective, randomized study has shown ACE-inhibitors to be superior to diuretics for treating hypertension and avoiding adverse events, such as heart disease and stroke, in older men.5 More trial results, including those from large numbers of subjects aged 80 and older, should become available in the next few years. tadacip 20 mg

Patients with Diabetes

The incidence of type-2 diabetes, a chronic condition with life-threatening complications, increases with age, and aging populations are at risk for type-2 diabetes as well as hypertension. Because diuretics adversely affect glucose (sugar) tolerance and plasma lipids (cholesterol), other antihyper-tensive agents are recommended for the initial and ongoing hypertension treatment in patients with risk factors for diabetes. ACE-inhibitors are particularly valued for treating hypertension in patients with one of the complications of diabetes—diabetic renal disease.