Chlortalidone

Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling (such as occurs in heart failure, liver failure, and nephrotic syndrome), diabetes insipidus, and renal tubular acidosis. Because chlortalidone is effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

Common adverse effects include low blood potassium, low blood sodium, high blood sugar, dizziness, and erectile dysfunction. Other adverse effects may include gout, low blood magnesium, high blood calcium, allergic reactions, and low blood pressure. Some reviews have found chlortalidone and hydrochlorothiazide to have a similar risk of adverse effects, while other reviews have found chlortalidone to have a higher risk. While it may be used in pregnancy it is a less preferred option. How it works is not completely clear but is believed to involve increasing the amount of sodium and water lost by the kidneys.

Chlortalidone was patented in 1957 and came into medical use in 1960. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 124th most commonly prescribed medication in the United States, with more than 5 million prescriptions.

Chlortalidone is considered a first-line medication for treatment of high blood pressure. Some recommend chlortalidone over hydrochlorothiazide. A meta-analysis of randomized controlled trials found that chlortalidone is more effective than hydrochlorothiazide for lowering blood pressure, while the two drugs have similar toxicity.

Trials of chlortalidone for high blood pressure found that lower doses of chlortalidone (e.g., 12.5 mg daily in ALLHAT study) had maximal blood pressure lowering effect and that higher doses did not lower it more. Chlortalidone and other thiazide diuretics are effective for lowering high blood pressure in persons with chronic kidney disease, although the risk of adverse effects is higher.

Chlortalidone is used to treat enlargement of the left ventricle of the heart; it works chiefly by lowering blood pressure, and thereby reducing systemic vascular resistance. There is evidence that chlortalidone is superior to hydrochlorothiazide for reducing the mass of the left ventricle of the heart in persons with enlargement of the left ventricle of the heart. Chlortalidone is superior to angiotensin converting enzyme Inhibitors or angiotensin II receptor blockers for inducing regression of enlargement of the left ventricle, which is the main pumping chamber of the heart.

Chlortalidone reduces edema (swelling) by increasing urinary salt and water excretion, lowering intravascular hydrostatic pressure and thereby lowering transcapillary pressure (see Starling Equation). Edema may be caused by either increased hydrostatic pressure or reduced oncotic pressure in the blood vessels. Edema due to increased hydrostatic pressure may be a result of serious cardiopulmonary disease (which reduces glomerular perfusion in the kidney) or to kidney injury or disease (which may reduce glomerular excretion of salt and water by the kidney) or due to relatively benign conditions such as menstrual-related fluid retention, or as an adverse effect of dihydropyridine calcium channel blockers, which commonly cause swelling of the feet and lower legs. Edema due to decreased oncotic pressure may be a result of leaking of blood proteins through the glomeruli of an injured kidney or a result of diminished synthesis of blood proteins by a damaged liver. Regardless of cause, chlortalidone may reduce the severity of edema by reducing intravascular volume and thereby reducing intravascular hydrostatic pressure.

Chlortalidone decreases mineral bone loss by promoting calcium retention by the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation. A Cochrane review found tentative evidence that thiazide exposure was associated with a reduced risk of hip fracture. A secondary analysis of data from the ALLHAT study found that chlortalidone reduced risk of hip and pelvis fracture.