Chlortalidone
Encyclopedia
Chlortalidone or chlorthalidone (USAN
) is a diuretic
drug used to treat hypertension
, originally marketed as Hygroton in the USA. It is described as a thiazide diuretic (or, rather, a thiazide-like diuretic
because it acts similarly to the thiazides but does not contain the benzothiadiazine
molecular structure). Compared with other medications of the thiazide class, chlorthalidone has the longest duration of action, but a similar diuretic effect at maximal therapeutic doses. It is often used in the management of hypertension and edema.
Unlike loop diuretics, chlorthalidone efficacy is diminished in patients with certain renal diseaes (e.g. Chronic Renal Disease). A clinical trial (ALLHAT) in 2002 compared chlorthalidone to doxazosin in the treatment of high-risk hypertensive patients. In this study, only chlorthalidone significantly reduced the risk of combined cardiovascular disease events, especially heart failure, when compared with drugs such as doxazosin
. Chlorthalidone was approved by the FDA in 1960. The ALLHAT study conclusions showed that there was no significant difference in all-cause mortality, fatal heart disease, or non-fatal myocardial infarction when chlorthalidone was compared with lisinopril or amlodipine but did show decrease rates of heart failure after 6 years when compared with amlodipine and decreased rates of cerebrovascular disease after 6 years when compared with lisinopril leading the study conclusions to say that thiazide-type diuretics are preferred first-step in antihypertensive therapy.
Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Eventually, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. The reduction in intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy.
atenolol, marketed in the UK as Co-tenidone
and in the US as Tenoretic.
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...
) is a diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
drug used to treat hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, originally marketed as Hygroton in the USA. It is described as a thiazide diuretic (or, rather, a thiazide-like diuretic
Thiazide-like diuretic
A thiazide-like diuretic is a sulfonamide diuretic that has similar physiological properties to a thiazide diuretic, but doesn't have the chemical properties of a thiazide, lacking the benzothiadiazine molecular structure....
because it acts similarly to the thiazides but does not contain the benzothiadiazine
Benzothiadiazine
Benzothiadiazine is a bicyclic heterocyclic benzene derivative with the heterocycle containing two nitrogens and one sulfur.Benzothiadiazine derivatives include:* bendroflumethiazide* chlorothiazide* cyclothiazide* hydrochlorothiazide* diazoxide...
molecular structure). Compared with other medications of the thiazide class, chlorthalidone has the longest duration of action, but a similar diuretic effect at maximal therapeutic doses. It is often used in the management of hypertension and edema.
Unlike loop diuretics, chlorthalidone efficacy is diminished in patients with certain renal diseaes (e.g. Chronic Renal Disease). A clinical trial (ALLHAT) in 2002 compared chlorthalidone to doxazosin in the treatment of high-risk hypertensive patients. In this study, only chlorthalidone significantly reduced the risk of combined cardiovascular disease events, especially heart failure, when compared with drugs such as doxazosin
Doxazosin
Doxazosin mesylate, a quinazoline compound sold by Pfizer under the brand names Cardura and Carduran, is an α1a-selective alpha blocker used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia ....
. Chlorthalidone was approved by the FDA in 1960. The ALLHAT study conclusions showed that there was no significant difference in all-cause mortality, fatal heart disease, or non-fatal myocardial infarction when chlorthalidone was compared with lisinopril or amlodipine but did show decrease rates of heart failure after 6 years when compared with amlodipine and decreased rates of cerebrovascular disease after 6 years when compared with lisinopril leading the study conclusions to say that thiazide-type diuretics are preferred first-step in antihypertensive therapy.
Mechanism of action
Chlorthalidone increases the excretion of sodium, chloride, and water into the renal lumen by inhibiting sodium ion transport across the renal tubular epithelium. Its primary site of action is in the cortical diluting segment of the ascending limb of the loop of Henle. Thiazides and related compounds also decrease the glomerular filtration rate, which further reduces the drug's efficacy in patients with renal impairment (e.g. renal insufficiency). By increasing the delivery of sodium to the distal renal tubule, chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism (i.e. apical ROMK/Na channels coupled with basolateral NKATPases). This can result in hypokalemia and hypochloremia as well as a mild metabolic alkalosis; however, the diuretic efficacy of chlorthalidone is not affected by the acid-base balance of the patient being treated.Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Eventually, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. The reduction in intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy.
Combination products
It is also available as a combination product with the beta blockerBeta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
atenolol, marketed in the UK as Co-tenidone
Co-tenidone
Co-tenidone is a non-proprietary name used to denote a combination of atenolol and chlortalidone. Co-tenidone is used in the treatment of hypertension...
and in the US as Tenoretic.