Chlortalidone

Chlortalidone
Systematic (IUPAC) name
(RS)-2-Chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide
Clinical data
Trade names Generic, many tradenames worldwide[1]
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a682342
Pregnancy
category
Routes of
administration		 Oral
Legal status
Pharmacokinetic data
Protein binding 75%
Biological half-life 40 hours
Excretion Renal
Identifiers
CAS Number 77-36-1 YesY
ATC code C03BA04 (WHO)
PubChem CID 2732
IUPHAR/BPS 7147
DrugBank DB00310 YesY
ChemSpider 2631 YesY
UNII Q0MQD1073Q YesY
KEGG D00272 YesY
ChEBI CHEBI:3654 YesY
ChEMBL CHEMBL1055 YesY
Chemical data
Formula C14H11ClN2O4S
Molar mass 338.766 g/mol
Chirality Racemic mixture
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Chlortalidone (INN/BAN) 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, chlortalidone 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, chlortalidone efficacy is diminished in patients with certain renal diseases (e.g. chronic renal disease). A clinical trial (ALLHAT) in 2002 compared chlortalidone to doxazosin in the treatment of high-risk hypertensive patients. In this study, only chlortalidone significantly reduced the risk of combined cardiovascular disease events, especially heart failure, when compared with drugs such as doxazosin.[2] Chlortalidone 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 chlortalidone was compared with lisinopril or amlodipine but did show decreased 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.

In terms of activity, chlorothalidone is very similar to hydrochlorothiazide and is used as an independent drug or in combination with other antihypertensive agents for lowering arterial blood pressure, and also as an adjuvant drug for treating edema caused by cardiac insufficiency and renal irregularities, including nephrotic syndrome.

Mechanism of action

Chlortalidone prevents reabsorption of sodium and chloride by inhibiting the Na+/Cl− symporter in the distal convoluted tubule. Thiazides and related compounds also decrease the glomerular filtration rate, which further reduces the drug's efficacy in patients with kidney impairment (e.g. kidney insufficiency). By increasing the delivery of sodium to the distal renal tubule, chlortalidone 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 chlortalidone 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.

Banned for some sports

Chlortalidone is banned for some sports (including cricket) because it is a diuretic.[3]

See also

References

This article is issued from Wikipedia - version of the Saturday, April 02, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.