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|Trade names||Generic, many tradenames worldwide|
|AHFS/Drugs.com||Consumer Drug Information|
|Elimination half-life||40 hours|
|Chemical and physical data|
|Molar mass||338.766 g/mol|
|3D model (JSmol)|
Chlortalidone (INN/BAN) or chlorthalidone (USAN) is a diuretic medication used to treat hypertension (high blood pressure), and fluid retention. It was 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).
Chlortalidone is more effective at lowering blood pressure than the similar drug, hydrochlorothiazide, particularly toward the end of the dosing interval. Chlortalidone and hydrochlorothiazide have a similar risk of hypokalemia and other adverse effects at the usual doses prescribed in routine clinical practice. Chlortalidone is sometimes used as the sole drug for treating high blood pressure. It is also often used in combination with other antihypertensive agents for lowering arterial blood pressure, and also as an adjuvant drug for treating edema caused by heart failure and kidney disorders, such as nephrotic syndrome.
Mechanism of action
Chlortalidone, a thiazide-like diuretic in the sulfamoylbenzamide class reduces reabsorption of sodium and chloride primarily through inhibition of the Na+/Cl− symporter in the apical membrane of distal convoluted tubule cells in the kidney. Some of chlortalidone's diuretic effect is also due to inhibition of carbonic anhydrase in the proximal tubule. Chronic exposure to chlortalidone decreases the glomerular filtration rate. Chlortalidone's diuretic effect is diminished in persons with kidney impairment. 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 Na+/K ATPases). This can result in a low blood concentration of potassium and chloride as well as a mild metabolic alkalosis; however, the diuretic effect of chlortalidone is not affected by the acid-base balance of the person being treated.
Blood pressure-lowering effect
There is uncertainty about the mechanism of the blood pressure-lowering effect that occurs during chronic exposure to chlortalidone. 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.
Milligram for milligram, at the doses used for treating high blood pressure, chlortalidone has a modestly greater effect on lowering blood pressure than does hydrochlorothiazide but the two drugs have similar effects on lowering potassium.
A clinical trial (ALLHAT) in 2002 compared chlortalidone to doxazosin, lisinopril, and amlodipine in the treatment of high-risk hypertensive patients. In this study, the rate of fatal or nonfatal myocardial infarction was the same for chlortalidone, lisinopril, and amlodipine. ALLHAT subjects treated with chlorthalidone had a lower rate of congestive heart failure than amlodipine or lisinopril or doxazosin. Also, compared to lisinopril subjects, chlortalidone subjects in ALLHAT had a lower risk of developing cardiovascular disease.
Banned for some sports
- drugs.com drugs.com international listing of Chlortalidone Page accessed May 13, 2015
- Gamba G (October 2009). "The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs". Am. J. Physiol. Renal Physiol. 297 (4): F838–48. doi:10.1152/ajprenal.00159.2009. PMC . PMID 19474192.
- Johnston MM, Li H, Mufson D (December 1977). "Chlorthalidone analysis using carbonic anhydrase inhibition". J Pharm Sci. 66 (12): 1735–8. PMID 411910.
- Shahin MH, Johnson JA (April 2016). "Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response". Curr Opin Pharmacol. 27: 31–7. doi:10.1016/j.coph.2016.01.005. PMC . PMID 26874237.
- name=Roush2013>Roush GC, Buddharaju V, Ernst ME (July 2013). "Is chlorthalidone better than hydrochlorothiazide in reducing cardiovascular events in hypertensives?". Curr. Opin. Cardiol. 28 (4): 426–32. doi:10.1097/HCO.0b013e3283622075. PMID 23736816.
- name=Ernst>Ernst ME, Carter BL, Zheng S, Grimm RH (April 2010). "Meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium". Am. J. Hypertens. 23 (4): 440–6. doi:10.1038/ajh.2010.1. PMID 20111008.
- ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group (18 December 2002). "Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)". JAMA. 288 (23): 2981–97. doi:10.1001/jama.288.23.2981. PMID 12479763.
- "Yasir Shah provisionally suspended after failed drugs test". BBC News. December 27, 2015.