Chlorthalidone: Difference between revisions

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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.  
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.  
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.


'''Other Forms:'''
==Effectiveness==
===Hypertension===
Among the [[thiazide]] diuretics, chlorthalidone may be more effective for blood pressure control than [[hydrochlorothiazide]].<ref name="pmid22939358">{{cite journal| author=Bakris GL, Sica D, White WB, Cushman WC, Weber MA, Handley A et al.| title=Antihypertensive Efficacy of Hydrochlorothiazide vs Chlorthalidone Combined with Azilsartan Medoxomil. | journal=Am J Med | year= 2012 | volume= 125 | issue= 12 | pages= 1229.e1-1229.e10 | pmid=22939358 | doi=10.1016/j.amjmed.2012.05.023 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22939358  }} </ref>
 
==Other Forms==


It is also available as a combination product with the [[beta blocker]] [[atenolol]], marketed in the UK as [[Co-tenidone]] and in the US as Tenoretic.
It is also available as a combination product with the [[beta blocker]] [[atenolol]], marketed in the UK as [[Co-tenidone]] and in the US as Tenoretic.

Revision as of 05:18, 4 December 2012

Synonyms / Brand Names:

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Chlorthalidone
File:Chlortalidone.svg
Clinical data
Pregnancy
category
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding75%
Elimination half-life40 hours
ExcretionRenal
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC14H11ClN2O4S
Molar mass338.766 g/mol

Overview

Chlorthalidone (spelled chlortalidone in the UK) is a drug used to treat hypertension. 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 recent clinical trial (ALLHAT) 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 similar drugs such as doxazosin. [1] Chlorthalidone was approved by the FDA in 1960.

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.

Effectiveness

Hypertension

Among the thiazide diuretics, chlorthalidone may be more effective for blood pressure control than hydrochlorothiazide.[2]

Other Forms

It is also available as a combination product with the beta blocker atenolol, marketed in the UK as Co-tenidone and in the US as Tenoretic.

References

  1. ↑ ALLHAT Collaborative Research Group. (2000). "The ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)". JAMA. 283: 1967–75.
  2. ↑ Bakris GL, Sica D, White WB, Cushman WC, Weber MA, Handley A; et al. (2012). "Antihypertensive Efficacy of Hydrochlorothiazide vs Chlorthalidone Combined with Azilsartan Medoxomil". Am J Med. 125 (12): 1229.e1–1229.e10. doi:10.1016/j.amjmed.2012.05.023. PMID 22939358.

Template:Symporter inhibitors Template:Diuretics

de:Chlortalidon hr:Klortalidon it:Clortalidone


Dosing and Administration



FDA Package Insert Resources
Indications, Contraindications, Side Effects, Drug Interactions, etc.

Publication Resources
Recent articles, WikiDoc State of the Art Review, Textbook Information

Trial Resources
Ongoing Trials, Trial Results

Guidelines & Evidence Based Medicine Resources
US National Guidelines, Cochrane Collaboration, etc.

Media Resources
Slides, Video, Images, MP3, Podcasts, etc.

Patient Resources
Discussion Groups, Handouts, Blogs, News, etc.

International Resources
en Español





FDA Package Insert Resources

Indications

Contraindications

Side Effects

Drug Interactions

Precautions

Overdose

Instructions for Administration

How Supplied

Pharmacokinetics and Molecular Data

[FDA label]

FDA on Chlorthalidone

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Publication Resources

Most Recent Articles on Chlorthalidone

Review Articles on Chlorthalidone

Articles on Chlorthalidone in N Eng J Med, Lancet, BMJ

WikiDoc State of the Art Review

Textbook Information on Chlorthalidone

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Trial Resources

Ongoing Trials with Chlorthalidone at Clinical Trials.gov

Trial Results with Chlorthalidone

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Guidelines & Evidence Based Medicine Resources

US National Guidelines Clearinghouse on Chlorthalidone

Cochrane Collaboration on Chlorthalidone

Cost Effectiveness of Chlorthalidone

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Media Resources

Powerpoint Slides on Chlorthalidone

Images of Chlorthalidone

Podcasts & MP3s on Chlorthalidone

Videos on Chlorthalidone

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Patient Resources

Patient Information from National Library of Medicine

Patient Resources on Chlorthalidone

Discussion Groups on Chlorthalidone

Patient Handouts on Chlorthalidone

Blogs on Chlorthalidone

Chlorthalidone in the News

Chlorthalidone in the Marketplace

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International Resources

Chlorthalidone en Español

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Adapted from the FDA Package Insert.

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