Chlortalidone

Source: Wikipedia, the free encyclopedia.

Chlortalidone
Clinical data
Trade namesHygroton, Thalitone, others
AHFS/Drugs.comMonograph
MedlinePlusa682342
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth
Drug classThiazide-like diuretic
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding75%
Elimination half-life40 hours
ExcretionKidney
Identifiers
  • (RS)-2-Chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide
JSmol)
ChiralityRacemic mixture
  • O=S(=O)(N)c1c(Cl)ccc(c1)C2(O)c3ccccc3C(=O)N2
  • InChI=1S/C14H11ClN2O4S/c15-11-6-5-8(7-12(11)22(16,20)21)14(19)10-4-2-1-3-9(10)13(18)17-14/h1-7,19H,(H,17,18)(H2,16,20,21) checkY
  • Key:JIVPVXMEBJLZRO-UHFFFAOYSA-N checkY
  (verify)

Chlortalidone, also known as chlorthalidone, is a

heart attack or stroke.[5]

Common adverse effects include

low blood pressure.[2][3][7] Some reviews have found chlortalidone and hydrochlorothiazide to have a similar risk of adverse effects,[8][9] while other reviews have found chlortalidone to have a higher risk.[1][10] While it may be used in pregnancy it is a less preferred option.[2] How it works is not completely clear but is believed to involve increasing the amount of sodium and water lost by the kidneys.[2]

Chlortalidone was patented in 1957 and came into medical use in 1960.

generic medication.[3] In 2021, it was the 127th most commonly prescribed medication in the United States, with more than 4 million prescriptions.[13][14]

Medical use

High blood pressure

Chlortalidone is considered a first-line medication for treatment

high blood pressure.[2] Some recommend chlortalidone over hydrochlorothiazide.[1][15] 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.[16][17][1][10]

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.[18][19][20] [21]

Left ventricular hypertrophy

Chlortalidone is used to treat

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.[23]

Swelling

Chlortalidone reduces

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[24] 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.[25]

Bone fracture prevention

Chlortalidone decreases mineral bone loss by promoting calcium retention by the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation.[26] A Cochrane review found tentative evidence that thiazide exposure was associated with a reduced risk of hip fracture.[27] A secondary analysis of data from the ALLHAT study found that chlortalidone reduced risk of hip and pelvis fracture.[28]

Kidney stone prevention

Chlortalidone reduces the amount of calcium excreted in urine, reducing the risk of

kidney stones.[29] In people who have had multiple episodes of calcium oxalate kidney stones, chlortalidone lowers the risk of having another episode of kidney stones.[30] Chlortalidone is more effective than hydrochlorothiazide for lowering urine calcium levels and is therefore probably more effective.[31]

Ménière's disease

Chlortalidone reduces the endolymph volume which reduces the hydrostatic pressure in the inner ear chambers; elevated endolymph pressure in the inner ear is thought to be the cause of Ménière's disease or ’Endolymphatic hydrops.’ Synthesis of evidence from multiple small, low-quality studies indicates that chlortalidone or other thiazide diuretics are effective for Ménière's Disease.[32]

Diabetes insipidus

Chlortalidone (or other thiazide medication) is a key component of treatment of

renal collecting tubule and renal medullary collecting duct. This reduced delivery of solute to the collecting tubule and medullary collecting duct allows increased water resorption and higher concentration of urine, which leads to reversal of nephrogenic diabetes insipidus by a means that is independent of vasopressin.[33]

Adverse effects

Some reviews have found a similar risk as hydrochlorothiazide,[8][9] while other reviews found a higher risk of side effects.[1][10]

The frequency and severity of these adverse effects is much reduced when chlortalidone is used at lower doses (e.g., 12.5 mg per day).

Mechanism of action

Chlortalidone 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.[44] Although chlortalidone is often referred to as a "thiazide-like" diuretic, it is unlike thiazide diuretics in that, in addition to its inhibition of the Na+/Cl− symporter, it also strongly inhibits multiple isoforms of carbonic anhydrase.[45] Some of chlortalidone's diuretic effect is also due to this inhibition of carbonic anhydrase in the proximal tubule.[46] 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.

There is uncertainty about the mechanism of the blood pressure-lowering effect that occurs during chronic exposure to chlortalidone.

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.

Pharmacokinetics

Chlortalidone is slowly absorbed from the gastrointestinal tract after oral ingestion. It has a long half-life and therefore a prolonged diuretic action, which results in continued diuretic effects despite a skipped dose. This prolonged action of chlortalidone despite missing doses may account for the higher efficacy of chlortalidone compared to the shorter half-life medication, hydrochlorothiazide. Chlortalidone is eliminated from the body mostly by the kidney, as unchanged drug. Thus, in persons with diminished kidney function, the clearance of chlortalidone is reduced and the elimination half-life is increased.[48]

As with other thiazide diuretics, chlortalidone crosses the placenta and is excreted in breast milk.[49] Chlortalidone may suppress lactation, and has been used for this indication. Due to its long half-life, chlortalidone may accumulate in newborns via breast milk, despite receiving only about 6% of the maternal weight-adjusted dose.[50]

Chemistry

Chlortalidone is in the sulfamoylbenzamide class. As it lacks the

dimethylsulfoxide (DMSO), and methanol; it is also soluble in warm ethanol.[48]

Chlortalidone is the official name of the medication according to the (

United States Pharmacopeial Convention (USP), and the American Pharmacists Association
(APhA).

Society and culture

Chlortalidone is banned for some sports (including

cricket) because it is a diuretic, and can be used to reduce body weight or to mask the concomitant use of performance-enhancing drugs.[52] Sports such as wrestling or boxing categorize athletes according to body weight; taking a diuretic such as chlortalidone may lower body weight, and thereby permit an athlete to compete in a lighter weight class, which would provide an advantage. Diuretics such as chlortalidone also reduce the urine concentration of concomitantly-taken performance-enhancing drugs or of their metabolites, thus making it more difficult to detect these drugs using urine testing.[53]

References

  1. ^
    PMID 30920924
    . A long-acting thiazide-like diuretic, specifically chlorthalidone, if available, is recommended over hydrochlorothiazide (HCTZ) given its superior efficacy and clear benefit demonstrated in multiple outcome studies of hypertension.
  2. ^ a b c d e f g h i j "Chlorthalidone Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 18 April 2019.
  3. ^
    ISBN 978-0-85711-338-2
    .
  4. PMID 35404993
    .
  5. S2CID 231649367
    .
  6. PMID 27168745.{{cite journal}}: CS1 maint: DOI inactive as of March 2024 (link
    )
  7. ^ "Chlorthalidone" (PDF). FDA. Retrieved 27 March 2020.
  8. ^
    PMID 31595024
    .
  9. ^
    PMID 30251403
    .
  10. ^
    PMID 26760416
    .
  11. ISBN 978-3-527-60749-5
    .
  12. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  13. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  14. ^ "Chlorthalidone - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  15. PMID 26049382
    .
  16. PMID 31595024
    .
  17. PMID 29357392
    .
  18. S2CID 49650101
    .
  19. S2CID 6108618
    .
  20. PMID 24869750
    .
  21. PMID 30425103
    . thiazides either alone or in combination with a loop diuretic in advanced CKD, and all show some degree of efficacy, whether for hypertension or diuresis
  22. PMID 30251403
    .
  23. S2CID 3423953
    .
  24. PMID 27324677
    .
  25. PMID 15952439
    .
  26. PMID 17656470
    .
  27. S2CID 28866803
    .
  28. PMID 27893045
    .
  29. S2CID 2514178
    .
  30. PMID 23546565
    .
  31. S2CID 10227907
    .
  32. S2CID 24741244
    .
  33. S2CID 33533827
    .
  34. PMID 29387426
    .
  35. PMID 11076102
    .
  36. PMID 2046107
    .
  37. PMID 25139696
    .
  38. PMID 24811554
    .
  39. PMID 28783044
    .
  40. ISBN 978-3-318-06383-7
    .
  41. PMID 26751196
    .
  42. ISBN 978-3-319-65647-2
    .
  43. PMID 29976236
    .
  44. PMID 19474192
    .
  45. PMID 20625074
    .
  46. PMID 411910
    .
  47. PMID 26874237
    .
  48. ^
    ISBN 978-0-12-260814-8
    .
  49. S2CID 22930934
    .
  50. PMID 30000622
    . NBK501562. Retrieved 13 December 2018.
  51. ^ National Center for Biotechnology Information. PubChem Compound Database; CID=2732, "Chlorthalidone". PubChem. U.S. National Library of Medicine.
  52. PMID 20718736
    .
  53. ^ "Yasir Shah provisionally suspended after failed drugs test". BBC News. 27 December 2015.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Chlortalidone&oldid=1213051014"