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Hydrochlorothiazide

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Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up.[4] Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine.[4] Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness.[4] Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis.[4][5] This initially increases urine volume and lowers blood volume.[6] It is believed to reduce peripheral vascular resistance.[6]

Hydrochlorothiazide
Clinical data
Trade namesHydrodiuril, others
Other namesHCTZ, HCT
AHFS/Drugs.comMonograph
MedlinePlusa682571
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • US: WARNING[2]Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityVariable (~70% on average)
MetabolismNot significant[3]
Elimination half-life5.6–14.8 h
ExcretionPrimarily kidney (>95% as unchanged drug)
Identifiers
  • 6-chloro-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.367 Edit this at Wikidata
Chemical and physical data
FormulaC7H8ClN3O4S2
Molar mass297.73 g·mol−1
3D model (JSmol)
  • O=S(=O)(N)c1c(Cl)cc2c(c1)S(=O)(=O)NCN2
  • InChI=1S/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13) checkY
  • Key:JZUFKLXOESDKRF-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Potential side effects include poor kidney function, electrolyte imbalances, including low blood potassium, and, less commonly, low blood sodium, gout, high blood sugar, and feeling lightheaded with standing.[4]

Two companies, Merck & Co. and Ciba Specialty Chemicals, state they discovered the medication which became commercially available in 1959.[7] It is on the World Health Organization's List of Essential Medicines.[8] It is available as a generic drug[4] and is relatively affordable.[9] In 2022, it was the twelfth most commonly prescribed medication in the United States, with more than 38 million prescriptions.[10][11]

Medical uses

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Hydrochlorothiazide is used for the treatment of hypertension, congestive heart failure, symptomatic edema, diabetes insipidus, renal tubular acidosis.[4] It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine.[4]

Multiple studies suggest hydrochlorothiazide could be used as initial monotherapy in people with primary hypertension; however, the decision should be weighed against the consequence of long-term adverse metabolic abnormalities.[12][13] Doses of hydrochlorothiazide of 50 mg or less over four years reduced mortality and development of cardiovascular diseases better than high-dose hydrochlorothiazide (50 mg or more) and beta-blockers.[5] A 2019 review supported equivalence between drug classes for initiating monotherapy in hypertension, although thiazide or thiazide-like diuretics showed better primary effectiveness and safety profiles than angiotensin-converting enzyme inhibitors and non-dihydropyridine calcium channel blockers.[12]

Low doses (50 mg or less) of hydrochlorothiazide as first‐line therapy for hypertension were found to reduce total mortality and cardiovascular disease events over a four-year study.[5] Hydrochlorothiazide appears be more effective than chlorthalidone in preventing heart attacks and strokes.[14] Hydrochlorothiazide is less potent but may be more effective than chlorthalidone in reducing blood pressure.[14][15] More robust studies are required to confirm which drug is superior in reducing cardiovascular events.[16] Side effect profile for both drugs appear similar and are dose dependent.[14]

Hydrochlorothiazide is also sometimes used to prevent osteopenia and treat hypoparathyroidism,[17] hypercalciuria, Dent's disease, and Ménière's disease.

A low level of evidence, predominantly from observational studies, suggests that thiazide diuretics have a modest beneficial effect on bone mineral density and are associated with a decreased fracture risk when compared with people not taking thiazides.[18][19][20] Thiazides decrease mineral bone loss by promoting calcium retention in the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation.[21]

The combination of fixed-dose preparation such as losartan/hydrochlorothiazide has added advantages of a more potent antihypertensive effect with additional antihypertensive efficacy at the dose of 100 mg/25 mg when compared to monotherapy.[22][23]

Adverse effects

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Package inserts contain vague and inconsistent data surrounding the use of thiazide diuretics in patients with allergies to sulfa drugs, with little evidence to support these statements.[26] A retrospective cohort study conducted by Strom et al. concluded that there is an increased risk of an allergic reaction occurring in patients with a predisposition to allergic reactions in general rather than cross reactivity from structural components of the sulfonamide-based drug.[27] Prescribers should examine the evidence carefully and assess each patient individually, paying particular attention to their prior history of sulfonamide hypersensitivity rather than relying on drug monograph information.[28]

There is an increased risk of non-melanoma skin cancer.[29] In August 2020, the Australian Therapeutic Goods Administration required the Product Information (PI) and Consumer Medicine Information (CMI) for medicines containing hydrochlorothiazide to be updated to include details about an increased risk of non-melanoma skin cancer.[30] In August 2020, the U.S. Food and Drug Administration (FDA) updated the drug label about an increased risk of non-melanoma skin cancer (basal cell skin cancer or squamous cell skin cancer).[31]

Society and culture

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Co-Diovan (valsartan and hydrochlorothiazide)
 
Two generic benazepril HCl 20 mg and hydrochlorothiazide 25 mg oral tablets

Brand names

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Hydrochlorothiazide is available as a generic drug under a large number of brand names, including Apo-Hydro, Aquazide, BPZide, Dichlotride, Esidrex, Hydrochlorot, Hydrodiuril, HydroSaluric, Hypothiazid, Microzide, Oretic and many others.[medical citation needed]

To reduce pill burden and in order to reduce side effects, hydrochlorothiazide is often used in fixed-dose combinations with many other classes of antihypertensive drugs such as:

Sport

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Use of hydrochlorothiazide is prohibited by the World Anti-Doping Agency for its ability to mask the use of performance-enhancing drugs.[34]

References

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  1. ^ "Hydrochlorothiazide Use During Pregnancy". Drugs.com. 30 July 2019. Retrieved 19 January 2020.
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ Beermann B, Groschinsky-Grind M, Rosén A (May 1976). "Absorption, metabolism, and excretion of hydrochlorothiazide". Clinical Pharmacology and Therapeutics. 19 (5 Pt 1): 531–537. doi:10.1002/cpt1976195part1531. PMID 1277708. S2CID 22159706.
  4. ^ a b c d e f g h "Hydrochlorothiazide". Drugs.com. 15 November 2022. Retrieved 31 May 2023.
  5. ^ a b c Wright JM, Musini VM, Gill R (April 2018). "First-line drugs for hypertension". The Cochrane Database of Systematic Reviews. 2018 (4): CD001841. doi:10.1002/14651858.CD001841.pub3. PMC 6513559. PMID 29667175.
  6. ^ a b Duarte JD, Cooper-DeHoff RM (June 2010). "Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics". Expert Review of Cardiovascular Therapy. 8 (6): 793–802. doi:10.1586/erc.10.27. PMC 2904515. PMID 20528637. NIHMSID: NIHMS215063.
  7. ^ Ravina E (2011). The evolution of drug discovery: from traditional medicines to modern drugs (1st ed.). Weinheim: Wiley-VCH. p. 74. ISBN 9783527326693. Archived from the original on 10 January 2015.
  8. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  9. ^ "Best drugs to treat high blood pressure The least expensive medications may be the best for many people". November 2014. Archived from the original on 3 January 2015. Retrieved 10 January 2015.
  10. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  11. ^ "Hydrochlorothiazide Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  12. ^ a b Suchard MA, Schuemie MJ, Krumholz HM, You SC, Chen R, Pratt N, et al. (November 2019). "Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis". Lancet. 394 (10211): 1816–1826. doi:10.1016/S0140-6736(19)32317-7. PMC 6924620. PMID 31668726.{{cite journal}}: CS1 maint: overridden setting (link)
  13. ^ Musini VM, Gueyffier F, Puil L, Salzwedel DM, Wright JM, et al. (Cochrane Hypertension Group) (August 2017). "Pharmacotherapy for hypertension in adults aged 18 to 59 years". The Cochrane Database of Systematic Reviews. 2017 (8): CD008276. doi:10.1002/14651858.CD008276.pub2. PMC 6483466. PMID 28813123.
  14. ^ a b c Hripcsak G, Suchard MA, Shea S, Chen R, You SC, Pratt N, et al. (April 2020). "Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension". JAMA Internal Medicine. 180 (4): 542–551. doi:10.1001/jamainternmed.2019.7454. PMC 7042845. PMID 32065600.{{cite journal}}: CS1 maint: overridden setting (link)
  15. ^ Peterzan MA, Hardy R, Chaturvedi N, Hughes AD (June 2012). "Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate". Hypertension. 59 (6): 1104–1109. doi:10.1161/HYPERTENSIONAHA.111.190637. PMC 4930655. PMID 22547443.
  16. ^ Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB (April 2011). "Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis". Hypertension. 57 (4): 689–694. doi:10.1161/HYPERTENSIONAHA.110.161505. PMID 21383313. S2CID 13017777.
  17. ^ Mitchell DM, Regan S, Cooley MR, Lauter KB, Vrla MC, Becker CB, et al. (December 2012). "Long-term follow-up of patients with hypoparathyroidism". The Journal of Clinical Endocrinology and Metabolism. 97 (12): 4507–4514. doi:10.1210/jc.2012-1808. PMC 3513540. PMID 23043192.{{cite journal}}: CS1 maint: overridden setting (link)
  18. ^ Aung K, Htay T, et al. (Cochrane Hypertension Group) (October 2011). "Thiazide diuretics and the risk of hip fracture". The Cochrane Database of Systematic Reviews (10): CD005185. doi:10.1002/14651858.CD005185.pub2. PMID 21975748.
  19. ^ Xiao X, Xu Y, Wu Q (July 2018). "Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies". Osteoporosis International. 29 (7): 1515–1524. doi:10.1007/s00198-018-4486-9. PMID 29574519. S2CID 4322516.
  20. ^ Solomon DH, Ruppert K, Zhao Z, Lian YJ, Kuo IH, Greendale GA, et al. (March 2016). "Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study". Osteoporosis International. 27 (3): 1181–1189. doi:10.1007/s00198-015-3332-6. PMC 4813302. PMID 26449354.
  21. ^ Dvorak MM, De Joussineau C, Carter DH, Pisitkun T, Knepper MA, Gamba G, et al. (September 2007). "Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by interacting with a sodium chloride co-transporter in bone". Journal of the American Society of Nephrology. 18 (9): 2509–2516. doi:10.1681/ASN.2007030348. PMC 2216427. PMID 17656470.{{cite journal}}: CS1 maint: overridden setting (link)
  22. ^ Lacourcière Y, Poirier L (December 2003). "Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension". American Journal of Hypertension. 16 (12): 1036–1042. doi:10.1016/j.amjhyper.2003.07.014. PMID 14643578. S2CID 26447230.
  23. ^ a b Musini VM, Nazer M, Bassett K, Wright JM (May 2014). "Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension". The Cochrane Database of Systematic Reviews. 2014 (5): CD003824. doi:10.1002/14651858.cd003824.pub2. PMC 10612990. PMID 24869750.
  24. ^ Hueskes BA, Roovers EA, Mantel-Teeuwisse AK, Janssens HJ, van de Lisdonk EH, Janssen M (June 2012). "Use of diuretics and the risk of gouty arthritis: a systematic review". Seminars in Arthritis and Rheumatism. 41 (6): 879–889. doi:10.1016/j.semarthrit.2011.11.008. PMID 22221907.
  25. ^ Wilson L, Nair KV, Saseen JJ (December 2014). "Comparison of new-onset gout in adults prescribed chlorthalidone vs. hydrochlorothiazide for hypertension". Journal of Clinical Hypertension. 16 (12): 864–868. doi:10.1111/jch.12413. PMC 8031516. PMID 25258088.
  26. ^ Johnson KK, Green DL, Rife JP, Limon L (February 2005). "Sulfonamide cross-reactivity: fact or fiction?". The Annals of Pharmacotherapy. 39 (2): 290–301. doi:10.1345/aph.1E350. PMID 15644481. S2CID 10642527.
  27. ^ Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, et al. (October 2003). "Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics". The New England Journal of Medicine. 349 (17): 1628–1635. doi:10.1056/NEJMoa022963. PMID 14573734.{{cite journal}}: CS1 maint: overridden setting (link)
  28. ^ Ghimire S, Kyung E, Lee JH, Kim JW, Kang W, Kim E (June 2013). "An evidence-based approach for providing cautionary recommendations to sulfonamide-allergic patients and determining cross-reactivity among sulfonamide-containing medications". Journal of Clinical Pharmacy and Therapeutics. 38 (3): 196–202. doi:10.1111/jcpt.12048. PMID 23489131.
  29. ^ Pedersen SA, Gaist D, Schmidt SA, Hölmich LR, Friis S, Pottegård A (April 2018). "Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark". Journal of the American Academy of Dermatology. 78 (4): 673–681.e9. doi:10.1016/j.jaad.2017.11.042. PMID 29217346.
  30. ^ "Hydrochlorothiazide". Therapeutic Goods Administration (TGA). 24 August 2020. Retrieved 22 September 2020.
  31. ^ "FDA approves label changes to hydrochlorothiazide". U.S. Food and Drug Administration (FDA). 20 August 2020. Retrieved 28 August 2020.   This article incorporates text from this source, which is in the public domain.
  32. ^ "List of nationally authorised medicinal products : Active substance: bisoprolol / hydrochlorothiazide Procedure no.: PSUSA/00000420/202111" (PDF). Ema.europa.eu. Retrieved 16 July 2022.
  33. ^ "Triamterene and Hydrochlorothiazide". MedlinePlus. 1 January 2020. Archived from the original on 2 January 2020. Retrieved 1 January 2020.
  34. ^ "Prohibited List" (PDF). World Anti-Doping Agency. January 2018.
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