Hydrochlorothiazide (HCTZ or HCT) is a diuretic medication often used to treat high blood pressure and swelling due to fluid build up.[3] 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.[3] Hydrochlorothiazide is less effective than chlortalidone for prevention of heart attack or stroke.[4][3][5] HCTZ is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness.[3]

Clinical data
Trade namesApo-hydro, others
License data
Routes of
By mouth (capsules, tablets, oral solution)
ATC code
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityVariable (~70% on average)
MetabolismNot significant[2]
Elimination half-life5.6–14.8 h
ExcretionPrimarily kidney (>95% as unchanged drug)
  • 6-chloro-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.000.367 Edit this at Wikidata
Chemical and physical data
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
 ☒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.[3] While allergies to HCTZ are reported to occur more often in those with allergies to sulfa drugs, this association is not well supported.[3] It may be used during pregnancy, but it is not a first-line medication in this group.[3]

It is in the thiazide medication class and acts by decreasing the kidneys' ability to retain water.[3] This initially reduces blood volume, decreasing blood return to the heart and thus cardiac output.[6] It is believed to lower peripheral vascular resistance in the long run.[6]

Two companies, Merck and Ciba, state they discovered the medication which became commercially available in 1959.[7] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[8] It is available as a generic drug[3] and is relatively affordable.[9] In 2018, it was the thirteenth most commonly prescribed medication in the United States, with more than 40 million prescriptions.[10][11]

Medical usesEdit

Hydrochlorothiazide is frequently used for the treatment of hypertension, congestive heart failure, symptomatic edema, diabetes insipidus, renal tubular acidosis.[3] It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine.[3]

A 2019 review found that it was less effective than chlortalidone but also had fewer side effects.[12]

Hydrochlorothiazide is also sometimes used to prevent osteopenia and for treatment of hypoparathyroidism,[13] hypercalciuria, Dent's disease, and Ménière's disease. For diabetes insipidus, the effect of thiazide diuretics is presumably mediated by a hypovolemia-induced increase in proximal sodium and water reabsorption, thereby diminishing water delivery to the ADH-sensitive sites in the collecting tubules and increasing the urine osmolality.[medical citation needed]

Thiazides are also used in the treatment of osteoporosis. Thiazides decrease mineral bone loss by promoting calcium retention in the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation.[14]

It may be given together with other antihypertensive agents in fixed-dose combination preparations, such as in losartan/hydrochlorothiazide (see below).[medical citation needed]

Adverse effectsEdit

The frequency of side effects increase as the medication dose is increased and the highest occurrence of side effects occur at doses greater than 25 mg per day.[medical citation needed]

Package inserts, based on case reports and observational studies, have reported that an allergy to a sulfa drug predisposes the patient to cross sensitivity to a thiazide diuretic. A 2005 review of the literature did not find support for this cross-sensitivity.[16]

There is an increased risk of non-melanoma skin cancer.[17] 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.[18] 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).[19]

Mechanism of actionEdit

Hydrochlorothiazide belongs to thiazide class of diuretics. It reduces blood volume by acting on the kidneys to reduce sodium (Na+) reabsorption in the distal convoluted tubule. The major site of action in the nephron appears on an electroneutral NaCl co-transporter by competing for the chloride site on the transporter. By impairing Na+ transport in the distal convoluted tubule, hydrochlorothiazide induces a natriuresis and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport.[20] Additionally, by other mechanisms, HCTZ is believed to lower peripheral vascular resistance.[6]

Society and cultureEdit

Two generic benazepril HCl 20 mg and HCTZ 25 mg oral tablets

Trade namesEdit

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:


Use of hydrochlorothiazide is prohibited by the World Anti-Doping Agency for its ability to mask the use of performance-enhancing drugs.[22]

See alsoEdit


  1. ^ a b "Hydrochlorothiazide Use During Pregnancy". Drugs.com. 30 July 2019. Retrieved 19 January 2020.
  2. ^ Beermann B, Groschinsky-Grind M, Rosén A (1976). "Absorption, metabolism, and excretion of hydrochlorothiazide". Clin Pharmacol Ther. 19 (5 (Pt 1)): 531–37. doi:10.1002/cpt1976195part1531. PMID 1277708. S2CID 22159706.
  3. ^ a b c d e f g h i j k "Hydrochlorothiazide". The American Society of Health-System Pharmacists. Archived from the original on 10 May 2017. Retrieved 30 November 2016.
  4. ^ Roush GC, Messerli FH (January 2021). "Chlorthalidone versus hydrochlorothiazide: major cardiovascular events, blood pressure, left ventricular mass, and adverse effects". J Hypertens. doi:10.1097/HJH.0000000000002771. PMID 33470735.
  5. ^ Wright, JM; Musini, VM; Gill, R (18 April 2018). "First-line drugs for hypertension". The Cochrane Database of Systematic Reviews. 4: CD001841. doi:10.1002/14651858.CD001841.pub3. PMC 6513559. PMID 29667175.
  6. ^ a b c Duarte JD, Cooper-DeHoff RM (June 2010). "Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics". Expert Rev Cardiovasc Ther. 8 (6): 793–802. doi:10.1586/erc.10.27. PMC 2904515. PMID 20528637. NIHMSID: NIHMS215063.
  7. ^ Ravina, Enrique (2011). The evolution of drug discovery: from traditional medicines to modern drugs (1 ed.). Weinheim: Wiley-VCH. p. 74. ISBN 9783527326693. Archived from the original on 10 January 2015.
  8. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  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 2021". ClinCalc. Retrieved 18 February 2021.
  11. ^ "Hydrochlorothiazide - Drug Usage Statistics". ClinCalc. Retrieved 18 February 2021.
  12. ^ Acelajado MC, Hughes ZH, Oparil S, Calhoun DA (March 2019). "Treatment of Resistant and Refractory Hypertension". Circ. Res. 124 (7): 1061–1070. doi:10.1161/CIRCRESAHA.118.312156. PMC 6469348. 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... However, chlorthalidone use is more frequently associated with adverse metabolic effects, particularly hypokalemia and hyponatremia, compared with HCTZ.
  13. ^ Mitchell DM, Regan S, Cooley MR, Lauter KB, Vrla MC, Becker CB, Burnett-Bowie SA, Mannstadt M (December 2012). "Long-term follow-up of patients with hypoparathyroidism". J. Clin. Endocrinol. Metab. 97 (12): 4507–14. doi:10.1210/jc.2012-1808. PMC 3513540. PMID 23043192.
  14. ^ Dvorak MM, De Joussineau C, Carter DH, et al. (2007). "Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by targeting a NaCl cotransporter in bone". J. Am. Soc. Nephrol. 18 (9): 2509–16. doi:10.1681/ASN.2007030348. PMC 2216427. PMID 17656470.
  15. ^ Rheumatology (Oxford) 2017;56(5):679-688
  16. ^ 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.
  17. ^ 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". J. Am. Acad. Dermatol. 78 (4): 673–681.e9. doi:10.1016/j.jaad.2017.11.042. PMID 29217346. Lay summary.
  18. ^ "Hydrochlorothiazide". Therapeutic Goods Administration (TGA). 24 August 2020. Retrieved 22 September 2020.
  19. ^ "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.
  20. ^ Uniformed Services University Pharmacology Note Set #3 2010, Lectures #39 & #40, Eric Marks
  21. ^ "Triamterene and Hydrochlorothiazide". MedlinePlus. 1 January 2020. Archived from the original on 2 January 2020. Retrieved 1 January 2020.
  22. ^ "Prohibited List" (PDF). World Anti-Doping Agency. January 2018.

External linksEdit