Hydrochlorothiazide

Hydrochlorothiazide
Clinical data
Trade names Apo-hydro, others
AHFS/Drugs.com Monograph
MedlinePlus a682571
License data
Pregnancy
category
  • B (D if used to treat pregnancy-induced hypertension)
Routes of
administration		 Oral (capsules, tablets, oral solution)
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability Variable (~70% on average)
Metabolism Not significant[1]
Elimination half-life 5.6–14.8 h
Excretion Primarily kidney (>95% as unchanged drug)
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.000.367 Edit this at Wikidata
Chemical and physical data
Formula C7H8ClN3O4S2
Molar mass 297.74 g/mol
3D model (JSmol)
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Hydrochlorothiazide (HCTZ or HCT) is a diuretic medication often used to treat high blood pressure and swelling due to fluid build up.[2] Other uses include diabetes insipidus, renal tubular acidosis, and to decrease the risk of kidney stones in those with high calcium level in the urine.[2] For high blood pressure it is often recommended as a first line treatment,[2][3] though the similar drug, chlorthalidone, may be better.[4] HCTZ is taken by mouth and may be combined with other blood pressure medications as a single pill to increase the effectiveness.[2]

Potential side effects include poor kidney function, electrolyte imbalances especially low blood potassium and less commonly low blood sodium, gout, high blood sugar, and feeling faint initially upon standing up.[2] While allergies to HCTZ are reported to occur more often in those with allergies to sulfa drugs, this association is not well supported.[2] It may be used during pregnancy but is not a first line medication in this group.[2]

It is in the thiazide medication class and acts by decreasing the kidneys' ability to retain water.[2] This initially reduces blood volume, decreasing blood return to the heart and thus cardiac output.[5] Long term, however, it is believed to lower peripheral vascular resistance.[5]

Two companies, Merck and Ciba, state they discovered the medication which became commercially available in 1959.[6] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[7] In 2008 it was the second most commonly used blood pressure medication in the United States.[5] It is available as a generic drug[2] and is relatively affordable.[8]

Medical uses

Hydrochlorothiazide is frequently used for the treatment of hypertension, congestive heart failure, symptomatic edema, diabetes insipidus, renal tubular acidosis.[2] It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine.[2]

Most of the research supporting the use of thiazide diuretics in hypertension was done using chlorthalidone, a different medication in the same class. Some more recent studies have suggested that chlorthalidone might be the more effective thiazide diuretic for lowering blood pressure in persons with high blood pressure.[9] Also, the thiazide-type diuretics (including hydrochlorothiazide) are less effective than the thiazide-like diuretics (chlortalidone and indapamide) for reducing the risk of heart attack, stroke, and heart failure in persons with high blood pressure[10]

It is also sometimes used for treatment of hypoparathyroidism,[11] 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.

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.[12]

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

Adverse effects

These side effects increase with the dose of the medication and are most common at doses of greater than 25 mg per day.

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.[13]

Mechanism of action

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.[14] Additionally, by other mechanisms, HCTZ is believed to lower peripheral vascular resistance.[15]

Society and culture

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

Trade names

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.

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

Use of hydrochlorothiazide is prohibited by the World Anti-Doping Agency for its ability to mask the use of performance-enhancing drugs.[17]

See also

References

  1. ↑ 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.
  2. 1 2 3 4 5 6 7 8 9 10 11 "Hydrochlorothiazide". The American Society of Health-System Pharmacists. Archived from the original on 2017-05-10. Retrieved 2016-11-30.
  3. ↑ 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. PMID 29667175.
  4. ↑ 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.
  5. 1 2 3 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.
  6. ↑ 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 2015-01-10.
  7. ↑ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
  8. ↑ "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.
  9. ↑ Messerli, Franz; Makani, Harikrishna; Benjo, Alexandre; Romero, Jorge; Alviar, Carlos; Bangalore, Sripal (2011). "Antihypertensive Efficacy of Hydrochlorothiazide as Evaluated by Ambulatory Blood Pressure Monitoring: A Meta-Analysis of Randomized Trials". Journal of the American College of Cardiology. 57 (5): 590–600. doi:10.1016/j.jacc.2010.07.053.
  10. ↑ Olde Engberink RH, Frenkel WJ, van den Bogaard B, Brewster LM, Vogt L, van den Born BJ (May 2015). "Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis". Hypertension. 65 (5): 1033–40. doi:10.1161/HYPERTENSIONAHA.114.05122. PMID 25733241.
  11. ↑ Mitchell, Deborah. "Long-Term Follow-Up of Patients with Hypoparathyroidism". J Clin Endocrin Metab. Endocrine Society. Retrieved 19 June 2013.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ Uniformed Services University Pharmacology Note Set #3 2010, Lectures #39 & #40, Eric Marks
  15. ↑ Duarte, JD; Cooper-Dehoff, RM (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
  16. ↑ "Triamterene and Hydrochlorothiazide" Archived 2011-12-23 at the Wayback Machine.. MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. September 1, 2008.
  17. ↑ "Prohibited List" (PDF). World Anti-Doping Agency. January 2018.
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