Hydrochlorothiazide

Hydrochlorothiazide

Hydrochlorothiazide
Systematic (IUPAC) name
6-chloro-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide
Clinical data
Trade names Apo-hydro, Aquazide h, Dichlotride among others, Oretic
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • B (D if used to treat pregnancy-induced hypertension)
Legal status
  • (Prescription only)
Routes of
administration
Oral (capsules, tablets, oral solution)
Pharmacokinetic data
Bioavailability Variably absorbed from GI tract. Bioavailability ~ 70%
Metabolism does not undergo significant metabolism (>95% excreted unchanged in urine)[1]
Biological half-life 5.6–14.8 h
Excretion Primarily excreted unchanged in urine
Identifiers
CAS Registry Number  Y
ATC code C03
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  N
ChEMBL  Y
Chemical data
Formula C7H8ClN3O4S2
Molecular mass 297.74 g/mol
 N   

Hydrochlorothiazide (abbreviated HCTZ, HCT, or HZT), is a health system.[6] In 2008 it was the second most commonly used blood pressure medication in the United States.[4] It is available as a generic drug[2] and is not very expensive.[7]

Contents

  • Medical uses 1
  • Adverse effects 2
  • Mechanism of action 3
  • Society and culture 4
    • Brand names 4.1
    • Sport 4.2
  • See also 5
  • References 6
  • External links 7

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.[8]

It is also sometimes used for treatment of hypoparathyroidism,[9] 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.[10]

It may be given together with other antihypertensive agents in fixed combination preparations, such as in hydrochlorothiazide/losartan.

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.[11]

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.[12] Additionally, by other mechanisms, HCTZ is believed to lower peripheral vascular resistance.[13]

Society and culture

Co-Diovan (valsartan and hydrochlorothiazide)
Benazepril hydrochloride 20 mg / hydrochlorothiazide 25 mg oral tablet

Brand names

Hydrochlorothiazide is sold both as a generic drug and under a large number of brand names, including BP Zide 12.5 & 25 (Stadmed), Apo-Hydro, Aquazide H, Dichlotride, Hydrodiuril, HydroSaluric, Hydrochlorot, Microzide, Esidrex, and Oretic.

Hydrochlorothiazide is also used in combination with many other classes of hypertensive drugs such as ACE inhibitors, angiotensin receptor blockers, and beta blockers. These are sold under brand names including Diovan HCT, Zestoretic, Ziac, Benicar HCT, Olmy-H, Atacand HCT, and Lotensin HCT, Temax-H and others.

Sport

Hydrochlorothiazide was detected in the urine of the Russian cyclist Alexandr Kolobnev during the 2011 Tour de France.[14] Kolobnev was the only cyclist to leave the 2011 race in connection with adverse findings at a doping control.[15] While hydrochlorothiazide is not itself a performance-enhancing drug, it may be used to mask the use of performance-enhancing drugs, and is classed by the World Anti-Doping Agency as a "specified substance". Kolobnev was subsequently cleared of all charges of intentional doping.[16][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)): 531–7. 
  2. ^ a b c d e f g h i j k "Hydrochlorothiazide". The American Society of Health-System Pharmacists. Retrieved Jan 2015. 
  3. ^ Wright, JM; Musini, VM (8 July 2009). "First-line drugs for hypertension.". The Cochrane database of systematic reviews (3): CD001841.  
  4. ^ 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.  
  5. ^ Ravina, Enrique (2011). The evolution of drug discovery : from traditional medicines to modern drugs (1 ed.). Weinheim: Wiley-VCH. p. 74.  
  6. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  7. ^ "Best drugs to treat high blood pressure The least expensive medications may be the best for many people". http://www.consumerreports.org/. November 2014. Retrieved 10 January 2015. 
  8. ^ 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". J.Am.Coll.Cardiol. 57 (5): 590–600.  
  9. ^ Mitchell, Deborah. "Long-Term Follow-Up of Patients with Hypoparathyroidism". J Clin Endocrin Metab. Endocrine Society. Retrieved 19 June 2013. 
  10. ^ 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.  
  11. ^ Johnson, KK; Green, DL; Rife, JP; Limon, L (February 2005). "Sulfonamide cross-reactivity: fact or fiction?". The Annals of pharmacotherapy 39 (2): 290–301.  
  12. ^ Uniformed Services University Pharmacology Note Set #3 2010, Lectures #39 & #40, Eric Marks
  13. ^ 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.   NIHMSID: NIHMS215063
  14. ^ "Tour de France: Alexandr Kolobnev positive for banned diuretic". Velonation. 2011-07-11. Archived from the original on 2011-07-12. Retrieved 2011-07-12. 
  15. ^ "Kolobnev denies knowledge of doping product, says not fired by Katusha". Velonation. 2011-07-12. Archived from the original on 2011-07-12. Retrieved 2011-07-12. 
  16. ^ "Press release: Adverse Analytical Finding for Kolobnev". Union Cycliste Internationale. 2011-07-11. Archived from the original on 2011-07-12. Retrieved 2011-07-12. 
  17. ^ "Kolobnev Tour de France's first doping case". Cycling News ( 

External links

  • NIH medlineplus druginfo
  • U.S. National Library of Medicine: Drug Information Portal - Hydrochlorothiazide