hydrochlorothiazide (HCTZ, HydroDIURIL, Oretic, Esidrix)
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Introduction
Tradenames: HCTZ, HydroDiuril, Oretic.
Indications
- hypertension
- thiazides may be more cardioprotective in overweight than in lean patients[12]
- chlorthalidone not associated with cardiovascular benefits vs HCTZ[14][18]
- edema
- hypocalcemia
- prevention of calcium stones
- nephrogenic diabetes insipidus
Dosage
Tabs: 25, 50, 100 mg
Solution: 50 mg/5 mL
Pharmacokinetics
- bioavailability is about 70%
- decreased in patients with CHF
- absorption is increased by food[7]
- 58% bound to plasma proteins
- 95% of the drug is excreted unchanged into the urine
- may not be effective in patients with creatinine clearance < 30 mL/min (< 15-20 mL/min or serum creatinine > 2.5 mg/dL[9])
- onset of diuresis is within 2 hours with duration of effect 6-8 hours
- onset of hypotensive effect is 3-4 days
elimination via liver
protein binding = 58 %
Adverse effects
- hypokalemia (1-10%) less than that with chlorthalidone[14]
- hyperuricemia
- rash maculopapular (not itchy)
- increased low-density lipoprotein (LDL)
- hypochloremic alkalosis
- dilutional hyponatremia & SIADH
- incidence may be higher than that indicated on drug labeling
- 2 year cumulative risk for serum sodium < 130 meq/L is < 4%[19]
- hyperglycemia
- glucosuria
- orthostatic hypotension
- GI complaints
- photosensitivity
- increased risk of lip cancer
- increased incidence of skin squamous cell carcinoma[13][15][16]
- increased incidence of basal cell carcinoma[15]
- increased incidence of cutaneous melanoma, specifically lentigo melanoma & nodular melanoma (RR=1.2)[13]
- generalized pruritus without rash or skin lesions[4]
- pancreatitis
- vasculitis
- electrolyte imbalances less than chlorthalidone[14]
- preserves bone mineral density (hip)[8]
- drug-induced lupus[17]
- acute interstitial nephritis[20]
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of thiazide diuretics
- drug adverse effects of sulfonamides
- drug adverse effects of diuretics
- drug adverse effects of antihypertensive agents
Drug interactions
- HCTZ may enhance hypokalemic effects of agents that lower serum K+ levels: i.e. beta-2 adrenergic agonists
- HCTZ may decrease lithium clearance
- HCTZ may increase requirements for oral hypoglycemic agents &/or insulin
- probenecid
- HCTZ may increase the risk of NSAID-induced renal failure
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) SGLT2 inhibitors (flozins) with diuretics
- drug interaction(s) of diuretics in combination with Zn+2
- drug interaction(s) of antiarrhythmic agents in combination with diuretics
- drug interaction(s) of beta-2 adrenergic receptor agonists with thiazide diuretics
- drug interaction(s) of calcium channel blockers with diuretics
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of antibiotics with warfarin
- drug interaction(s) of benzodiazepines with thiazide diuretics
- drug interaction(s) of lithium carbonate with thiazide diuretics
- drug interaction(s) of diuretics with angiotensin II receptor antagonists
- drug interaction(s) of diuretics with ACE inhibitors
- drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
- drug interaction(s) of NSAIDs, diuretics & ACE inhibitors
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- enhances secretion of Na+, Cl- & H2O by interfering with Na+ & Cl- transport across the renal tubular epithelium mediated by SLC12A3
- site of action: distal tubule.
- thiazides also effect the excretion of other electrolytes including K+ & HCO3-
- inhibits tubular excretion of Ca+2
More general terms
Component of
- hydrochlorothiazide/reserpine
- bisoprolol/fumarate/hydrochlorothiazide
- hydrochlorothiazide/valsartan
- hydrochlorothiazide/telmisartan
- hydrochlorothiazide/quinapril
- hydrochlorothiazide/olmesartan (Benicar HCT)
- hydrochlorothiazide/moexipril
- hydrochlorothiazide/irbesartan (Avalide)
- fosinopril/hydrochlorothiazide
- eprosartan/hydrochlorothiazide
- candesartan/hydrochlorothiazide
- amlodipine/hydrochlorothiazide/valsartan
- amlodipine/hydrochlorothiazide/olmesartan (Tribenzor)
- aliskiren/amlodipine/hydrochlorothiazide (Amturnide)
- aliskiren/hydrochlorothiazide (Tekturna HCT)
- hydrochlorothiazide/spironolactone; HCTZ/spironolactone (Aldactazide)
- hydrochlorothiazide/methyldopa; HCTZ/methyldopa (Aldoril)
- hydralazine/hydrochlorothiazide; hydralazine/HCTZ (Apresazide)
- captopril/hydrochlorothiazide; captopril/HCTZ (Capozide)
- guanethidine/hydrochlorothiazide; guanethidine/HCTZ (Esmil)
- hydrochlorothiazide/losartan; HCTZ/losartan (Hyzaar)
- hydrochlorothiazide/propranolol; HCTZ/propranolol (Inderide)
- hydrochlorothiazide/metoprolol; HCTZ/metoprolol (Lopressor HCTZ, Dutoprol)
- benazepril/hydrochlorothiazide; benazepril/HCTZ (Lotensin HCTZ)
- hydrochlorothiazide/triamterene; HCTZ/triamterene (Dyazide, Maxzide, Maxide)
- amiloride/hydrochlorothiazide; amiloride/HCTZ (Moduretic)
- hydralazine/hydrochlorothiazide/reserpine; hydralazine/HCTZ/reserpine (Ser Ap Es)
- hydrochlorothiazide/timolol; HCTZ/timolol (Timolide)
- enalapril/hydrochlorothiazide; enalapril/HCTZ (Vaseretic)
- hydrochlorothiazide/lisinopril; HCTZ/lisinopril (Prinzide, Zestoretic)
- bisoprolol/hydrochlorothiazide; bisoprolol/HCTZ (Ziac)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
- ↑ Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 123
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 4.0 4.1 Medical Knowledge Self Assessment Program (MKSAP) 11, 18. American College of Physicians, Philadelphia 1998, 2018
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 6.0 6.1 Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ 7.0 7.1 Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 470
- ↑ 8.0 8.1 LaCroix AZ et al, Low-dose hydrochlorthiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo- controlled trial. Ann Intern Med 133:516, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11015164
- ↑ 9.0 9.1 MicroMedex
- ↑ 10.0 10.1 Prescriber's Letter 18(3): 2011 COMMENTARY: Thiazides for Hypertension CHART: Comparison of Commonly Used Diuretics Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=270304&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Friedman GD et al Antihypertensive Drugs and Lip Cancer in Non-Hispanic Whites Archives of Internal Medicine, August 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22869299 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1307567
- ↑ 12.0 12.1 Weber MA et al. Effects of body size and hypertension treatments on cardiovascular event rates: Subanalysis of the ACCOMPLISH randomised controlled trial. Lancet 2013 Feb 16; 381:537 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23219284
Messerli FH and Bangalore S. Diuretic-based regimens for obese patients? Lancet 2013 Feb 16; 381:512. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23219285 - ↑ 13.0 13.1 13.2 Pottegard A, Pedersen SA, Schmidt SAJ et al Association of Hydrochlorothiazide Use and Risk of Malignant Melanoma. JAMA Intern Med. Published online May 29, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29813157 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2682616
Pedersen SA, Gaist D, Schmidt SAJ et al Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol. 2018 Apr;78(4):673-681.e9. Epub 2017 Dec 4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29217346 Free Article - ↑ 14.0 14.1 14.2 14.3 Hripcsak G, Suchard MA, Shea S et al Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Intern Med. Published online February 17, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32065600 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2760777
- ↑ 15.0 15.1 15.2 FDA. Aug 20, 2020 FDA approves label changes to hydrochlorothiazide to describe small risk of non-melanoma skin cancer. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-label-changes-hydrochlorothiazide-describe-small-risk-non-melanoma-skin-cancer
- ↑ 16.0 16.1 Schneider R, Reinau D, Stoffel S et al Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group. Br J Dermatol. Published online February 20, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33609289
- ↑ 17.0 17.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ 18.0 18.1 Ishani A, Cushman WC, Leatherman SM et al Chlorthalidone vs. Hydrochlorothiazide for Hypertension - Cardiovascular Events. N Engl J Med 2022. Dec 14 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26760416 https://www.nejm.org/doi/10.1056/NEJMoa2212270
- ↑ 19.0 19.1 Andersson NW, Wohlfahrt J, Feenstra B, Hviid A, Melbye M, Lund M. Cumulative Incidence of Thiazide-Induced Hyponatremia. A Population-Based Cohort Study. Ann Inter Med 2023. Dec 19. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38109740 https://www.acpjournals.org/doi/full/10.7326/M23-1989
- ↑ 20.0 20.1 NEJM Knowledge+