thiazide diuretic
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Indications
- treatment of hypertension
- isolated systolic hypertension in the elderly*
- hypertension in black patients*
- thiazides may be more cardioprotective in overweight than in lean patients[8]
- treatment of edema
- may be useful in treatment of hypocalcemia
* calcium channel blocker is alternative except in patients with heart failure[2]
* chlorthalidone no better than hydrochlorothiazide[16]
Contraindications
- caution
- gout, hyponatremia, glucose intolerance
- concurrent use of lithium carbonate[2]
- do not change loop diuretic to thiazide diuretic for hyperkalemia in patients with hyperkalemia & systolic heart failure[18]
Pharmacokinetics
- renally cleared
- NOT useful in patients with creatinine clearance < 30 mL/min
Adverse effects
- hypercalcemia[11]
- hyperparathyroidism present in 34-43% of patients with thiazide-associated hypercalcemia[11]
- hyperuricemia
- hyperglycemia[2]
- increased risk of diabetes, relative risk 1.2-1.5[5]
- mean increase in fasting blood glucose = 3.6 mg/dL[12]
- hypokalemia
- no justification switching from loop diuretic to thiazide diuretic in patients with hyperkalemia & systolic heart failure[18]
- hypomagnesemia
- hyponatremia
- incidence may be higher than that indicated on drug labeling
- 2 year cumulative risk for serum sodium < 130 meq/L is < 4%[17]
- glucose intolerance
- hypochloremic metabolic alkalosis
- increased low-density lipoprotein (LDL)
- increased triglycerides
- rash & photosensitivity
- increased risk of squamous cell carcinoma skin[13]
- increased risk of keratinocyte carcinoma (40%) basal cell carcinoma & squamous cell carcinoma skin & cutaneous melanoma (60%)[14]
- pancreatitis
- hepatitis
- vasculitis
- mesenteric infarction
- impotence[2]
- thiazide users more likely to present to an emergency department with
- acute kidney injury (21% vs 7%)
- hyponatremia (22% vs 10%)
- hypokalemia (19% vs 11%)
- recent falls (21% vs 7%)
- recent syncope (6% vs 3%)[15]
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of thiazide diuretics
- drug adverse effects of diuretics
- drug adverse effects of antihypertensive agents
Drug interactions
- potentiation of lithium toxicity
- lessening of anticoagulant effect of warfarin
- enhancement of digitalis toxicity
- enhancement of effects of muscle relaxants
- combination of thiazide & benzodiazepine increases risk for severe hyponatremia[10]
- 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 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
More specific terms
- bendroflumethiazide; bendrofluazide (Naturetin)
- benzthiazide (Exna)
- chlorothiazide (Diuril)
- chlorthalidone (Hygroton)
- hydrochlorothiazide (HCTZ, HydroDIURIL, Oretic, Esidrix)
- hydroflumethiazide (Diucardin)
- indapamide (Lozol)
- methyclothiazide (Aquatensin Enduron)
- metolazone (Zaroxolyn, Diulo, Mykrox)
- polythiazide (Renese)
- trichlormethiazide (Metahydrin, Naqua)
Component of
References
- ↑ Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 137
- ↑ 2.0 2.1 2.2 2.3 2.4 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 473
- ↑ 5.0 5.1 Taylor EN et al, Antihypertensive medications and the risk of incident type 2 diabetes. Diabetes Care 2006; 29:1065 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16644638
- ↑ Prescriber's Letter 14(1): 2007 Thiazides and Diabetes Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230103&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 18(3): 2011 Prescriber's Letter 19(2): 2012 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 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280223&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 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 - ↑ Palmer BF, Naderi AS. Metabolic complications associated with use of thiazide diuretics. J Am Soc Hypertens. 2007 Nov-Dec;1(6):381-92 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20409871
- ↑ 10.0 10.1 Liamis G, Rodenburg EM, Hofman A, et al. Electrolyte disorders in community subjects: prevalence and risk factors. Am J Med. 2013;126:256-263 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23332973
- ↑ 11.0 11.1 11.2 Griebeler ML et al. Thiazide-associated hypercalcemia: Incidence and association with primary hyperparathyroidism over two decades. J Clin Endocrinol Metab 2016 Mar; 101:1166. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26751196 <Internet> http://press.endocrine.org/doi/10.1210/jc.2015-3964
- ↑ 12.0 12.1 Hall JJ et al. Thiazide diuretic-induced change in fasting plasma glucose: A meta-analysis of randomized clinical trials. J Gen Intern Med 2020 Jun; 35:1849. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32157653 Review. https://link.springer.com/article/10.1007/s11606-020-05731-3
- ↑ 13.0 13.1 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
- ↑ 14.0 14.1 Carroll L Common Blood Pressure Medications Linked to Increased Skin Cancer Risk. Medscape cites Reuters Health Information April 13, 2021 https://www.medscape.com/viewarticle/949153
Drucker AM, Hollestein L, Na Y et al Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study. CMAJ. 2021 Apr 12;193(15):E508-E516. Apr 12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33846199 Free article. https://www.cmaj.ca/content/193/15/E508 - ↑ 15.0 15.1 Ravioli S et al. Risk of electrolyte disorders, syncope, and falls in patients taking thiazide diuretics: Results of a cross-sectional study. Am J Med 2021 Sep; 134:1148. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33974908 https://www.amjmed.com/article/S0002-9343(21)00289-8/fulltext
- ↑ 16.0 16.1 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
- ↑ 17.0 17.1 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
- ↑ 18.0 18.1 18.2 NEJM Knowledge+