Contents

Search

thiazide diuretic

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: 1) renally cleared 2) NOT useful in patients with creatinine clearance < 30 mL/min Adverse effects: 1) hypercalcemia [11] - hyperparathyroidism present in 34-43% of patients with thiazide-associated hypercalcemia [11] 2) hyperuricemia 3) hyperglycemia [2] - increased risk of diabetes, relative risk 1.2-1.5 [5] - mean increase in fasting blood glucose = 3.6 mg/dL [12] 4) hypokalemia - no justification switching from loop diuretic to thiazide diuretic in patients with hyperkalemia & systolic heart failure [18] 5) hypomagnesemia 6) hyponatremia - incidence may be higher than that indicated on drug labeling - 2 year cumulative risk for serum sodium < 130 meq/L is < 4% [17] 7) glucose intolerance 8) hypochloremic metabolic alkalosis 9) increased low-density lipoprotein (LDL) 10) increased triglycerides 11) 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] 12) pancreatitis 13) hepatitis 14) vasculitis 15) mesenteric infarction 16) impotence [2] 17) 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 interactions: 1) potentiation of lithium toxicity 2) lessening of anticoagulant effect of warfarin 3) enhancement of digitalis toxicity 4) enhancement of effects of muscle relaxants 5) combination of thiazide & benzodiazepine increases risk for severe hyponatremia [10] Mechanism of action: 1) enhances secretion of Na+, Cl- & H2O by interfering with Na+ & Cl- transport across the renal tubular epithelium mediated by SLC12A3 2) site of action: distal tubule. 3) thiazides also effect the excretion of other electrolytes including K+ & HCO3- 4) inhibits tubular excretion of Ca+2

Interactions

drug interactions drug adverse effects (more general classes) monitor with thiazide diuretics

Specific

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)

General

diuretic

Properties

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 137
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 473
  5. Taylor EN et al, Antihypertensive medications and the risk of incident type 2 diabetes. Diabetes Care 2006; 29:1065 PMID: 16644638
  6. Prescriber's Letter 14(1): 2007 Thiazides and Diabetes Detail-Document#: 230103 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 18(3): 2011 Prescriber's Letter 19(2): 2012 COMMENTARY: Thiazides for Hypertension CHART: Comparison of Commonly Used Diuretics Detail-Document#: 270304 Detail-Document#: 280223 (subscription needed) http://www.prescribersletter.com
  8. 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: 23219284 - Messerli FH and Bangalore S. Diuretic-based regimens for obese patients? Lancet 2013 Feb 16; 381:512. PMID: 23219285
  9. Palmer BF, Naderi AS. Metabolic complications associated with use of thiazide diuretics. J Am Soc Hypertens. 2007 Nov-Dec;1(6):381-92 PMID: 20409871
  10. 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: 23332973
  11. Griebeler ML et al. Thiazide-associated hypercalcemia: Incidence and association with primary hyperparathyroidism over two decades. J Clin Endocrinol Metab 2016 Mar; 101:1166. PMID: 26751196 http://press.endocrine.org/doi/10.1210/jc.2015-3964
  12. 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: 32157653 Review. https://link.springer.com/article/10.1007/s11606-020-05731-3
  13. 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: 33609289
  14. 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: 33846199 Free article. https://www.cmaj.ca/content/193/15/E508
  15. 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: 33974908 https://www.amjmed.com/article/S0002-9343(21)00289-8/fulltext
  16. Ishani A, Cushman WC, Leatherman SM et al Chlorthalidone vs. Hydrochlorothiazide for Hypertension - Cardiovascular Events. N Engl J Med 2022. Dec 14 PMID: 26760416 https://www.nejm.org/doi/10.1056/NEJMoa2212270
  17. 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: 38109740 https://www.acpjournals.org/doi/full/10.7326/M23-1989
  18. NEJM Knowledge+

Component-of

polypill (Polycap) reserpine/thiazide