II. Indications

  1. Hypertension (first-line agent)
  2. Osteoporosis Prevention (investigational)
  3. Severe Congestive Heart Failure
    1. Adjunct to Loop Diuretics (e.g. Metolazone)
  4. Meniere's Disease

III. Contraindications

  1. Hyponatremia
    1. Do not use Thiazide Diuretics in patients with a history of Hyponatremia
    2. See adverse effects below

IV. Mechanism

  1. nephron.png
  2. Thiazide Diuretics inhibit Sodium and chloride reabsorption in the distal tubule
  3. Also associated with mild diuresis and Potassium loss

V. Precautions: Renal Insufficiency (GFR <30 ml/min)

  1. Thiazide Diuretics are minimally effective when GFR falls below 30 ml/min
  2. Switch to Loop Diuretics at this level of Renal Insufficiency

VII. Adverse Effects

  1. Hyperuricemia
    1. Occurs more often with doses of Hydrochlorothiazide over 25 mg
    2. Less of an issue if no Hypokalemia
    3. Avoid Thiazide Diuretics in gout!
  2. Hyperglycemia
  3. Hyperlipidemia
    1. Increase serum Cholesterol and Serum Triglycerides
  4. Hypokalemia
    1. Hypokalemia is less common when Thiazide Diuretic is combined with ACE Inhibitor, ARB or Potassium sparing Diuretic
    2. One banana a day is sufficient Potassium Replacement (each inch of banana supplies 1 meq of Potassium)
    3. Cost benefit is lost when Potassium supplement used
  5. Hyponatremia
    1. Thiazide associated Hyponatremia is particularly common in the elderly
    2. Liamis (2016) J Geriatr Cardiol 13(2):175-82 +PMID: 27168745 [PubMed]
  6. Hypomagnesemia
  7. Nonmelanoma Skin Cancer (esp. Squamous Cell Skin Cancer) with Hydrochlorothiazide
    1. NNH: 16,000 for one new case of Squamous Cell Skin Cancer per year with Hydrochlorothiazide
    2. Hydrochlorothiazide 25 mg daily for 5.5 years is associated with one new case of SCC per 6700
    3. May be associated with Hydrochlorothiazide associated photosensitivity
    4. (2020) presc lett 27(10):60
    5. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-label-changes-hydrochlorothiazide-describe-small-risk-non-melanoma-skin-cancer
    6. Pedersen (2018) J Am Acad Dermatol 78(4):673-81 [PubMed]

VIII. Safety

  1. Pregnancy
    1. Thiazides are considered Category D when used for Pregnancy Induced Hypertension
    2. However most risks have been disproven (neonatal Thrombocytopenia, IUGR, fluid and Electrolyte abnormalities)
    3. Other than chlorthiazide which is Pregnancy Category C, all other Thiazides are considered pregnancy category B
    4. Hydrochlorothiazide is likely safe in pregnancy
    5. al Balas (2009) Can Fam Physician 55(1): 44-5 [PubMed]
  2. Lactation
    1. Doses of 50 mg/day or less appear safe (minimal concentration in Breast Milk, no significant Breast Milk suppression)
    2. At doses higher than 50 mg daily do appear to suppress Breast Milk
    3. LactMed
      1. https://www.ncbi.nlm.nih.gov/books/NBK500965/

IX. Drug Interactions

  1. Lithium
    1. Increases Lithium levels via decreased Lithium excretion
  2. NSAIDs and COX-2 Inhibitors
    1. Decrease Thiazide efficacy as Diuretic and Antihypertensive

X. Efficacy

  1. Well, tolerated Antihypertensives
  2. Likely reduce cardiovascular events and Heart Failure risk
  3. When combined with ACE Inhibitors reduce CVA risk
  4. Reinhart (2023) Cochrane Database Syst Rev 7(7):CD008161 +PMID: 37439548 [PubMed]

XI. References

  1. (2021) Presc Lett, Resource #370507, Commonly Used Diuretics
  2. (2020) Med Lett Drugs Ther 62(1598): 73-80
  3. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 62-3
  4. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  5. (2011) J Clin Hypertens 13:639-43 [PubMed]

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