II. Indications
- Hypertension (first-line agent)
- Osteoporosis Prevention (investigational)
- Severe Congestive Heart Failure
- Adjunct to Loop Diuretics (e.g. Metolazone)
- Meniere's Disease
III. Contraindications
-
Hyponatremia
- Do not use Thiazide Diuretics in patients with a history of Hyponatremia
- See adverse effects below
IV. Mechanism
V. Precautions: Renal Insufficiency (GFR <30 ml/min)
- Thiazide Diuretics are minimally effective when GFR falls below 30 ml/min
- Switch to Loop Diuretics at this level of Renal Insufficiency
VI. Medications
VII. Adverse Effects
-
Hyperuricemia
- Occurs more often with doses of Hydrochlorothiazide over 25 mg
- Less of an issue if no Hypokalemia
- Avoid Thiazide Diuretics in gout!
- Hyperglycemia
-
Hyperlipidemia
- Increase serum Cholesterol and Serum Triglycerides
-
Hypokalemia
- Hypokalemia is less common when Thiazide Diuretic is combined with ACE Inhibitor, ARB or Potassium sparing Diuretic
- One banana a day is sufficient Potassium Replacement (each inch of banana supplies 1 meq of Potassium)
- Cost benefit is lost when Potassium supplement used
-
Hyponatremia
- Thiazide associated Hyponatremia is particularly common in the elderly
- Liamis (2016) J Geriatr Cardiol 13(2):175-82 +PMID: 27168745 [PubMed]
- Hypomagnesemia
-
Nonmelanoma Skin Cancer (esp. Squamous Cell Skin Cancer) with Hydrochlorothiazide
- NNH: 16,000 for one new case of Squamous Cell Skin Cancer per year with Hydrochlorothiazide
- Hydrochlorothiazide 25 mg daily for 5.5 years is associated with one new case of SCC per 6700
- May be associated with Hydrochlorothiazide associated photosensitivity
- (2020) presc lett 27(10):60
- https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-label-changes-hydrochlorothiazide-describe-small-risk-non-melanoma-skin-cancer
- Pedersen (2018) J Am Acad Dermatol 78(4):673-81 [PubMed]
VIII. Safety
- Pregnancy
- Thiazides are considered Category D when used for Pregnancy Induced Hypertension
- However most risks have been disproven (neonatal Thrombocytopenia, IUGR, fluid and Electrolyte abnormalities)
- Other than chlorthiazide which is Pregnancy Category C, all other Thiazides are considered pregnancy category B
- Hydrochlorothiazide is likely safe in pregnancy
- al Balas (2009) Can Fam Physician 55(1): 44-5 [PubMed]
-
Lactation
- Doses of 50 mg/day or less appear safe (minimal concentration in Breast Milk, no significant Breast Milk suppression)
- At doses higher than 50 mg daily do appear to suppress Breast Milk
- LactMed
IX. Drug Interactions
- Lithium
-
NSAIDs and COX-2 Inhibitors
- Decrease Thiazide efficacy as Diuretic and Antihypertensive
X. Efficacy
- Well, tolerated Antihypertensives
- Likely reduce cardiovascular events and Heart Failure risk
- When combined with ACE Inhibitors reduce CVA risk
- Reinhart (2023) Cochrane Database Syst Rev 7(7):CD008161 +PMID: 37439548 [PubMed]
XI. References
- (2021) Presc Lett, Resource #370507, Commonly Used Diuretics
- (2020) Med Lett Drugs Ther 62(1598): 73-80
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 62-3
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- (2011) J Clin Hypertens 13:639-43 [PubMed]