Thiazide Diuretic

Aka: Thiazide Diuretic, Thiazide

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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

VI. Medications

  1. Hydrochlorothiazide (HCTZ)
  2. Chlorthalidone
  3. Metolazone (Zaroxolyn)
  4. Indapamide (Lozol)
  5. Chlorothiazide (Diuril)

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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Related Studies

Ontology: Thiazide Diuretics (C0012802)

Definition (NCI) Any benzothiadiazide derivative or other thiazide-like agent with diuretic and anti-hypertensive activity. Thiazide diuretics inhibit the sodium-chloride transporter in the distal tubule in the kidneys, thereby suppressing sodium and chloride reabsorption from the distal convoluted tubules (DCT) and increasing the excretion of sodium, chloride, potassium and water. In addition, thiazide diuretics decrease excretion of calcium and uric acid. These agents cause vasodilation possibly by activating calcium-activated potassium channels in vascular smooth muscle and inhibiting various carbonic anhydrases in vascular tissue.
Definition (MSH) Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1-dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D049993
SnomedCT 371342005, 350616005, 371343000, 372747003, 45518007
English Thiazide Diuretic, THIAZIDES/RELATED DIURETICS, thiazides, thiazide diuretics, thiazide diuretics (medication), [CV701] THIAZIDES/RELATED DIURETICS, thiazide diuretic, diuretic thiazide, diuretics thiazide, diuretic thiazides, Thiazide-related diuretic product (product), Thiazide-related diuretic (product), Thiazide diuretic product (product), Thiazide-related diuretic product, Thiazide diuretic, Thiazide diuretic (substance), Thiazide diuretic (product), Thiazide diuretic product, Thiazide Diuretics, Thiazide diuretic, NOS, Thiazide-related diuretic (substance), Thiazide-related diuretic, Thizaide-related diuretic, Benzothiadiazine Diuretics, Diuretics, Benzothiadiazine, Diuretics, Thiazide
French Diurétiques thiazides, Diurétiques thiazidiques, Benzothiadiazides, Diurétiques thiaziques
Czech diuretika thiazidová
German Diuretika, Thiazid-, Benzothiadiazindiuretika, Thiaziddiuretika
Italian Diuretici tiazidici
Spanish diurético tipo tiazida, producto con diurético tiazídico (producto), diurético relacionado con las tiazidas, producto con diurético tiazídico, diurético relacionado con las tiazidas (producto), diurético tiazídico (sustancia), diurético tiazídico, producto (producto), diurético tiazídico, producto, diurético tiazídico, diurético tipo tiazida (producto), diurético tipo tiazida (sustancia), diurético tiazídico (producto), tiazida
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Thiazides (C0541746)

Definition (CSP) family of bicyclic compounds in which one ring has a sulfony l and 2 nitrogen heteroatoms; they inhibit renal sodium resorption, and so are used as diuretics and antihypertensives.
Definition (MSH) Heterocyclic compounds with SULFUR and NITROGEN in the ring. This term commonly refers to the BENZOTHIADIAZINES that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D049971
LNC LP18072-6, MTHU003336
Italian Tiazidi
Swedish Tiazider
Czech thiazidy
Finnish Tiatsididiureetit
Russian TIAZIDY, ТИАЗИДЫ
English Thiazides, Thiazides [Chemical/Ingredient], thiazides, thiazide
Croatian Not Translated[Thiazides]
Polish Tiazydu pochodne
Spanish Tiacidas, Tiazidas
Portuguese Tiazidas
German Thiazide
French Thiazides
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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