Thiazide
Thiazide | |
---|---|
C03A | |
Biological target | sodium-chloride symporter |
External links | |
MeSH | D049971 |
Legal status | |
In Wikidata |
Thiazide (
Thiazide organic molecules are bi-cyclic structures that contain adjacent sulfur and nitrogen atoms on one ring.[5] Confusion sometimes occurs because thiazide-like diuretics such as indapamide are referred to as thiazides despite not having the thiazide chemical structure.[6] When used this way, "thiazide" refers to a drug which acts at the thiazide receptor.[7] The thiazide receptor is a sodium-chloride transporter that pulls NaCl from the lumen in the distal convoluted tubule. Thiazide diuretics inhibit this receptor, causing the body to release NaCl and water into the lumen, thereby increasing the amount of urine produced each day.[6] An example of a molecule that is chemically a thiazide but not used as a diuretic is methylchloroisothiazolinone, often found as an antimicrobial in cosmetics.[8]
Medical uses
Thiazide diuretics are primarily used to treat the hypertension (high blood pressure) and edema (swelling) caused by water overload as well as certain conditions related to unbalanced calcium metabolism.
Water balance
Hypertension
There are many causes of hypertension (high blood pressure), including advancing age, smoking and obesity.[9] Sometimes the underlying cause of hypertension can not be determined, resulting in a diagnosis of idiopathic hypertension. Regardless of the cause, someone may have very high hypertension without any initial symptoms. Uncontrolled hypertension will eventually cause damage to the heart, kidneys and eyes. Lifestyle changes, including reducing dietary salt, increasing exercise and losing weight can help to reduce blood pressure.[9]
Thiazides and thiazide-like diuretics have been in constant use since their introduction in 1958. Decades as a cornerstone of hypertension treatment show how well these drugs perform for most patients.[10] Low-dose thiazides are tolerated as well as the other classes of medications for hypertension, including ACE inhibitors, beta blockers and calcium channel blockers.[9] In general, the thiazides and thiazide-like diuretics reduce the risk of death, stroke, heart attack, and heart failure due to hypertension.[11]
Drug Type | Generic Drug Name | Low Dose
Threshold (mg/day)[9] |
---|---|---|
Thiazide Diuretic | Chlorothiazide | 500 |
Hydrochlorothiazide | 50 | |
Bendroflumethiazide | 5 | |
Methyclothiazide | 5 | |
Trichlormethiazide | 2 | |
Thiazide-like Diuretic | Chlorthalidone
|
50 |
Indapamide | 5 |
Diabetes insipidus
Thiazides can be used to paradoxically decrease urine flow in people with nephrogenic diabetes insipidus.[16] Thiazides may also be useful in treating hyponatremia (low blood sodium) in infants with central diabetes insipidus.[17]
Calcium balance
Urinary stones
Thiazides are useful in treating
Dent's disease
Thiazides may be used to treat the symptoms of Dent's disease, an X-linked genetic condition that results in electrolyte imbalance with repeated episodes of kidney stones. A case study of two brothers with the condition, two years of treatment with hydrochlorothiazide reduced the incidence of kidney stones and improved kidney function.[20] The thiazide-like diuretic chlortalidone reduced urine calcium oxalate in seven of the eight males with inactivated CLCN5 gene that participated in the study.[21] Inactivation of the CLCN5 gene causes Dent's disease Type 1.[22] The rare nature of Dent's disease makes it difficult to coordinate large controlled studies, so most evidence for thiazide use is with too few patients to make broad recommendations possible.[22] Long-term thiazide use may not be advisable due to the risk of significant adverse side effects.[citation needed]
Osteoporosis
Other uses
Bromine intoxication can be treated by giving intravenous saline with either thiazides or Loop diuretics.[25]
Contraindications
Contraindications include: [citation needed]
- Hypotension
- Allergy to sulphur-containing medications
- Gout
- Kidney failure
- Lithium therapy
- Hypokalemia
- May worsen diabetes
Thiazides reduce the clearance of uric acid since they compete for the same transporter, and therefore raise the levels of uric acid in the blood. Hence, they are prescribed with caution in patients with gout or hyperuricemia.[26][27]
Chronic administration of thiazides is associated with the increase of insulin resistance which can lead to hyperglycemia.[28]
Thiazides cause loss of blood potassium, while conserving blood calcium.[citation needed]
Thiazides can decrease placental perfusion and adversely affect the fetus, so should be avoided in pregnancy.[27][29]
Adverse effects
- Hyperglycemia
- Hyperlipidemia
- Hyperuricemia
- Hypercalcemia
- Hyponatremia
- Hypomagnesemia
- Hypocalciuria
Mechanism of action
Thiazide diuretics control hypertension in part by inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter.[31] The term "thiazide" is also often used for drugs with a similar action that do not have the thiazide chemical structure, such as chlorthalidone, metolazone and indapamide. These agents are more properly termed thiazide-like diuretics.[citation needed]
Thiazide diuretics also increase calcium reabsorption at the
Thiazides are also thought to increase the reabsorption of Ca2+ by a mechanism involving the reabsorption of sodium and calcium in the proximal tubule in response to sodium depletion. Some of this response is due to augmentation of the action of parathyroid hormone.[33]
Breastfeeding
Thiazides pass into breast milk and can decrease the flow of breast milk.[34] Thiazides have been associated with significant side effects in some nursing infants and should be administered to nursing mothers with caution.[35]
History
The thiazide diuretics were developed by scientists Karl H. Beyer, James M. Sprague, John E. Baer, and Frederick C. Novello of
References
- ^ Thiazides at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ Thiazide+Diuretics at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ PMID 8349332.
- S2CID 3211922.
- ^ "MeSH Browser". meshb.nlm.nih.gov. Retrieved 2019-07-22.
- ^ PMID 30422513, retrieved 2019-07-18
- ^ thiazide+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- S2CID 208506926.
- ^ PMID 29667175.
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- ^ "escardio.org". Archived from the original on 2008-05-17. Retrieved 2007-08-30.
- ^ a b National Institute for Health and Clinical Excellence (NICE) guideline on the management of primary hypertension in adults (CG127) accessed 5/3/2012 at "CG127 - Hypertension - National Institute for Health and Clinical Excellence". Archived from the original on 2012-01-31. Retrieved 2012-03-05.
- ^ Guide to management of hypertension 2008. National Heart Foundation Australia. 2008. accessed online at "Archived copy" (PDF). Archived from the original (PDF) on 2013-05-15. Retrieved 2013-07-10.
{{cite web}}
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- ^ "THIAZIDE DIURETICS FOR STONE PREVENTION | Kidney Stone Evaluation And Treatment Program". kidneystones.uchicago.edu. Retrieved 2019-07-22.
- PMID 8813907.
- PMID 11427657.
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- ^ a b "Dent Disease". NORD (National Organization for Rare Disorders). Retrieved 2019-07-22.
- ^ a b Aung K, Htay T. Thiazide diuretics and the risk of hip fracture. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD005185. DOI: 10.1002/14651858.CD005185.pub2.
- PMID 17656470.
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- ^ "Medication Update".
- ^ a b "Hydrochlorothiazide, HCTZ (Microzide) Contraindications and Precautions". Archived from the original on 2010-10-09. Retrieved 2010-05-14.
- ISSN 1040-9165.
- ^ "Hypertension in Pregnancy - Gynecology and Obstetrics".
- ISBN 978-0-323-44595-5. Retrieved 4 November 2017.
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- ISBN 978-0-07-174887-2.
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- ISBN 978-1-60831-708-0.
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- ^ "Drugs@FDA: FDA Approved Drug Products".
- ^ "The Lasker Foundation - Awards".