Chlorothiazide

Last updated
Chlorothiazide
Chlorothiazide.svg
Chlorothiazide-from-xtal-3D-balls.png
Clinical data
Trade names Diuril, others
Other names6-Chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide
AHFS/Drugs.com Monograph
MedlinePlus a682341
Routes of
administration
By mouth, IV
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability low
Metabolism Nil
Elimination half-life 45 to 120 minutes
Excretion Renal
Identifiers
  • 6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.368 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C7H6ClN3O4S2
Molar mass 295.71 g·mol−1
3D model (JSmol)
Melting point 342.5–343 °C (648.5–649.4 °F)
  • O=S(=O)(c1c(Cl)cc2c(c1)S(=O)(=O)/N=C\N2)N
  • InChI=1S/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H,10,11)(H2,9,12,13) Yes check.svgY
  • Key:JBMKAUGHUNFTOL-UHFFFAOYSA-N Yes check.svgY
   (verify)

Chlorothiazide, sold under the brand name Diuril among others, is an organic compound used as a diuretic and as an antihypertensive. [1] [2]

Contents

It is used both within the hospital setting or for personal use to manage excess fluid associated with congestive heart failure. Most often taken in pill form, it is usually taken orally once or twice a day. In the ICU setting, chlorothiazide is given to diurese a patient in addition to furosemide (Lasix). Working in a separate mechanism from furosemide and absorbed enterically as a reconstituted suspension administered through a nasogastric tube (NG tube), the two drugs potentiate one another.

It was patented in 1956 and approved for medical use in 1958. [3] It is on the World Health Organization's List of Essential Medicines. [4]

Indications

Contraindications

Side effects

History

The research team of Merck Sharp and Dohme Research Laboratories of Beyer, Sprague, Baer, and Novello created a new series of medications, the thiazide diuretics, which includes chlorothiazide. They won an Albert Lasker Special Award in 1975 for this work. [6]

The structure has been determined by X-ray crystallography. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Furosemide</span> Loop diuretic medication

Furosemide is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. It has had many trade names including Discoid, Frusemide, Lasix and Uremide. Furosemide may also be used for the treatment of high blood pressure. It can be taken intravenously or orally. When given intravenously, furosemide typically takes effect within five minutes; when taken orally, it typically metabolizes within an hour.

<span class="mw-page-title-main">Hydrochlorothiazide</span> Diuretic medication

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Enalapril</span> ACE inhibitor medication

Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosemide. It is given by mouth or by injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to a day.

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Indapamide</span> Thiazide-like diuretic drug

Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril are available. The thiazide-like diuretics reduce risk of major cardiovascular events and heart failure in hypertensive patients compared with hydrochlorothiazide with a comparable incidence of adverse events. Both thiazide diuretics and thiazide-like diuretics are effective in reducing risk of stroke. Both drug classes appear to have comparable rates of adverse effects as other antihypertensives such as angiotensin II receptor blockers and dihydropyridine calcium channel blockers and lesser prevalence of side-effects when compared to ACE-inhibitors and non-dihydropyridine calcium channel blockers.

<span class="mw-page-title-main">Hypokalemia</span> Medical condition with insufficient potassium

Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnormal heart rhythm, which is often too slow and can cause cardiac arrest.

<span class="mw-page-title-main">Loop diuretic</span> Diuretics that act along the loop of Henle in the kidneys

Loop diuretics are pharmacological agents that primarily inhibit the Na-K-Cl cotransporter located on the luminal membrane of cells along the thick ascending limb of the loop of Henle. They are often used for the treatment of hypertension and edema secondary to congestive heart failure, liver cirrhosis, or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

<span class="mw-page-title-main">Bumetanide</span> A loop diuretic

Bumetanide, sold under the brand name Bumex among others, is a medication used to treat swelling and high blood pressure. This includes swelling as a result of heart failure, liver failure, or kidney problems. It may work for swelling when other medications have not. For high blood pressure it is not a preferred treatment. It is taken by mouth, or by injection into a vein or muscle. Effects generally begin within an hour and last for about six hours.

<span class="mw-page-title-main">Amiloride</span> Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.

<span class="mw-page-title-main">Chlortalidone</span> Thiazide-like diuretic drug

Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling, diabetes insipidus, and renal tubular acidosis. Because chlortalidone is effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

<span class="mw-page-title-main">Thiazide</span> Class of chemical compounds

Thiazide refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available.

<span class="mw-page-title-main">Diazoxide</span> Medication used to treat low blood sugar and high blood pressure

Diazoxide, sold under the brand name Proglycem and others, is a medication used to treat low blood sugar due to a number of specific causes. This includes islet cell tumors that cannot be removed and leucine sensitivity. It can also be used in refractory cases of sulfonylurea toxicity. It is generally taken by mouth.

<span class="mw-page-title-main">Hydralazine</span> Anti-hypertension medication

Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has been found to be particularly useful in heart failure, together with isosorbide dinitrate, for treatment of people of African descent. It is given by mouth or by injection into a vein. Effects usually begin around 15 minutes and last up to six hours.

<span class="mw-page-title-main">Metolazone</span> Chemical compound

Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Metoz, Zaroxolyn, and Mykrox. It is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with loop diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities.

<span class="mw-page-title-main">Torasemide</span> Diuretic medication

Torasemide, also known as torsemide, is a diuretic medication used to treat fluid overload due to heart failure, kidney disease, and liver disease. It is a less preferred treatment for high blood pressure. It is taken by mouth or by injection into a vein.

<span class="mw-page-title-main">Acute decompensated heart failure</span> Medical condition

Acute decompensated heart failure (ADHF) is a sudden worsening of the signs and symptoms of heart failure, which typically includes difficulty breathing (dyspnea), leg or feet swelling, and fatigue. ADHF is a common and potentially serious cause of acute respiratory distress. The condition is caused by severe congestion of multiple organs by fluid that is inadequately circulated by the failing heart. An attack of decompensation can be caused by underlying medical illness, such as myocardial infarction, an abnormal heart rhythm, infection, or thyroid disease.

The modern history of hypertension begins with the understanding of the cardiovascular system based on the work of physician William Harvey (1578–1657), who described the circulation of blood in his book De motu cordis. The English clergyman Stephen Hales made the first published measurement of blood pressure in 1733. Descriptions of what would come to be called hypertension came from, among others, Thomas Young in 1808 and especially Richard Bright in 1836. Bright noted a link between cardiac hypertrophy and kidney disease, and subsequently kidney disease was often termed Bright's disease in this period. In 1850 George Johnson suggested that the thickened blood vessels seen in the kidney in Bright's disease might be an adaptation to elevated blood pressure. William Senhouse Kirkes in 1855 and Ludwig Traube in 1856 also proposed, based on pathological observations, that elevated pressure could account for the association between left ventricular hypertrophy to kidney damage in Bright's disease. Samuel Wilks observed that left ventricular hypertrophy and diseased arteries were not necessarily associated with diseased kidneys, implying that high blood pressure might occur in people with healthy kidneys; however, the first report of elevated blood pressure in a person without evidence of kidney disease was made by Frederick Akbar Mahomed in 1874 using a sphygmograph. The concept of hypertensive disease as a generalized circulatory disease was taken up by Sir Clifford Allbutt, who termed the condition "hyperpiesia". However, hypertension as a medical entity really came into being in 1896 with the invention of the cuff-based sphygmomanometer by Scipione Riva-Rocci in 1896, which allowed blood pressure to be measured in the clinic. In 1905, Nikolai Korotkoff improved the technique by describing the Korotkoff sounds that are heard when the artery is ausculted with a stethoscope while the sphygmomanometer cuff is deflated. Tracking serial blood pressure measurements was further enhanced when Donal Nunn invented an accurate fully automated oscillometric sphygmomanometer device in 1981.

<span class="mw-page-title-main">Diuretic</span> Substance that promotes the production of urine

A diuretic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine.

An ACE inhibitor and thiazide combination is a drug combination used to treat hypertension. They are given by mouth. ACE inhibitors reduce the activity of angiotensin-converting enzyme (ACE) which produces angiotensin II, a hormone that constricts blood vessels. Thiazides are a class of diuretics that inhibit the thiazide receptor, thereby increasing urine production and reducing excess water and salt in the body. Several organizations recommend combination therapy for hypertension in cases of failure of a single drug to achieve target blood pressure, or even as a first line treatment for some patients.

References

  1. Ernst ME, Grimm J, Richard H (November 2008). "Thiazide diuretics: 50 years and beyond". Current Hypertension Reviews. 4 (4): 256–65. doi:10.2174/157340208786241264.
  2. Duarte JD, Cooper-DeHoff RM (June 2010). "Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics". Expert Review of Cardiovascular Therapy. 8 (6): 793–802. doi:10.1586/erc.10.27. PMC   2904515 . PMID   20528637.
  3. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 456. ISBN   9783527607495.
  4. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  5. 1 2 "Diuril (Chlorothiazide): Side Effects, Interactions, Warning, Dosage & Uses". RxList. Retrieved 2019-10-07.
  6. "Historical Awards - The Lasker Foundation". The Lasker Foundation.
  7. Johnston A, Bardin J, Johnston BF, Fernandes P, Kennedy AR, Price SL, Florence AJ (2011). "Experimental and Predicted Crystal Energy Landscapes of Chlorothiazide". Crystal Growth & Design. 11 (2): 405–413. doi:10.1021/cg1010049.