Chlorothiazide
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| Chlorothiazide | |
|---|---|
| IUPAC name | 6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide |
| Width | 200 |
| Tradename | Diuril, others |
| Drugs.com | monograph, chlorothiazide |
| MedlinePlus | a682342 |
| Routes of administration | By mouth, intravenous |
| Bioavailability | ~10% (oral) |
| Protein bound | 95% |
| Metabolism | Not metabolized |
| Elimination half-life | 45–120 minutes |
| Excretion | Kidney |
| CAS number | 58-94-6 |
| PubChem | 2720 |
| ChemSpiderID | 2619 |
| UNII | 0J48LPH2TH |
| ChEBI | 3661 |
| ChEMBL | 40 |
| ATC prefix | C03 |
| ATC suffix | AA04 |
| License US | Chlorothiazide |
Chlorothiazide. It is a thiazide diuretic medication primarily used to treat hypertension and edema associated with conditions like congestive heart failure and liver cirrhosis. Marketed under the brand name Diuril, it was the first drug of its class to be discovered, representing a major advance in pharmacotherapy. Its introduction fundamentally changed the management of fluid-retaining diseases and paved the way for subsequent antihypertensive drug development.
Medical uses
Chlorothiazide is indicated for the management of essential hypertension, often as a first-line agent or in combination with other drugs like beta blockers or ACE inhibitors. It is also prescribed for edema due to various causes, including nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. In heart failure, it helps reduce preload and the workload on the left ventricle. Its use is sometimes extended to the treatment of diabetes insipidus, particularly nephrogenic diabetes insipidus, and in the prevention of kidney stones in patients with hypercalciuria.
Adverse effects
Common adverse effects include electrolyte imbalance such as hypokalemia, hyponatremia, and hypochloremic alkalosis. It can also cause hyperglycemia and impair glucose tolerance, which is a concern for patients with diabetes mellitus. Other potential effects are hyperuricemia, which may precipitate gout, and photosensitivity. More serious but rare reactions include pancreatitis, intrahepatic cholestasis, and severe skin reactions like toxic epidermal necrolysis. Its effect on lithium (medication) clearance requires careful monitoring in patients with bipolar disorder.
Pharmacology
Chlorothiazide acts by inhibiting the sodium-chloride symporter in the distal convoluted tubule of the nephron, thereby increasing the excretion of sodium, chloride, and water. This natriuresis reduces plasma volume and cardiac output, contributing to its antihypertensive effect. With chronic use, it reduces peripheral vascular resistance, an action mediated through direct vasodilation. It is not metabolized by the liver and is excreted unchanged by the kidneys via active tubular secretion, primarily through the organic anion transporter 1.
Chemistry
Chlorothiazide is a benzothiadiazine derivative with the chemical name 6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide. It is a white or practically white crystalline powder with a molecular formula of C7H6ClN3O4S2. The molecule features a sulfonamide group, which is critical for its carbonic anhydrase inhibitory activity, and a chlorinated benzene ring. It is sparingly soluble in water but soluble in solutions of sodium hydroxide and is typically administered as the sodium salt for intravenous use.
History
Chlorothiazide was discovered in 1957 by a team at Merck & Co. led by James M. Sprague, following research into more potent derivatives of sulfanilamide. Its development was a direct outcome of work on carbonic anhydrase inhibitors like acetazolamide. The drug received approval from the Food and Drug Administration in 1958 and was launched as Diuril, rapidly becoming a cornerstone therapy. Its success spurred the synthesis of numerous analogues, including hydrochlorothiazide, and earned recognition from institutions like the American Chemical Society.
Society and culture
Chlorothiazide is on the World Health Organization's List of Essential Medicines. It is available as a generic medication and under various brand names globally. The drug's discovery is considered a landmark in the history of the pharmaceutical industry, marking the beginning of modern diuretic therapy. It has been the subject of numerous clinical trials, such as those conducted by the Veterans Administration Cooperative Study Group on Antihypertensive Agents, which helped establish the benefits of treating hypertension.
Category:Drugs