药品详细
Chlorothiazide(氯噻嗪)
化学结构式图
中文名
氯噻嗪
英文名
Chlorothiazide
分子式
C7H6ClN3O4S2
化学名
6-chloro-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide
分子量
Average: 295.723
Monoisotopic: 294.948824782
Monoisotopic: 294.948824782
CAS号
58-94-6
ATC分类
C03A 未知;C03A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍
A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
生产厂家
- Abc holding corp
- App pharmaceuticals llc
- Lederle laboratories div american cyanamid co
- Lundbeck inc
- Mylan pharmaceuticals inc
- Salix pharmaceuticals inc
- Sandoz inc
- Watson laboratories inc
- West ward pharmaceutical corp
封装厂家
- APP Pharmaceuticals
- Ben Venue Laboratories Inc.
- Endo Pharmaceuticals Inc.
- Lundbeck Inc.
- Major Pharmaceuticals
- Merck & Co.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- PD-Rx Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Salix Pharmaceuticals
- Sandhills Packaging Inc.
- UDL Laboratories
- Watson Pharmaceuticals
- West-Ward Pharmaceuticals
参考
| Synthesis Reference | Not Available |
| General Reference | Not Available |
剂型
规格
化合物类型
| Type | small molecule |
| Classes |
|
| Substructures |
|
适应症
药理
| Indication | Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. | ||||||
| Pharmacodynamics | Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. | ||||||
| Mechanism of action | As a diuretic, chlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like chlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of chlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. | ||||||
| Absorption | Rapidly absorbed following oral administration. | ||||||
| Volume of distribution | Not Available | ||||||
| Protein binding | Approximately 40% bound to plasma proteins. | ||||||
| Metabolism |
Chlorothiazide is not metabolized but is eliminated rapidly by the kidney.
|
||||||
| Route of elimination | Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. | ||||||
| Half life | 45-120 minutes | ||||||
| Clearance | Not Available | ||||||
| Toxicity | Oral, rat LD50: > 10 g/kg. Signs of overdose include those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered hypokalemia may accentuate cardiac arrhythmias. | ||||||
| Affected organisms |
|
||||||
| Pathways |
|
理化性质
| Properties | |||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
|
||||||||||||||||||||||||||||||||||||||||||
| Predicted Properties |
|
||||||||||||||||||||||||||||||||||||||||||
药物相互作用
| Drug | Interaction |
|---|---|
| Amifostine | Antihypertensives may enhance the hypotensive effect of amifostine. When amifostine is used at doses recommended for chemotherapy, antihypertensive medications should be withheld for 24 hours prior to amifostine administration to avoid excessive hypotension during or immediately after infusion. If antihypertensive therapy can not be withheld, then that patient should not receive amifostine. Caution is recommended when using amifostine at the lower doses recommended for radiotherapy, but routine interruption of antihypertensive therapy is not recommended in these patients. |
| Cholestyramine | Bile acid sequestrants may decrease the absorption of thiazide diuretics such as chlorothiazide. The diuretic response is likewise decreased. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. If these agents are used concomitantly, separate doses 2 or more hours to minimize the interaction. |
| Colestipol | Bile acid sequestrants may decrease the absorption of thiazide diuretics such as chlorothiazide. The diuretic response is likewise decreased. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. If these agents are used concomitantly, separate doses 2 or more hours to minimize the interaction. |
| Digoxin | Possible electrolyte variations and arrhythmias |
| Dofetilide | Thiazide diuretics such as chlorothiazide may enhance the QTc-prolonging effect of dofetilide. Thiazide diuretics may increase the serum concentration of dofetilide. The concomitant use of hydrochlorothiazide and dofetilide is contraindicated by the manufacturer of dofetilide. Monitor for increased risk of QTc-prolongation and associated ventricular arrythmias during concomitant use of dofetilide and thiazide diuretics. |
| Lithium | The thiazide diuretic, chlorothiazide, may increase serum levels of lithium. |
| Rituximab | Antihypertensives such as chlorothiazide may enhance the hypotensive effect of Rituximab. Consider temporarily withholding antihypertensive medications for 12 hours prior to rituximab infusion to avoid excessive hypotension during or immediately after infusion. |
| Topiramate | Thiazide diuretics such as chlorothiazide may enhance the hypokalemic effect of topiramate. Thiazide diuretics may increase the serum concentration of topiramate. Monitor for increased topiramate concentrations/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. |
| Trandolapril | The thiazide diuretic, Chlorothiazide, may increase the hypotensive effect of Trandolapril. Chlorothiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy. |
| Treprostinil | Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. |
食物相互作用
Not Available
收藏