Tìm theo
Chlorothiazide
Các tên gọi khác (9 ) :
  • 6-Chloro-1,1-dioxo-1,2-dihydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic acid amide
  • 6-chloro-7-Sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxide
  • Chlorothiazid
  • Chlorothiazide
  • Chlorothiazidum
  • Chlorthiazide
  • Clorotiazida
  • Mechlozid
  • Uroflux
antihypertensive agents, diuretics, sodium chloride symporter inhibitors
Thuốc Gốc
Small Molecule
CAS: 58-94-6
ATC: C03AA03, C03AA04
ĐG : APP Pharmaceuticals , http://www.apppharma.com
CTHH: C7H6ClN3O4S2
PTK: 295.723
A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C7H6ClN3O4S2
Phân tử khối
295.723
Monoisotopic mass
294.948824782
InChI
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)
InChI Key
InChIKey=JBMKAUGHUNFTOL-UHFFFAOYSA-N
IUPAC Name
6-chloro-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide
Traditional IUPAC Name
chlorothiazide
SMILES
NS(=O)(=O)C1=C(Cl)C=C2NC=NS(=O)(=O)C2=C1
Độ tan chảy
342.5-343
Độ hòa tan
266 mg/L (at 30 °C)
logP
-0.24
logS
-3.05
pKa (strongest acidic)
9.1
pKa (Strongest Basic)
1.15
PSA
118.69 Å2
Refractivity
62.51 m3·mol-1
Polarizability
24.55 Å3
Rotatable Bond Count
1
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
caco2 Permeability
-6.72
pKa
6.85
Dược Lực Học : 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.
Cơ Chế Tác Dụng : A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812) 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.
Dược Động Học :
▧ Absorption :
Rapidly absorbed following oral administration.
▧ 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
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • 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.
Liều Lượng & Cách Dùng : Suspension - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00880
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2720
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507032
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07461
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00519
ChemSpider
http://www.chemspider.com/Chemical-Structure.2619.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-0150-01
PharmGKB
http://www.pharmgkb.org/drug/PA448953
Wikipedia
http://en.wikipedia.org/wiki/Chlorothiazide
RxList
http://www.rxlist.com/cgi/generic2/chloroth.htm
Drugs.com
http://www.drugs.com/cdi/chlorothiazide.html
... loading
... loading