用户名： 密   码：
注册 | 忘记密码？
药品详细

Spironolactone(安体舒通)

化学结构式图
中文名
安体舒通
英文名
Spironolactone
分子式
C24H32O4S
化学名
(1'S,2R,2'R,9'R,10'R,11'S,15'S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan]-6'-ene-5,5'-dione
分子量
Average: 416.573
Monoisotopic: 416.202130202
CAS号
52-01-7
ATC分类
C03D 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)

生产厂家
  • Actavis elizabeth llc
  • Amneal pharmaceuticals
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Gd searle llc
  • Ivax pharmaceuticals inc
  • Lederle laboratories div american cyanamid co
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Superpharm corp
  • Upsher smith laboratories inc
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals llc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Berardesca E, Gabba P, Ucci G, Borroni G, Rabbiosi G: Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris. Int J Tissue React. 1988;10(2):115-9. Pubmed
  2. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17. Pubmed
  3. Wandelt-Freerksen E: [Aldactone in the treatment of sarcoidosis of the lungs (author’s transl)] Z Erkr Atmungsorgane. 1977 Jul;149(1):156-9. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Carboxylic Acids and Derivatives
  • Alkanes and Alkenes
  • Acetates
  • Lactones
  • Ethers
  • Esters
  • Heterocyclic compounds
  • Furans
  • Cyclohexenes and Derivatives
  • Ketones
适应症
药理
Indication Used primarily to treat low-renin hypertension, hypokalemia, and Conn's syndrome.
Pharmacodynamics Spironolactone is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. Due to its anti-androgen effect, it can also be used to treat hirsutism, and is a common component in hormone therapy for male-to-female transgendered people. Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptor in the distal tubule cells. This increases the secretion of water and sodium, while decreasing the excretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly.
Mechanism of action Spironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents which act more proximally in the renal tubule. Aldosterone interacts with a cytoplasmic mineralocorticoid receptor to enhance the expression of the Na+, K+-ATPase and the Na+ channel involved in a Na+ K+ transport in the distal tubule . Spironolactone bind to this mineralcorticoid receptor, blocking the actions of aldosterone on gene expression. Aldosterone is a hormone; its primary function is to retain sodium and excrete potassium in the kidneys.
Absorption Fairly rapidly absorbed from the gastrointestinal tract. Food increases the bioavailability of unmetabolized spironolactone by almost 100%.
Volume of distribution Not Available
Protein binding Spironolactone and its metabolites are more than 90% bound to plasma proteins.
Metabolism
Rapidly and extensively metabolized. The metabolic pathway of spironolactone is complex and can be divided into two main routes: those in which the sulfur moiety is retained and those in which the sulfur moiety is removed by dethioacetylation. Spironolactone is transformed to a reactive metabolite that can inactivate adrenal and testicular cytochrome P450 enzymes. It also has anti-androgenic activity.
Route of elimination The metabolites are excreted primarily in the urine and secondarily in bile.
Half life 10 minutes
Clearance Not Available
Toxicity The oral LD50 of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits. Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00134 Spironolactone Pathway SMP00134
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 134.5 °C PhysProp
water solubility 22 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 2.78 HANSCH,C ET AL. (1995)
logS -4.28 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 1.98e-03 g/l ALOGPS
logP 3.1 ALOGPS
logP 3.64 ChemAxon
logS -5.3 ALOGPS
pKa (strongest acidic) 18.01 ChemAxon
pKa (strongest basic) -4.9 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 60.44 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 113.5 ChemAxon
polarizability 46.03 ChemAxon
药物相互作用
Drug Interaction
Benazepril Increased risk of hyperkalemia
Candesartan Increased risk of hyperkalemia
Captopril Increased risk of hyperkalemia
Cholestyramine Increased risk of acidosis and hyperkalemia
Cilazapril Increased risk of hyperkalemia
Digoxin Increased digoxin levels and decreased effect in presence of spironolactone
Enalapril Increased risk of hyperkalemia
Eplerenone This association presents an increased risk of hyperkalemia
Eprosartan Increased risk of hyperkalemia
Fosinopril Increased risk of hyperkalemia
Irbesartan Increased risk of hyperkalemia
Lisinopril Increased risk of hyperkalemia
Losartan Increased risk of hyperkalemia
Mitotane Spironolactone antagonizes the effect of mitotane
Perindopril Increased risk of hyperkalemia
Polystyrene sulfonate Risk of alkalosis in renal impairment
Potassium Increased risk of hyperkalemia
Quinapril Increased risk of hyperkalemia
Ramipril Increased risk of hyperkalemia
Telmisartan Telmisartan may increase the hyperkalemic effect of Spironolactone. Monitor for increased serum potassium concentrations during concomitant therapy.
Tobramycin Increased risk of nephrotoxicity
Trandolapril Increased risk of hyperkalemia. Monitor serum potassium levels.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
食物相互作用
  • Avoid alcohol.
  • Food increases the bioavailability of spironolactone by almost 100%.
  • Spironolactone may decrease the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.

返回 | 收藏