Tìm theo
Captopril
Các tên gọi khác (20 ) :
  • (2S)-1-[(2S)-2-Methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
  • Acepress
  • Apopril
  • Capoten
  • Captolane
  • Captoprilum
  • Captopryl
  • Captoril
  • Cesplon
  • CP
  • D-2-Methyl-3-mercaptopropanoyl-L-proline
  • D-3-Mercapto-2-methylpropanoyl-L-proline
  • Dilabar
  • Garranil
  • Hypertil
  • L-Captopril
  • Lopirin
  • Tenosbon
  • Tensobon
  • Tensoprel
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 62571-86-2
ATC: C09AA01
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C9H15NO3S
PTK: 217.285
Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C9H15NO3S
Phân tử khối
217.285
Monoisotopic mass
217.077264041
InChI
InChI=1S/C9H15NO3S/c1-6(5-14)8(11)10-4-2-3-7(10)9(12)13/h6-7,14H,2-5H2,1H3,(H,12,13)/t6-,7+/m1/s1
InChI Key
InChIKey=FAKRSMQSSFJEIM-RQJHMYQMSA-N
IUPAC Name
(2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
Traditional IUPAC Name
captopril
SMILES
C[C@H](CS)C(=O)N1CCC[C@H]1C(O)=O
Độ tan chảy
103-104
Độ hòa tan
Freely soluble
logP
0.34
logS
-1.7
pKa (strongest acidic)
4.02
pKa (Strongest Basic)
-1.2
PSA
57.61 Å2
Refractivity
54.63 m3·mol-1
Polarizability
21.72 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
3
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
1
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Captopril, an ACE inhibitor, antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain its effects by causing increased vasodilation and decreased blood pressure.
Cơ Chế Tác Dụng : Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension. There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Captopril, one of the few ACE inhibitors that is not a prodrug, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Captopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Captopril’s affinity for ACE is approximately 30,000 times greater than that of ATI.
Dược Động Học :
▧ Absorption :
60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)
▧ Protein binding :
25-30% bound to plasma proteins, primarily albumin
▧ Metabolism :
Hepatic. Major metabolites are captopril-cysteine disulfide and the disulfide dimer of captopril. Metabolites may undergo reversible interconversion.
▧ Half Life :
2 hours
Độc Tính : Symptoms of overdose include emesis and decreased blood pressure. Side effects include dose-dependent rash (usually maculopapular), taste alterations, hypotension, gastric irritation, cough, and angioedema.
Chỉ Định : For the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). May be used to treat congestive heart failure in combination with other drugs (e.g. cardiac glycosides, diuretics, β-adrenergic blockers). May improve survival in patients with left ventricular dysfunction following myocardial infarction. May be used to treat nephropathy, including diabetic nephropathy.
Tương Tác Thuốc :
  • Amiloride Increased risk of hyperkalemia
  • Aprotinin In study of nine patients with untreated hypertension, aprotinin infused intravenously in a dose of 2 million KIU over two hours blocked the acute hypotensive effect of 100mg of captopril.
  • Azilsartan medoxomil Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
  • Drospirenone Increased risk of hyperkalemia
  • Icatibant Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Lithium The ACE inhibitor increases serum levels of lithium
  • Potassium Increased risk of hyperkalemia
  • Spironolactone Increased risk of hyperkalemia
  • Terbinafine Terbinafine may reduce the metabolism and clearance of Captopril. Consider alternate therapy or monitor for therapeutic/adverse effects of Captopril if Terbinafine is initiated, discontinued or dose changed.
  • Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
  • Tobramycin Increased risk of nephrotoxicity
  • Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
  • Triamterene Increased risk of hyperkalemia
Liều Lượng & Cách Dùng : Tablet - Oral - 100 mg
Tablet - Oral - 12.5 mg
Tablet - Oral - 25 mg
Tablet - Oral - 50 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01197
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=44093
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506879
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00251
ChemSpider
http://www.chemspider.com/Chemical-Structure.40130.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=21642
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-3007-01
PharmGKB
http://www.pharmgkb.org/drug/PA448780
Wikipedia
http://en.wikipedia.org/wiki/Captopril
RxList
http://www.rxlist.com/cgi/generic/captop.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cap1064.shtml
Drugs.com
http://www.drugs.com/captopril.html
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