Tìm theo
Enalapril
Các tên gọi khác (7 ) :
  • (S)-1-(N-(1-(Ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline
  • (S)-1-{(S)-2-[1-((S)-ethoxycarbonyl)-3-phenyl-propylamino]-propionyl}-pyrrolidine-2-carboxylic acid
  • 1-(N-((S)-1-Carboxy-3-phenylpropyl)-L-alanyl)-L-proline 1'-ethyl ester
  • Analapril
  • Enalapril
  • Enalaprila
  • Enalaprilum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 75847-73-3
ATC: C09AA02
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C20H28N2O5
PTK: 376.4467
Enalapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to enalaprilat following oral administration. Enalaprilat is a potent, competitive inhibitor of 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). Enalapril may be used to treat essential or renovascular hypertension and symptomatic congestive heart failure.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C20H28N2O5
Phân tử khối
376.4467
Monoisotopic mass
376.199822016
InChI
InChI=1S/C20H28N2O5/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25)/t14-,16-,17-/m0/s1
InChI Key
InChIKey=GBXSMTUPTTWBMN-XIRDDKMYSA-N
IUPAC Name
(2S)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid
Traditional IUPAC Name
enalapril
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O
Độ tan chảy
143-144.5 °C
Độ hòa tan
1.64E+004 mg/L (at 25 °C)
logP
0.07
logS
-3.2
pKa (strongest acidic)
3.67
pKa (Strongest Basic)
5.2
PSA
95.94 Å2
Refractivity
99.57 m3·mol-1
Polarizability
40.41 Å3
Rotatable Bond Count
10
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
caco2 Permeability
-5.64
pKa
2.97 (the carboxyl group) and 5.35 (the amine group) at 25°C
Dược Lực Học : Enalapril is a prodrug that is rapidly metabolized by liver esterases to enalaprilat following oral administration. Enalapril itself has little pharmacologic activity. Enalaprilat lowers blood pressure by antagonizing 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 the effects of enalaprilat by causing increased vasodilation and decreased blood pressure.
Cơ Chế Tác Dụng : Enalapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to enalaprilat following oral administration. Enalaprilat is a potent, competitive inhibitor of 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). Enalapril may be used to treat essential or renovascular hypertension and symptomatic congestive heart failure. 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. Enalaprilat, the principle active metabolite of enalapril, 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. Enalapril 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. Enalaprilat's affinity for ACE is approximately 200,000 times greater than that of ATI and 300-1000 times greater than that enalapril.
Dược Động Học :
▧ Absorption :
55-75%, absorption is unaffected by food; enalaprilat (clinically administered IV) is poorly absorbed, 3-12%, due to its high polarity.
▧ Protein binding :
50-60% of enalaprilat is bound to plasma proteins
▧ Metabolism :
~ 60% of absorbed dose is extensively hydrolyzed to enalaprilat, primarily by liver esterases
▧ Route of Elimination :
Excretion of enalapril is primarily renal.
▧ Half Life :
< 2 hours for unchanged enalapril in health individuals, may be increased in those with congestive heart failure (3.4 and 5.8 hours for single 5- and 10-mg doses, respectively). The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours.
Độc Tính : Overdosage may result in marked hypotension and stupor. Most common adverse effects include hypotension, headache, dizziness and fatigue.
Chỉ Định : For the treatment of essential or renovascular hypertension and symptomatic congestive heart failure. It may be used alone or in combination with thiazide diuretics.
Tương Tác Thuốc :
  • Amiloride Increased risk of hyperkalemia
  • 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.
  • Insulin Lispro Concomitant therapy with ACE inhibitors may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
  • Lithium The ACE inhibitor increases serum levels of lithium
  • Potassium Increased risk of hyperkalemia
  • Rifampicin Rifampin, a strong CYP3A4 inducer, may increase the metabolism of enalapril. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of enalapril if rifampin is initiated, discontinued or dose changed.
  • Spironolactone Increased risk of hyperkalemia
  • 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 : Injection, solution - Intravenous - 1.25 mg/ml
Tablet - Oral - 10 mg
Tablet - Oral - 2.5 mg
Tablet - Oral - 20 mg
Tablet - Oral - 5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Alphapharm
    Sản phẩm biệt dược : Acetec
  • Công ty : Grünenthal
    Sản phẩm biệt dược : Acetensil
  • Công ty : Ranbaxy
    Sản phẩm biệt dược : Alapren
  • Công ty : Mass Pharma
    Sản phẩm biệt dược : Amotac
  • Sản phẩm biệt dược : Amprace
  • Công ty : Cipla
    Sản phẩm biệt dược : Dilvas
  • Công ty : Mintlab
    Sản phẩm biệt dược : Diotensil
  • Công ty : Fada
    Sản phẩm biệt dược : Drepatil
  • Công ty : Abbott
    Sản phẩm biệt dược : Enace
  • Công ty : Sandoz
    Sản phẩm biệt dược : EnaHexal
  • Công ty : East West
    Sản phẩm biệt dược : Enal
  • Công ty : Del Bel
    Sản phẩm biệt dược : Enalapoten
  • Công ty :
    Sản phẩm biệt dược : Enalaprilat
  • Công ty : Wockhardt
    Sản phẩm biệt dược : Enpril
  • Công ty : Silanes
    Sản phẩm biệt dược : Feliberal
  • Sản phẩm biệt dược : Gadopril
  • Công ty : Bago
    Sản phẩm biệt dược : Glioten
  • Sản phẩm biệt dược : Kinfil
  • Sản phẩm biệt dược : Vasotec
  • Công ty : Sandoz (Canada)
    Sản phẩm biệt dược : Vasotec IV
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00584
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06977
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-1051-01
PharmGKB
http://www.pharmgkb.org/drug/PA449456
Wikipedia
http://en.wikipedia.org/wiki/Enalapril
RxList
http://www.rxlist.com/cgi/generic/enalap.htm
PDRhealth
http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=Vas1477.html&contentName=Vasotec&contentId=6
Drugs.com
http://www.drugs.com/enalapril.html
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