Tìm theo
Lisinopril
Các tên gọi khác (5 ) :
  • (S)-1-(N(2)-(1-Carboxy-3-phenylpropyl)-L-lysyl)-L-proline
  • [N2-[(S)-1-CARBOXY-3-phenylpropyl]-L-lysyl-L-proline
  • Lisinopril
  • Lisinopril anhydrous
  • Lisinoprilum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 83915-83-7
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C21H31N3O5
PTK: 405.4879
Lisinopril 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). Lisinopril may be used to treat hypertension and symptomatic congestive heart failure, to improve survival in certain individuals following myocardial infarction, and to prevent progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C21H31N3O5
Phân tử khối
405.4879
Monoisotopic mass
405.226371117
InChI
InChI=1S/C21H31N3O5/c22-13-5-4-9-16(19(25)24-14-6-10-18(24)21(28)29)23-17(20(26)27)12-11-15-7-2-1-3-8-15/h1-3,7-8,16-18,23H,4-6,9-14,22H2,(H,26,27)(H,28,29)/t16-,17-,18-/m0/s1
InChI Key
InChIKey=RLAWWYSOJDYHDC-BZSNNMDCSA-N
IUPAC Name
(2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid
Traditional IUPAC Name
lisinopril
SMILES
NCCCC[C@H](N[C@@H](CCC1=CC=CC=C1)C(O)=O)C(=O)N1CCC[C@H]1C(O)=O
Độ hòa tan
9.7E+004 mg/L
logP
-1.01
logS
-3.3
pKa (strongest acidic)
3.17
pKa (Strongest Basic)
10.21
PSA
132.96 Å2
Refractivity
107.37 m3·mol-1
Polarizability
43.5 Å3
Rotatable Bond Count
12
H Bond Acceptor Count
7
H Bond Donor Count
4
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
pKa
2.5 (at 25 °C)
Dược Lực Học : Lisinopril is an orally active ACE inhibitor that 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 further sustain the effects of lisinopril by causing increased vasodilation and decreased blood pressure.
Cơ Chế Tác Dụng : Lisinopril 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). Lisinopril may be used to treat hypertension and symptomatic congestive heart failure, to improve survival in certain individuals following myocardial infarction, and to prevent progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy. 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. Lisinopril, 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. Lisinopril 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.
Dược Động Học :
▧ Absorption :
Approximately 25%, but widely variable between individuals (6 to 60%) in all doses tested (5-80 mg); absorption is unaffected by food
▧ Protein binding :
Lisinopril does not appear to be bound to serum proteins other than ACE.
▧ Metabolism :
Does not undergo metabolism, excreted unchanged in urine.
▧ Route of Elimination :
Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine.
▧ Half Life :
Effective half life of accumulation following multiple dosing is 12 hours.
▧ Clearance :
* 10 L/h [child weighting 30 kg receiving doses of 0.1 to 0.2 mg/kg]
Độc Tính : Symptoms of overdose include severe hypotension, electrolyte disturbances, and renal failure. LD50= 2000 mg/kg(orally in rat). Most frequent adverse effects include headache, dizziness, cough, fatigue and diarrhea.
Chỉ Định : For the treatment of hypertension and symptomatic congestive heart failure. May be used in conjunction with thrombolytic agents, aspirin and/or β-blockers to improve survival in hemodynamically stable individuals following myocardial infarction. May be used to slow the progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.
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
  • Lithium The ACE inhibitor increases serum levels of lithium
  • Potassium Increased risk of hyperkalemia
  • 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 : Tablet - Oral - 10 mg
Tablet - Oral - 2.5 mg
Tablet - Oral - 20 mg
Tablet - Oral - 30 mg
Tablet - Oral - 40 mg
Tablet - Oral - 5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Acebitor
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Acemin
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Acerbon
  • Công ty : sanofi-aventis
    Sản phẩm biệt dược : Acinopril
  • Công ty : Ranbaxy
    Sản phẩm biệt dược : Bellisin
  • Công ty : Biochem
    Sản phẩm biệt dược : Biopril
  • Công ty : Medochemie
    Sản phẩm biệt dược : Dapril
  • Công ty : Sigma
    Sản phẩm biệt dược : Fibsol
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Fisopril
  • Công ty : Micro Labs
    Sản phẩm biệt dược : Hipril
  • Công ty : Klinger (Brazil)
    Sản phẩm biệt dược : Linopril
  • Sản phẩm biệt dược : Lisipril
  • Công ty : Dexa (Indonesia)
    Sản phẩm biệt dược : Noperten
  • Công ty : Magnachem
    Sản phẩm biệt dược : Presiten
  • Công ty : Merck Frosst
    Sản phẩm biệt dược : Prinivil
  • Công ty : Ranbaxy
    Sản phẩm biệt dược : Ranolip
  • Công ty : Ranbaxy
    Sản phẩm biệt dược : Ranopril
  • Công ty : Biotech
    Sản phẩm biệt dược : Rantex
  • Công ty : Ranbaxy
    Sản phẩm biệt dược : Sinopren
  • Sản phẩm biệt dược : Sinopril
  • Công ty : Merck
    Sản phẩm biệt dược : Tensopril
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Zestril
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00722
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5362119
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504893
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00362
ChemSpider
http://www.chemspider.com/Chemical-Structure.4514933.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0006-0019-54
PharmGKB
http://www.pharmgkb.org/drug/PA450242
Wikipedia
http://en.wikipedia.org/wiki/Lisinopril
RxList
http://www.rxlist.com/cgi/generic/lisinop.htm
PDRhealth
http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=zes1498.html&contentName=Zestril&contentId=861
Drugs.com
http://www.drugs.com/lisinopril.html
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