药品详细
Quinapril(喹那普利)
化学结构式图
中文名
喹那普利
英文名
Quinapril
分子式
C25H30N2O5
化学名
(3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
分子量
Average: 438.5161
Monoisotopic: 438.21547208
Monoisotopic: 438.21547208
CAS号
85441-61-8
ATC分类
C09A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍
Quinapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to quinaprilat (quinapril diacid) following oral administration. Quinaprilat is a 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). Quinapril may be used to treat essential hypertension and congestive heart failure.
生产厂家
- Actavis totowa llc
- Apotex inc
- Genpharm inc
- Invagen pharmaceuticals inc
- Lupin ltd
- Mylan pharmaceuticals inc
- Pfizer pharmaceuticals ltd
- Ranbaxy laboratories ltd
- Sandoz inc
- Sun pharmaceutical industries ltd
- Teva pharmaceuticals usa inc
- Watson laboratories inc florida
封装厂家
- Actavis Group
- Apotex Inc.
- A-S Medication Solutions LLC
- Atlantic Biologicals Corporation
- Aurobindo Pharma Ltd.
- Cardinal Health
- Direct Dispensing Inc.
- Dispensing Solutions
- Doctor Reddys Laboratories Ltd.
- Eon Labs
- Goedecke GmbH
- Greenstone LLC
- Heartland Repack Services LLC
- InvaGen Pharmaceuticals Inc.
- Lupin Pharmaceuticals Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- Ohm Laboratories Inc.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pfizer Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmacia Inc.
- Physicians Total Care Inc.
- Prepackage Specialists
- Ranbaxy Laboratories
- Rebel Distributors Corp.
- Resource Optimization and Innovation LLC
- Southwood Pharmaceuticals
- Sun Pharmaceutical Industries Ltd.
- Teva Pharmaceutical Industries Ltd.
参考
Synthesis Reference | Not Available |
General Reference |
|
剂型
规格
化合物类型
Type | small molecule |
Classes |
|
Substructures |
|
适应症
药理
Indication | For the treatment of hypertension and as adjunct therapy in the treatment of congestive heart failure. May also be used to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy. | ||||||
Pharmacodynamics | Quinapril is a nonpeptide, non-sulfhydryl prodrug that is deesterified to quinaprilat (quinapril diacid), its major active metabolite following oral administration. Quinaprilat 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 quinaprilat by causing increased vasodilation and decreased blood pressure. | ||||||
Mechanism of action | 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. Quinaprilat, the principle active metabolite of quinapril, 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. Quinaprilat 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. | ||||||
Absorption | Peak plasma concentrations of quinapril occur within one hour following oral administration. The extent of absorption is at least 60%. The rate and extent of quinapril absorption are diminished moderately (approximately 25-30%) when ACCUPRIL tablets are administered during a high-fat meal. | ||||||
Volume of distribution | Not Available | ||||||
Protein binding | 97% | ||||||
Metabolism |
Hepatic.
|
||||||
Route of elimination | Quinaprilat is eliminated primarily by renal excretion, up to 96% of an IV dose | ||||||
Half life | Elimination half life is 2 hours with a prolonged terminal phase of 25 hours. | ||||||
Clearance | Not Available | ||||||
Toxicity | Overdose may lead to severe hypotension. LD50=1739mg/kg (orally in mice). The most common adverse effects observed in controlled clinical trials were dizziness, cough, chest pain, dyspnea, fatigue, and nausea/vomiting. | ||||||
Affected organisms |
|
||||||
Pathways |
|
理化性质
Properties | |||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
State | solid | ||||||||||||||||||||||||||||||||||||||||||
Experimental Properties |
|
||||||||||||||||||||||||||||||||||||||||||
Predicted Properties |
|
药物相互作用
Drug | Interaction |
---|---|
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. |
Lithium | The ACE inhibitor increases serum levels of lithium |
Potassium | Increased risk of hyperkalemia |
Spironolactone | Increased risk of hyperkalemia |
Tetracycline | Quinapril may decrease the absorption of tetracycline. |
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 |
Trovafloxacin | Quinapril may decrease the absorption of orally administered Trovafloxacin. The Quinapril formulation contains magnesium ions that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Quinapril dose to minimize the interaction. |
食物相互作用
- Do not take with a high-fat meal.
- Herbs that may attenuate the antihypertensive effect of quinapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
- High salt intake may attenuate the antihypertensive effect of quinapril.
- Quinapril may decrease the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.