Quinapril

Abstract

Following systemic absorption, quinapril is converted by de-esterification to quinaprilat (the active diacid metabolite), an inhibitor of angiotensin converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition of ACE both in plasma and at tissue sites, such as the arterial wall and heart, following administration of quinapril. Tissue ACE inhibition may be an important component of the mechanism of action of quinapril (and other ACE inhibitors) in achieving favourable effects in cardiovascular disorders. Quinaprilat has a short elimination half-life (approximately 2 hours), but binds potently to and dissociates slowly from ACE, thus allowing once or twice daily administration of quinapril in the treatment of patients with hypertension or congestive heart failure. Quinapril 10 to 40 mg/day has achieved adequate control of blood pressure in most patients with essential hypertension in clinical trials. Some patients required quinapril dosages up to 80 mg/day and/or concomitant diuretic therapy. Titrating quinapril dosages from 10 to 40 mg/day increased response rates without increasing the incidence or severity of adverse events. Addition of hydrochlorothiazide to quinapril therapy improved response rates by approximately 10 to 20% in patients with hypertension. In general, blood pressure control with quinapril monotherapy was similar to that achieved with enalapril or other standard antihypertensive agents in comparative trials. Quinapril < or = 40 mg/day improved exercise tolerance, reduced the severity and frequency of symptoms, and improved functional (New York Heart Association) class in most clinical studies of patients with congestive heart failure. In addition, beneficial haemodynamic and echocardiographic changes achieved with quinapril were maintained for up to 1 year with continued administration to such patients, but its effect on survival in patients with congestive heart failure has not been reported. The tolerability profile of quinapril is broadly similar to that of other ACE inhibitors; pooled data from clinical trials indicated that 12% of patients with hypertension or congestive heart failure receiving quinapril experienced a treatment-related adverse effects compared with 15% of enalapril recipients and 16% of captopril recipients. Thus, quinapril has clearly established a role as an effective and well tolerated alternative to other ACE inhibitors for the treatment of hypertension and congestive heart failure. While effects of quinapril on survival of patients with congestive heart failure have not been determined, large intervention studies have demonstrated improved mortality rates with other ACE inhibitors. Further studies, including a large ongoing trial of normotensive patients with coronary artery disease but normal left ventricular function, may also establish a role for quinapril in treating patients with ischaemic heart disease.

Modern antihypertensive therapy: the effectiveness of a unique Russian fixed-dose combination of ramipril and indapamide

“…По способности блокировать активность АПФ в плазме крови рамипирил может считаться одним из наиболее мощных иАПФ [18]. Все иАПФ влияют на активность АПФ плазмы крови, но рамиприл относят к немногочисленной группе ингибиторов АПФ, которые способны подавлять активность тканевого АПФ у человека [19][20][21].…”

Reações Multicomponente – Uma Ferramenta Valiosa na Descoberta e Produção de Fármacos

“…Recentemente, a síntese do fármaco quinapril (Acupril®) também foi reportada através de uma reação de Ugi de três componentes. Este pró-fármaco, que é ativado por metabolismo à sua forma ativa, um diácido, através da hidrólise do grupo éster, é usado no tratamento da hipertensão, pertencendo ao grupo dos inibidores da enzima conversora da angiotensina (IECA), considerado o grupo terapêutico de primeira escolha para esta patologia crónica [46]. A sua síntese através da reação de Ugi permite a formação de um precursor com a cadeia α-amino amida, uma característica estrutural de vários fármacos da classe dos IECA, de forma rápida e eficaz, num total de quatro passos reacionais (Esquema 8) [47].…”

Determination of the angiotensin-converting enzyme inhibitor quinapril and its metabolite quinaprilat in pharmaceuticals and urine by capillary zone electrophoresis and solid-phase extraction

“…This mechanism provides a more gradual onset of its antihypertensive effect [1,2]. These antihypertensive agents share a common mechanism of action of ACE inhibition, which ends in the blockage of the reninangiotensin system.…”

“…Quinaprilat is eliminated in the urine and accounts for 30% of the administered dose. Only 3% of a dose is recovered as unchanged quinapril [1,8]. This drug has a very short plasma half-life, but strong tissue binding affinity, which offers long-term activity [9].…”