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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six control dogs, six dogs treated with 1.5 mg/kg b.i.d. quinapril, and six dogs treated with 8 mg/kg q.d. minoxidil underwent 6 hours daily of hindquarter compression for 9 weeks. Minoxidil significantly decreased baseline blood pressure (-17 mm Hg; p less than or equal to 0.01), whereas quinapril decreased baseline blood pressure 11 mm Hg but not significantly (p = 0.15). Hindquarter compression elicited blood pressure increases in all three groups (control +18, quinapril +13, minoxidil +19 mm Hg). After 9 weeks, left ventricular mass in control dogs increased 22% (p less than 0.004); a similar increase was seen in minoxidil-treated dogs (+22%, p less than 0.0001) but not in the quinapril-treated group (+4%, p less than 0.15). The increase in left ventricular mass in control dogs was concentric (increased epicardial volume only), whereas in the minoxidil group, the hypertrophy was eccentric (both epicardial and endocardial volumes increased). The minimal hypertrophy in the quinapril group was concentric (no change in epicardial, but a decrease in endocardial volume). Quinapril had little hypotensive effect, but prevented the development of left ventricular hypertrophy, whereas minoxidil did not prevent hypertrophy in spite of its hypotensive effect. The mechanism of this differential effect of direct vasodilation versus converting enzyme inhibition on left ventricular hypertrophy is not fully elucidated. The results with quinapril suggest that some antihypertensive agents may positively affect left ventricular hypertrophy in spite of the absence of a large effect on baseline blood pressure or on blood pressure reactivity.
Hypertension 1991 Jun
PMID:Quinapril, an angiotensin converting enzyme inhibitor, prevents cardiac hypertrophy during episodic hypertension. 182 58

Quinapril hydrochloride is the newest member of a family of angiotensin-converting enzyme (ACE) inhibitors. On completion of laboratory and animal studies, a clinical program was initiated to evaluate the antihypertensive and other properties of the drug in human subjects. The initial phase of clinical development was concerned with the pharmacokinetics and pharmacology of quinapril. The latter studies established a dose range for the drug and explored its effect on human hemodynamics and blood pressure. Safety and interactions with other drugs were also examined. Subsequent studies explored the safety and efficacy of quinapril in patients with mild to moderate hypertension and, later, in patients with more severe hypertension. Results of these studies supported the recommendation of a once daily dosage of quinapril, 10-40 mg, as first-line therapy in the management of hypertension, with diuretics as concomitant therapy as required in patients with severe hypertension. Quinapril has also been found to be the most potent of all available ACE inhibitors in binding to tissue ACE, which may contribute to its potent and sustained duration of action. Clinical evaluation of quinapril has also been undertaken in patients with congestive heart failure. Initial findings indicate that doses of 10-20 mg/day, given twice daily, are therapeutic when administered with diuretic or digitalis. Safety of the drug has been established in 2700 patients.
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PMID:Overview of the clinical development of quinapril. 218 16

Major studies comparing the efficacy and safety of quinapril and captopril in the treatment of moderate to severe or severe hypertension are reviewed. Given concurrently with hydrochlorothiazide 25 mg/day to patients with moderate to severe hypertension, quinapril 20-80 mg/day twice daily was found to be more effective than captopril 50-200 mg/day twice daily, and quinapril 10-40 mg/day once daily was found to be as effective as captopril 25-100 mg/day twice daily. Given as initial monotherapy to patients with severe hypertension, quinapril 10-40 mg/day twice daily was found to be as effective as captopril 50-200 mg/day twice daily. Quinapril was found to be well tolerated, both when administered against a diuretic background and when diuretic was added to a quinapril regimen.
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PMID:The efficacy and safety of quinapril in the treatment of moderate to severe and severe hypertension: comparison to captopril. 218 18

The safety of quinapril hydrochloride, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action, has been evaluated in 3,031 patients with hypertension and congestive heart failure (CHF) and has been compared with other ACE inhibitors. A comparison of double-blind studies showed quinapril to have a lower incidence of adverse effects and withdrawals than reported for captopril or enalapril. Analysis of onset of adverse events or withdrawals did not show either a time-dependent or dose-dependent relationship with quinapril. The proportion of patients who experienced orthostatic hypotension was less than that of patients on captopril or enalapril. Double-blind, long-term, and open-label studies with quinapril showed no increase in the incidence of events reported in patients with CHF compared with hypertensive patients. Quinapril produced minimal adverse effects on renal function in both patients with normal renal function and in those with pre-existing renal impairment. Age analysis of data from all studies showed no increase in total reporting of adverse events in older patients who did not take concomitant diuretics.
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PMID:The safety profile of quinapril: is there a difference among ACE inhibitors? 218 20

Quinapril hydrochloride, a new, orally active, nonpeptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, has been studied extensively in a variety of in vitro and in vivo animal models. Quinapril inhibits the contractile and pressor effects of angiotensin I in rabbit aorta and in rats, respectively, and lowers blood pressure in both high- and normal-renin rodent and diuretic-treated dog models of hypertension. No tolerance to the antihypertensive effects of quinapril was noted in spontaneously hypertensive rats treated with quinapril for up to 14 consecutive days. As with other ACE inhibitors, quinapril had virtually no effect on the development of hypertension in the renin-independent one-kidney deoxycorticosterone (DOCA)-salt hypertensive rat. Antihypertensive activity best correlates with the inhibition of tissue (vascular) ACE, and thus the reduction in peripheral vascular resistance associated with plasma and tissue ACE most likely accounts for the therapeutic benefit of quinapril. Preliminary data from a trial of quinapril in cardiomyopathic hamsters show that the drug prevents the anticipated decline in left ventricular contractile function and retards the temporal progression of left ventricular failure. ACE inhibitors have been found to have a lipid-neutral profile, unlike some other classes of antihypertensives. Quinapril is rapidly absorbed and extensively distributed to all tissues except brain. It is rapidly hydrolyzed to quinaprilat, its pharmacologically active diacid form. Metabolism to other compounds is not extensive. Quinapril's preclinical toxicologic profile is similar to that of other ACE inhibitors. Long-term toxicology studies show that quinapril is not teratogenic, carcinogenic, or mutagenic.
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PMID:Quinapril: overview of preclinical data. 218 23

Hypertension is a major potential problem among the increasing number of older persons in the population, threatening their health and shortening their life expectancy due particularly to stroke and congestive heart failure (CHF). Controlled studies have shown that antihypertensive drug therapy reduces the incidence of severe CHF, stroke and cardiovascular mortality in the elderly. Special consideration should be given to altered drug metabolism, altered responses to drugs, and concomitant medications when pharmacotherapy is instituted in the elderly. Angiotensin-converting enzyme (ACE) inhibitors are acceptable in the hypertensive older patient as first-line therapy for all grades of hypertension and as second-line therapy for the patient with CHF. Use of ACE inhibitors avoids many of the symptoms and metabolic disturbances associated with beta-blockers and diuretics. Quinapril is a new non-sulphydryl ACE inhibitor whose active metabolite, quinaprilat, has a relatively short accumulation half-life compared with enalapril and lisinopril but has an enhanced affinity for the converting enzyme, allowing rapid excretion of the drug while retaining a 24-hour antihypertensive effect with once-daily dosing. Quinapril is a valuable addition to the ACE inhibitor class, with demonstrated efficacy and safety in the older patient.
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PMID:ACE inhibitors in the treatment of hypertension in the older patient. 219 9

Quinapril is an orally active, non-peptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor that acts potently and specifically to interrupt the conversion of angiotensin I to angiotensin II in both plasma and tissue. Quinapril is enzymatically hydrolyzed to a pharmacologically active diacid form quinaprilat. Quinapril is efficacious in hypertensive models exhibiting both high (renal hypertensive rats, diuretic-treated dogs) and normal (spontaneously hypertensive rats) plasma renin activity. Quinapril does not prevent the development of hypertension when plasma renin activity (PRA) is markedly suppressed as in the deoxycorticosterone-saline treated rat. Hemodynamic studies in dogs indicate that quinapril decreases total peripheral and renal vascular resistance. Quinaprilat produces natriuresis and mild diuresis at doses that do not alter mean arterial blood pressure. Quinapril has the potential to affect plasma lipids beneficially or at least be "lipid neutral." Oral absorption of quinapril is rapid in rats, dogs, and monkeys. There is rapid and extensive distribution of radiolabel to most tissues except brain. Plasma radiolabel concentration-time profiles exhibit polyexponential decay with a prolonged terminal phase at low concentrations in all species. Metabolism to compounds other than quinaprilat is not extensive. Quinapril is excreted primarily as quinaprilat and to a lesser degree as quinapril. Quinapril is well tolerated in a variety of pharmacologic safety screens and its toxicity profile is similar to that of other ACE inhibitors. Quinapril does not adversely affect reproduction; it is not teratogenic, carcinogenic, or mutagenic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quinapril--a preclinical review of the pharmacology, pharmacokinetics, and toxicology. 253 61

Quinapril is converted to quinaprilat, a long-acting angiotensin converting enzyme (ACE) inhibitor, and is currently being studied for the treatment of hypertension and congestive heart failure. In studies of healthy volunteers, single quinapril doses of 0.625 mg to 80 mg inhibited plasma ACE activity for up to forty-eight hours. Dose-related inhibition of angiotensin I pressor response occurred after administration of quinapril doses of 0.625 mg to 20 mg. In addition, plasma renin activity increased and aldosterone and angiotensin II concentrations decreased following single or multiple doses of quinapril. Subsequently, dose-ranging studies were conducted in patients with mild to moderate hypertension and congestive heart failure. Pilot studies suggested that 5 mg of quinapril given once daily had minimal antihypertensive effect. Therefore, a definitive, multiple-dose, placebo-controlled, double-blind study of 5, 10, and 20 mg once daily doses of quinapril was performed. Quinapril doses of 10 mg and 20 mg were statistically significantly superior to placebo (p less than 0.05) in lowering sitting diastolic blood pressure (DBP), whereas 5 mg of quinapril had only marginal clinical effectiveness. A twenty-four-hour blood pressure monitoring study indicated that quinapril administered once or twice daily effectively lowered DBP in patients with mild to moderate hypertension. This study suggested, however, that some patients may not achieve sustained reductions in DBP over the entire twenty-four-hour interval with quinapril administered once daily and may require twice daily therapy. In studies of patients with refractory congestive heart failure, acute favorable hemodynamic effects were demonstrated after the administration of quinapril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacology of quinapril in healthy volunteers and in patients with hypertension and congestive heart failure. 253 62

A comprehensive analysis of the reporting of adverse events, withdrawals due to adverse events, and serious adverse events has been conducted on 2,010 patients treated with quinapril hydrochloride. An analysis of all events (from both double-blind and open label studies combined) showed no increase in the incidence of events reported in congestive heart failure (CHF) patients compared to hypertensive patients. When the data for all studies were combined, an age analysis showed no increase in the total reporting of adverse events in the 379 elderly patients studied. The incidence of events was lower in those patients who did not take concomitant diuretic therapy. A comparison of the double-blind phases showed quinapril to have a lower incidence of adverse events than captopril, enalapril, or chlorthalidone. An analysis of the onset of events, or withdrawals, did not show an increase with time on quinapril therapy, and no dose-relationship. A review of serious adverse events did not reveal an unexpected occurrence or a high incidence of serious events considered to be related to quinapril therapy. The proportion of patients who experienced "first-dose" hypotension, or symptomatic hypotension was similar to captopril or enalapril. Quinapril, a nonsulfhydryl ACE inhibitor, has been extensively studied and is equally well tolerated in the young and elderly for the treatment of hypertension and CHF.
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PMID:Overall tolerance and safety of quinapril in clinical trials. 265 May 83

Possible non-renin antihypertensive actions of two angiotensin-converting enzyme inhibitors, the sulfhydryl compound captopril and the new nonsulfhydryl inhibitor quinapril (CI-906), were compared in rats with one-kidney deoxycorticosterone-salt hypertension. Plasma renin activity remained low during the 12-day treatments and showed very strong suppression of the renin-angiotensin system. Quinapril did not influence the rapidly increasing blood pressure. Although captopril tended to reduce the development of hypertension (p = 0.08), it did not have any significant effect, either. The results indicate that these ACE inhibitors with different chemical structures lack any significant blood pressure lowering mechanism in severe deoxycorticosterone-salt hypertension, a model in which they cannot act through their established antihypertensive mechanism, the inhibition of the renin-angiotensin system.
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PMID:Effects of two structurally different angiotensin-converting enzyme inhibitors, captopril and quinapril (CI-906), in rats with one-kidney deoxycorticosterone-salt hypertension. 302 83


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