Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0010200 (cough)
23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The successful introduction of angiotensin converting enzyme (ACE) inhibitors in the treatment of patients with essential hypertension or heart failure has increased interest in the (patho)physiological role of the renin-angiotensin system (RAS). ACE is not only involved in the formation of angiotensin II from angiotensin I, but also inactivates vasoactive substances such as bradykinin and substance P. Accumulation of these substances during treatment with ACE inhibitors may contribute to both their therapeutic action and certain adverse effects associated with their use, such as cough and angioneurotic oedema. Renin inhibitors offer an alternative approach to inhibit the RAS. The major advantage of these, still experimental, drugs is their high specificity for the RAS since angiotensinogen is the only known substrate of renin. The currently available renin inhibitors are pseudopeptides that are rapidly taken up by the liver and excreted in the bile. Consequently, these drugs are subjected to a considerable first pass effect which limits their oral bioavailability. Additionally, plasma elimination half-life times are short and the duration of action is limited. Despite these shortcomings, single oral or intravenous administration results in a 80 to 90% inhibition of plasma renin activity and a slight reduction in blood pressure in patients with hypertension. The extent of blood pressure reduction is dependent on the patient's salt balance. After 1 week of oral treatment with the renin inhibitor remikiren, the antihypertensive effect was reduced in salt-repleted hypertensive patients. Subsequent intravenous administration of the drug did not further affect blood pressure, indicating that it was not the first pass effect that was limiting the efficacy of remikiren.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacokinetics and efficacy of renin inhibitors. 758 99

A combination of benazepril 10 mg plus hydrochlorothiazide 12.5 mg once daily was investigated in the treatment of patients with mild-to-moderate essential hypertension who had not responded to monotherapy with benazepril 10 mg. Patients failing to respond to 4 weeks of benazepril 10 mg/d were randomized to continue with the monotherapy (n = 47) or receive the combination therapy (n = 46). After 4 weeks of double-blind treatment, reductions in blood pressure were significantly greater among patients given the combination than among those receiving benazepril alone: a 4.7 +/- 1.5 mm Hg difference in mean sitting diastolic blood pressure was noted in favor of the combination therapy (P = 0.0037). The incidence of adverse events, particularly cough, was lower with benazepril + hydrochlorothiazide than with benazepril alone; no notable changes in body weight or heart rate were seen in either group.
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PMID:Efficacy and safety of benazepril plus hydrochlorothiazide versus benazepril alone in hypertensive patients unresponsive to benazepril monotherapy. 769 91

This study investigated the effect of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on blood pressure in patients with essential hypertension [defined as a sitting diastolic blood pressure (DBP) between 95-120 mm Hg]. The study group comprised 43 patients (24 men and 19 women; mean age, 51 +/- 10 years) with uncomplicated essential hypertension. In an open single-center design, all subjects were treated with a once-daily dose of cilazapril for 6 weeks, following a 1-week washout period. The initial dose was 2.5 mg/day. In nonresponders, this dose was doubled after 3 weeks of treatment. Thirty-eight patients completed the study. One was withdrawn due to symptomatic hypotension, and four others due to noncompliance. Treatment produced a useful and significant reduction in blood pressure (systolic from 155 +/- 3 to 138 +/- 3 mm Hg, p < 0.01; diastolic from 103 +/- 1 to 90 +/- 2 mm Hg, p < 0.001). No significant variations in mean heart rate were recorded. Normalization of DBP, or its reduction by > 10 mm Hg, was found in 28 patients (efficacy in 74% of cases). Cough was reported by one patient. There was no significant variation in laboratory profiles during the trial. Cilazapril proved to be a well-tolerated antihypertensive drug effective on a once-daily regimen in a high percentage of patients with essential hypertension.
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PMID:Efficacy and tolerability of cilazapril in patients with essential hypertension. 770 74

In this multicentre, double-blind trial in 461 patients with essential hypertension, amlodipine (5-10 mg once daily) and enalapril (10-40 mg once daily) were compared in terms of quality of life, efficacy and tolerability after 1 year of treatment (part 1). In part 2, 177 patients successfully treated with amlodipine in part 1 continued in an open evaluation of efficacy and safety of antihypertensive treatment with amlodipine for a further 2 years. In part 1, both drugs were similarly effective in lowering blood pressure (BP) (although significantly more enalapril patients required a diuretic) while maintaining quality of life. Apart from class-typical effects, such as oedema for calcium antagonists and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients (eight amlodipine (4%), nine enalapril (4%)) were withdrawn from the trial because of drug-related adverse events, demonstrating that the tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. The BP reduction seen in the amlodipine patients after part 1 was maintained during part 2. Also, blood lipids and safety variables remained virtually constant. It is concluded that, at similar BP reduction, quality of life is equally well maintained on amlodipine and enalapril therapy. Thus, amlodipine compares favourably with enalapril as an effective and well-tolerated anti-hypertensive agent over the first year. Additionally, amlodipine patients evaluated over a 2-year extension maintained good BP control and the drug was well tolerated.
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PMID:Evaluation and quality-of-life assessment of amlodipine and enalapril in patients with hypertension. 778 9

In a double-blind double-dummy multicenter study, patients with mild to moderate essential hypertension were randomized to receive either nifedipine (n = 416, 47.6% women) or lisinopril (n = 412, 50% women), and side effects were registered by specific questioning, by spontaneous reports, and by use of visual analog scales. Cough was spontaneously reported to occur in 8.5% with lisinopril compared to 3.1% with nifedipine. Women treated with lisinopril reported cough spontaneously three times more often than men, 12.6% v 4.4%, whereas no differences between the sexes were observed during the placebo period or during nifedipine treatment. Similar gender differences were observed during specific questioning. Furthermore, nonsmokers reported an increase in cough more often than did smokers.
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PMID:Female preponderance for lisinopril-induced cough in hypertension. 784 15

The Accupril Canadian Clinical Evaluation and Patient Teaching (ACCEPT) study was a multicenter, 6-month, open-label, postmarketing surveillance study where the efficacy and safety of quinapril, an angiotensin-converting enzyme (ACE) inhibitor, was evaluated in a general population of patients with essential hypertension. Participating physicians followed their normal office procedures for the initiation of quinapril therapy (a dose of 10 mg QD in the majority of cases). The dose was titrated to blood pressure response, generally at 2-week intervals, for a maintenance dose of 10 mg QD to 20 mg QD in most cases (86% at 6 months) and not to exceed 40 mg QD. The use of concomitant antihypertensive medications was left to the discretion of the physician. By random assignment, physicians obtained patient informed consent on either a detailed form that listed possible quinapril side effects or a less specific form, which did not list particular side effects. The purpose of using two different forms was to assess any potential association between the frequency of adverse-event reporting and patient's awareness of quinapril side effects. The patients also received an educational package that provided general information on hypertension and lifestyle modifications known to reduce cardiovascular risk factors. An intent-to-treat analysis included data from 3742 patients in whom the median age was 56 years and the median duration of hypertension was 5 years. The demographic characteristics of these patients were similar to those identified in Canadian hypertensive patients in a recent population-based survey. Nearly 80% of the ACCEPT study patients had more than one cardiovascular risk factor, in addition to hypertension. Among 2979 patients receiving quinapril at 3 months, 77% were stabilized. Among 2517 patients continuing to receive quinapril at 6 months, 84% were stabilized. Greater declines in both diastolic and systolic blood pressures were evident among patients who continued to receive quinapril as part of an antihypertensive regimen than among those who discontinued quinapril treatment. Blood pressure responses to quinapril were similar in newly diagnosed patients and those with a history of hypertension. A total of 980 patients (26.2%) reported one or more adverse events. Cough was most frequently reported and was deemed as definitely related to quinapril therapy by the treating physician in 3.6% of cases. Serious adverse events occurred in 55 patients (1.5%) and were assessed as possibly related to quinapril in only three patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A postmarketing surveillance evaluation of quinapril in 3742 Canadian hypertensive patients: the ACCEPT Study. Accupril Canadian Clinical Evaluation and Patient Teaching. 785 44

The aim of the present study was to evaluate the effect of dihydropyridine calcium antagonist isradipine on left ventricular (LV) structure and function in patients with essential hypertension. Cuff blood pressure and Doppler echocardiographic variables were assessed in 26 patients with mild to moderate hypertension (diastolic blood pressure range 95-110 mmHg) before and after 12 weeks of therapy with either isradipine 5 mg daily or enalapril 20 mg daily. The study was of double-blind, parallel design, with a placebo run-in period of 15 days. Three subjects withdrew from isradipine treatment because of flushing and 2 from enalapril treatment due to cough before completing the study. Both drugs significantly reduced cuff systolic and diastolic blood pressure (p < 0.001) without affecting heart rate. By virtue of the decrease in both septal wall (p < 0.01) and posterior wall thicknesses (p < 0.05), isradipine treatment produced a significant reduction in LV mass adjusted for height (p < 0.001) in comparison with placebo; also LV end-systolic dimension showed a slight decrease (p < 0.05). Enalapril induced a similar reduction in LV end-systolic dimension (p < 0.05) but the changes of wall thickness and LV mass did not reach statistical significance. In conclusion, our results indicate that isradipine treatment improves LV systolic function and causes a significant reduction in LV mass. This reduction is observed early in the course of antihypertensive treatment and is effective in both patients with and without LV hypertrophy.
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PMID:Reduction of left ventricular mass by short-term antihypertensive treatment with isradipine: a double-blind comparison with enalapril. 792 33

This study compared the efficacy and tolerability of monotherapy with felodipine and enalapril in patients with essential hypertension using a double-blind randomised crossover design. Thirty-five subjects (22 male, 13 female--ages: median 48 years, range 31-69 years) entered the randomised phases of the study and 32 subjects completed the study. Following a 4-week run-in placebo phase, the treatments were felodipine ("Plendil ER") 5-20 mg and enalapril 5-20 mg orally once daily for 8 weeks, each with matching placebos. Dose titration was at 2 and/or 4 weeks in each phase. Number of subjects with each different end-of-phase dose were for felodipine: 5 mg--8, 10 mg--11, 20 mg--13 and enalapril: 5 mg--6, 10 mg--9, 20 mg--17. Predose supine blood pressure (mean +/- SEM) was reduced in both active treatment phases compared with the run-in phase (159 + 2/101 +/- 1), but there was no significant difference in blood pressure between the active phases: felodipine 143 +/- 2/90 +/- 1 and enalapril 146 +/- 2/92 +/- 1. The most common adverse effects were for felodipine: headache, flushing, ankle swelling; and for enalapril: cough. Felodipine and enalapril as once daily monotherapy are thus of similar antihypertensive efficacy but with predictably different adverse effect profiles.
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PMID:Comparison of felodipine and enalapril monotherapy in essential hypertension. 819 32

A postmarketing surveillance study in 2273 Canadian office practices provided the largest body of clinical experience to date with the angiotensin-converting enzyme (ACE) inhibitor lisinopril in the treatment of mild to moderate essential hypertension. The principal emphasis in this uncontrolled study was safety, assessed in 10,289 patients. Patients with a diastolic blood pressure > 90 mmHg were considered for the study. Both previously untreated patients and those who were experiencing adverse effects from their current antihypertensive regimen were included. Lisinopril was begun at a dose of 10 mg/day. Subsequent dose adjustments, to a maximum of 40 mg/day, were made to achieve optimal blood pressure control (diastolic blood pressure < or = 90 mmHg or > or = 10 mmHg below baseline for > or = 4 weeks at the same dose). Therapy was continued for a minimum of 4 weeks to a maximum of 12 weeks, with patients examined every 2 weeks. The frequencies of adverse effects and laboratory abnormalities were analyzed in all treated patients. All 10,289 patients enrolled were considered in the analysis of safety. One or more adverse effects were reported for 1593 (15.5%) patients, and 802 (7.8%) withdrew from the study because of adverse effects. The most frequent adverse effects were cough (4.0%), dizziness (2.3%), headache (2.1%), asthenia (1.7%), and nausea (1.0%). The physicians' global assessment rated overall tolerability as very good or good for 77.1% of the patients. Antihypertensive effect was evaluated in 5886 patients who met the criteria for efficacy analysis. The criterion response was attained in 5141 (87.3%) patients, with 68.6% responding to 10 mg/day of lisinopril, 26.3% to 20 mg/day, and 3.2% to 40 mg/day (the other 1.9% responded at nonstandard doses). Lisinopril was safe and well-tolerated. Except for cough, class effects of ACE inhibitors were rarely encountered. The results of the efficacy analysis confirm the established efficacy of lisinopril in patients with mild to moderate essential hypertension.
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PMID:Lisinopril in the treatment of hypertension: a Canadian postmarketing surveillance study. 839 Sep 18

Forty patients with mild or moderate essential hypertension were studied. They received daily doses of either 240 mg verapamil or 10 mg enalapril, as well as a placebo. Total duration of trial was 24 weeks: a "washout" period of 2 weeks, a treatment period of 6 weeks with one of the two drugs, another "washout" period of 2 weeks, and another treatment period of 6 weeks with the alternate drug. Those patients with persistence of diastolic blood pressure (DBP) above 90 mmHg received simultaneously both drugs for an additional period of 8 weeks. Patients were assigned alternately to one of the groups. When each drug was given during the first treatment period, DBP was reduced below 90 mmHg in 15 of 19 patients receiving verapamil, and in 12 of 20 that received enalapril. When the drugs were given during the second treatment period, DBP became normal in 16 of 19 patients receiving enalapril, and in all the 18 patients treated with verapamil. Three patients achieved normal DBP when received simultaneously both drugs. Two patients withdrew from the trial for personal reasons and one for experimenting cough as reaction to enalapril. There were no other undesirable side effects. Laboratory tests did not show changes. Both products were similarly effective. Synergy was shown by the improvement of patients unresponsive to either drug when given singly, but responding when both were given simultaneously.
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PMID:[A comparison and synergy in the treatment of essential arterial hypertension]. 850 14


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