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: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a randomized, cross-over, single-dose study of 19 elderly hypertensive patients (aged 62-84 y, SBP greater than 160 mmHg, DBP greater than 100 mmHg, creatinine clearance 11-93 ml.min-1) we have studied the pharmacokinetics of the angiotensin converting enzyme (ACE) inhibitor enalapril after a single oral dose of either 10 mg enalapril or 10 mg enalapril + 25 mg hydrochlorothiazide. The pharmacokinetics of enalapril were unaffected by hydrochlorothiazide, but there was a significant reduction in renal clearance and a significant increase in AUC(0-24 h) of enalaprilat after hydrochlorothiazide, resulting in higher serum concentrations of the active drug. This was independent of the individual degree of renal impairment and might be due either to an initial reduction of GFR by hydrochlorothiazide or to interference with the tubular secretion of enalaprilat. The relationships between serum enalaprilat and serum ACE activity were similar after both treatments, both consistent with a value for Ki of enalaprilat of about 0.1 nmol.l-1. Thus, serum ACE activity was not affected by hydrochlorothiazide but completely reflected the pharmacokinetics of enalaprilat in both treatments.
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PMID:The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients. 133 May 74

A double-blind, parallel group multicentre study was carried out to compare the effects of adding once daily treatment with lisinopril 10 or 20 mg and placebo to the treatment of 100 patients whose blood pressure was inadequately controlled with once daily atenolol 50 mg. Following a two-week run-in period, patients with a lying DBP between 95 mmHg and 115 mmHg were randomised to either lisinopril 10 mg or placebo once daily for four weeks. Blood pressure measurements were made approximately 24 h after the previous dose of study medication. After four weeks' treatment the dose of study medication was doubled for those patients whose lying DBP was greater than or equal to 90 mmHg and a final assessment was made after a further two weeks of treatment. Overall, six weeks' treatment with lisinopril produced a greater fall in lying blood pressures than placebo when added to atenolol therapy. The difference in favour of the additional ACE inhibitor therapy was 7.1 +/- 2.6/5.4 +/- 1.5 mmHg (mean +/- SEM) (P less than 0.01). Standing blood pressures showed similar behaviour in favour of the additional ACE inhibitor treatment (7.6 +/- 2.4/4.7 +/- 1.6 mmHg) (P less than 0.005). Heart rate was not altered significantly by either lisinopril or placebo treatment. The addition of lisinopril to treatment with atenolol produced a slight increase in the reported number of adverse events compared with placebo. The results of this study indicate that the addition of lisinopril 10-20 mg once daily to treatment with a beta-adrenoceptor blocking drug produces a worthwhile decrease in blood pressure in patients not responsive to beta-blocker therapy alone.
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PMID:A study of the effects of lisinopril when used in addition to atenolol. 133 43

In elderly hypertensive patients effect of antihypertensive treatment with Ca antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean +/- SEM, 71 +/- 1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension (EH: SBP greater than or equal to 160 mmHg and DBP greater than or equal to 95 mmHg, 70 +/- 1 years) and 11 had isolated systolic hypertension (ISH: SBP greater than or equal to 160 mmHg and DBP less than 95 mmHg, 74 +/- 2 years). Blood pressure (BP) and heart rate were measured every two weeks. In all patients, M-mode echocardiography was performed to measure left ventricular mass index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin activity and aldosterone concentration), were assessed before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 149 +/- 4/84 +/- 2 mmHg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mmHg in ISH. LVMI was significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes in either group. In ISH, the change in LVMI was significantly correlated with the change in systolic BP (r = 0.74, p less than 0.05). In EH, there was no significant relation between BP and LVMI changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of antihypertensive treatment in elderly hypertensive patients with cardiac hypertrophy]. 138 12

Blood pressure (BP) was recorded directly and automatically by a microcomputer aid system for 48 h in normotensive and Goldblatt hypertensive goats. By population-mean cosinor fitting, significant circadian rhythms were found for SBP and DBP in both groups of goats. The BP during nighttime was higher than that during daytime in our goats. An angiotensin converting enzyme inhibitor, captopril, was given to hypertensive goats with usual schedule of drug administration (25mg, t.i.d) or form of chronotherapy (62.5 mg, given before the acrophase of BP, q.n). BP significantly decreased throughout the whole day in both treated groups. But there was no statistical difference of cosinor parameters between the effects of BP in these two groups. BP could be decreased by the method of chronotherapy with less amount of drug and less frequency of drug administration.
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PMID:[Circadian rhythm of blood pressure in renovascular hypertensive goats treated with captopril]. 145 52

The aim of this 3-month double-blind multicenter trial was to compare the antihypertensive efficacy and tolerability of the ACE inhibitor perindopril with those of a diuretic combination. After 1 month of receiving placebo, 165 patients with essential hypertension were randomised to perindopril 4 mg (n = 82) or to 50 mg hydrochlorothiazide + 5 mg amiloride (n = 83). The patients were treated for 3 months with monthly assessments, "uncontrolled" patients (DBP greater than 90 mm Hg) had their dosage doubled and then, if necessary, atenolol 50 mg was added. At the end of the 3-month study, mean decreases in supine and standing systolic and diastolic blood pressures were similar in both groups. In the perindopril group, BP control was obtained in 56% of the patients with the 4 mg dosage and required an increase to 8 mg alone in 16% and with atenolol in 5%. The corresponding percentages in the diuretic group were 48, 23 and 13%. The overall percentage of "controlled" patients was similar in the 2 groups, respectively 78 and 84%. The nature and incidence of complaints were comparable in the 2 groups. Adverse laboratory changes were more frequent in the diuretic group: decrease in blood sodium (140.5 vs 139.1 mmol/l; P less than 0.01), potassium (4.2 vs 3.9 mmol/l; P less than 0.01) with 10 patients having significant hypokalemia, increase in blood urea, triglycerides and uric acid. By contrast, a transient increase in blood potassium with a decrease in triglycerides was observed in the perindopril group.
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PMID:A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension. 168 28

This 6-week, double-blind, parallel-group study compared the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitors quinapril and captopril as initial monotherapies in patients with severe hypertension (diastolic blood pressure [DBP] greater than or equal to 115 and less than or equal to 130 mm Hg). A total of 97 patients, aged between 18 and 70 years, were randomized to 5 mg oral quinapril twice daily or 25 mg captopril twice daily with maximum titration to 20 mg quinapril twice daily or 100 mg captopril twice daily. With the morning dose 25 mg hydrochlorothiazide (HCTZ) could be added at week 4 of the double-blind phase or earlier if required for safety considerations. For the monotherapy phase, mean reductions in DBP of 12.1 mm Hg were achieved with both treatments. Clinical response rates (reduction in DBP greater than or equal to 10 mm Hg) were 58% for quinapril and 44% for captopril. At the end of therapy, with optional HCTZ, mean reductions in DBP were 19.0 mm Hg for the quinapril-treated group and 16.2 mm Hg for the captopril-treated group. None of the differences achieved statistical significance. Headache was the most frequently reported adverse event in both treatment groups with 8 reports each. No clinically significant changes in laboratory data were observed in any parameter for either treatment group. Quinapril and captopril provide comparable efficacy and safety in treatment of severe hypertension when used as initial monotherapy and with the addition of optional HCTZ.
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PMID:Angiotensin converting enzyme inhibitors as initial monotherapy in severe hypertension. Quinapril and captopril. 174 16

1. The importance of total dose to the initial hypotensive response with an angiotensin converting enzyme inhibitor (quinapril) was assessed using a suggested 'maintenance' dose (20 mg) or matched placebo in a randomised double-blind study in patients with uncomplicated hypertension. 2. Thirty-two patients were recruited who were not on therapy or had not received diuretic therapy in their existing drug treatment in the preceding 4 weeks. Secondary causes of hypertension had previously been excluded and sustained clinic blood pressures of SBP greater than 160 mmHg and/or DBP greater than 90 mmHg were taken as indications for a trial of adjuvant or monotherapy with an ACE inhibitor. 3. After uneventful supervised therapy with quinapril in an open pilot study (n = 5) 27 patients entered a double-blind, randomised, crossover study of quinapril or placebo using ambulatory monitoring to assess BP response. 4. All patients remained asymptomatic and both therapy and monitoring were well tolerated. A smooth onset of antihypertensive effect was noted with an overall 24 h placebo corrected fall in systolic BP of 9.9 mmHg (7.2-12.6 95% CI) and diastolic BP of 6.4 mmHg (4.2-8.8) with no significant effect on heart rate. Individual placebo corrected maximal responses during the first 8 h following quinapril showed a wide range for both systolic (+1.56 to 44.0 mmHg) and diastolic (+2.3 to -35.6 mmHg) pressure. Larger falls tended to be associated with higher baseline pretreatment pressures but in no case did absolute systolic pressure fall below 100 mmHg during the first 8 h following administration of placebo or quinapril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The response to the first dose of an angiotensin converting enzyme inhibitor in uncomplicated hypertension--a placebo controlled study utilising ambulatory blood pressure recording. 177 77

Seventeen patients with mild to moderate hypertension, as indicated by a diastolic blood pressure (DPB) of 95-115 mmHg (WHO I), were treated in a randomized, double-blind, parallel study, with either 5 mg of fosinopril, a new phosphinic acid-containing angiotensin converting enzyme (ACE) inhibitor, or 25 mg of hydrochlorothiazide administered orally once daily for 4 weeks after a 4- to 6-week run-in period of placebo. The doses were increased to 10 mg of fosinopril or 50 mg of hydrochlorothiazide if DBP remained above 95 mmHg. The blood pressure (BP) fell from 157 +/- 12/104 +/- 7 mmHg (mean value +/- SD) at the start of the study to 146 +/- 21/97 +/- 8 mmHg (P less than 0.02) after 4 weeks, and to 149 +/- 19/97 +/- 7 mmHg (P less than 0.02) after 8 weeks of fosinopril treatment (n = 8). In the hydrochlorothiazide-treated patients (n = 9), BP fell from 153 +/- 9/105 +/- 5 mmHg at the start of the study to 140 +/- 11/97 +/- 7 mmHg (P less than 0.01) after 4 weeks, and to 131 +/- 11/94 +/- 7 mmHg (P less than 0.01) after 8 weeks. After the first dose, DBP fell from 102 to 99 mmHg (NS) in fosinopril-treated patients, and from 105 to 96 mmHg (P less than 0.02) in hydrochlorothiazide-treated subjects. Serum active fosinoprilate concentration increased to 5.6 ng ml-1, 25.9 ng ml-1, and 43.8 ng ml-1 after 30, 60 and 120 min, respectively, and remained at a level of 6.6-7.7 ng ml-1 after 4 and 8 weeks, respectively. Serum ACE activity decreased from 21.6 +/- 11.0 mumol min-1 l-1 at the start to 9.3 +/- 13.7, 4.4 +/- 4.6, and 2.9 +/- 2.8 mumol min-1 l-1 after 30, 60 and 120 min, respectively. No side-effects and no changes in blood counts, electrolytes or kidney function were attributed to fosinopril during the study. Fosinopril is a safe, long-acting antihypertensive drug with a smooth onset of action. Hydrochlorothiazide treatment caused potassium loss and an increase in the levels of uric acid and triglycerides. Diastolic blood pressure decreased to the same extent as a result of treatment with either drug, while systolic blood pressure was better controlled by hydrochlorothiazide.
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PMID:Comparison of fosinopril and hydrochlorothiazide in patients with mild to moderate hypertension. 183 20

Triatec is a new ACE inhibitor. The initial recommended dose is a single daily intake of 2.5 to 10 mg. In order to validate a dose escalation schedule allowing each patient to be treated with the minimal effective dose, a multicenter clinical trial has been conducted by 102 general practitioners, under conditions close to their habits, on 770 mild hypertension patients with a 16 weeks follow-up. The trial consisted in 4 periods: after a placebo run-in period, the patients whose hypertension remained (supine diastolic blood pressure -DBP-between 95 and 115 mmHg) would receive 2.5 mg of Triatec a day, for 3 weeks. After completion of this first treatment period, non-responders (DBP greater than 90 mmHg) to Triatec 2.5 mg would receive 5 mg of Triatec a day, during 3 weeks. Non responders to Triatec 5 mg a day would then be randomized into a 6 weeks double-blind parallel group trial comparing monotherapy by 10 mg of Triatec to the association of Triatec 5 mg with Lasilix 20 mg. In France, Good Clinical Practice (GCP) is a set of recommendations aiming to ensure a high quality standard for clinical trials. To put these recommendations into practice within the context of a large study of Triatec, national and local structures were implemented for a computer-assisted follow-up. Real-time data control for the 770 patients enrolled in this trial made a first presentation of the results to the Scientific Committee possible a mere 10 weeks after the last visit of the last patient was recorded. It also ensured the most reliable data to be processed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[French multicenter study of Triatec (ramipril) in ambulatory patients: methodology and trial structure]. 214 95

ISH is a distinct pathogenetic entity defined by SBP readings of greater than or equal to 160 and DBP less than 90 mmHg. The etiology, although not well understood, is in some manner related to a reduction in connective tissue elasticity of large blood vessels and an increase in aortic impedance or a decrease in aortic wall compliance. The pathophysiologic consequences include an increased resistance to systolic ejection of blood and a disproportionate increase in SBP. Although not directly related, there is an important increase in peripheral vascular resistance. The prevalence of ISH in several studies is about 7 percent in those over age 60 and increases with age to nearly 20 percent in those over age 80. There is higher prevalence in females and nonwhites. The guidelines for detection of ISH are similar to those for blood pressure evaluation in general. Precautions for detection and evaluation in the elderly include multiple blood pressure measurements in the fasting state and sitting and supine blood pressure measurements before and during therapy. Pseudohypertension, although rare, should be kept in mind. There is a clear risk associated with ISH for stroke, CVD, and premature death, which increases with age and rising levels of SBP. ISH can be controlled effectively with pharmacologic therapies. A reasonable goal is a 20 mmHg reduction in systolic pressure. Proof of reduced risk for stroke, CHD, and death in those with controlled ISH remains to be demonstrated. The SHEP pilot study has demonstrated feasibility of addressing this issue. The full-scale SHEP study addresses this issue and has completed recruitment of the desired sample size and is in follow-up phase. Scheduled completion is in 1991. While we wait for the SHEP full-scale trial results, the prudent approach is for nonpharmacologic therapy and use of pharmacologic agents in that group of patients who demonstrate a large cardiovascular risk burden or increasing symptoms specifically associated with hypertension. The decision to treat must be on an individual patient basis. Pharmacologic therapy is possible in most patients with few or no adverse effects. The "low and slow" approach to therapy is helpful in minimizing these adverse effects. Low-dose diuretics have been documented to be effective in blood pressure control. Chlorthalidone, 12.5 or 25 mg per day, is suggested. Other agents, such as beta-blockers, reserpine, ACE inhibitors, and calcium channel blockers, are best used as Step 2 agents.
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PMID:Systolic hypertension in the elderly: controlled or uncontrolled. 218 67


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