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

The pharmacology of angiotensin-converting-enzyme (ACE) inhibitors and their role in the renin-angiotensin system (RAS) are described, and pharmacokinetic properties and common adverse events are presented. ACE inhibitors play a vital role in the RAS by regulating the potent vasoconstrictor angiotensin II. All ACE inhibitors share the same basic structure; however, they can be separated on the basis of their functional (binding) group: carboxyl, sulfhydryl, or phosphinyl. These functional groups are, in part, responsible for differences in the pharmacokinetic and safety profiles of these agents. Captopril and lisinopril are the only ACE inhibitors that are not prodrugs requiring activation through hepatic biotransformation. Differences among the ACE inhibitors in lipophilicity are described; fosinopril has the greatest lipophilicity and lisinopril the least. ACE is found in numerous tissues, and there is increasing evidence of differences among ACE inhibitors in their ability to inhibit tissue ACE. Most ACE inhibitors are eliminated mainly by the kidneys and to a lesser extent through the liver. Lisinopril is the only ACE inhibitor that does not require hepatic metabolism. In the selection of an ACE inhibitor for once-daily use to treat hypertension, differences in trough-peak ratios are clinically relevant. Fosinopril, ramipril, and trandolapril have minimum trough-peak ratios of 50% or greater. ACE inhibitors are generally well tolerated, with hypotension, cough, and hyperkalemia being the most frequently reported adverse effects for the entire class. Drug interactions across the ACE inhibitor class as well as agent-specific interactions are described. Factors to be considered in the selection of an ACE inhibitor include differences in potency, affinity for ACE, pharmacokinetics, and toxicity that are related to structural properties of the drug; whether the trough-peak ratio enables use of a once-daily dose; and potential adverse effects related to a drug's functional (binding) group.
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PMID:Overview of the angiotensin-converting-enzyme inhibitors. 1103 16

OBJECTIVE: Cough frequency and severity with fosinopril and enalapril were assessed in hypertensive patients with previous angiotensin-converting enzyme inhibitor (ACEI)-associated cough. DESIGN: Prospective, multicenter, randomized, 8-week double-blind treatment. PATIENTS: One hundred seventy-nine patients (mild-to-moderate hypertension, nonsmokers, mean age 58 years; 55% females; 72% Caucasian, 6% black, 19% Hispanic) were studied. Patients with other cough etiologies, significant co-morbidity, or confounding medications were excluded. INTERVENTIONS: Patients were randomized to fosinopril 10 mg (n = 85) or enalapril 5 mg (n = 94) once daily. Dosage could be doubled for blood pressure control after 4 weeks. Outcome measurements: The primary end point was all-cough frequency based on patient daily diary ratings; a cumulative cough frequency score was calculated. Secondary end points included cough severity, nonproductive cough frequency, night awakenings, cough time of day, and spontaneously reported cough. RESULTS: Fosinopril and enalapril demonstrated similar blood pressure control. Significant cough profile differences were observed in favor of fosinopril: all-cough frequency was 40.6 plus minus 3.8 (mean plus minus SE) versus 52.8 plus minus 3.6 (p = 0.02); nonproductive cough frequency was 26.7 plus minus 3.5 versus 40.3 plus minus 3.4 (p less-than-or-equal 0.01); and cough time of day was 49.2 plus minus 5.2 versus 66.0 plus minus 5.0 (p = 0.02), for fosinopril and enalapril, respectively. Subgroup analysis revealed all-cough frequency was 33.5 plus minus 6.3 versus 56.6 plus minus 5.3 (p = 0.006) for fosinopril and enalapril, respectively, in patients who previously had cough on one of these two ACEI (predominantly enalapril). Ten (12%) fosinopril and 25 (27%) enelapril patients spontaneously reported cough (p = 0.01). CONCLUSIONS: Hypertensive patients with previous ACEI-associated cough reported less frequent cough with fosinopril compared to enalapril, based on cumulative patient diary scores and spontaneously reported cough. This difference was most apparent in the subgroup of patients who previously experienced cough associated with enalapril therapy. Patients with prior ACEI-associated cough may experience less frequent with fosinopril.
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PMID:A Comparison of the Cough Profile of Fosinopril and Enalapril in Hypertensive Patients with a History of ACE Inhibitor-Associated Cough. 1185 91

Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
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PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

Hypertension and diabetes are commonly found conditions, which predispose to premature cardiovascular morbidity and mortality. A strong consensus has emerged in support of aggressive blood pressure reduction in order to forestall the almost inevitable complications that follow from being a hypertensive diabetic. As of yet though it is not clearly determined as to what represents the best class(es) of antihypertensive medications to effect such blood pressure reduction. In this regard, considerable debate has arisen as to the cost/benefit ratio of dihydropyridine calcium channel blockers in the hypertensive diabetic. Although studies such as the Fosinopril vs. Amlodipine Cardiovascular Events Trial and the Appropriate Blood Pressure Control in Diabetes study would seem to argue against the use of dihydropyridine calcium channel blockers in the diabetic hypertensive, other studies such as the subset analyses of the Syst-Eur and the Syst-China and the Hypertension Optimal Treatment study provide almost compelling evidence for the safety of low to moderate doses of a dihydropyridine calcium channel blockers in this population. Safety issues of dihydropyridine calcium channel blockers will remain unresolved until the release of the Antihypertensive and Lipid Lowering Study to Prevent Heart Attack results at which time a resolution to this question should be forthcoming. (c)2000 by CHF, Inc.
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PMID:Pharmacotherapy in congestive heart failure: reflections on diabetes, clinical trials, and cardiovascular morbidity and mortality. 1202 96

Microvascular remodeling contributes to increased cardiovascular risk in hypertension. The dual angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitor omapatrilat improves small artery remodeling in hypertension. The aim of the present study was to compare effects of omapatrilat to the ACE inhibitor fosinopril and the AT(1) antagonist irbesartan on the coronary microvasculature in spontaneously hypertensive rats (SHR). Ten-week-old SHR were treated for 10 weeks with omapatrilat (20 or 40 mg/kg/d), irbesartan (50 mg/kg/d), or fosinopril (20 mg/kg/d). Arterioles and capillaries were identified in the myocardium by immunolabeling. After 10 weeks, systolic blood pressure (BP) was significantly reduced in treated versus untreated SHR (P <.01). Myocardial arteriolar density/mm(2) was higher (P <.05) in untreated SHR versus Wistar-Kyoto (WKY), and was reduced by omapatrilat (at both high and low doses) and by fosinopril (P <.01). Irbesartan decreased only subepicardial arteriolar density (P <.05). Myocardial capillary density/mm(2) was decreased in untreated SHR versus WKY (P <.01), associated with increase in cardiomyocyte cross-sectional area and cardiomyocyte-to-capillary ratio, and a decrease in myocyte density. Omapatrilat (at both high and low doses) resulted in increased capillary density, decreased myocyte hypertrophy and cardiomyocyte to capillary ratio, and increased myocyte density (P <.01). Fosinopril and irbesartan reduced myocyte hypertrophy of SHR, but had no effect on capillary density. Dual ACE/NEP inhibition was more effective than ACE inhibition or AT(1) antagonism in improving microvascular and cardiomyocyte remodeling in the hypertensive heart. This suggests a role for NEP inhibition added to blockade of the renin-angiotensin system that may explain the greater efficacy of omapatrilat.
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PMID:Effect of dual angiotensin converting enzyme/neutral endopeptidase inhibition, angiotensin converting enzyme inhibition, or AT1 antagonism on coronary microvasculature in spontaneously hypertensive rats. 1457 31

We evaluated the efficacy, safety, and dose-response relationship of fosinopril in children aged 6 to 16 years with hypertension or high-normal blood pressure with an associated medical condition requiring treatment. The study was a prospective, double-blind, placebo-controlled trial conducted in 78 clinical sites in the United States, Russia, and Israel. There were 4 phases: a screening phase of 10 days maximum, a 4-week dose-response phase, a placebo withdrawal phase of 2 weeks maximum, and a 52-week open-label safety phase. The primary objective of the dose-response phase was to determine whether low (0.1 mg/kg), medium (0.3 mg/kg), or high (0.6 mg/kg) doses of fosinopril based on established adult dosing affect trough seated systolic blood pressure. During the dose-response phase, all 3 doses were equally effective in lowering systolic blood pressure. During the placebo withdrawal phase, there was an adjusted mean systolic blood pressure increase of 5.2 mm Hg for the placebo group and 1.5 mm Hg for the fosinopril group, a net withdrawal effect of 3.7 mm Hg (P=0.013). Fosinopril was well tolerated; serious adverse events occurred infrequently and were generally not attributed to fosinopril. Because children appear to be more sensitive to lower doses of fosinopril than adults, starting doses for children should be < or =0.1 mg/kg.
Hypertension 2004 Sep
PMID:Is the extrapolated adult dose of fosinopril safe and effective in treating hypertensive children? 1526 2

Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity. We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects, without renal disease. In addition, we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor. In this substudy of the Prevention of Renal and Vascular Endstage Disease Intervention Trial, 384 microalbuminuric patients were included. Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded, randomized treatment (fosinopril 20 mg or placebo). Mean age was 51.1+/-11.5 years, and 65.6% were male. Median urinary albumin excretion was 22.2 mg per 24 hours. At baseline, mean arterial pressure (beta(standardized)=0.161; P=0.006), urinary sodium excretion (beta(standardized)=0.154; P=0.011), and estimated renal function were independently associated with albumin excretion. In these predominantly normotensive to prehypertensive subjects, fosinopril reduced albumin excretion by 18.5% versus a 6.1% increase on placebo after 3 months (P<0.001). Fosinopril use and blood pressure reduction independently predicted the change in urinary albumin excretion. Baseline urinary albumin excretion independently predicted the antialbuminuric effect of fosinopril (beta(standardized)=-0.303; P<0.001). In conclusion, at baseline, sodium intake and blood pressure were positively associated with urinary albumin excretion. Fosinopril reduced albuminuria more than might be expected from its blood pressure-lowering effect alone, and this effect was more outspoken in subjects with higher baseline albumin excretion. Based on our data, we hypothesize that angiotensin-converting enzyme inhibition may result in superior cardiovascular protection when compared with other blood pressure-lowering agents in subjects with higher baseline levels of albuminuria.
Hypertension 2006 Nov
PMID:Predictors of angiotensin-converting enzyme inhibitor-induced reduction of urinary albumin excretion in nondiabetic patients. 1701 69

The tolerability and antihypertensive efficacy of Fosinopril were assessed in 34 elderly patients with mild to moderate hypertension. Twenty-four-hour ambulatory blood pressure (BP) was measured before and after 5 months of therapy. The patients' mean age was 67 years. At the end of the treatment the mean 24-hour systolic BP (SBP) fell from 153.4 +/- 14 to 137.7 +/- 13 mmHg and the mean 24-hour diastolic BP from 91 +/- 11 to 84.2 +/- 9 mmHg (p < 0.01). The mean decrease in SBP was 15.9 mmHg during the day and 10.3 during the night, and in diastolic BP (DBP) 8.3 mmHg during the day and 10.3 mmHg during the night (p < 0.05 between day and night). There was no significant percentage difference between the SBP and DBP decreases. The mean morning maximum of SBP decreased from 171 +/- 18 to 158 +/- 19 mmHg and there was a reduction in pressure increase between the night and day. The number of SBP peaks over 180 mmHg and 160 mmHg numerically decreased to 20.1% and 37.6% versus baseline, those of DBP over 105 mmHg and 95 mmHg to 41.6% and 58.3% versus baseline, respectively. There were no variations in the blood chemistry parameters and the drug had no adverse side effects. The authors conclude that Fosinopril is useful and well tolerated in the treatment of moderate hypertension in the elderly.
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PMID:Tolerability and antihypertensive efficacy of Fosinopril on 24-hr ambulatory blood pressure in hypertensive elderly subjects. 1865 16

Renal dysfunction is an independent risk factor of chronic cardiac failure (CCF) and death due to this disease. CCF patients are elderly patients with diabetes mellitus, arterial hypertension and long-term chronic cardiac insufficiency. CCF patients do not often have left ventricular systolic dysfunction, renal affection is not associated with low ejection syndrome. Renal affection in CCF is primarily caused by activation of the system rennin-angiotensin, inflammation, disturbed bioavailability of nitric oxide, hyperactivation of the sympathetic nervous system. ACE inhibitors correct pathophysiological disorders of renal flow in CCF. Fosinopril shows the highest efficacy and safety in management of cardiorenal syndrome in CCF patients. Fosinopril can also prevent renal dysfunction in CCF patients.
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PMID:[Fosinopril in the treatment of cardiorenal syndrome in chronic cardiac failure]. 1953 94

Optimal blood pressure (BP) targets are still controversial in end-stage renal disease. Recent data have highlighted shortcomings of the usual BP hypothesis in other patient populations and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events. The Fosinopril in Dialysis Study failed to demonstrate the efficacy of 2-year angiotensin-converting enzyme inhibition with fosinopril versus placebo in 397 hemodialysis patients with left ventricular hypertrophy but provided an opportunity to assess the influence of BP variability on cardiovascular events. The primary end point was the occurrence of a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina, stroke, revascularization, hospitalization for heart failure, and resuscitated cardiac arrest. The variations in BP throughout the 17 visits were assessed by within-patient overall variability of systolic, diastolic, and pulse pressures between adjacent readings, by within-patient overall variability of systolic/diastolic/pulse pressures, and the residual of the linear fit. Compared with our previous predictive model of cardiovascular events occurrence based on stroke, peripheral arterial disease, coronary artery disease, diabetes mellitus, left ventricular mass, and age (which exhibited similar coefficients herein), the percentage of explained variance improved by 30.1% (R(2)=0.141-0.183) when adding the coefficient of variation of within-patient overall variability of systolic BP. Usual BP parameters were neither cardiovascular events predictors nor correlated to BP variability. Visit-to-visit BP variability was extremely high in hemodialysis patients compared with other populations and a major determinant of cardiovascular events. Such assessments should be prioritized for testing prevention strategies in end-stage renal disease.
Hypertension 2012 Aug
PMID:Visit-to-visit blood pressure variability is a strong predictor of cardiovascular events in hemodialysis: insights from FOSIDIAL. 2277 36


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