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

Although there is impressive documentation linking severe hypertension to renal insufficiency, corresponding data for mild-to-moderate hypertension are only now starting to emerge. As a result, it is only now becoming evident that a much larger portion of the hypertensive population could be susceptible to drug accumulation owing to renal insufficiency. Angiotensin-converting enzyme (ACE) inhibitor therapy routinely requires dosage adjustment in the instance of renal insufficiency, as all currently marketed ACE inhibitors are renally eliminated. Such dosage adjustments are usually considered a way to minimize side effects and to limit the duration of any induced hypotension. Dosage adjustment is usually considered at creatinine clearance levels between 30 and 60 ml/min. This is somewhat problematic, as physicians generally rely on serum creatinine determinations to assess renal function, and serum creatinine values are notoriously poor predictors of actual creatinine clearance. This is particularly true in the elderly population, where a greater disparity between the serum creatinine and creatinine clearance commonly exists, with moderate renal insufficiency frequently going unrecognized. Thus, the development of other ACE inhibitors eliminated via renal/hepatic routes may prove to be advantageous in that dosage adjustments might not be required in the setting of declining renal function, whether age-related or not. Fosinopril, a new phosphorus-containing ACE inhibitor, is administered as a prodrug and is hydrolyzed to the pharmacologically active diacid, fosinoprilat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of angiotensin-converting enzyme inhibitors in renal failure. 128 26

Fosinopril, the first agent in a new chemical class of phosphorus-containing angiotensin-converting enzyme (ACE) inhibitors, has unique pharmacologic properties. Fosinopril administration leads to complete inhibition of plasma ACE activity for 12-24 h. In patients with normal renal function, approximately equal amounts of the drug are eliminated via the hepatic and renal routes. With worsening renal function, increasing amounts of fosinopril are eliminated hepatically. This dual elimination allows for the administration of fosinopril using the same starting dosage to any patient, regardless of renal function. Fosinopril may provide end-organ protection against the effects of hypertension and antihypertensive therapy; this drug potentially protects the kidney by increasing renal functional reserve, while maintaining cardiac left ventricular performance. Moreover, despite marked blood reductions, cerebral blood flow is maintained. Controlled trials show that fosinopril in single daily doses of 10-40 mg is efficacious and safe for the long-term treatment of hypertension. At these doses, favorable responses were seen in up to 80% of patients. Fosinopril is equally effective in elderly as well as younger patients and works in black as well as in nonblack patients. The incidence of adverse events does not differ significantly between fosinopril- and placebo-treated patients. Fosinopril represents a clinically useful agent for the treatment of hypertension.
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PMID:Fosinopril: a new generation of angiotensin-converting enzyme inhibitors. 128 29

This multicenter, dose-ranging study evaluated the antihypertensive effectiveness of once-daily administration of fosinopril sodium in 220 patients with supine diastolic blood pressure of 95-115 mm Hg. After a 4-week placebo period, patients were randomly assigned to double-blind therapy with either placebo or 10, 40, or 80 mg fosinopril once daily for 4 weeks. If treatment goals were not met, chlorthalidone 25 mg/day was added for weeks 5 to 8. Thereafter, patients could enter the long-term, open-label phase and receive 10-80 mg/day fosinopril plus chlorthalidone, if needed. After 4 weeks of monotherapy, the average decreases in supine diastolic blood pressure were 9% (10 mg), 11.5% (40 mg), and 12.5% (80 mg) compared with 6% in the placebo group. After 8 weeks, the average decreases, with or without diuretic therapy, were 12.5-18.2%, compared with 10.8% with placebo. Blood pressure continued to be well controlled, and the patients showed no evidence of tachyphylaxis or tolerance through 12-15 months of treatment. Fosinopril was well tolerated. During the short-term phase, no patient withdrew because of adverse events possibly related to fosinopril; during the long-term phase, nine of 148 patients (6.1%) withdrew for that reason. In patients with mild-to-moderate hypertension, once-daily fosinopril (40 and 80 mg) provided significant antihypertensive effects with or without diuretic therapy. The 10 mg dose was effective in some patients and may be considered a starting dose.
Hypertension 1991 May
PMID:Once-daily fosinopril in the treatment of hypertension. 182 86

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

It has been suggested that angiotensin-converting enzyme inhibitors may induce a significant regression of cardiovascular hypertrophy not only through blood pressure reduction but also as a possible consequence of growth factor inhibition. The aim of this study was to evaluate the effects of the angiotensin-converting enzyme inhibitor fosinopril, given either at a hypotensive high dose or a nonhypotensive low dose, on structural and functional alterations of mesenteric resistance arteries and on cardiac mass in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats. Fosinopril was administered in the drinking water from 6 to 12 weeks of age. Rats were killed at 12 weeks, and the ratio of heart weight to body weight was measured. Mesenteric arterioles were dissected and mounted on a micromyograph (Mulvany's technique). Vascular morphology (media-lumen ratio, media thickness) and endothelial function (response to acetylcholine) were then assessed. During the 6 weeks of treatment, systolic pressure in SHR treated with high-dose fosinopril was significantly lower compared with that in untreated SHR, whereas no difference was observed with low-dose fosinopril. In SHR treated with both high-dose and low-dose fosinopril, a statistically significant reduction of vascular structural alterations, in terms of both media-lumen ratio and media thickness, was observed. The ratio of heart weight to body weight was reduced only in SHR treated with high-dose fosinopril. An improvement in the endothelium-dependent relaxation to acetylcholine was observed in SHR treated with high-dose fosinopril compared with untreated SHR, whereas in SHR treated with low-dose fosinopril no improvement in endothelial function was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jul
PMID:Effects of low and high doses of fosinopril on the structure and function of resistance arteries. 760 14

Fosinopril is distinguished from other ACE inhibitors by a pharmacokinetic pecularity in the sense that is can be metabolized either by liver or kidney. This was the rationale of the present research the aim of which was to verify if administered to patients with liver cirrhosis the drug was liable to alter global liver function and ability to metabolize drugs. Eight cirrhotic males, mean age 56 years, also suffering from high blood pressure, were studied. In these patients, liver and kidney function tests (BUN, creatinine blood level, serum and urinary electrolytes, creatinine clearance, calcium and phosphor blood level, transaminases, alkaline phosphatase prothrombin time, cholinesterase, gamma-glutamyl-transpeptidase) were carried out at baseline and after 30 days' fosinopril treatment (1 capsule every morning in the fasting state); in addition total functioning liver mass was assessed by the galactose test, and drug-metabolizing capacity by the antipyrine test. Treatment resulted in a significant improvement of pressure values in all patients (p < 0.01) and did not alter liver and kidney function parameters. Besides, no side effects were registered, especially no case of orthostatic hypotension. The antipyrine test was not influenced by fosinopril treatment. Therefore, short-term treatment with this ACE-inhibitor can be concluded to be effective and not to cause additional alterations of liver function in patients with liver cirrhosis.
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PMID:[Evaluation of the total hepatic function after treatment with fosinopril in hypertensive patients with liver cirrhosis]. 772 Mar 55

This study evaluated the effects of medium-term once daily administration of fosinopril (20 mg) on BP profile and on BP response to exercise in patients with mild to moderate hypertension. Twenty patients (14 males and 6 females; 25-57 years of age), after a six week drug wash-out phase, underwent 24h ambulatory BP monitoring (ABPM) (Spacelabs 90207) and, the day after, maximal bicycle exercise testing. Patients then received a once daily treatment with fosinopril and ABPM and exercise testing were repeated 45-60 days later. Fosinopril decreased average 24h SBP and DBP (-13.5 mmHg and -9.7 mmHg, respectively, P < 0.002); a significant BP reduction was observed both in day and in nighttime, without alteration in diurnal BP profile. The antihypertensive effect was still evident 24h after dosing. Trough to peak ratio was 0.58 +/- 0.16. Fosinopril induced a reduction of SBP and DBP during exercise testing (-20 and -11 mmHg at baseline; -17 and -8 mmHg at peak exercise; -24 and -14 mmHg at the sixth minute of recovery; P < 0.002), with a slight prolongation of exercise time (+46 seconds, P = 0.041). These results indicate that fosinopril at a once daily dose of 20 mg provides a sustained 24h BP reduction associated with BP reduction during physical exercise. These effects have been obtained without altering diurnal BP profile, without excessive hypotension at the time of maximal antihypertensive effect and with a slight improvement of exercise tolerance.
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PMID:Fosinopril in the treatment of hypertension: effects on 24h ambulatory blood pressure and on blood pressure response to exercise. 808 33

Angiotensin converting enzyme inhibitors are effective in the treatment of hypertension and congestive heart failure. Within the past two years, four new agents in this class-benazepril, fosinopril, quinapril and ramipril--have been approved in the United States for use in the treatment of hypertension. These agents have been shown to be as effective as the older angiotensin converting enzyme inhibitors in treating hypertension and, in limited trials, congestive heart failure. The side effect profiles of the new agents are similar to those of other agents in this class that do not contain a sulfhydryl group. Fosinopril has a unique route of elimination that may make it the preferred agent in patients with renal failure. Otherwise, the new angiotensin converting enzyme inhibitors have no proven clinical advantages over other available agents. However, at moderate to high doses, the new agents may be substantially less expensive.
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PMID:ACE inhibitors: review of four new agents. 821 15

Angiotensin-converting enzyme (ACE) inhibitors are an effective, well-tolerated option for management of mild-to-moderate hypertension. An increase of nearly 250% in prescriptions between 1986 and 1990 testifies to the growing importance of this drug class. With the development of newer ACE inhibitors, the debate on pharmacokinetic and pharmacodynamic differences and the clinical relevance of such differences has also been growing in importance. It is in this context that the clinical data on fosinopril will be reviewed. Fosinopril has several intriguing features, among them a unique chemical structure and elimination profile. In addition, preliminary data on cardiac effects and on risk for cough are provocative and support further study. The antihypertensive efficacy of fosinopril is comparable to other ACE inhibitors. Thus, fosinopril represents an interesting and useful addition to this antihypertensive class.
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PMID:Fosinopril: an overview. 828 78

Overall, angiotensin-converting enzyme (ACE) inhibitors have a very low side-effect profile. However, several reports in the literature cite cough as a possible complication of ACE inhibitor therapy. These reports have prompted speculation that the risk of cough may differ among ACE inhibitors and that the risk may be greater in patients with renal impairment, perhaps because of excessive drug accumulation. However, these hypotheses have not been tested in prospective, controlled studies. Fosinopril is a long-acting ACE inhibitor with a unique chemical structure and an elimination profile that is associated with stable clearance, regardless of the degree of renal impairment. Favorable clinical experience with fosinopril led to the evaluation of this agent's cough profile in a prospective, open-label study. This study focused on the frequency of cough in patients with mild-to-moderate hypertension who had previously experienced cough while taking another ACE inhibitor. Whereas most prior controlled studies and postmarketing surveillance trials measured the frequency of cough through spontaneous adverse-event reporting, in this study a methodology previously validated in antitussive and mucolytic studies was adapted to provide accurate and sensitive measure of fosinopril's cough profile. Twenty-four patients were switched from another ACE inhibitor to fosinopril, 10 mg once daily for 6 weeks. At study end, the mean occurrence of cough, frequency of cough, and cough severity significantly changed from baseline (p < or = 0.0002). Thus, fosinopril use was associated with a less frequent, less severe cough in patients who experienced cough while taking other ACE inhibitors.
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PMID:Safety update: focus on cough. 828 82


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