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 orally active angiotensin-converting inhibitors (ACE inhibitors) such as captopril and enalapril represent a significant therapeutic advance in the treatment of hypertension and congestive heart failure. Enalapril differs from captopril in several respects. It is a prodrug converted by hepatic esterolysis to the active (but more poorly absorbed) diacid, enalaprilat. Enalaprilat is more potent than captopril, more slowly eliminated and does not possess a sulfhydryl (SH) group. Enalapril was rapidly followed by a number of newer ACE inhibitors, the majority of which are similar to enalapril in that they are prodrugs, converted by hepatic esterolysis to a major active but poorly absorbed diacid metabolite. In one case (delapril) there are 2 active metabolites; in another (alacepril) the prodrug is converted in vivo to captopril. Lisinopril is an exception in that it is an enalaprilat-like diacid but with acceptable oral bioavailability, so that the prodrug route is not employed. The newer ACE inhibitors are at widely different stages of development, and it is not yet clear how many will reach regular clinical use. Of these newer drugs, lisinopril is the longest established and is the subject of the widest published literature. For a number there is as yet little published pharmacokinetic information. A variety of assay methods have been employed to characterise the pharmacokinetics of the ACE inhibitors, including enzymatic techniques, radioimmunoassay and chromatography. The peak plasma concentrations of the prodrugs are generally observed at around 1 hour and those of the diacid metabolites at about 2 to 4 hours. However, there is considerable variation within and between drugs, with benazepril and benazeprilat reaching peak concentrations early and enalapril and enalaprilat typical of later times to peak. Absorption of the active diacids is generally poor, and moderate (typically 30 to 70%) for the prodrugs. The bioavailability of lisinopril is about 25%. It is difficult to talk meaningfully about half-lives of the active drugs. The declines in their plasma concentrations are polyphasic and, if analytical sensitivity allows, active drug may be found at 48 hours or more following administration. This may reflect binding to ACE in plasma. Half-lives of accumulation are of the order of 12 hours; protein binding varies from little (lisinopril) to 90% (benazeprilat). Elimination is mostly renal but there may be biliary elimination for some, such as benazeprilat and fosinopril. The half-lives of the prodrugs are short. Impaired renal function decreases the elimination rate of the diacids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of the newer ACE inhibitors. A review. 220 79

The antihypertensive efficacy and safety of lisinopril, a long-acting angiotensin-converting enzyme inhibitor, were assessed in 23 patients with hypertension associated with impaired renal function (glomerular filtration rate 60 ml/min or less) in an open study of 12 weeks' duration. Lisinopril was given orally in single daily doses. The starting dose was 2.5 mg in patients with glomerular filtration rate (GFR) of less than 30 ml/min and 5 mg in all other patients. This was titrated to a maximum of 40 mg daily according to blood pressure response. A diuretic was then added if blood pressure was not controlled. Mean sitting and standing blood pressures were significantly reduced by lisinopril treatment. The median dose of lisinopril taken was 10 mg daily (range 2.5-40 mg), and only three patients required the addition of a diuretic. The mean glomerular filtration rate was unchanged during the study (38 +/- 16.4 ml/min at baseline, 41 +/- 21.0 ml/min after 12 weeks of treatment). Twenty-two patients completed the study. One patient was withdrawn because of nausea and vomiting due to reflux oesophagitis which was probably not drug related. Another patient had transient mild angioneurotic oedema and continued on lisinopril. No clinically significant haematological or biochemical changes were observed. In conclusion, lisinopril provided effective blood pressure control and was well tolerated in this group of hypertensives who are typically difficult to treat.
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PMID:Lisinopril in hypertension associated with renal impairment. 244 56

Lisinopril, a long-acting angiotensin converting enzyme inhibitor, and the calcium channel blocker nifedipine in its retard formulation, were compared as monotherapy in a group of 45 patients with essential hypertension. Lisinopril in single daily doses (range 20-80 mg, median dose 40 mg) and nifedipine retard in twice daily doses (total daily dose range 40-80 mg, median dose 60 mg) were equally effective in controlling hypertension. The lisinopril group (n = 30), at baseline supine blood pressure 178/109 +/- 23/9 mm Hg (mean +/- 1 SD), after 12 weeks' therapy measured 148/88 +/- 27/14 mm Hg; the nifedipine group (n = 15), at baseline 185/110 +/- 23/11 mm Hg, after 12 weeks' therapy measured 151/89 +/- 14/10 mm Hg. The number of patients who experienced clinical adverse effects was significantly greater in the nifedipine group: 8 of 15 (53%) compared to 4 of 30 (13%) in the lisinopril group. The commonest adverse effects of patients on nifedipine were swollen ankles, flushing, and headache. Two patients on nifedipine were withdrawn from the study because of their adverse experiences. Of the patients on lisinopril there were single reports of flushing, ankle swelling, tiredness, and chest pain. No patient withdrew from lisinopril because of an adverse experience. No adverse laboratory experiences were recorded in either group. In conclusion, lisinopril and nifedipine retard were equally effective in controlling essential hypertension. Lisinopril was, however, better tolerated during this study.
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PMID:Comparative efficacy of lisinopril and nifedipine retard in essential hypertension: a double-blind, placebo-controlled trial. 245 54

Lisinopril (L), a novel angiotensin converting enzyme inhibitor, was studied as sole drug in the management of hypertensive, dialysis-treated, end-stage renal failure patients to assess its efficiency, tolerance, and removal by dialysis. High blood pressure (BP) was defined as sitting diastolic (D) BP greater than or equal to 95 mm Hg. Ten patients, two females and eight males, were treated for 12 weeks. Their features were age 49 +/- 14 years; dialysis duration 43 +/- 25 months; body weight 61 +/- 10 kg; and body mass index 21.7 +/- 3 (mean +/- SD). Serum L concentrations were measured regularly by radioimmunoassay, both before and after dialysis, which was performed with Cuprophane membranes three times per week. L, 2.5 mg orally, was given every 24 h initially; in six patients, dosage was decreased to an alternate or once-a-week schedule, because of a hypotensive effect during dialysis. At 12 weeks, BP--as compared to prestudy BP--was decreased in eight of nine patients (one patient had been withdrawn after kidney transplantation), and not changed in one patient (mean +/- SD): sitting DBP from 107 +/- 7 to 87 +/- 10 mm Hg, p less than 0.001; erect DBP from 105 +/- 5 to 86 +/- 10 mm Hg, p less than 0.001. L serum concentration was decreased by dialysis, the mean ratio of post-/predialysis serum L concentrations was 0.47 +/- 0.07 (n = 67). No side effects were disclosed, except for three patients, in whom hemoglobin decreased, while two of them also received quinine for a febrile illness of viral origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of hypertension with lisinopril in end-stage renal failure. 248 55

One-hundred patients suffering from slight-moderate hypertension (53 m, 47 f, aged between 18 and 78, average 49.08) have been studied in order to assess the effectiveness and tolerance of lisinopril ("Zestril", ICI-Pharma), a new ACE inhibitor in a single daily administration at doses of between 10 and 80 mg in relation to pressure values. Monotherapy with Lisinopril proved effective in 84 patients (88.4%), in 74 of whom (7.9%) pressure values were returned to normal. 11 patients (11.6%) did not respond to treatment. In most cases, the result was obtained with a dose of 20 mg in a single administration (32.6%). The incidence of side-effects was limited and in no case required the withdrawal of the drug.
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PMID:[Multicenter clinical study of the antihypertensive activity of lisinopril]. 253 7

1. The population pharmacokinetics of lisinopril were investigated using data collected from two multicentre trials of lisinopril in the treatment of hypertension in elderly patients (n = 40) and patients with renal disease (n = 20). 2. Lisinopril was started at doses of 2.5-5 mg daily and increased at 2-4 weekly intervals as required for control of blood pressure. Steady-state concentration-time profiles were measured after at least 2 weeks at a constant dose. 3. All concentration-time data were analysed simultaneously using the program NONMEM and the influence of clinical factors on clearance/F and volume of distribution/F was tested. 4. Clearance was significantly influenced by creatinine concentration, age, weight and cardiac failure. No clinical features tested were found to influence volume of distribution. 5. The influence of renal function and cardiac failure on lisinopril clearance has been confirmed using a population pharmacokinetic analysis technique.
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PMID:Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension. 253 50

Lisinopril is a synthetic, nonsulfhydryl, angiotensin-converting enzyme inhibitor. Its bioavailability is approximately 25% and is not affected by food. Hepatic metabolism is not required for pharmacologic effect, which occurs 1 hour after administration. Peak serum concentration and effect are delayed, occurring 6-8 hours after a single dose and lasting for at least 24 hours. The drug is eliminated primarily by the kidneys. The elimination half-life is 12.6 hours and is prolonged in renal impairment. Lisinopril 10-80 mg once a day is effective in lowering blood pressure in all grades of essential and renovascular hypertension. It is as effective as hydrochlorothiazide, atenolol, metoprolol, and nifedipine. Combining lisinopril with hydrochlorothiazide produces a greater degree of blood pressure reduction. Patients with congestive heart failure have demonstrated immediate and prolonged beneficial hemodynamic effects and increased exercise tolerance. Lisinopril is well tolerated. Clinically significant drug interactions have not been reported, but caution should be used when lisinopril is administered with diuretics, nifedipine, or agents that may increase concentrations of potassium. The usual initial oral dosage of lisinopril is 10 mg once a day (range 20-40 mg/day). Lower dosages may be necessary in patients with renal impairment or congestive heart failure, elderly persons, and those receiving diuretics.
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PMID:Lisinopril: a new angiotensin-converting enzyme inhibitor. 254 99

We studied the effects of lisinopril on mean arterial blood pressure (MAP), plasma renin activity (PRA), and renal hemodynamics in nine patients with chronic renal disease and hypertension, before, and after three months of therapy. Lisinopril normalized blood pressure in five of nine patients (responders) and did not in the remaining four (nonresponders). PRA rose after lisinopril (4.8 +/- 2.6 ng/mL/h to 25 +/- 15 ng/mL/h, P less than 0.05) in responders, but not in nonresponders (2.0 +/- 1.4 ng/mL/h to 3.4 +/- 2.9 ng/mL/h). Glomerular filtration rate remained stable in both groups (responders: 43 +/- 11 mL/min to 43 +/- 22 mL/min; nonresponders: 39 +/- 25 mL/min to 32 +/- 21 mL/min). In the responders renal hemodynamics remained stable after lisinopril (renal plasma flow: 223 +/- 80 mL/min to 216 +/- 91 mL/min; filtration fraction: .20 +/- .04 to .20 +/- .05; renal vascular resistance: 386 +/- 179 to 326 +/- 209 units). In the nonresponders, renal plasma flow decreased (228 +/- 141 mL/min to 162 +/- 117 mL/min, P less than 0.005), filtration fraction increased (.19 +/- .08 to .24 +/- .12, P less than 0.05), and renal vascular resistance increased (695 +/- 747 to 1265 +/- 1574 units, P less than 0.05) after chronic lisinopril therapy. We conclude (1) there is a heterogeneous response to lisinopril in patients with chronic renal disease and hypertension, (2) lisinopril monotherapy may result in effective blood pressure control without renal hemodynamic compromise, and (3) an increase in PRA following converting enzyme inhibition may identify those in whom the circulating renin angiotensin system is participating in systemic hypertension and intrarenal hemodynamic changes.
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PMID:Hemodynamic responses to converting enzyme inhibition in patients with renal disease. 255 29

Established essential hypertension is characterised haemodynamically by a normal cardiac output and elevated total peripheral resistance. As hypertensive cardiovascular disease progresses, and the patient grows older, cardiac output falls and total peripheral resistance is further elevated. The activity of the renin-angiotensin-aldosterone (RAA) system declines throughout life and reaches its lowest levels in the elderly, unless there is congestive heart failure. In long-standing hypertension, target organ disease such as left ventricular hypertrophy, nephrosclerosis and cerebrovascular damage is commonly observed. Rational antihypertensive therapy should therefore aim to lower total peripheral resistance, spare cardiac output, and maintain or improve blood flow to target organs. ACE inhibitors lower arterial pressure by decreasing total peripheral resistance, they maintain or improve cardiac contractility, promote regression of left ventricular hypertrophy, and increase renal blood flow. Lisinopril is a novel ACE inhibitor that does not contain a sulphydryl group. It is not a prodrug and thus does not require bioactivation by the liver. Lisinopril has a long duration of action, allowing it to be used as a single daily dose in the treatment of hypertension. Preliminary studies from our laboratory indicate that lisinopril reduces cardiac output and preload to the left ventricle. Lisinopril also reduces left ventricular hypertrophy and lowers renal vascular resistance, thereby increasing renal blood flow. In patients with mild to moderate hypertension, lisinopril is more effective than hydrochlorothiazide in reducing both systolic and diastolic blood pressure, and is at least as effective as atenolol or metoprolol in reducing diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lisinopril in the treatment of hypertension. 255 Jun 40

The antihypertensive effects of lisinopril 20 mg once daily and slow-release nifedipine 20 mg twice daily were compared in a double-blind, parallel group, 10-week study involving 274 patients with mild to moderate hypertension. During the first 6 weeks of treatment, slow-release nifedipine and lisinopril produced similar reductions in lying and standing blood pressure (BP), except for lying systolic BP (SBP) which was reduced to a greater extent by lisinopril. After 6 weeks of double-blind treatment, hydrochlorothiazide 25 mg once daily was added if BP remained uncontrolled (lying DBP greater than or equal to 95 mmHg); a significantly greater proportion of patients in the nifedipine group than in the lisinopril group required additional diuretic treatment (29% versus 14%, respectively; P = 0.005). Moreover, after a further 4 weeks of treatment BP was adequately controlled (lying DBP less than 95 mmHg) in significantly more lisinopril-treated patients than in the nifedipine group (91.4% versus 78.3%, respectively; P = 0.006). Lisinopril was better tolerated than slow-release nifedipine. The frequency of drug-related events was significantly lower (threefold) for lisinopril than for nifedipine (P = 0.001) and the number of withdrawals from treatment with nifedipine was more than three times that in the lisinopril treatment group (P = 0.009). Lisinopril appears to provide an effective once-daily antihypertensive treatment which is at least as effective as, and better tolerated than, slow-release nifedipine.
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PMID:Lisinopril versus slow-release nifedipine in the treatment of mild to moderate hypertension: a multicentre study. The Cooperative Study Group. 255 Jun 43


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