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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.
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PMID:The pharmacokinetics of perindopril in patients with liver cirrhosis. 157 57

The acceptability of perindopril in the long-term treatment of patients with mild to severe essential hypertension was assessed in a large European multicenter trial including 856 patients. Diastolic blood pressure (DBP) at inclusion was 95-125 mm Hg after 1 month of placebo. Normalization of blood pressure was defined as a DBP less than or equal to 90 mm Hg. Treatment was started with perindopril 4 mg once daily and increased when necessary to 8 mg daily. If DBP was not controlled, a second drug (hydrochlorothiazide) and finally a third drug were added. After 1 year of treatment in all 690 evaluable patients, supine systolic and diastolic blood pressure decreased by 29 mm Hg (from 172 +/- 1 to 143 +/- 1 mm Hg, p less than 0.001) and 19 mm Hg (from 105 +/- 1 to 86 +/- 1 mm Hg, p less than 0.001), respectively. Perindopril monotherapy normalized blood pressure in 55% of patients and total percentage of normalization was 78%. The overall incidence of withdrawals for side effects was 6.8%, the most common side effect being cough (2.2%). The most frequent complaints reported were cough (7.0%), headache (5.6%), asthenia (5.1%), mood and/or sleep disturbance (5.1%), and dizziness (3.2%). The small changes observed in hematologic and biochemical parameters were not clinically relevant.
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PMID:Long-term acceptability of perindopril: European multicenter trial on 856 patients. 158 Feb 87

Perindopril is a long acting angiotensin converting enzyme (ACE) inhibitor, which displays similar pharmacodynamic properties to other agents in this class. In common with enalapril, it is also a prodrug. After absorption, perindopril is hydrolysed to the active metabolite, perindoprilat, and with once daily administration adequate 24-hour inhibition of ACE is obtained. Perindopril 4 to 8mg once daily is usually effective for blood pressure control in patients with mild to moderate essential hypertension. Those patients who do not respond adequately to monotherapy with perindopril usually respond with the addition of a second agent, such as a thiazide diuretic. General practice trials indicate that perindopril is at least as effective and as well tolerated as usual therapeutic dosages of captopril, atenolol or hydrochlorothiazide plus amiloride in mild to moderate essential hypertension. Preliminary results indicate that perindopril may also be effective in patients with severe hypertension or congestive heart failure. Perindopril is generally well tolerated and has an adverse effect profile similar to that of other ACE inhibitors. It further clinical experience confirms initial findings, perindopril is likely to represent a useful alternative to other members of the ACE inhibitor class in all grades of hypertension and congestive heart failure.
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PMID:Perindopril. A review of its pharmacological properties and therapeutic use in cardiovascular disorders. 171 88

Perindopril is an orally active non-thiol angiotensin-converting enzyme (ACE) inhibitor that is hydrolysed by esterases to a biologically active diacid metabolite. Perindopril decreases plasma concentrations of angiotensin II, increases plasma renin activity and reduces systolic and diastolic blood pressure in patients with essential hypertension. Most data support the hypothesis that the beneficial haemodynamic effects of perindopril are caused by ACE inhibition and the consequent reduction in angiotensin II, which either directly or indirectly results in dilatation of peripheral vessels and reduced vascular resistance. The marked blood pressure reduction after perindopril administration in hypertensive patients has not been accompanied by significant changes in heart rate. Furthermore, the lack of reflex tachycardia does not appear to be related to a reduction in baroreceptor sensitivity.
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PMID:Vascular haemodynamic effects of perindopril in essential hypertension. 240 92

Perindopril is an orally active, non-thiol angiotensin-converting enzyme (ACE) inhibitor, which in doses of 4 to 8mg is effective in the control of essential hypertension. As monotherapy it is as effective as once-daily atenolol and possibly more effective than twice-daily captopril. A synergistic response has been noted when perindopril is combined with a thiazide diuretic. Maximal pharmacodynamic effects (ACE inhibition, increase in plasma renin activity and angiotensin I, reduction in aldosterone and angiotensin II and blood pressure) are seen 4 to 6 hours after dosing, with substantial effects still present at 24 hours. Perindopril is a prodrug which requires de-esterification to perindoprilat for useful ACE inhibition. Maximal plasma perindoprilat concentrations are reached 2 to 6 hours after oral administration of perindopril, and 70% of the active metabolite is cleared by the kidneys. The other major metabolite of perindopril is an inactive glucuronide. Ageing is associated with increased serum perindoprilat concentrations, which are probably caused by a combination of enhanced conversion to the active metabolite and diminished renal clearance. Compensated cirrhosis does not appear to have an independent effect. There is little published experience of the use of perindopril in patients with cardiac failure or other cardiac disease, but preliminary evidence would support the general value of this class of agent as adjunctive therapy.
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PMID:Perindopril. A review of its pharmacokinetics and clinical pharmacology. 240 93

Perindopril is a new inhibitor of converting enzyme activity with a prolonged half-life. Thirty-two patients with essential hypertension and a diastolic blood pressure greater than 95 mm Hg were stratified into two groups according to their 24 h urine sodium excretion. They were randomized in a double-blind fashion to placebo or perindopril and a dose titration made in steps of 2, 4, 6, and 8 mg given once daily at weekly intervals. The goal diastolic blood pressure was 90 mm Hg. Goal blood pressure was achieved in 11 of 16 patients on perindopril and 3 of 6 patients on placebo. Perindopril caused a fall in BP of 22/11 (supine) and 27/14 (erect) mm Hg while the placebo group had falls of 3/2 (supine) and 3/0 (erect) mm Hg. Most of the blood pressure fall occurred in the first week of therapy with 2 mg/day. Side effects were few and occurred mainly in the placebo phase. There was no alteration in urine protein, white cell count, plasma urea, or creatinine. The fall in blood pressure achieved at the end of the titration or with 2 mg did not differ between the two groups. There was no correlation between blood pressure response and 24 h urine sodium or plasma renin activity. These results indicate that perindopril is an effective antihypertensive drug that appears to work equally well in patients on high or low sodium intake.
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PMID:The effect of perindopril on blood pressure in humans on different sodium intakes. 248 43

Perindopril is a new angiotensin converting enzyme (ACE) inhibitor which is activated after hydrolysis in vivo to a diacid (S9780). Oral administration of perindopril (1-16 mg) to groups of 6 healthy males led to a long lasting and dose-elated inhibition of plasma ACE and rises in plasma renin activity with no evidence of accumulation of drug or effect. At higher doses there was a modest fall in blood pressure. S9780 given intravenously in doses of 1,2 or 4 mg caused an immediate inhibition of plasma ACE. The concentration of S9780 in plasma which led to 50% inhibition of plasma ACE was 1.55 +/- 1.14 ng/ml (mean +/- S.D.). Clinical trials with 2-8 mg once daily in essential hypertension are currently in progress.
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PMID:Perindopril, a new angiotensin converting enzyme inhibitor--clinical pharmacological studies in healthy subjects. 303 95

Blood pressure, forearm arterial haemodynamics and echocardiographic parameters were studied in patients with sustained essential hypertension before and after administration of the angiotensin converting enzyme (ACE) inhibitor perindopril for 1 year. Perindopril significantly reduced blood pressure and at the same time increased brachial artery blood flow, diameter and compliance. As part of the haemodynamic investigation, a 5-min period of wrist occlusion was performed. Blood flow velocity decreased significantly to the same extent with perindopril and with placebo, but the corresponding reductions in arterial diameter were smaller with perindopril than with placebo, indicating that the increase in diameter following perindopril could not be explained solely on the basis of a flow-dependent dilation. After 3 months, treatment was stopped for 4 weeks. Blood pressure and forearm arterial haemodynamics returned towards baseline values. However, cardiac mass, which was significantly decreased after perindopril administration, remained decreased 4 weeks after cessation of treatment. In seven responder patients, perindopril was continued as sole therapy for 8 months. Arterial compliance remained elevated and cardiac mass diminished. The study showed that the arterial changes caused by perindopril involved a drug-related relaxation of arterial smooth muscle and that there was a differential response in cardiac and arterial changes following long-term treatment.
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PMID:Treatment for one year with perindopril: effect on cardiac mass and arterial compliance in essential hypertension. 322 88

Brachial artery mean arterial pressure (MAP), blood flow velocity (BFV), blood flow (BF), and arterial compliance (AC) were measured using pulsed Doppler systems in patients with sustained essential hypertension. The hemodynamic investigation was performed before (T0) and after 3 months (T1) of chronic treatment with the converting enzyme inhibitor Perindopril and after a further month with placebo (T2). Following treatment with Perindopril, BFV, BF, and AC significantly increased while MAP significantly decreased. The changes in AC and BFV were negatively and significantly correlated both between T0 and T1 and between T1 and T2. The study showed that the increase in arterial compliance produced by Perindopril was inversely related to the extent of arteriolar dilatation, indicating that factors other than the blood pressure reduction itself were involved in the brachial artery changes.
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PMID:Enhanced brachial artery compliance following perindopril in essential hypertension. 341 79

The effect of perindopril, an angiotensin-converting enzyme inhibitor, on glucose and lipid metabolism was evaluated in 12 patients with mild-to-moderate essential hypertension and glucose intolerance. Perindopril was administered at a dosage of 2 to 8 mg once daily for 12 weeks. Both the systolic and diastolic blood pressures were significantly reduced throughout the treatment period. There were no significant changes in the insulinogenic index (delta plasma immunoreactive insulin/delta plasma glucose) calculated from the results of 75-g oral glucose tolerance tests performed before and after perindopril treatment. Serum levels of glycosylated hemoglobin, fructosamine, lipids, lipoproteins, and apolipoproteins were also not affected. These results suggest that perindopril can be used effectively to treat hypertension in patients with glucose intolerance without affecting glucose and lipid metabolism.
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PMID:Effects of perindopril on glucose and lipid metabolism in patients with mild-to-moderate essential hypertension and glucose intolerance. 792 13


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