Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coadministration of captopril has been shown to increase serum digoxin concentration. The effects of ramipril, a new angiotensin converting enzyme inhibitor, on serum digoxin concentration after multiple dosing were studied in 12 healthy volunteers. All subjects were receiving steady-state digoxin medication (0.5 mg daily), and ramipril (5 mg daily) was coadministered for 14 days. Serum digoxin concentration was measured repeatedly before, during and up to 1 week after ramipril coadministration at 8 a.m. (trough values) and on selected trial days at 11 a.m., 3 hours after the morning medication. Simultaneously, blood levels of ramipril and its active metabolite diacid were determined. Volunteers were followed closely for side effects and for changes in blood pressure, heart rate and electrocardiogram. Safety pharmacology included serial determination of sodium, potassium, serum glutamic oxaloacetic transaminase, creatinine and a full blood count. Mean serum digoxin concentration was not significantly influenced by ramipril coadministration with trough levels of 0.90 +/- 0.24 before, 0.93 +/- 0.38 during and 0.82 +/- 0.33 ng/ml after ramipril medication. The increase in serum digoxin concentration 3 hours after the morning dose was also not significantly affected by ramipril. Serum levels of ramipril and its diacid showed a wide range of variation. Mean serum potassium increased by 0.3 mmol/liter during ramipril coadministration with development of symptomless hyperkalemia (6.0 mmol/liter) in 1 subject. The only other side effect possibly related to ramipril was a dry cough in 1 subject. Both drugs were well tolerated. Ramipril showed no significant influence on serum digoxin levels in healthy volunteers.
Am J Cardiol 1987 Apr 24
PMID:Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers. 303 35

The pharmacokinetics and pharmacodynamics of the novel angiotensin converting enzyme (ACE) inhibitor ramipril were studied in 6 patients with a glomerular filtration rate of less than 20 ml/min/1.73 m2 of body surface area. A single oral dose of 5 mg was given and serum concentrations of the compound and its diacid, the active metabolite (ramiprilat), as well as ACE activity, blood pressure and pulse rate were monitored for 28 days. The original compound reached peak serum concentrations of 42.8 +/- 26.5 ng/ml about 1 hour after dosing and was completely eliminated from the serum after 24 hours. Ramiprilat reached peak values of 14.4 +/- 11.6 ng/ml after about 6 hours. In contrast with the parent compound, low concentrations of ramiprilat were still detected in the serum after 28 days. ACE activity decreased to approximately 5% of baseline values, remained low for the next 48 hours, then increased slowly thereafter but reached only 84.5% of initial values after 28 days. Blood pressure decreased significantly and remained low for 24 hours after dosing. The drug was well tolerated in all patients. It is concluded that a single 5 mg dose of ramipril was effective in inhibiting plasma ACE activity and lowering blood pressure in patients with renal failure. There was a slower decline in ramiprilat concentrations compared with subjects with normal renal function.
Am J Cardiol 1987 Apr 24
PMID:Pharmacokinetics and pharmacodynamics of ramipril in renal failure. 303 36

The pharmacokinetics of ramipril (HOE 498) were studied after oral administration of a single 10 mg dose to 24 hypertensive patients with different degrees of renal function. The creatinine clearance ranged between 4.1 and 126 ml/min/1.73 m2 and was below 35 ml/min/1.73 m2 in 16 patients. Angiotensin converting enzyme activity and the concentrations of ramipril and its active diacid metabolite ramiprilat were measured in plasma up to 10 days after drug intake. Urine levels of ramipril, ramiprilat, their glucuronides and 2 major metabolites (a diketopiperazine and a diketopiperazine acid) were measured up to 4 days after medication. The plasma concentration-time curve of ramiprilat was polyphasic with an initial steep decline after the peak level and a subsequent very long terminal phase at low concentrations. Impaired renal function resulted in higher peak levels of ramiprilat, longer times to peak and a markedly slower decline of plasma ramiprilat levels. Hence, the duration of angiotensin converting enzyme inhibition was considerably prolonged in renal failure and depended on the severity of renal impairment. The urinary excretion of ramipril and its metabolites decreased with decreasing renal function and was linearly related to the creatinine clearance, suggesting an alternative pathway of elimination. The pattern of excretion rates of ramipril and its various metabolites was not affected by renal failure. In contrast to the marked changes in the renal elimination, no relevant differences were observed in the absorption of ramipril from the gastrointestinal tract. Systolic and diastolic blood pressure decreased in all groups. The single 10 mg dose of ramipril was well tolerated.
Am J Cardiol 1987 Apr 24
PMID:Influence of renal function on the pharmacokinetics of ramipril (HOE 498). 303 37

The kinetics of blood pressure changes and plasma angiotensin converting enzyme (ACE) inhibition in response to ramipril (HOE 498), 10 mg orally, were studied in 6 nephrectomized subjects 12 hours after ultrafiltration and in 10 patients with essential hypertension. Ramipril lowered supine and standing blood pressure in both groups, but the effect was greater in essential hypertension. The maximal blood pressure response followed the effect on plasma ACE after a lag time of 3 to 4 hours in both groups. These data provide indirect evidence that ramipril lowers blood pressure, at least in part, independently of its effect on the circulating renin-angiotensin system, possibly by acting on tissue ACE.
Am J Cardiol 1987 Apr 24
PMID:Blood pressure response of nephrectomized subjects and patients with essential hypertension to ramipril: indirect evidence that inhibition of tissue angiotensin converting enzyme is important. 303 41

Thirty-two patients with arterial hypertension (diastolic blood pressure greater than 95 mm Hg) were treated with ramipril for 3 months. The aim of the study was to achieve an effective decrease in blood pressure and demonstrate reliably and reproducibly that regression of left ventricular hypertrophy takes place with ramipril treatment. Nuclear magnetic resonance images and echocardiographic measurements of the left ventricle were therefore made before treatment started, 4 hours after the first dose, 14 days after the start of treatment and after 3 months of treatment. The thickness of the septum decreased from 19.57 to 15.20 mm on magnetic resonance scans and from 18.78 to 14.57 mm on echocardiograms. The values were reproduced 3 times at the same measuring point and means were calculated. The septum and posterior wall of the left ventricle were also measured at 3 different points. With negligible scatter, the values obtained were reproducible and the differences were highly significant (p = 0.001). A parallel decrease in blood pressure to levels 15% below baseline was also observed. The therapeutic aim of achieving diastolic blood pressure levels of less than or equal to 90 mm Hg was achieved in all patients. In addition to reducing the blood pressure significantly, the angiotensin converting enzyme inhibitor ramipril caused a significant regression of pathologic left ventricular hypertrophy, which was demonstrated clearly using magnetic resonance imaging and echocardiography.
Am J Cardiol 1987 Apr 24
PMID:Use of nuclear magnetic resonance imaging to show regression of hypertrophy with ramipril treatment. 303 42

Ten patients with congestive heart failure (CHF) (NYHA II-IV) on adjusted doses of digitalis and diuretics underwent a careful clinical assessment including an evaluation of exertion dyspnoea and the usual echocardiographic indices of cardiac performance. A cardiopulmonary exercise test with an increment of 20W every 3 minutes was prolonged until exhaustion. Systemic arterial pressure, ECG, VO2, VCO2 and VE were monitored throughout. Gas tensions, plasma catecholamines and lactate were measured in blood samples taken at the first and third minute of each exercise stage. The above measurements were carried out before and after 3 months of treatment with Captopril, 50 mg b.i.d. or t.i.d. A highly significant correlation between arterial lactate and plasma norepinephrine (NE) was observed in each patient during both exercise tests (r = 0.77 to 0.99; p less than 0.05 at least). Left ventricular end-diastolic dimensions were reduced by Captopril (from 69.9 +/- 1.7 to 65.2 +/- 1.4 mm, p less than 0.01) along with a concomitant increase in percent fractional shortening. Most of the patients were reclassified at a lower NYHA class and a significant decrease in dyspnoea score was observed. The exercise time was significantly increased (from 11.2 +/- 1.8 to 12.9 +/- 1.9 min; p less than 0.05), but the peak values of NE, arterial lactate and VO2 were not affected by the treatment. The predicted value of VE at a VCO2 of 1 L/min, regarded as an index of dyspnoea, was significantly decreased by Captopril (from 41.4 +/- 2.9 to 38.9 +/- 2.7 L/min; p less than 0.05). The positive effects of long-term treatment with Captopril on cardiac performance in CHF are confirmed. Sympathetic activity is linked to anaerobic muscular metabolism during exercise and seems to be independent of pharmacological ACE inhibition. The discrepancy between the exercise tolerance and the peak VO2 might be explained by a better utilization of the available energy.
Acta Cardiol 1988
PMID:Sympathetic activation on effort in patients with chronic heart failure. Long term effects of captopril. 314 3

A multicenter, randomized, controlled, double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone, for the long-term management of middle-aged adults with "mild" hypertension. Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population; mild hypertension's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy, and other trials that failed to demonstrate beneficial impact on morbidity and mortality, possibly due to residual questions concerning aspects of benefit to risk ratios with these medications; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors, angiotensin converting enzyme inhibitors and calcium channel blockers; paucity of data from trials on long-term combined effects of diet and drug therapy, and of diet alone, for people with mild hypertension. During the next few years, phase 1 of the trial will study 6 groups of drugs. The step-1 drugs are angiotensin converting enzyme inhibitor (enalapril), alpha 1 inhibitor (doxazosin), beta blocker (acebutolol), calcium channel blocker (amlodipine), diuretic (chlorthalidone) and placebo. All participants are to receive vigorous sustained nutritional counseling to reduce obesity, moderate sodium intake and avoid heavy use of alcohol. Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension, side effects (i.e., clinical and biochemical) and consequent need to discontinue drug and quality of life. Phase-1 data are to be used to complete the phase-2 design, with the ultimate aim to assess effects on morbidity and mortality.
Am J Cardiol 1987 May 29
PMID:Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). 329 21

A 42-year-old woman was transferred to our hospital for evaluation of bradycardia with a complete atrioventricular block. Her pulse was 41 regular beats/min with blood pressure 166/92 mmHg. There were no skin lesions, edema, or lymphadenopathy. The white blood cell count was 6300/mm3. The serum glutamic oxaloacetic transaminase was 21 IU and creatine phosphokinase was 34 IU. C-reactive protein was negative. The level of serum angiotensin converting enzyme was slightly increased at 25.8 IU/l/37.0 degrees C (normal range: 7-24.0). Chest radiography showed congestive heart failure with a cardiothoracic ratio of 54%. There was no bilateral lymphadenopathy or fibrous changes during her clinical course. The coronary arteries were completely normal angiographically. Left ventriculograms revealed slight hypokinesis and dilatation (end-diastolic volume index of 112 ml/m2, ejection fraction of 53%). Left ventricular end-diastolic pressure was slightly abnormal at 16 mmHg. Two right and two left ventricular endomyocardial biopsies were performed. Right ventricular biopsy demonstrated edematous tissue and a slight mononuclear cell infiltration with little fibrosis. Left ventricular specimens showed an extensive area of fibrosis, with large, multinucleated giant cells with an asteroid body and chronic inflammation without epithelioid cells. The less affected areas of another specimen showed mild interstitial fibrosis and degenerative myocytes with vacuolation, and some multinucleated myocytes without an asteroid body were present. This case was diagnosed as cardiac sarcoidosis rather than idiopathic giant cell myocarditis. The patient has been implanted with a permanent pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)
Clin Cardiol 1988 May
PMID:Myocarditis with multinucleated giant cells detected in biopsy specimens. 338 73

Angiotensin-converting enzyme kininase II reduces bradykinin metabolism in vitro and in vivo. However, consistent changes in circulating bradykinin levels after the angiotensin-converting enzyme inhibitor captopril have not been reported. The kallikrein-kinin system has been suggested to be a local hormonal system concerned with regional blood flow, and hence circulating levels may not reflect local tissue levels of kinins. Anesthetized dogs given captopril had a significant increase in urinary kinin excretion without a change in circulating bradykinin levels or in urinary kallikrein. These changes in renal kinins were accompanied by a decrease in blood pressure and renal vasodilation. The hypotension and renal vasodilation produced by captopril were not attenuated either by pretreatment with the angiotension receptor antagonist Sar1-Ileu8-angiotensin II or by reduction of endogenous prostaglandin production with indomethacin. Postischemic renal vasodilation after temporary renal artery occlusion was also associated with increased urinary kinin levels. These results demonstrate that captopril effectively inhibits renal angiotensin-converting enzyme and that the renal kallikrein-kinin system may play an important role in regulating the renal vasculature and may contribute to the renal hemodynamic effects of captopril. Many polypeptide hormone membrane receptors are self-regulated by endogenous tissue concentrations of the peptide hormone. Infusions of bradykinin into rats reduced specific bradykinin receptors. A similar decrease in bradykinin receptor numbers without change in receptor affinity was demonstrated after captopril administration. These results provide indirect evidence that angiotensin-converting enzyme/kininase inhibition by captopril increases local tissue concentration of kinins, which may contribute to the hypotensive effect.
Am J Cardiol 1982 Apr 21
PMID:Effect of angiotensin-converting enzyme inhibition on circulating and local kinin levels. 612 71

This study was designed to compare the activity of three structurally different drugs (SQ 14225 [captopril], SA 446 and MK 421) as inhibitors of angiotensin I-converting enzyme in vivo and to compare their effects on blood pressure in spontaneously hypertensive rats and one clip, two kidney renal hypertensive rats. All the three drugs were potent, orally effective converting enzyme inhibitors. The relative durations of their actions as inhibitors of angiotensin-converting enzyme, from longest to shortest, were as follows: MK 421, SQ 14225 and SA 446. MK 421 appears the most potent on a molar basis. In renal hypertensive rats the drugs appeared equipotent, although the duration of action of MK 421 was prolonged and SA 446 shorter than that of SQ 14225. SA 446 was less effective than the other two compounds in spontaneously hypertensive rats.
Am J Cardiol 1982 Apr 21
PMID:In vivo comparison of three orally active inhibitors of angiotensin-converting enzyme. 628 Apr 78


<< Previous 1 2 3 4 5 6 7 8 9 10