Drugs online research references
Jpn Circ J. 1985 Jan;49(1):46-51.
Serum concentration and effects of a single dose of enalapril maleate in patients with essential hypertension.
Shionoiri H, Gotoh E, Miyazaki N, Yasuda G, Takagi N, Uneda S, Kaneko Y.
The antihypertensive effect of a non-sulfhydryl, long acting ACE (angiotensin converting enzyme) inhibitor, MK-421, was evaluated by administering a single dose of 10 mg to 13 patients with mild to moderate essential hypertension. The pharmacokinetic profile of MK-421 and its potent active metabolite, MK-422, was also assessed, together with the effect on the various components of the renin-angiotensin system. A single dose of MK-421 produced a significant fall in MBP from 2 to 24 hours post-drug. As could be expected, plasma ACE activity was suppressed up to 24 hours after MK-421. The half-life of MK-422, Cmax and [AUC]24(0) of MK-421 and MK-422 were measured. No significant change in plasma bradykinin or urinary excretion rate of kallikrein was observed, whereas a slight increase was observed in the urinary excretion rate of kinins after MK-421 in 8 patients. Significant correlations were observed between pretreatment PRA levels and the maximum fall in MBP.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2982051&dopt=Abstract
J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):1067-75.
Comparative hemodynamic effects of MK-422, a converting enzyme inhibitor, and a renin inhibitor in dogs with acute left ventricular failure.
Sweet CS, Ludden CT, Frederick CM, Bush LR, Ribeiro LG.
The angiotensin-converting enzyme (ACE) inhibitor MK-422 (enalaprilat) was compared with the potent renin inhibitor SCRIP for its ability to improve left ventricular function in closed-chest dogs. Acute left ventricular failure (ALVF) was induced by repeated embolization (EMB) of the left coronary arterial vasculature with 50-micron plastic microspheres. Baseline stability data were obtained in 30 dogs in which the evolution of ALVF was monitored over time. Guided by a progressive rise in left ventricular end-diastolic pressure (LVEDP), a stepwise perturbation of the coronary circulation with microspheres over 30 min caused reductions in left ventricular dP/dt and cardiac output, averaging 47 and 40%, respectively. EMB reduced heart rate (20 beats/min) and mean arterial pressure by approximately 20 mm Hg which, along with other hemodynamic variables remained stable after induction of heart failure. MK-422 (100 micrograms/kg i.v.) given 45 min after ALVF was induced, decreased mean arterial pressure by 20 mm Hg (p less than 0.05) and reduced total peripheral resistance (TPR) from 5,453 to 4,150 dyne X s X cm-5 (p less than 0.05). The decline in LVEDP (from 14 +/- 1 to 11 +/- 1 mm Hg) and TPR suggests that MK-422 dilates resistance and, conceivably, capacitance vessels. In dogs with sham EMB (vehicle injections into coronary circulation), MK-422 reduced arterial pressure but had no important effects on the other hemodynamic indices.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6084762&dopt=Abstract
Eur J Pharmacol. 1989 Aug 22;167(2):211-20.
Beneficial hemodynamic effects of milrinone and enalapril in conscious rats with healed myocardial infarction.
DeFelice A, Harris A, Frering R, Horan P.
Department of Pharmacology, Sterling Research Group, Rensselaer, NY 12144.
Milrinone and enalapril, which inhibit PDE-III and ACE, respectively, are able to prolong survival of myocardially infarcted (MI) rats. This study sought to identify oral hemodynamic effects of these agents which could underlie such efficacy in this heart failure model. Four weeks after ligation of the left main coronary artery, basal left ventricular (LV) systolic pressure and dP/dtmax, heart rate and mean blood pressure of the MI rats were significantly less than that of sham-operated controls, and LV end-diastolic pressure (LVEDP) was markedly elevated. Milrinone, at 2.0 mg/kg, reduced LVEDP and renal blood flow of these 4-week MI rats by an average of 39 and 18%, respectively (P less than 0.05) within 1 h. At 4.0 mg/kg, it reduced LVEDP by 46% and raised heart rate by 16% (P less than 0.05). Enalapril (1.0 mg/kg) increased small intestine blood flow of these compromised rats by 16% (P less than 0.05), and tended to reduce LVEDP (-28%) within 1.5 h. Treatment with milrinone (2.0 mg/kg) plus enalapril (1.0 mg/kg) promoted LV dP/dtmax, coronary blood flow, and heart rate by 48, 40 and 13%, and reduced LVEDP by 40% (P less than 0.05 for all effects). Thus these agents can reduce LVEDP and redistribute cardiac output of MI rats. Furthermore, the combination of enalapril and milrinone can restore LVEDP and LV dP/dtmax of MI rats to near normal and promote coronary blood flow without compromising cardiac output or renal blood flow. Such effects, it timely or sustained, may prolong survival.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2556283&dopt=Abstract
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