ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08670.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08671.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummaryA short review is given of possible mechanisms of action of the organic “calcium antagonists”. Calcium antagonists comprise a chemically heterogenous group of drugs, and the term may be used to denote agents that inhibit Ca2+‐dependent processes or regulatory mechanisms without acting at other sites. Such drugs may be subdivided into those that decrease the availability of Ca2+ to the myoplasm, and those that decrease the cellular effects of Ca2+ without lowering the intracellular Ca2+ concentration. Accordingly, calcium channel blockers, such as verapamil, nifedipine, and diltiazem, form a subgroup of calcium availability inhibitors, as they block influx of extracellular calcium through ion selective channels in the membrane both in cardiac and smooth muscle. However, it cannot be excluded that some of these drugs, particularly in smooth muscle, may have additional sites of action, which must be taken into consideration when they are used as investigational

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08672.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummaryCalcium antagonists have been used in the treatment of various medical disorders for more than 10 years, but their pharmacokinetics properties are poorly investigated. Available data on the pharmacokinetics of calcium antagonists in normal men are summarized in the present paper. Information on the influence of renal impairment and old age on the handling of calcium‐antagonists are only available for verapamil. Patients with advanced renal disease had a significant reduction in the apparent volume of distribution, a shortened serum elimination half life, a decreased total body clearance of verapamil due to a decrease in the renal excretion of verapamil and its active metabolite norverapamil and also to a decrease in metabolic clearance. Pharmacokinetic parameters obtained after oral administration were not significantly different from those after intravenous dosing. The mean biologic availability (22.8%) was in the same range as reported for normal persons, but individual variations would seem to be greater. Elderly patients with a mean age of 87 years also had a significantly reduced volume of distribution of verapamil and decreased total body clearance of the drug, although this last change did not reach statistical significance. The biologic availability in the elderly was higher than in younger persons with a mean value of 37.69% and a wide range from 9.16 to 82.76%. These findings imply that verapamil dosage should be reduced in patients with impaired renal function and elderly patient

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08673.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummarySeveral investigators have independently discovered that the calcium antagonist, verapamil, causes a 60–80% increase in plasma digoxin. Pharmacokinetic studies indicate, that the elevated plasma digoxin level is due to verapamil‐induced inhibition of both renal and extrarenal digoxin clearance. No significant changes in single‐dose digoxin pharmacokinetics were observed during nifedipine coadministration.To elucidate the clinical relevance of this interaction, we investigated the influence of verapamil on digoxin‐induced inotropism as assessed from systolic time intervals. In single‐dose trials, the verapamil‐induced elevation of plasma digoxin was associated with a more sustained reduction in left ventricular ejection time as compared to control. Correspondingly, the concentration‐response relationship of digoxin inotropism was unaffected by verapamil.In‐vitro studies showed that verapamil had no influence on the number of digitalis receptors on human lymphocytes. In accordance, verapamil enhanced the digoxin‐induced elevation of intracellular sodium concentration possibly reflecting an increased receptor effect.The plasma digoxin elevation resulting from verapamil coadministration seems cardioactive with regard to both inotropism

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08674.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummaryVerapamil has previously been found to inhibit insulin release from pancreatic β‐cells in laboratory animals. In our department, however, both oral pretreatment with verapamil for one week and a 3‐hour iv infusion of the drug improved the tolerance to oral glucose in type II diabetics without affecting insulin release. It failed, however, to potentiate the hypoglyemic effect of oral glibenclamide therapy in patients with type II diabetes. Since iv infusion of verapamil left the portal vein glucose response to glucose ingestion unaffected in normoglycaemic patients (being portal vein catheterised for diagnostic purposes), it seems unlikely that the hypoglyceamic effect of verapamil could have been due to reduced glucose absorption from the gut. More likely is that verapamil, in the diabetic patients, influenced metabolic processes inside the hepatocytes that are of importance for glucose homeostasis.In‐vitro experiments have shown that calcium affects factors of importance for the glucose metabolism. Accordingly, calcium triggers the stimulus‐secretion coupling process which leads to insulin release from the pancreatic β‐cells (1). Calcium also tightens cell membranes, thereby decreasing their permeability to various substances, including glucose (2). Finally, calcium mediates cellular responses to glucagon stimulation (3,4) and thus affects the hepatic glucose output. Calcium apparently influences glucose metabolism by several pathways and different overall effects on the blood glucose concentration may be forthcoming depending on which of these pathways is the dominating one.In view of these well‐documented in‐vitro effects of calcium on some of the metabolic processes which determine the glucose tolerance, it is surprising to find that relatively few clinical studies have been carried out to investigate whether calcium antagonists influence glucose tolerance in man. Although a few such studies, dealing with the effect of nifedipine (5,6) and verapamil (7,8,9,10) on human glucose tolerance have been performed recently, the result obtained in these investigations have been highly conflicting. Our intention has therefore been to elucidate how oral and iv administration of verapamil affects glucose tolerance not only in normoglycaemic subjects, but also in patients with untreated, and sulfonylurea‐treated

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08675.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummarySince several β‐blocking agents increase the atherogenic VLDL‐triglycerides and decrease the atheroprotective HDL‐cholesterol we studied if verapamil also affects these lipoproteins or the most atherogenic LDL‐cholesterol. Twelve patients (three females), mean age 56 years, with angina pectoris or hypertension/tachyarrhythmias were treated with verapamil 240–320 mg/day. Serum lipoproteins were measured before and after 6 and 24 weeks of therapy. Initial total serum cholesterol averaged 7.27 mmol/1. After 6 weeks of treatment it decreased by 9%, p<0.02. These results remained significant, p<0.01 after 24 weeks. The decrease was due to a fall in LDL‐cholesterol by 12%, p<0.01. The reduction in LDL‐cholesterol was correlated to initial LDL‐cholesterol concentration, r=‐ 0.73, p<0.01. Within LDL there was a parallel decrease in phospholipids, p<0.05. There were no changes in total or VLDL‐triglycerides or total HDL‐cholesterol. In the HDL fraction HDL2decreased insignificantly but HDL3cholesterol increased by 12%, p<0.05.We conclude that verapamil has a beneficial effect on serum lipoproteins in that it lowers the atherogenic LDL‐cholesterol and does not affect the other lipoprotei

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08676.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummaryFasting levels of serum lipids and lipoproteins were measured in survivors of acute myocardial infarction after 6 months of treatment with placebo (n = 19) or verapamil 360 mg daily (n = 13). There were no significant differences between the groups and values had not changed in the verapamil group 2 weeks after cessation of treatment.

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08677.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummaryThe effect of verapamil on plasma lipids and lipoproteins was studied in 64 patients taking part in a double blind controlled trial of verapamil versus placebo in post myocardial infarction. During a six month treatment period no significant difference was seen in plasma cholesterol, triglycerides, high density lipoproteins or low density lipoproteins.

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08678.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SummaryThe efficacy and safety of verapamil and nifedipine were objectively assessed in patients with chronic stable angina. Twenty four patients entered a double blind randomized cross over trial of nifedipine (10 mg thrice daily) and placebo. In this dosage nifedipine did not show any significant change in exercise duration and the variables obtained using computer assisted exercise testing when compared to placebo. The next stage consisted of another double blind randomized cross over trial comparing the effects of verapamil (120 mg thrice daily) and nifedipine (20 mg thrice daily) with an initial placebo run‐in period in 32 patients. At this dose level nifedipine showed a definite and significant improvement in all the objective variables; however an increase in side effects was observed resulting in withdrawal of the drug in seven patients. A common problem was tachycardia precipitating angina after nifedipine ingestion. On the other hand verapamil produced a marked improvement in exercise tolerance and other variables as compared to placebo and nifedipine, was well tolerated and produced a mild bradycardia. This study clearly indicates that verapamil is distinctly superior to nifedipine in efficacy side effects and safety in patients with chronic stable angina. This may be attributable to the differential effect on heart rates induced by these drug

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1984.tb08679.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY