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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction between beta-adrenoreceptor blockers and calcium antagonists may occasionally be dangerous. The effects of the new calcium antagonist PN 200-110 (isradipine) were compared with those of verapamil in 3 groups of conscious rabbits pretreated with either pindolol 0.3 mg/kg, propranolol 1 mg/kg intravenously or placebo. Each animal received PN 200-110 (0.01, 0.03 and 0.1 mg/kg) and 2 or more days later verapamil (0.1, 0.3 and 1 mg/kg). The calcium antagonists were given to lower mean blood pressure to the same extent as in the placebo group. This blood pressure effect remained unchanged after pretreatment with pindolol or propranolol. Both PIN 200-110 and verapamil increased heart rate to the same extent as in the placebo group. Both beta blockers blunted the effect of PN 200-110 on heart rate but converted the verapamil-induced tachycardia to bradycardia. Propranolol blunted the PN 200-110-induced increase in cardiac output and total peripheral conductance, whereas the high verapamil dose decreased cardiac output and caused peripheral vasoconstriction in propranolol-pretreated animals. Thus, both agents lowered blood pressure by peripheral vasodilatation in the placebo group, after beta blockade; however, the mechanism of the verapamil-induced blood pressure decrease changed from pure vasodilation to a decrease in cardiac output, i.e., cardiac depression. Verapamil but not PN 200-110 prolonged the PQ interval, especially in animals who had received beta blockade. Most differences in the interaction were attributable to differences between the 2 calcium antagonists; the differences between the beta blockers were small and in favor of pindolol.
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PMID:Interaction between two calcium antagonists and two beta blockers in conscious rabbits: hemodynamic consequences of differing cardiodepressant properties. 288 Apr 95

Nephrotoxicity is a serious side effect that limits the use of cyclosporine (CyA) as an immunosuppressive agent. The purpose of this study was to develop a model of CyA nephrotoxicity in the isolated perfused rat kidney and to evaluate the effects of adenosine triphosphate (ATP)-MgCl2 and verapamil treatment on this model. Kidneys were perfused for 90 minutes in a 7.5% albumin-Krebs-HCO3 solution containing 3H-inulin (glomerular marker) and 5.0 micrograms/ml 14C-cytochrome C (cyt) (marker of tubular protein absorption). After 10-minute equilibration, perfusate and urine samples were collected with 10-minute clearance periods. After two control clearance periods, 500 ng/ml CyA was added to the perfusate. In some experiments, 1 micrograms/ml of verapamil was added 10 minutes before CyA and in others 2 mmol/l ATP-MgCl2 was added with CyA. Cyt and inulin radioactivity, [Na+] and [K+], were measured in perfusate and urine. Tissue ATP levels were also determined. The results demonstrate that CyA treatment leads to a marked depression of glomerular filtration rate (GFR), tubular absorption of protein, urine output, and renal flow. ATP-MgCl2 cotreatment improved GFR, tubular absorption, and renal perfusate flow but the increase in urine output was not dramatic. Verapamil pretreatment markedly improved GFR and urine and renal perfusate flow but not tubular function. The combination of verapamil and ATP-MgCl2 treatment with CyA returned GFR to control values, significantly improved tubular absorption, urine and renal perfusate flow, and enhanced renal tissue ATP of isolated kidneys to levels seen in vivo. These data lead us to conclude that ATP-MgCl2 cotreatment with CyA after verapamil pretreatment greatly reduces the nephrotoxic potential of this immunosuppressive agent.
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PMID:Treatment with verapamil and adenosine triphosphate-MgCl2 reduces cyclosporine nephrotoxicity. 295 Jun 8

The efficacy of a once daily, sustained release formulation of verapamil (Verapamil SR, 360 mg) was evaluated in 19 patients with chronic angina pectoris using a double-blind placebo-controlled crossover protocol. Evaluation by exercise testing, 24 hour electrocardiographic ambulatory monitoring and blood drug level assays was performed at the end of each 2 week phase, 21 to 23 hours after the last dose. After the crossover protocol, all patients were given sustained release verapamil for 4 weeks and the evaluation was repeated. Exercise time (mean +/- SEM) increased from 7.4 +/- 0.6 minutes with placebo to 9.6 +/- 0.8 minutes with verapamil (p less than 0.001) and to 9.5 +/- 0.7 minutes (p less than 0.001) after 4 weeks of therapy. The mean time to 1 mm ST depression also increased significantly, from 4.5 +/- 0.4 and 4.8 +/- 0.5 minutes in bipolar leads CM5 and CC5, respectively, with placebo, to 5.5 +/- 0.6 (p less than 0.05) and 6.2 +/- 0.5 minutes (p less than 0.01) with verapamil. Maximal ST depression and rest and peak heart rates were not altered significantly. The mean rate-pressure product was 208 +/- 9.9 with placebo and decreased to 189 +/- 7.7 (p less than 0.05) with verapamil but rose to 200.6 +/- 10.4 (p = NS) after 4 weeks of therapy. The mean hourly heart rates were lower with the drug than with placebo throughout the 24 hour period but there was no significant bradycardia, arrhythmia or heart block.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sustained release verapamil, a once daily preparation: objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina. 310 85

The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with beta-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with beta-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium channel antagonists. Part III: Use and comparative efficacy in hypertension and supraventricular arrhythmias. Minor indications. 315 29

Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.
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PMID:Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram. 317 79

The effects of verapamil (0.3 to 30 microM) on potentiated rest contractions (PRC) were studied in isometric contractions of left ventricular papillary muscles of the rat. The post-rest potentiation was studied after rest periods of 5, 10, 15, 30, 60 and 120 s. Verapamil reduced the steady-state force and PRC in a dose-dependent manner. However, PRC were less depressed and the magnitude of this depression decreased as the rest period increased. The time constant of the recovery of steady state force after rest potentiation was shortened. These results indicate that the first PRC are less dependent on calcium entering the cell through the slow channels and apparently more dependent on an intracellular calcium store.
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PMID:The effect of verapamil on potentiated rest contractions in the rat ventricular myocardium. 324 Mar 84

1. The protective effects of ten slow channel inhibitor drugs against severe progressive hypoxia were investigated in rats breathing spontaneously during light anaesthesia. Respiration, heart rate, electrocorticogram (ECoG) and/or electroencephalogram (EEG) were recorded. 2. Tolerance times were monitored from hypoxia onset until cessation of respiration, ECoG, EEG synchronization, and 'background-EEG'. Drugs were administered i.v. 5 min before the onset of hypoxia. 3. Verapamil, gallopamil, and nimodipine resulted in a significant increase of tolerance times; fendiline and bepridil showed a small increase (not significant); bencyclan and prenylamine were ineffective; cinnarizine and diltiazem slightly reduced tolerance times as did flunarizine at low doses. 4. At protective doses, verapamil, gallopamil, and nimodipine significantly raised the respiration rate but had little or no cardiac depressor effects. Bencyclan showed ventilatory drive but cardiocirculatory depression. A clear-cut ventilatory drive did not occur with the other ineffective slow channel inhibitors. 5. It is suggested that the protective actions observed were not due to slow channel inhibition per se, nor to spasmolytic potency or increased cerebral blood flow. Ventilatory drive associated with other cardiopulmonary actions which secondarily raise the brain oxygen supply are likely to be responsible for this effect.
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PMID:Slow channel inhibitor effects on brain function: tolerance to severe hypoxia in the rat. 326 35

Isolated hamster hearts were perfused with 2% ethanol for 30 min and then reequilibrated with control medium. One group of hamsters was pretreated with verapamil. Another group received diltiazem. Myocardial verapamil levels were 9.5 +/- 0.7 mg/g dry wt; diltiazem levels were 22 +/- 7 mg/g dry wt. Energy metabolites were assessed by using 31P NMR standardized with high-pressure liquid chromatography of freeze-clamped tissue. Intracellular calcium was measured by atomic absorption spectrophotometry, marking the extracellular space with K(CoEDTA). After 30 min of perfusion, untreated hamster hearts showed a 74% decrease in developed pressure, a marked increase in end-diastolic pressure, a decrease of ATP from 9.8 to 8.8 mmol, and an increase of Pi from 6.7 to 9.8 mmol, but no change of phosphocreatine (PCr) or intracellular pH (pHi). Verapamil pretreatment partially prevented cardiac depression during alcohol perfusion. Whereas diltiazem had no protective effect. After reequilibration, developed pressure and oxygen consumption significantly exceeded control values. ATP decreased to 8 mmol; pHi, PCr, and Pi showed no significant change. Verapamil-pretreated hearts showed better performance than untreated hearts without change in PCr and Pi, whereas ATP dropped slightly to 8.7 mmol. Thus, functional cardiac depression resulting from acute alcohol exposure is reversible. Increased intracellular calcium levels during alcohol exposure normalized after the removal of alcohol. There was no major change in high-energy phosphates during alcohol exposure or after the removal of alcohol. Verapamil protects the heart from functional depression during alcohol exposure without affecting energy resources.
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PMID:Reversibility of acute alcohol cardiac depression: 31P NMR in hamsters. 335 Feb 37

The effects were studied of several calcium channel blocking agents on muscle twitch, and possible interactions between these drugs and pancuronium and suxamethonium, using a rat phrenic-hemidiaphragm preparation. Nicardipine, verapamil and diltiazem each caused a concentration-related depression of muscle response. Nicardipine had the most, and diltiazem the least, potent effect. Verapamil and diltiazem 5 and 10 mumol litre-1 caused a concentration-dependent enhancement of suxamethonium-induced neuromuscular blockade, but increased the effect of pancuronium only at 10 mumol litre-1. Nicardipine 10 mumol litre-1 significantly enhanced pancuronium-induced neuromuscular blockade, but not that produced by suxamethonium.
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PMID:Differential effects of calcium channel blocking agents on pancuronium- and suxamethonium-induced neuromuscular blockade. 337 24

Using a modified Langendorff system, a special ECG recording technique and appropriate placement of two silver wire electrodes, early atrial and His bundle activity can be detected continuously from the surface of intact and spontaneously beating guinea pig hearts. This new method was applied to measure the direct and inhibitory effects of nifedipine and verapamil on impulse generation and conduction in isolated and perfused guinea pig hearts. Depression of sinoatrial conduction was the most prominent effect of nifedipine. In all concentrations applied (10(-7) M, 10(-6) M, 10(-5) M) nifedipine predominantly led to sinoatrial blocks of different degrees. Heart rate decreased slightly in a dose-dependent manner. PQ and HV duration remained essentially constant. In the highest concentration of nifedipine (10-5) M), sinus node activity was so depressed that AV dissociation or ventricular rhythm developed. Only in one out of eight experiments with cumulative increase of nifedipine concentrations to 10(-5) M was the AV node affected by nifedipine and a second-degree AV block developed (10(-6) M). Verapamil's inhibitory effects on the rate of impulse initiation in the sinus node were more pronounced than those of nifedipine, but the inhibition of sinoatrial conduction by verapamil was less marked. At 10(-6) M verapamil, the incidence of sinoatrial blocks and of ventricular rhythm was similar to the incidence of first degree AV blocks. PQ time (+14%) but also HV time (+12%) were prolonged under the influence of this concentration of verapamil. At the highest concentration of verapamil (10(-5) M) applied for 10 min, ventricular rhythm developed in five out of eight experiments, as well as one second and two third-degree AV blocks. The results confirm that the simultaneous measurements of sinus node activity of sinoatrial and atrioventricular conduction and of HV duration is feasible with this ECG technique, to evaluate the inhibitory effects of Ca-antagonists on sinus and AV node activity in the intact heart.
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PMID:Modulation of cardiac impulse generation and conduction by nifedipine and verapamil analyzed by a refined surface ECG technique in Langendorff perfused guinea pig hearts. 339 17


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