Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intravenous (iv) verapamil (0.01 to 1.0 mg/kg) on the constant neuromuscular block produced by an iv infusion of either pancuronium or succinylcholine were studied on the indirectly stimulated gastrocnemius and tibialis-anterior muscles of the rabbit anesthetized with halothane in oxygen. Verapamil alone (n = 6) had no significant effect. However, the drug did significantly potentiate the 50% twitch depression of the gastrocnemius muscle produced by a constant iv infusion of either pancuronium (n = 5) or succinylcholine (n = 5) to 36 +/- 6% and 45 +/- 1% of control, respectively. This effect of verapamil occurred with doses of 0.1 mg/kg for pancuronium and 0.01 mg/kg for succinylcholine; these doses of verapamil were the lowest which produced a significant effect. In contrast, verapamil had no significant effect on the progression of the neuromuscular blockade of either the gastrocnemius or tibialis-anterior muscles produced by alpha-bungarotoxin (n = 5). Verapamil also significantly prolonged the P-R interval of the ECG from a control value of 71 +/- 2 ms to 78 +/- 3 ms at a dose of 0.1 mg/kg and to 93 +/- 6 ms at a dose of 0.3 mg/kg. The possible mechanisms of the neuromuscular actions of verapamil are discussed and it is concluded that verapamil can produce potentiation of either pancuronium- or succinylcholine-induced neuromuscular block at doses within the therapeutic range.
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PMID:Potentiation of neuromuscular blockade by verapamil. 670 85

The cardiovascular and neuromuscular interactions of verapamil and dantrolene were evaluated in 20 chloralose-anesthetized swine. The animals were randomly divided into three groups. Group I, ten animals, received a bolus intravenous injection of 0.1 mg . kg-1 of verapamil followed by the continuous infusion of 5 micrograms . kg-1 . min-1. This group was then randomly divided into two equal subgroups. Five of these animals, Group Ia, continued to receive the verapamil infusion alone. The other five animals, Group Ib, received dantrolene in incremental doses of 1.0, 3.3, and 5.6 mg . kg-1 while the verapamil infusion was continued. An additional group of five animals, Group II, received the same incremental doses of dantrolene but did not receive verapamil. Five control animals, Group III, received the alpha-chloralose anesthetic without dantrolene or verapamil. Neuromuscular function, as measured by twitch height, was affected only by dantrolene, which produced a dose-dependent depression. Verapamil resulted in initial decreases in heart rate, arterial blood pressure, cardiac output, left ventricular dP/dt, and an increase in PR interval. Dantrolene alone produced a mild increase in arterial blood pressure. Dantrolene administration to verapamil-pretreated animals resulted in a profound depression in cardiac function, marked elevation in serum K+ (8.0 +/- 0.7 mEq . l-1), and no change in arterial pH (7.39 +/- 0.02). Cardiac arrest preceded by complete atrioventricular heart block occurred in one animal before and in four animals after the final dantrolene dose was given to animals pretreated with verapamil. Although we cannot extrapolate data from our porcine model to humans, further studies are indicated to help evaluate a possible fatal drug interaction before verapamil and dantrolene are used concomitantly in a clinical setting.
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PMID:Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine. 671 41

Verapamil and nifedipine, two calcium-antagonist drugs, were evaluated in a double-blind cross-over trial. The study was performed in 15 patients admitted to our Coronary Care Unit for spontaneous angina. Before and after a 24 hours placebo period, oral verapamil 480 mg daily and oral nifedipine 60 mg daily were administered alternatively. Symptomatic as well as asymptomatic ischemic episodes with ST segment elevation or depression and ventricular and supraventricular ectopic beats were documented by continuous electrocardiographic Holter monitoring. The average number of attacks during the placebo periods was 243; the number of attacks decreased to 129 during verapamil treatment (P less than 0.05) and to 57 during nifedipine treatment (P less than 0.01). Ventricular ectopic beats decreased with both drugs while supraventricular ectopic beats decreased only during verapamil treatment. The difference was not statistically significant because of a small number of observations. In conclusion the two drugs appear to be effective in the management of patients with unstable angina at rest, especially in the variant form.
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PMID:Effects of oral calcium-antagonists in spontaneous angina. Verapamil and nifedipine in a double-blind cross-over trial. 675 85

Verapamil hydrochloride, a prototype calcium antagonist, is now marketed in the United States for the acute treatment of supraventricular tachyarrhythmias and for chronic management of vasospastic and chronic stable angina. It inhibits the slow inward channel in in the heart and blocks calcium influx in smooth muscle. Its intrinsic negative inotropic action, which is apparent in isolated tissues, is offset in vivo by peripheral vasodilation. It has a mild, noncompetitive sympathetic antagonist effect; its most important electrophysiologic action is a depression of AV nodal conduction, accounting for its effect in supraventricular tachyarrhythmias. Its hemodynamic actions are characterized by a complex interplay of changes in preload, afterload, contractility, heart rate, and coronary blood flow. It does not depress cardiac function, except in severe heart failure. The drug has a mild dilator action on coronary arteries and reverses ergonovine-induced vasoconstriction. Controlled trials have established its role in Prinzmetal's variant angina, unstable angina, and chronic stable angina. It has also been found to be effective in obstructive cardiomyopathies. The potential role of verapamil in such conditions as hypertension, cardioprotection, and Raynaud's phenomenon needs further evaluation; at present these indications have not been approved by the Food and Drug Administration. The most common side effects include constipation, skin rash, and dizziness; AV block, heart failure, and sinus arrest may occasionally be encountered, especially when ventricular function is compromised or conduction system disease is present.
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PMID:Verapamil hydrochloride: pharmacological properties and role in cardiovascular therapeutics. 676 30

Because severe muscular weakness was noted in animals receiving verapamil in doses exceeding those used in humans, we studied the effects of verapamil on neuromuscular function and its correlation with myocardial conduction. The flexor carpi radialis and its nerves were surgically exposed in mechanically ventilated dogs during pentobarbital anesthesia. Indirect and direct electrical stimulation was applied and twitch height recorded following the intravenous administration of verapamil. Twenty animals received one of four dose schedules. The results showed a significant dose-related depression of twitch height to indirect stimulation. Twitch height to direct stimulation was reduced only with the highest dose. The onset of depression of indirect stimulation was temporally associated with onset of A-V conduction delay. However, recovery following indirect stimulation lagged behind recovery of the ECG by 30 min. Recovery times of twitch height following indirect stimulation ranged from 60-208 min and also were dose-related. The qualitative similarity of pancuronium and verapamil on indirect twitch height suggests a similar site of action, i.e., the neuromuscular junction. A presynaptic or postsynaptic effect of verapamil could not be discerned in this study. Verapamil may produce an unrecognized source of weakness in the anesthetized patient either alone or through interaction with anesthetic agents or adjuncts.
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PMID:Neuromuscular and electrocardiographic responses to verapamil in dogs. 684 9

Electrophysiologic evaluation before and after the serial administration of verapamil, lidocaine, propranolol, and procainamide was undertaken in 4 young, asymptomatic patients with recurrent, sustained ventricular tachycardia (VT). No patient had obvious organic heart disease. The electrocardiogram during sinus rhythm showed S-T depression and T-wave inversion over the inferior and lateral precordial leads in 3 patients. QRS morphologic characteristics during episodes of VT showed a pattern of right bundle branch block and left axis deviation. In all 4 patients, VT could be both induced and terminated with electrical stimulation. Verapamil terminated VT and prevented the induction of sustained VT in 3 patients, and markedly slowed the rate of VT in 1 patient. Procainamide effectively prevented the induction of sustained VT in 2 patients, and although ineffective in preventing induction in 2 patients, it slowed the rate of tachycardia in both. Lidocaine and propranolol did not prevent the induction of VT in any patient. These findings suggest that slow-response tissues may be involved in the genesis of VT in these patients, and that VT in these patients may represent a unique clinical entity with distinct electrocardiographic, electrophysiologic, and electropharmacologic properties.
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PMID:Idiopathic paroxysmal ventricular tachycardia with a QRS pattern of right bundle branch block and left axis deviation: a unique clinical entity with specific properties. 685 37

The relative efficacy of two calcium antagonist drugs, verapamil, 120 mg three times a day and nifedipine, 20 mg three times a day, was examined in a double-blind randomised trial. Patients were assessed at the end of four week periods by a maximal treadmill exercise test, the frequency of anginal attacks, glyceryl trinitrate consumption, and side effects. Sixteen point praecordial maps were recorded at rest, immediately after exercise, and at minute intervals for 10 minutes. Total ST segment depression (epsilon ST) was used as a measure of myocardial ischaemia. Both verapamil and nifedipine increased maximal work capacity but epsilon ST at the termination of the test remained constant. Both drugs reduced the frequency of anginal attacks and glyceryl trinitrate consumption. Systolic blood pressure at rest and on exercise was reduced by both drugs. Verapamil and nifedipine were equally effective in treating angina, but side effects were more common with nifedipine.
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PMID:Calcium antagonist drugs in chronic stable angina. Comparison of verapamil and nifedipine. 703 54

In 18 patients with stable effort angina, verapamil, 80 mg four times daily, was compared with propranolol, 80 mg four times daily, in a double-blind, placebo-controlled trial to assess the effects on anginal threshold, exercise capacity and left ventricular function measured by gated equilibrium blood pool scanning. Both propranolol and verapamil improved exercise capacity (placebo 424 +/- 135 W-min; propranolol 513 +/- 168 W-min, p less than 0.01; verapamil 545 +/- 215 W-min, p less than 0.005) and prolonged the time to 1 mm of ST depression (placebo 4.5 +/- 1.3 minutes; propranolol 7.4 +/- 1.4 minutes, p less than 0.005; verapamil 6.6 +/- 1.9 minutes, p less than 0.005). At rest, the mean left ventricular ejection fraction did not change significantly during drug therapy (placebo 57 +/- 13%, propranolol 55 +/- 12%, verapamil 55 +/- 13%). While taking placebo, all 18 patients had a decrease in exercise ejection fraction. In contrast, 12 patients taking propranolol and 14 patients taking verapamil had a 5% or greater increase in ejection fraction during exercise. Verapamil is an effective primary therapy and a satisfactory alternative to propranolol in patients with stable effort angina.
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PMID:A double-blind randomized trial of propranolol and verapamil in the treatment of effort angina. 704 90

A 35-year-old man with class 2 angina pectoris was enlisted in a serial exercise test protocol to evaluate oral verapamil therapy for angina pectoris. During both the single-blind open dose titration phase and the double-blind phase, short salvoes of ventricular tachycardia (VT) were followed by angina and ischemic ST segment depression during exercise with placebo. With verapamil therapy, no ventricular ectopy was noted during exercise, and the patient exercised longer before angina or ischemic ECG changes developed. Twenty-four hour ECG monitoring revealed multiform ventricular premature depolarizations and three-beat salvoes of VT with placebo and no ventricular ectopy whatsoever with verapamil. Verapamil's antiarrhythmic effect may be secondary to its anti-ischemic action, or, by inhibiting slow channel conduction (with its propensity for enhanced automaticity and reentry) induced by ischemia and the sympathetic response to exercise, exerts a primary antiarrhythmic action.
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PMID:Suppression of ischemic related ventricular tachycardia by verapamil during treadmill exercise testing. 708 17

Two patients with classical effort-induced angina pectoris associated with abnormal ST-segment depression on graded exercise testing and normal coronary arteriograms are described. Both patients deteriorated during treatment with propranolol, and became asymptomatic during treatment with verapamil with normal graded exercise tests. Verapamil may thus improve an inadequate vasodilatatory response of the coronary vascular bed to effort.
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PMID:Verapamil in effort-induced angina pectoris in patients with normal coronary arteries. 710 8


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