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 cardiovascular profile of SC-36602, a new class 1A/1B antiarrhythmic agent, was compared to those of disopyramide, lidocaine, mexiletine, flecainide, encainide, lorcainide, and quinidine. These drugs were compared at their respective canine antiarrhythmic doses in a hemodynamic evaluation using anesthetized dogs. In another test using anesthetized dogs, the cardiovascular effects of cumulative doses of SC-36602 were assessed. The direct negative inotropic potential of each drug was also determined using isolated cat papillary muscles. In the hemodynamic study, SC-36602 and quinidine did not cause significant myocardial depression, measured as a decrease in the maximal first derivative of the left ventricular pressure. (Heart rate and diastolic filling pressure were not controlled in order to mimic clinical conditions). SC-36602, mexiletine, flecainide, and quinidine increased heart rate. SC-36602 and mexiletine caused a small increase in mean arterial pressure, whereas disopyramide and quinidine decreased it. Disopyramide was the only drug studied that increased left ventricular end-diastolic pressure. SC-36602, quinidine, and mexiletine increased index of cardiac effort. Disopyramide caused a decrease in the latter. Disopyramide, flecainide, encainide, and lorcainide lengthened the ECG intervals. Cumulative intravenous doses of SC-36602 up to 50 mg/kg produced significant decreases in mean arterial pressure, increases in heart rate, and increases in P-R and QRS intervals of the ECG relative to placebo-matched controls. SC-36602 had the least direct negative inotropic action of the drugs studied, as measured in isolated papillary muscles. These data suggest SC-36602, when compared to the other antiarrhythmic drugs studied, has the least amount of hemodynamic side-effects at its antiarrhythmic dose.
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PMID:SC-36602, a new antiarrhythmic agent: comparison of its cardiovascular profile with that of other antiarrhythmic drugs. 245 60

The voltage- and frequency-dependent blocking actions of disopyramide were assessed in canine Purkinje fibers within the framework of concentrations, membrane potentials, and heart rates which have relevance to the therapeutic actions of this drug. Vmax was used to assess the magnitude of sodium channel block. Disopyramide produced a concentration- and rate-dependent increase in the magnitude and kinetics of Vmax depression. Effects on activation time (used as an estimate of drug effect on conduction) were exactly analogous to effects on Vmax. A concentration-dependent increase in tonic block was also observed. Despite significant increases in tonic block at more depolarized potentials, rate-dependent block increased only marginally with membrane potential over the range of potentials in which propagated action potentials occur. Increases in extracellular potassium concentration accentuated drug effect on Vmax but attenuated drug effect on action potential duration. Recovery from rate-dependent block followed two exponential processes with time constants of 689 +/- 535 ms and 15.7 +/- 2.7 s. The latter component represents dissociation of drug from its binding site and the former probably represents recovery from slow inactivation. A concentration-dependent increase in the amplitude of the first component suggested that disopyramide may promote slow inactivation. There was less than 5% recovery from block during intervals equivalent to clinical diastole. Thus, depression of beats of all degrees of prematurity was similar to that of basic drive beats. Prolongation of action potential duration by therapeutic concentrations of drug following a long quiescent interval was minimal. However, profound lengthening of action potential duration occurred following washout of drug effect at a time when Vmax depression had reverted to normal, suggesting that binding of disopyramide to potassium channels may not be readily reversed. Variable effects on action potential duration may thus be attributed to a block of the window current flowing during the action potential being partially or over balanced by block of potassium channels. Purkinje fiber refractoriness was prolonged in a frequency-dependent manner. Disopyramide did not significantly alter the effective refractory period of basic beats but did increase the effective refractory period of sequential tightly coupled extra stimuli. The results can account for the antiarrhythmic actions of disopyramide during a rapid tachycardia and prevention of its initiation by programmed electrical stimulation.
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PMID:Frequency- and voltage-dependent effects of disopyramide in canine Purkinje fibers. 276 2

The electrophysiological effects of bunaftine were studied using the glass microelectrode technique. Bunaftine at 1, 5 and 10 mg/l produced a concentration-dependent depression of the maximum rate of rise of the action potential in guinea pig papillary muscle preparations without affecting the resting membrane potential and the action potential amplitude. The action potential duration (APD50, APD90) was significantly prolonged by the treatment with 1 and 5 mg/l bunaftine, while it was not changed by the treatment with 10 mg/l. The absolute refractory period (ARP) was also prolonged dose-dependently by the treatment of bunaftine; It was excessively prolonged (177% of control) at the concentration of 10 mg/l. Disopyramide produced similar electrophysiological changes to those of bunaftine except for the prolongation of ARP. ARP/APD90 ratio was significantly increased by bunaftine, but not by disopyramide. These electrophysiological effects of bunaftine and disopyramide observed in guinea pig ventricular preparations were similarly found in canine ventricular muscle preparations. These results indicate that the electrophysiological characteristics of bunaftine are similar to those of disopyramide in that the most prominent effect was the prolongation of ARP.
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PMID:[Electrophysiological effects of bunaftine, an antiarrhythmic drug, on action potential characteristics in ventricular muscle preparations]. 309 38

Disopyramide is an oral antiarrhythmic drug which reduces conduction velocity, prolongs duration of action potential and the effective refractory period, and exerts vagolytic properties. The drug is usually well absorbed orally. The principal use of the drug is to suppress ventricular extrasystoles with usual oral dosage of 100 to 200 mg every 6 h, until blood levels of 2 to 4 micrograms/mL are attained. The use of the drug for suicide is uncommon as it is a prescription drug. Two cases of fatal disopyramide intoxication seen at the Los Angeles County Medical Examiner's Office will be discussed followed by a review of the literature of fatal suicidal disopyramide overdose. Case 1 was a 31-year-old male pharmacist with known history of depression and no history of heart disease. His decomposed remains were found with a suicide note and with several disopyramide tablets. At autopsy the blood level for disopyramide was 146 micrograms/mL. Case 2 is a 40-year-old male with history of alcoholism and prior suicidal attempts who regularly took disopyramide to control ventricular arrhythmias. He apparently ingested 36 100-mg tablets of disopyramide before his final collapse. At autopsy his blood level of disopyramide was 63 micrograms/mL.
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PMID:Fatal disopyramide intoxication from suicidal/accidental overdose. 332 13

Milrinone (M) has been shown to improve left ventricular (LV) performance in animal and human studies. M has strong vasodilator action, and whether increased LV performance is due primarily to vasodilation or to a direct positive inotropic effect is unclear. Ten mongrel dogs were studied. Disopyramide caused a significant and sustained decrease in LV function and was a good model for myocardial depression. At equal reduction in systemic vascular resistance (SVR), M reversed this LV depression to a significantly greater degree than nitroprusside (NP) did. At equal levels of vasodilation, M produced significantly greater improvement in indices of LV function than NP did in our model of disopyramide-induced LV failure. This suggest that its effect on LV function is not due entirely to afterload reduction, or to reflex sympathetic stimulation, but has a substantial component of direct inotropic stimulation. This study also demonstrated a reversal of disopyramide-induced LV dysfunction by M, which may be clinically useful since, as in many antiarrhythmics, myocardial depression may be a limiting factor in its use.
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PMID:Evaluation of the vasodilator vs inotropic effect of milrinone using an animal model of left ventricular failure: reversal of disopyramide depression of the myocardium with milrinone. 366 8

In order to use antiarrhythmic drugs safely, one must understand their hemodynamic effects. Quinidine and the calcium antagonists have direct cardiac effects and frequently opposing autonomically mediated or indirect cardiac effects. Lidocaine is exceptionally well tolerated, even by patients with severe left ventricular dysfunction. Phenytoin and procainamide have the potential for serious adverse effects, but are generally well tolerated at usual doses. Disopyramide causes serious depression of left ventricular function in many patients because of its direct myocardial depressant and peripheral vasoconstricting actions. Although bretylium causes an immediate increase in contractility, it can ultimately result in important hypotension. In this review the in vitro and in vivo hemodynamic effects of these and other antiarrhythmic drugs are discussed to provide information that will assist the clinician in using these drugs properly.
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PMID:Hemodynamic effects of antiarrhythmic drugs. 641 78

We performed electrophysiologic studies before and after oral administration of disopyramide phosphate, 200 mg every 6 hours, in 20 patients with atrioventricular (AV) reentrant tachycardia using a retrogradely conducting accessory pathway. Disopyramide markedly depressed retrograde accessory pathway conduction by increasing the mean ventricular paced cycle length that produced ventriculoatrial block (less than or equal to 287 +/- 4 to greater than or equal to 392 +/- 22 msec, p less than 0.01); it also depressed antegrade normal pathway AV conduction by increasing the atrial paced cycle length that produced AV block (287 +/- 9 to 328 +/- 7 msec, p less than 0.01). In 14 patients, tachycardia could not be induced or sustained after disopyramide phosphate. In 13 patients, this reflected depression of the retrograde limb with either absence of atrial echoes (nine patients) or induction of nonsustained tachycardia that terminated after the QRS complex (four patients), and in one, it reflected depression of the antegrade limb with induction of a single atrial echo not followed by a QRS response. In six patients, sustained tachycardia could still be induced after disopyramide. Oral disopyramide phosphate is effective in preventing induction of sustained AV reentrant tachycardia in most patients. This effect is achieved by depression of the retrograde limb of the reentrant circuit.
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PMID:Effects of oral disopyramide phosphate on induction and sustenance of atrioventricular reentrant tachycardia incorporating retrograde accessory pathway conduction. 680 67

Intracellular microelectrode recording techniques were used to elucidate the mechanism of the antiarrhythmic action of disopyramide in an isolated rabbit ventricular muscle perfused by hypoxic Tyrode's solution. Hypoxia induced no significant changes of the resting membrane potential or action potential amplitude but decreased the maximum upstroke velocity of the action potential (dV/dt max) and shortened the action potential duration and the effective refractory period. Disopyramide in a dose of 5 microgram/ml induced a significant decrease of resting membrane potential and action potential amplitude of hypoxic muscle while it did not alter these parameters in oxygenated muscle. Disopyramide depressed dV/dt max in hypoxic muscle as well as in oxygenated muscle. However, there was much greater depression in hypoxic cells. After disopyramide, action potential duration at the 90% level of repolarization and the effective refractory period were prolonged in both hypoxic and oxygenated ventricular muscle. However, disopyramide lengthened the effective refractory period of hypoxic muscle to a much greater degree than that of oxygenated muscle. This resulted in a decrease of disparity in refractoriness. The above differential effects of disopyramide in oxygenated and hypoxic tissue may account for its effectiveness in postinfarction re-entrant arrhythmias.
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PMID:Electrophysiological effects of disopyramide on hypoxic rabbit ventricular muscle. 709 72

By means of intracardiac recordings and programmed electrical stimulation of the heart, the combination effect of verapamil and disopyramide on induction of circus movement tachycardia was studied in 8 patients with anomalous extranodal atrioventricular (A-V) pathway. In 4 of 6 patients who manifested reproducible circus movement tachycardia, verapamil, 0.2 mg/kg intravenously administered, prevented the induction of tachycardia by increasing the A-V nodal refractoriness. Disopyramide in a dose of 2 mg/kg was injected 30 minutes after the start of verapamil administration, when prolongation of the A-V nodal conduction time (A-H interval) had continued in most of the patients. Disopyramide lengthened the effective refractory period of the anomalous pathway in all patients in whom this could be determined. The A-H interval, which had been prolonged by verapamil, was shortened in 4 patients and about unchanged in the remaining 4. After addition of disopyramide, sustained tachycardia could be induced in 2 patients who had lost the ability of initiating circus movement tachycardia after verapamil administration. Thus, disopyramide, when administered together with verapamil, may block the effect of verapamil on the A-V node by its anticholinergic action. A concomitant prescription of disopyramide with verapamil in expectation of the depression of both the anomalous pathway and the A-V node may have an untoward outcome.
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PMID:Combined effect of verapamil and disopyramide on induction of circus movement tachycardia in patients with pre-excitation. 729 93

The electrophysiologic actions of disopyramide phosphate on reentrant ventricular tachycardia induced by premature ventricular stimuli were evaluated in conscious dogs 2 to 4 days after myocardial infarction. Disopyramide was administered as a series of intravenous infusions to obtain successive steady state plasma disopyramide concentrations of 1.02 +/- 0.02, 2.05 +/- 0.08, 3.94 +/- 0.09 and 7.69 +/- +/- 0.18 micrograms/ml (mean values +/- standard error of the mean). Disopyramide plasma concentrations of 1.02 +/- 0.02 micrograms/ml produced an increase in the rate and duration of ventricular tachycardia as well as in the interval during which premature ventricular stimuli produced ventricular tachycardia. The effective refractory period of normal myocardium was decreased and conduction (activation time) was improved in ischemic myocardium. Increasing steady state plasma disopyramide concentrations slowed the rate of ventricular tachycardia without decreasing its duration. Slowing of the rate of tachycardia occurred simultaneously with a depression of conduction in normal and ischemic myocardium and an increase in ventricular refractoriness. Induction of ventricular tachycardia was prevented only at steady state plasma disopyramide concentrations of 7.69 +/- 0.18 micrograms/ml. The results of this study suggest that subtherapeutic plasma concentrations of disopyramide may facilitate the development of reentrant ventricular arrhythmia in the electrically unstable heart. Ventricular tachycardia or fibrillation, or both, may be prevented only by plasma disopyramide concentrations that are in excess of the normal therapeutic range of 2 to 4 micrograms/ml.
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PMID:Electrophysiologic effects of disopyramide phosphate on reentrant ventricular arrhythmia in conscious dogs after myocardial infarction. 743 89


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