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At least 1,243 records · Page 69Linked to original sources
PubMed2003

Ropivacaine combined with various anti-arrhythmic drugs results in mild alterations in myocardial contractility in pigs.

PURPOSE: The present study was undertaken following the observation of a marked decrease in myocardial contractility after ropivacaine in a patient on amiodarone, in order to investigate the cardiovascular effects of combining ropivacaine with anti-arrhythmic drugs (AARD). METHODS: Anesthetized domestic pigs were treated with disopyramide, flecainide, atenolol, amiodarone, diltiazem or nicardipine at a dose leading to blood levels obtained in treated patients, then received 1 mg*kg(-1) ropivacaine. Blood pressure (BP), left venticular (LV) dP/dt max, sinus heart rate, and intraventricular conduction time were measured before and following the administration of AARD, and following ropivacaine at different time points. RESULTS: All tested AARD induced the expected hemodynamic and electrophysiologic effects. Following ropivacaine, a 20 to 35% decrease in LV dP/dt max of prolonged duration was observed with amiodarone only. A brief 10 to 20% decrease in mean BP was observed in all animals, except those treated with nicardipine who sustained an important and prolonged decrease in BP. All other variables were not significantly affected. DISCUSSION: The combination of ropivacaine with AARD was always associated with a slight drop in LV dP/dt max. The effect on mean BP was slight, except with nicardipine. Clinicians should be aware of the interactions of ropivacaine with AARD, especially amiodarone and nicardipine.

Amides↗
PubMed2002

Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities.

OBJECTIVE: Alpha(1)-acid glycoprotein (AAG) is a major binding protein for neutral and basic drugs because of its great drug affinity. AAG has three main genetic variants--F1, S, and A variants. Several attempts have been made to elucidate the differences in compositions of the carbohydrate moiety and structure-function relationships such as drug-binding differences. However, there have been few reports on age- and gender-related differences in compositions or concentrations of the carbohydrate moiety of AAG variants. The aim of this study was to clarify the age- and gender-related differences in carbohydrate concentrations and in drug-binding capacities of AAG glycoforms. METHODS: The sera used in this study were obtained from 32 healthy subjects (17 men and 15 women, aged 16-84 years). The AAG glycoforms were isolated by hydroxyapatite chromatography. The binding capacity of AAG to disopyramide (DP), which is a basic drug, was determined using the ultrafiltration method. The concentrations of N-acetylneuraminic acid (NeuAc) and monosaccharides in AAG were determined using high-pH anion-exchange chromatography with pulsed-amperometric detection. RESULTS: The mean plasma AAG concentration in the female subjects was significantly lower than that in the male subjects (0.67 +/- 0.12 mg/ml, mean +/- SD, in females, n = 15, versus 0.81 +/- 0.17 mg/ml in males, n = 17, P < 0.05), but no age-related differences were found (0.75 +/- 0.18 mg/ml in young subjects, n = 24, versus 0.77 +/- 0.12 mg/ml in older subjects, n = 8, n.s.). However, the degree of branching of the glycan chain in the female subjects was significantly lower than that in the male subjects (1.61 +/- 0.17 mol/mol, mean +/- SD, in females, n = 15, versus 1.75 +/- 0.23 mol/mol in males, n = 17, P < 0.05). There was a significant inverse relationship between the binding capacity of AAG to DP (Cb/AAG) and the degree of branching of the glycan chain. The binding capacity (Cb/AAG) decreased as the degree of branching in AAG glycans increased. The binding capacity (Cb/AAG) in the female subjects was significantly higher than that in the male subjects (2.79 +/- 0.59 mg/g AAG in females, mean +/- SD, n = 15, versus 2.37 +/- 0.29 mg/g AAG in males, n = 17, P < 0.05). CONCLUSION. The degree of branching of the glycan chain in AAG plays an important role in drug-binding capacity. Gender-related differences in drug-binding capacity (Cb/AAG) may be caused by differences in the ratios of the extent of branching of the glycan chain in AAG.

Adolescent↗
PubMed2004

Simultaneous supraventricular tachycardias in both fetuses of a twin gestation.

BACKGROUND: Fetal supraventricular tachycardia confers an increased risk of cardiac failure, hydrops, and eventual intrauterine death. Although protocols for prenatal anti-arrhythmic treatment are now well established, few published reports discuss this condition in the setting of multiple pregnancies. CASE REPORT: A 20-year-old primigravida woman with a twin pregnancy presented at 31 weeks of gestation for routine obstetrical check-up which revealed simultaneous supraventricular tachycardia in both fetuses. She was treated with oral digoxin, resulting in successful cardioversion in both of the fetuses, which was maintained until they were delivered by caesarian section at 38 weeks gestation. However, several hours after birth, tachyarrhythmias recurred in each of the infants. Combined disopyramide therapy with digoxin was necessary to control their heart rates. CONCLUSION: The treatment of arrhythmia in fetuses of a multiple gestation presents unique issues, particularly when diagnosed prior to fetal lung maturity.

Administration, Oral↗
PubMed2004

Pharmacological treatment of reflex syncope.

Patient education, identification of possible triggers of syncope and reassurance are a central feature of the management of patients with reflex syncope. Patients should be advised as to the importance of adequate hydration and taught physical countermaneuvers to enhance cardiac venous return. These maneuvers are sufficient for most patients, however, for a small number of patients who continue to have recurrent syncopal events, pharmacological intervention may be considered. Volume expansion can be enhanced with salt and fludrocortisone. Agents from diverse pharmacological classes have been used to attenuate the reflex response, enhance vasoconstriction and attenuate vagal outflow. Alpha adrenoreceptor agonists, anticholinergic agents, theophylline, beta adrenoreceptor antagonists, serotonin reuptake inhibitors and disopyramide are the most widely studied. None of these agents has shown a consistent therapeutic benefit in clinical trials.

Adrenergic Agents↗
PubMed1982

Drug conversion of nonsustained ventricular tachycardia to sustained ventricular tachycardia during serial electrophysiologic studies: identification of drugs that exacerbate tachycardia and potential mechanisms.

Eleven of 83 patients who had ventricular tachycardia (VT) and underwent serial electrophysiologic study (EPS) had a more severe VT induced while receiving a particular antiarrhythmic drug as compared to control study. For all patients only nonsustained VT was initiated during control study, while sustained VT occurred during drug testing with disopyramide (2 patients), quinidine (2 patients), amiodarone (4 patients), and encainide (7 patients), although spontaneous arrhythmias appeared well-controlled prior to repeat testing. Pacing techniques used to induce sustained VT were the same as those used in the control study in eight patients and "less aggressive" in three patients. Almost all episodes of sustained VT resulted in substantial hypotension, especially in patients who were taking encainide. Drugs associated with sustained VT increased the median tachycardia cycle length by 112 msec (p less than 0.005) but increased the median ventricular effective refractory period by only 30 msec (p less than 0.02). Assuming re-entry was responsible for VT, we postulate that drugs facilitated initiation of sustained VT by prolonging activation time but only minimally increasing refractoriness of the tachycardia circuit.

Adult↗
PubMed1983

Electropharmacology of antiarrhythmic drugs.

Cardiac arrhythmias may be caused by abnormalities of impulse initiation, impulse propagation, or a combination of the two. The specific mechanisms that may induce arrhythmias are reviewed, as are the means whereby antiarrhythmic drugs might be expected to modify arrhythmias. The cellular electrophysiologic effects of the following antiarrhythmic drugs are discussed: quinidine, procainamide, disopyramide, lidocaine, tocainide, mexiletine, phenytoin, beta-blocking and slow-channel-blocking drugs, aprindine, bretylium, ethmozin, and amiodarone. A knowledge of the similarities and differences of their actions on the determinants of conduction, on repolarization and refractoriness, on automatic mechanisms, and on afterdepolarizations, when considered in the context of the mechanism of clinically occurring tachyarrhythmias, may provide the correct framework for the choice of an appropriate agent for the control of an individual disorder of rhythm. However, it is emphasized that neither the precise mechanism of various dysrhythmias nor the fundamental basis for the salutary action of antiarrhythmic compounds is completely understood.

Action Potentials↗
PubMed1978

Pharmacokinetics of antiarrhythmic drugs.

A knowledge of the determinants of the plasma concentrations of antiarrhythmic drugs is important because variation in plasma levels is often greater than the desired therapeutic range. The basic principles of pharmacokinetics are outlined and their application to the design of dosage regimens described. These principles are illustrated in a review of the pharmacokinetics of lidocaine and its congeners, procainamide and its active metabolite (N-acetylprocainamide), quindine, disopyramide, phenytoin and propranolol, with particular emphasis of the factors that contribute to altered disposition.

Administration, Oral↗
PubMed1983

Hemodynamic effects of antiarrhythmic drugs.

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.

Amiodarone↗
PubMed1992

On the mechanism of termination and perpetuation of atrial fibrillation.

In an effort to further clarify the mechanism of termination and perpetuation of atrial fibrillation (AF), the intraatrial potentials during AF induced by programmable electrical stimulation were analyzed using the concept of wavelength which represents the size of a microreentrant circuit. Thirty patients with inducible AF were divided into 2 groups: 20 patients with AF that terminated spontaneously (group 1) and 10 patients with AF that did not terminate spontaneously (group 2). Wavelength is the product of refractory period and conduction velocity. During AF, the refractory period of the local atrial tissue was considered to correlate with the mean interval between each intraatrial potential (mean ff). An inverse relation was considered present between conduction velocity of the impulse and the width of intraatrial potentials (f width). Thus, the wavelength index was defined as (mean ff)/(mean f width). Ten intraatrial potentials at the high right atrium were sampled for measurement. Group 1 had higher wavelength indexes just after the induction of AF than did group 2 (1.33 +/- 0.31 vs 1.10 +/- 0.05, p less than 0.05). In group 1, the wavelength indexes were increased from the initial value to 1.49 +/- 0.36 just before termination of AF (p less than 0.001). In 3 group 2 patients, AF stopped after disopyramide was administered intravenously, whereas the wavelength indexes at the end of AF were higher than those before drug administration (1.27 +/- 0.08 vs 1.16 +/- 0.04, p less than 0.05). In conclusion, prolongation of the wavelength appears to be a major determinant for termination of AF, and shorter wavelengths are necessary for perpetuation of AF.

Adult↗
PubMed1984

Long-term antiarrhythmic therapy. Problem of low drug levels and patient noncompliance.

Maintenance of adequate serum blood levels is crucial to successful antiarrhythmic therapy. Serum levels of four antiarrhythmic agents (long-acting procainamide, quinidine sulfate, quinidine gluconate, and disopyramide) were determined in 98 consecutive ambulatory patients receiving long-term oral therapy. Medication dosages, dosing intervals, and time elapsed from last dosage until blood sampling were determined. Seventy-five patients (76.5 percent) had subtherapeutic blood levels (with mean levels less than 50 percent of the suggested minimum), and only 22 patients (22.5 percent) had therapeutic levels. Even among the 61 patients who claimed to have taken their medications within the six hours prior to blood sampling, 43 (70 percent) had subtherapeutic levels. These ratios held among all subgroups studied. Physicians should be aware of the high proportion of patients receiving long-term oral antiarrhythmic therapy with inadequate serum blood levels when planning therapeutic regimens.

Adult↗
PubMed1991

Utility of upright tilt-table testing in the evaluation and management of syncope of unknown origin.

PURPOSE: Vasovagally mediated hypotension and bradycardia are believed to be common, but difficult to diagnose, causes of syncope. Upright tilt-table testing has been proposed as a possible way to test for vasovagal episodes. This study investigated the clinical utility of this technique in the evaluation and management of patients with syncope of unknown origin. PATIENTS AND METHODS: Twenty-five patients with recurrent unexplained syncope and six control subjects were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/minute given intravenously), in an attempt to provoke bradycardia, hypotension, or both. Of the 25 patients, there were 14 males and 11 females, with a mean age of 50 +/- 16 years. Six control patients with no history of syncope were also studied. All tilt-positive patients received therapy with either beta-blockers, disopyramide, transdermal scopolamine, or hydroflurocortisone, the efficacy of which was evaluated by another tilt-table test. RESULTS: Syncope occurred in six patients (24%) during the baseline tilt and in nine patients (36%) during isoproterenol infusion (total positives, 60%). None of the controls had syncope during the test. All patients who had positive test results eventually became tilt-table-negative by therapy, and over a mean follow-up period of 16 +/- 2 months no further episodes have occurred. CONCLUSION: From this study we conclude that upright tilt-table testing combined with isoproterenol infusion is clinically useful in the diagnosis of vasovagal syncope and the evaluation of pharmacologic therapy.

Adolescent↗
PubMed1991

Membrane stabilising properties of the selective 5-HT2 receptor agonist, (+/-)-DOI.

The effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2 receptor agonist, on nerve conduction in the isolated frog sciatic nerve trunk were examined. Compound action potential amplitude was concentration dependently decreased by (+/-)-DOI (EC50 = 1.2 mM), an effect that was not altered by the presence of ketanserin and with a similar potency to lignocaine. (+/-)-propranolol and disopyramide. The results indicate that (+/-)-DOI has membrane stabilising properties, in addition to its reported 5-HT2 agonist actions.

Action Potentials↗
PubMed1990

Simple in vitro method to characterize antiarrhythmic agents.

A simple, nonmicroelectrode method was developed for the in vitro identification and characterization of potential antiarrhythmic agents. To evaluate the method, standard antiarrhythmic agents from three different classifications (I, III, IV) were tested in isolated right ventricular guinea pig papillary muscles for their effect on developed tension (DT), excitability (EX), and effective refractory period (ERP). ERP was measured with the use of paired field stimuli. Depression or reversal of the force frequency relationship was an index of an agent's effect on DT. A shift in the stimulus strength-duration relationship was an index of an agent's effect on EX. A computer program was developed for data handling and analysis. Disopyramide phosphate (D, 3.0 x 10(-5) M), sotalol (S, 3.0 x 10(-5) M), clofilium phosphate (C, 1.0 x 10(-5) M), and N-acetyl procainamide hydrochloride (N, 3.0 x 10(-5) M) significantly prolonged ERP (+20, +35, +24, +16 ms, respectively), while verapamil (V, 3.0 x 10(-7) M) and the distilled water vehicle (W) did not. D and V significantly decreased DT (-78% and -57% at 1 Hz, respectively) while W, S, C, and N did not. Only D decreased EX. These data correspond well with findings in other models reported in the literature, supporting the use of this simple in vitro method for identification and characterization of potential antiarrhythmic agents.

Acecainide↗
PubMed1977

Toxicological evaluation of Norpace after intravenous administration to rat and dog.

Norpace (disopyramide phosphate) is a drug for treating cardiac arrhythmias. It has been evaluated for potential toxicological effects in albino rats and Beagle dogs, to provide safety support for clinical studies involving intravenous infusion. The compound was dissolved in Sodium Chloride for Injection, U.S.P. and administered daily by continuous intravenous infusion to groups of rats and dogs. Dose levels to 4.95 mg/kg/h for 14 and 28 consecutive days, respectively were employed. Rats received the formulation for 6--12 h daily; dogs were infused for 6 h daily. Conventional physical, cardiovascular, hematology, clinical chemistry and postmortem gross and microscopic examinations were performed. No compound-related changes were observed in the physical examinations (including ophthalmic), blood pressure (rat), ECG (dog), body weight, or clinical lab parameters evaluated; Food consumption was unontinuous restraining procedure employed during infusions reduced food consumption in all dogs, however, Postmortem examination did not reveal any lesions unique to treated animals. Some dogs exhibited intravenous fibrin thrombi at the site of injection. Organizing blood clots were occasionally present in the thoracic cavity of the rat. These findings were considered related to the infusion technique employed, rather than the drug administered. It was concluded that daily intravenous infusions of Norpace at doses up to 4.65 mg/kg/h to rats and dogs for 14 and 28 consecutive rays respectively, cause no biologically meaningful detrimental effects.

Animals↗
PubMed1991

Effects of antiarrhythmic drugs on canine atrial flutter due to reentry: role of prolongation of refractory period and depression of conduction to excitable gap.

Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial flutter (cycle length 120 +/- 4 to 131 +/- 3 ms) caused by reentry. Atrial flutter was induced in 32 anesthetized open chest dogs after placement of an intercaval crush. The excitable gap ranged from 9 +/- 2% to 11 +/- 4% of the basic flutter cycle length. The effective refractory period in the reentrant circuit during atrial flutter was estimated by subtracting the excitable gap from the basic flutter cycle length. Prolongation of flutter cycle length by the test drugs was proportional to the interatrial conduction time (r = 0.87, p less than 0.001). Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each. E-4031 prolonged the refractory period during atrial flutter to 129 +/- 6 ms, which did not differ significantly from the flutter cycle length immediately before termination (134 +/- 4 ms). The refractory period during atrial flutter after injection of the other drugs was shorter than the flutter cycle length before termination of atrial flutter (for example, flecainide 126 +/- 5 vs. 179 +/- 11 ms, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Characterisation of recombinant HERG K+ channel blockade by the Class Ia antiarrhythmic drug procainamide.

Class Ia antiarrhythmic drugs, including procainamide (PROC), are associated with cardiac sodium channel blockade, delayed ventricular repolarisation and with a risk of ventricular pro-arrhythmia. The HERG K(+) channel is frequently linked to drug-induced pro-arrhythmia. Therefore, in this study, interactions between PROC and HERG K(+) channels were investigated, with particular reference to potency and mechanism of drug action. Whole-cell patch-clamp recordings of HERG current (I(HERG)) were made at 37 degrees C from human embryonic kidney (HEK 293) cells stably expressing the HERG channel. Following activating pulses to +20 mV, I(HERG) tails were inhibited by PROC with an IC(50) value of approximately 139 microM. I(HERG) blockade was found to be both time- and voltage-dependent, demonstrating contingency upon HERG channel gating. However, I(HERG) inhibition by PROC was relieved by depolarisation to a highly positive membrane potential (+80 mV) that favoured HERG channel inactivation. These data suggest that PROC inhibits the HERG K(+) channel by a primarily 'open' or 'activated' channel state blocking mechanism and that avidity of drug-binding is decreased by extensive I(HERG) inactivation. The potency of I(HERG) blockade by PROC is much lower than for other Class Ia agents that have been studied previously under analogous conditions (quinidine and disopyramide), although the blocking mechanism appears similar. Thus, differences between the chemical structure of PROC and other Class Ia antiarrhythmic drugs may help provide insight into chemical determinants of blocking potency for agents that bind to open/activated HERG channels.

Anti-Arrhythmia Agents↗
PubMed1982

Simultaneous analysis of antiarrhythmic drugs and metabolites by high performance liquid chromatography: interference studies and comparisons with other methods.

Our previously described HPLC method for the simultaneous analysis of several antiarrhythmic drugs and metabolites in serum [Clin. Biochem. 14. 113-118 (1981)] was correlated with an enzyme immunoassay technique (EMIT) for quinidine, procainamide, N-acetyl procainamide, and disopyramide. Correlation coefficients in each case was greater than 0.95. Our method compared favorably with a fluorescent procedure for the quantitation of propranolol in plasma. Interference studies with 34 drugs indicated that the measurements of quinidine and monodealkyldisopyramide were affected by quinine and lidocaine, respectively. Carbamazepine and glutethimide interfered with propranolol, but additional clean-up extractions removed these interferences.

Anti-Arrhythmia Agents↗
PubMed1981

Myocardial conduction time and antiarrhythmic drugs.

Complete a-v block was induced in anesthetized mongrel dogs by direct electrocoagulation of the a-v node. The ventricles were paced by steady stimulation (S1) at a rate of 100/min. and by test stimuli (S2) with varying post S1 delay. Right ventricular myocardial tension was measured from the S2 stimulation site of a specially designed miniature strain gage and from a different site by a Walton-Brodie strain gage. A reproducible time lag between the two sites could be measured by comparing the differences in mechanical response to S2 stimuli. This time difference was called delta IT. delta IT varied markedly (from 10-60 msec) when measured at different sites but no linear relationship between delta IT and the inter-gage distance could be observed. Increasing the S2 current intensity induced shortening of delta IT from 37 +/- 13 msec (mean +/- S.D.) at the threshold current to 16 +/- 10 msec (mean +/- S.D.) with 10 mA. A strength-delta IT curve could be constructed and was found to be remarkably reproducible during the experiment. Quinidine and disopyramide induced upward displacement of the curve, lidocaine did not change it while verapamil lowered the delta IT values. We suggest that delta IT can be used as a reliable indicator of myocardial conduction rate. The possible reasoning for this suggestion has been discussed.

Animals↗