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Biomedical subjects

J Morganroth

Publications and source records attributed to J Morganroth.

At least 91 records · Page 5Linked to original sources
PubMed1986

Pharmacokinetics of cibenzoline after single and repetitive dosing in healthy volunteers.

Twenty-five healthy, adult male volunteers entered two open-label parallel studies, each designed to define the pharmacokinetics of single and multiple oral doses of cibenzoline. Each volunteer received a single 160-mg oral dose of cibenzoline followed two or three days later by 160 mg of cibenzoline q12h for seven days. Plasma concentration-time profiles and urinary excretion rate data were used to determine pharmacokinetic parameters for unchanged drug. The apparent half-life following administration of the last dose (9.7 hours) was slightly longer than that observed after the first dose (8.4 hours). Total body clearance and nonrenal clearance were decreased after the last dose compared with the first dose, whereas renal clearance was not significantly altered. After both the first and last dose, the renal clearance greatly exceeded the glomerular filtration rate, suggesting that tubular secretion participates in the renal excretion of cibenzoline. Plasma concentrations from samples collected during the multiple-dose regimen suggest that a slight but statistically significant diurnal variation in the absorption and/or clearance of drug occurred during the course of the study. Overall, the pharmacokinetics of cibenzoline are characterized by a slightly longer half-life during multiple dosing than that observed following a single dose, due to a decrease in the nonrenal clearance. The multiple-dose pharmacokinetics reported herein are consistent with bid dosing for the maintenance of therapeutic plasma concentrations in patients taking chronic therapy.

Adult↗
PubMed1986

Flecainide: steady state electrophysiologic effects in patients with remote myocardial infarction and inducible sustained ventricular arrhythmia.

The effect of flecainide in 24 patients with inducible sustained ventricular arrhythmia and a history of remote myocardial infarction was determined. Flecainide was administered in oral doses individually adjusted to suppress all spontaneous ventricular tachycardia and 80% of ventricular premature complexes on 24 hour ambulatory (Holter) electrocardiography. Antiarrhythmic therapy, as assessed by Holter monitoring, was adequate in 20 (83%) of the study patients at a mean dose of 144 +/- 28 mg every 12 hours; the mean plasma flecainide level was 583 +/- 329 ng/ml. In 18 patients, the mean sinus cycle length, sinus node recovery time and atrial, atrioventricular nodal and ventricular refractory periods were unchanged. The AH interval increased by 15 +/- 15%, the HV interval by 35 +/- 32% and the QRS duration by 24 +/- 21%. Toxicity or failure to suppress ventricular premature complexes and ventricular tachycardia by Holter monitoring precluded electrophysiologic study with flecainide in four patients; two patients refused electrophysiologic study with flecainide for nonmedical reasons. Ventricular tachycardia was not inducible in 4 (22%) of 18 patients receiving flecainide. Sustained arrhythmia remained inducible in 14 patients (78%) despite evidence of antiarrhythmic efficacy on Holter monitoring, but the rate of the induced ventricular tachycardia was slower and symptoms were alleviated during ventricular tachycardia in 10 (56%) of 18 patients. The 4 patients who had no inducible ventricular tachycardia with flecainide, and the 10 patients who had inducible ventricular tachycardia with a longer cycle length and alleviation of their symptoms, have been followed up as outpatients for 16 +/- 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Classification by type of ventricular arrhythmia predicts frequency of adverse cardiac events from flecainide.

Antiarrhythmic therapy is known to be associated with a significant risk of adverse cardiac reactions, including a proarrhythmic response. This study assessed in 1,330 patients followed up for 292 +/- 393 days the predictive value for cardiovascular safety of a system by which patients were classified according to ventricular arrhythmias on entry, presence or absence of organic heart disease and drug dose for flecainide acetate. Baseline arrhythmia subgroups included patients with premature ventricular complexes only, nonsustained ventricular tachycardia, and sustained ventricular tachycardia. Proarrhythmic events occurred in 6.8% of patients overall and were serious in 2.3% and lethal in 1.0%. However, proarrhythmia was highly dependent on arrhythmia class on entry: serious nonlethal proarrhythmic events occurred in 6.6% of patients with sustained ventricular tachycardia, only 0.9% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes (p less than 0.01). Proarrhythmic death occurred in 3.1% of patients with sustained ventricular tachycardia, 0.2% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes only (p less than 0.01). Proarrhythmia was also influenced by the presence of structural heart disease: serious nonlethal proarrhythmia occurred in 2.6% of patients with versus 0.4% of those without organic heart disease, and death occurred in 1.2 versus 0%, respectively. These adverse events were also dependent on dosing regimen. Flecainide caused premature discontinuation due to new or worsened heart failure in 1.4% of patients, all with underlying organic heart disease; however, heart failure was not clearly related to dose or type of arrhythmia. Symptomatic conduction disturbances occurred in 2.2%, and were predicted by preexistent sinus node disease but not by other baseline features.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1986

Comparative study of encainide and quinidine in the treatment of ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral encainide hydrochloride and quinidine sulfate were compared in a nine center double-blind crossover study in 187 outpatients with benign or potentially lethal ventricular arrhythmias. Patients with at least 30 premature ventricular complexes/h were randomized to receive either encainide, 25 mg four times/day, or quinidine, 200 mg four times/day, for 2 weeks. These doses were continued for another 2 weeks if a 75% or greater reduction in premature ventricular complexes was observed. If this reduction was not seen, encainide was increased to 50 mg four times/day or quinidine to 400 mg four times/day for an additional 2 weeks. Both drugs produced a statistically significant reduction in premature ventricular complex frequency compared with baseline values. Encainide produced a statistically significant greater mean reduction in total premature ventricular complexes than did quinidine during the initial dose phase and after dose adjustment. More patients required dose increases of quinidine (60%) than of encainide (51%). Early discontinuation of treatment resulting in advancement to the next study period occurred in 12 patients taking encainide and 38 patients taking quinidine (p less than 0.05). PR and QRS intervals increased significantly during encainide treatment, as did QTc and JT intervals during quinidine treatment. No adverse reactions resulted from these electrocardiographic changes. Adverse reactions were more common with quinidine than with encainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effect of orally administered celiprolol in patients with chronic atrial fibrillation.

The heart rate increase induced by dynamic exercise in patients with chronic atrial fibrillation is competitively attenuated by beta-blockade. The influence of oral celiprolol on exercise induced tachycardia was evaluated in 23 patients with chronic stable atrial fibrillation in a dose-titration study. This was succeeded by a placebo-controlled double-blind, crossover multi-center trial. During the dose-titration phase each patient underwent a single-blind three week dose escalation period-taking celiprolol 200 mg once daily for one week, celiprolol 400 mg once daily for the third week. After a one week placebo washout, patients then entered a double-blind crossover phase, consisting of one week each of placebo or celiprolol according to a pre-determined randomization. After one week of placebo washout, each patient was crossed-over. In 21 patients celiprolol reduces exercise-induced increased heart rate by approximately 35% when compared with placebo. These results indicate that celiprolol should be effective in controlling the exercise-induced increase in heart rate in patients with chronic atrial fibrillation. In addition, results of 24 h ambulatory ECG monitoring (Holtor monitoring) indicate that celiprolol reduces the ventricular premature contractions.

Administration, Oral↗
PubMed1986

Cardiac arrhythmias in the elderly: antiarrhythmic drug treatment.

The frequency of ventricular arrhythmias increases with age. Several factors make elderly people more prone to antiarrhythmic drug toxicity. Familiarity with the changes in the pharmacokinetics and pharmacodynamics of antiarrhythmic agents may reduce or prevent adverse response in this patient population.

Aged↗
PubMed1986

A noninvasive perspective of electrophysiologic testing.

In this article, the author addresses the comparison between non-invasive and invasive approaches to detect and follow treatment of cardiac arrhythmias. Four major areas are discussed: determination of the mechanism of arrhythmias, arrhythmia diagnosis, defining the patient's risk from arrhythmia, and selection of therapy.

Arrhythmias, Cardiac↗
PubMed1986

Oral antiarrhythmic agents for ventricular arrhythmias.

Ventricular tachyarrhythmia is the most common terminal event causing sudden cardiac death. Risk stratification using 24-hour Holter monitoring to identify ventricular ectopy and noninvasive techniques to detect abnormal left ventricular function is becoming routine. Many cardiologists treat patients with potentially lethal ventricular arrhythmias even though it is unknown as yet whether sudden cardiac death can be prevented. Patients with lethal ventricular arrhythmias are always treated. A number of new oral antiarrhythmic agents have become available to the clinician. The modified Vaughan-Williams classification system categorizes the drugs according to their electrophysiologic and clinical characteristics. The class IC antiarrhythmic agents are emerging as the potential drugs of first choice for patients with benign or potentially lethal ventricular arrhythmias. The betablockers (class II) are used as antiarrhythmic agents, particularly in the presence of active myocardial ischemia or high catecholamine levels and in the postmyocardial infarction patient. Amiodarone (class III) may cause serious side effects and is reserved for patients with lethal ventricular arrhythmias when all other available agents have failed.

Administration, Oral↗
PubMed1986

Silent myocardial ischemia as a mechanism of sudden cardiac death.

Sudden death, a major cause of mortality in the Western world, usually results from electrophysiologic phenomena in chronically damaged hearts with advanced coronary atherosclerosis. The exact pathophysiologic mechanisms are not known, but there is reasonable circumstantial evidence to implicate myocardial ischemia--clinically manifest or silent--as one of probably multiple factors of pathogenetic significance. This may be on the basis of coronary artery spasm, platelet aggregation, left ventricular dysfunction perpetuating a vicious circle of hypoperfusion and ventricular vulnerability to electrical instability. The increasing use and quality of continuous ambulatory electrocardiographic (Holter) monitoring have allowed improved detection of ST-segment changes and arrhythmias. The majority of sudden deaths result from ventricular tachyarrhythmias degenerating into ventricular fibrillation, and a more significant proportion of these than had been previously thought may be ischemically mediated. Importantly, as many as 20 to 25 per cent of the approximately 450,000 yearly terminal events represent bradyarrhythmias that may be preceded or accompanied by silent myocardial ischemia. Research is still required to determine the incidence, role, and mechanisms of silent myocardial ischemia in sudden death, with the hope that this common catastrophic event can be better prevented.

Aged↗
PubMed1985

Comparative efficacy and tolerance of esmolol to propranolol for control of supraventricular tachyarrhythmia.

This multicenter, double-blind, randomized, parallel study compared the effectiveness and tolerance of intravenous esmolol with intravenous propranolol in patients with supraventricular tachyarrhythmia (heart rate [HR] greater than 120 beats/min). Efficacy was evaluated in 53 patients receiving esmolol and in 57 patients receiving propranolol. Patients randomized to esmolol received infusions of various doses of esmolol ranging from 50 to 300 micrograms/kg/min (each dose infused for 5 minutes) over a 30-minute titration period with intermittent placebo boluses of propranolol. Those randomized for propranolol received 1 mg/min for the first 3 minutes, and then another 3 mg from minutes 5 to 8 with continuous placebo esmolol infusion during the 30-minute titration period. A therapeutic response, defined by 20% or greater reduction in HR, HR less than 100 beats/min or conversion to normal sinus rhythm, was achieved in 72% of patients on esmolol compared with 69% of patients on propranolol (difference not significant). The therapeutic response was maintained in 67% of patients on esmolol and 58% of patients on propranolol (difference not significant) during a 4-hour maintenance period. Conversion to normal sinus rhythm occurred in 14% of esmolol patients and 16% of propranolol patients during titration and 10% of esmolol and 8% of propranolol patients during maintenance. After discontinuation of study drugs, a more rapid reversal of the reduction in HR was observed in esmolol patients compared with those patients receiving propranolol. Adverse reactions were seen in 29 (45%) patients on esmolol and 11 (18%) patients on propranolol. The principle adverse reaction was hypotension, which was predominantly asymptomatic and found in 23 patients receiving esmolol and 4 receiving propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

Comparative efficacy and safety of oral tocainide and quinidine for benign and potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral tocainide hydrochloride and quinidine sulfate were compared in a double-blind, 3-center, parallel trial involving 133 patients with benign and potentially lethal ventricular arrhythmias. Baseline demographic, etiologic, functional and ventricular arrhythmia data were not significantly different between the 2 groups. Two weeks of an initial placebo period were followed by 8 weeks of active drug treatment, concluding with 4 weeks of washout. Frequent 24-hour ambulatory electrocardiographic monitoring was used to judge efficacy. Ten of 27 patients (37%) receiving tocainide and 12 of 24 patients (50%) receiving quinidine had a 75% reduction with drug treatment compared with the initial placebo period (p greater than 0.25). Total abolition of ventricular tachycardia occurred in 6 of 16 patients (37%) receiving tocainide and 6 of 13 patients (43%) receiving quinidine (p greater than 0.25). Conditions that required discontinuation of therapy occurred in 18 of 67 patients (27%) receiving tocainide and 16 of 66 (24%) receiving quinidine (difference not significant). More patients had dizziness during tocainide treatment and diarrhea during quinidine treatment. Quinidine caused a prolongation in the QT interval (0.03 second); tocainide caused a slight reduction (0.01 second). No important changes in vital signs or laboratory measurements were observed in left ventricular ejection fraction when measured. Thus, tocainide, the new oral analog of lidocaine, appears to be as safe as quinidine but is slightly less effective in suppressing ventricular arrhythmias.

Administration, Oral↗
PubMed1985

Incidence of proarrhythmic effects from quinidine in the outpatient treatment of benign or potentially lethal ventricular arrhythmias.

To determine the prevalence and importance of proarrhythmic events secondary to the initiation of quinidine therapy in outpatients with benign or potentially lethal ventricular arrhythmias, the data from 360 patients treated with quinidine as part of 3 outpatient drug trials were retrospectively reviewed. These patients had at least 30 ventricular premature complexes per hour during placebo treatment and had no evidence of unstable clinical states, hypokalemia, digitalis toxicity, atrial fibrillation or a prolonged QT interval (longer than 0.50 second). The quinidine dose varied from 200 to 400 mg 4 times a day for 2 to 4 weeks. Proarrhythmic effect was defined on Holter monitoring as a 400% increase in frequency of ventricular premature complexes, the presence of new ventricular tachycardia not previously identified or a 10-fold increase in the number of beats of ventricular tachycardia. There was no difference in the demography, response to quinidine therapy or side effects on quinidine among the 3 trials. Six of 360 patients (2%) had a proarrhythmic response and none of these patients had hemodynamic symptoms, required hospitalization or died from the proarrhythmic event. Thus, quinidine can be safely initiated to outpatients who meet the inclusion criteria cited herein.

Ambulatory Care↗
PubMed1985

Effects of intravenous infusion of esmolol and propranolol on biventricular performance at rest and during exercise as assessed by quantitative radionuclide angiography.

This double-blind, randomized, crossover study examined the effects of intravenous infusion of esmolol (a new ultra-short-acting beta-receptor blocking agent) and propranolol on cardiovascular performance at rest and during peak upright exercise in 15 patients. Biventricular function was assessed by means of first-pass radionuclide ventriculography with a computerized multicrystal camera. At rest, significant treatment differences between esmolol and propranolol vs baseline were found for the heart rate, systolic blood pressure, double product, left ventricular ejection fraction (EF), systolic blood pressure to end-systolic volume ratio, cardiac index and right ventricular EF. During exercise, significant treatment differences were also found for the heart rate, systolic blood pressure, double product, right ventricular EF and cardiac index. The mean baseline measurements were higher than the mean treatment measurements, but no significant differences were found between mean esmolol and mean propranolol measurements at rest and during exercise except for the exercise systolic blood pressure, which was lower during esmolol infusion. The magnitude of drug effect was greater at the time of exercise than at rest. The blood level of esmolol decreased markedly by 30 minutes after infusion. Esmolol was well tolerated, with no important local, systemic or laboratory abnormalities. Thus, the effects of esmolol on cardiovascular performance at rest and exercise are similar to those of propranolol.

Aged↗
PubMed1985

Usefulness of electrophysiologic testing in evaluation of amiodarone therapy for sustained ventricular tachyarrhythmias associated with coronary heart disease.

The prognostic importance of electrophysiologic studies in patients with sustained ventricular tachyarrhythmias treated with amiodarone was prospectively studied in 100 consecutive patients. Sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) was inducible in all patients before amiodarone therapy. After amiodarone administration 2 groups of patients were identified. In group 1 patients the ventricular tachyarrhythmia was no longer inducible and in group 2 patients the arrhythmia remained inducible. In group 1, no recurrent arrhythmia occurred during a follow-up of 18 +/- 10 months. In group 2, 38 of 80 patients (48%) had arrhythmia recurrence during a follow-up of 12 +/- 9 months. The difference between group 1 and 2 could not be explained by clinical variables, amiodarone doses or plasma concentrations, or electrocardiographic variables. In patients in whom cardiovascular collapse or other severe symptoms where noted during electrophysiologic study after amiodarone treatment, recurrences caused sudden death (n = 12). However, in patients in whom the induced arrhythmia produced moderate symptoms, the recurrent arrhythmia was nonfatal VT (n = 26). Electrophysiologic testing provides clinical guidance and predicts prognosis in patients treated with amiodarone as it does for the evaluation of other antiarrhythmic agents.

Adult↗
PubMed1985

Comparative efficacy and safety of short-acting and sustained release quinidine in the treatment of patients with ventricular arrhythmias.

A comparative, fixed-dose, parallel, randomized, blinded trial to define the efficacy and safety of a new once-a-day quinidine preparation, Quiniday, at 1200 mg per day, was compared to quinidine sulfate (as Quinora, 300 mg four times daily, and Quinidex Extentabs, 600 mg twice daily) and to quinidine gluconate (as Quinaglute Dura-Tabs, 648 mg twice daily). After placebo washout from all prior antiarrhythmic agents, 76 patients with at least 30 ventricular premature complexes (VPCs)/hr on 48-hour ambulatory monitoring were randomized to 3 weeks of treatment with one of the four study drugs. There was no difference in the etiologic, demographic, New York Heart Association therapeutic classification, or ventricular arrhythmia frequency at baseline between the patients randomized to the four groups. There was no statistically significant difference between the percent efficacy for VPC reduction on any drug compared to baseline or in the percent efficacy of reduction in beats of ventricular tachycardia. There was no difference between the four agents in terms of types of side effects noted nor in their overall prevalence or need for premature discontinuation of therapy. This study demonstrated that a variety of quinidine preparations exist that do not differ in terms of their efficacy or safety, but that a long-acting, once-a-day preparation (Quiniday) was as effective and safe as other forms of quinidine despite its once-a-day dosing schedule. More compliant dosing regimens with effective well-known antiarrhythmic agents are important in the treatment of patients with potentially lethal ventricular arrhythmias, in the hope that sudden cardiac death can be prevented.

Arrhythmias, Cardiac↗