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Biomedical subjects

J Morganroth

Publications and source records attributed to J Morganroth.

At least 55 records · Page 3Linked to original sources
PubMed1990

Placement of moricizine in the selection of antiarrhythmic drug therapy.

The selection of antiarrhythmic drug therapy requires a careful assessment of the benefits of ventricular arrhythmia suppression compared with the risks of antiarrhythmic drug use. Since reduction in sudden cardiac death from ventricular arrhythmia suppression has not been demonstrated, the only indications for antiarrhythmic drug suppression involve the reduction of hemodynamic symptoms such as syncope (a major benefit) or the reduction of nonhemodynamic symptoms such as palpitations or dizziness (a minor benefit). Noncardiac adverse effects and organ toxicity as well as cardiac side effects must be considered when antiarrhythmic drug therapy is initiated. For reduction of nonhemodynamically important symptoms in patients with benign or potentially lethal ventricular arrhythmias, beta blockers are chosen as first-line therapy. Because of moricizine's relatively high effectiveness in suppressing ventricular arrhythmias and its low potential for noncardiac adverse effects and organ toxicity as well as a low incidence of induced proarrhythmia and heart failure, moricizine is selected as the next drug in line. All other class I antiarrhythmic drugs either have been shown to have the potential for increasing sudden cardiac death or have major rates of noncardiac adverse effects or organ toxicity that preclude their use in these patient groups except in special circumstances. In patients with malignant ventricular arrhythmias who present with hemodynamic consequences such as syncope or worse, moricizine also is preferred as an initial drug for consideration. When compared to drugs with class IA and IB action, moricizine has comparable efficacy yet lower rates of noncardiac adverse effects, organ toxicity, proarrhythmia and heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1990

Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available.

To define the practice habits of United States cardiologists and the treatment of ventricular arrhythmias, a random sample of 1,000 of 12,000 cardiologists was sent a pretested questionnaire. After follow-up procedures, 252 responded, of which 18% were academically-based, 29% were hospital-based and 53% were office-based. Attitudes about antiarrhythmic drug therapy for the treatment of ventricular arrhythmias were influenced by the presence and severity of cardiac disease, the presence and severity of cardiac disease, the presence of symptoms and the type of ventricular arrhythmias. In this survey, only 1% of cardiologists treated patients with asymptomatic ventricular premature complexes and no heart disease, but 17% treated such patients if unsustained ventricular tachycardia was present. The treatment rate among cardiologists increased to 38% when coronary artery disease with left ventricular dysfunction was present in patients with asymptomatic ventricular premature complexes. The presence of any cardiac disease and symptomatic ventricular arrhythmias increased the treatment rate to 80 to 100%. Approximately 50% of responding physicians treated patients comparable to the Cardiac Arrhythmia Suppression Trial study population with antiarrhythmic drugs. Beta blockers were the most common antiarrhythmic drug class chosen as the most appropriate initial therapy in new patients with ventricular arrhythmias. Whereas no cardiologists thought that amiodarone was appropriate to initiate in new patients with benign or potentially malignant ventricular arrhythmias, as many as 33 to 43% of cardiologists would use amiodarone for refractory patients with such arrhythmias, a response contradictory to the approved labeling for this drug. Less than one half of cardiologists recognize the high potential organ toxicity for quinidine, procainamide and tocainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1990

Determination of antiarrhythmic drug efficacy in the treatment of ventricular arrhythmias.

The presence of ventricular arrhythmias mark an individual with underlying structural heart disease as a candidate at high risk for sudden cardiac death. It is still unknown whether suppression of those ventricular arrhythmias by all drugs will in fact prevent sudden cardiac death. Therefore, the efficacy of an antiarrhythmic drug at present must be defined as only its pharmacologic activity that relates to its ability to reduce the frequency of ventricular arrhythmias rather than to a potential beneficial effect on patient outcome. Ventricular arrhythmias can be differentiated using a prognostic classification into those that are benign, potentially lethal, or lethal. Benign and potentially lethal ventricular arrhythmias undergo a high degree of spontaneous variability, and therefore the degree of frequency suppression needed to differentiate drug suppression from spontaneous variability must be carefully considered. It therefore is important to establish the mean ventricular premature complex frequency per hour over at least 24 hours at baseline using quantitative continuous ambulatory electrocardiographic (Holter) monitoring. To eliminate spontaneous variability, a repeat Holter monitoring session after the initiated therapy has reached steady state should show at least a 75% reduction in the mean VPC/hr frequency and at least a 90% suppression in the number of beats in the form of nonsustained ventricular tachycardia (NSVT). Exercise testing is a complementary technique and is best suited for patients with NSVT developing during exercise testing from either a "catecholamine" or an "ischemic" mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1989

Prevalence and characteristics of proarrhythmia from moricizine (Ethmozine).

Moricizine was studied in 908 patients with ventricular arrhythmia. Proarrhythmia occurred in 29 (3.2%). When the type of proarrhythmia and the type of ventricular arrhythmia were correlated, no proarrhythmic events occurred in patients with benign ventricular arrhythmia. Three of the 4 deaths due to proarrhythmia occurred in patients with lethal ventricular arrhythmia and 14 of the 15 serious proarrhythmic events occurred in patients with potentially lethal ventricular arrhythmia. The overall proarrhythmia incidence in lethal and potentially lethal ventricular arrhythmias was not different (3.2 vs 3.7%, respectively). Proarrhythmia occurred in patients with more significant structural heart disease or conduction defects at baseline, but was not related to the baseline frequency of ventricular premature complexes. There was no relation between dose of moricizine and incidence of proarrhythmia. All 29 proarrhythmic events occurred within 10 days and 26 of 29 (90%) took place within 7 days of therapy start. Thus, moricizine has a low proarrhythmic potential, especially in patients with lethal ventricular arrhythmias, and may have the best risk/benefit ratio among first-line drugs used in these patients.

Adult↗
PubMed1989

Mechanisms and risk factors for proarrhythmia with type Ia compared with Ic antiarrhythmic drug therapy.

Proarrhythmia defined as the exacerbation of existing arrhythmias or the genesis of new arrhythmias de novo may result from any antiarrhythmic agent. The two general clinical syndromes of sustained arrhythmias that result appear to have distinct clinical properties that are consistent with the proposed basic mechanisms of arrhythmogenesis. Torsades de points occurs most commonly in association with administration of type Ia antiarrhythmic agents and has characteristics most consistent with triggered activity mediated by early after depolarization. Conversely, incessant, sustained, monomorphic, wide complex ventricular tachycardia occurs most commonly in association with type Ic antiarrhythmic agents and has characteristics most consistent with incessant reentry. These general subdivisions are probably oversimplified, and in fact, much overlap likely exists. In addition, these proposed mechanisms may not apply to other forms of proarrhythmia such as an increased frequency of isolated ventricular premature couplets or repetitive forms. Furthermore, proarrhythmia may also occur during treatment of supraventricular arrhythmias; although some of these described syndromes are consistent with incessant reentry, the clinical syndromes are not sufficiently defined to better characterize potential mechanisms. Further investigation, therefore, is needed to better define the mechanisms in question, but the mechanisms proposed in this article help to provide a rational approach toward understanding and dealing with clinical proarrhythmia.

Animals↗
PubMed1988

Evaluation of antiarrhythmic therapy using Holter monitoring.

Premature ventricular complexes and nonsustained ventricular tachycardia mark a person with structural cardiac disease as a high--risk candidate for sudden cardiac death. Such ventricular arrhythmias are considered potentially lethal and should be distinguished from both those that are benign and those that cause hemodynamic consequences (i.e., lethal or malignant arrhythmias). Noninvasive Holter monitoring is the principal technique for detecting and evaluating the presence of potentially lethal ventricular arrhythmias. These arrhythmias undergo a high degree of spontaneous variability. Thus, to define a therapeutic drug effect, a reduction in the frequency of premature ventricular complexes of at least 75% and a reduction in the frequency of nonsustained ventricular tachycardia by at least 90% are required to eliminate the likelihood of spontaneous variability as the cause of this change in the frequency of arrhythmia. To define proarrhythmia, a different algorithm must be applied. When using antiarrhythmic drugs, a quantitative ventricular arrhythmia baseline for both frequency and type of arrhythmia must be established so that after therapeutic intervention repeat Holter monitoring can determine whether efficacy, inefficacy or proarrhythmia had occurred. Holter monitoring clearly reveals differential antiarrhythmic response rates among classes of antiarrhythmic drugs in patients with benign or potentially lethal arrhythmias. However, preliminary data have not clearly defined the relation between antiarrhythmic pharmacotherapy and a reduction in sudden cardiac death. The results of large-scale clinical trials that have only recently been undertaken must be assessed to determine whether sudden cardiac death can be prevented by adequately suppressing potentially lethal ventricular arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1988

Management of arrhythmias in ischemic heart disease. The role of beta blockers.

Ventricular arrhythmias can lead to sudden cardiac death (SCD), and they can be classified according to the risk they present. Lethal ventricular arrhythmias, the least common, present the highest risk for SCD and usually manifest as paroxysmal sustained ventricular tachycardia. Most of the patients have serious left ventricular dysfunction and important hemodynamic symptoms, which must be treated immediately. Potentially lethal arrhythmias are much more common, accounting for most SCD cases. The patients generally have coronary artery disease, and the ventricular arrhythmias usually do not cause hemodynamic symptoms. Premature ventricular complexes (PVCs) and nonsustained ventricular tachycardia are the usual forms. PVCs are classified as benign in the absence of coronary artery disease, structural heart disorders, and hemodynamic symptoms, and in these cases the risk for SCD is low. Beta blockers have been shown to reduce the SCD rate, and although the precise mechanism is unknown, the effect may be in part on an antiarrhythmic basis. Like the class IA and IB antiarrhythmic agents (the Vaughan Williams classification), beta blockers are effective in about 50% of patients with either potentially lethal or benign ventricular arrhythmias. However, compared with such agents, beta blockers have a more favorable side effects profile.

Adrenergic beta-Antagonists↗
PubMed1988

Noninvasive testing for ventricular arrhythmias.

Before treating patients with ventricular arrhythmias, it is important to classify the arrhythmias as benign, potentially lethal, or lethal. The vast majority of patients seen in clinical practice have benign or potentially lethal forms, which can be evaluated with noninvasive electrocardiographic techniques, such as continuous Holter monitoring and exercise testing. Lethal ventricular arrhythmias are probably best managed with invasive electrophysiologic testing. Quantitative Holter monitoring is essential both before starting antiarrhythmic therapy to establish a baseline and after starting therapy to determine whether treatment is effective, ineffective, or causing proarrhythmia. Whether adequate suppression of ventricular arrhythmias prevents sudden cardiac death is still unknown but is currently being evaluated by the Cardiac Arrhythmia Suppression Trial of the National Institutes of Health, Bethesda. The results are expected in the mid-1990s.

Anti-Arrhythmia Agents↗
PubMed1988

New antiarrhythmic drugs.

While controversy still exists as to the precise indications for the treatment of all forms of ventricular arrhythmia, advances in the number and, more importantly, type of antiarrhythmic drugs can provide the clinician with a rational basis for selecting antiarrhythmic drug therapy. A host of new agents with different pharmacokinetic and electrophysiological actions are now available, and can be compared or contrasted to conventional antiarrhythmic agents such as quinidine, procainamide, disopyramide, lignocaine (lidocaine) and bretylium. This review summarises the electrophysiological, haemodynamic, pharmacokinetic, and efficacy and safety data of mexiletine, tocainide, flecainide, encainide, propafenone, amiodarone, sotalol, pirmenol, cibenzoline (cifenline) and ethmozine (moracizine, moricizine), and aims to provide a basis on which clinicians can compare and contrast these agents and form an algorithm for selection of antiarrhythmic drug therapy in the treatment of patients with ventricular arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1987

Comparative efficacy and safety of oral mexiletine and quinidine in benign or potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral mexiletine hydrochloride and quinidine sulfate were compared at 29 clinical centers in a double-blind, parallel-group trial involving 491 patients with benign or potentially lethal ventricular arrhythmias. Responders were defined as those who had at least a 70% reduction in the frequency of ventricular premature complexes (VPCs) that persisted for 12 weeks, and who experienced no intolerable side effects that required discontinuation of therapy. Of the patients available for analysis, 71 of 232 (31%) in the mexiletine and 73 of 225 (32%) in the quinidine group met these criteria. The dose range used for mexiletine was 200 to 400 mg every 8 hours, and that for quinidine 200 to 400 mg every 6 hours. More than half of the patients in each group were successfully treated with the smallest dose (200 mg every 8 hours mexiletine vs 200 mg every 6 hours for quinidine). Quinidine significantly prolonged the QT interval, whereas mexiletine did not. Proarrhythmic reactions were recorded in 18 of 221 (9%) patients taking quinidine and 10 of 217 (5%) patients taking mexiletine. There was no difference in the incidence of adverse reactions between the 2 groups; in both, the most common side effects were related to the gastrointestinal and central nervous systems. Mexiletine thus represents an alternative to quinidine for the treatment of patients with ventricular arrhythmias.

Administration, Oral↗
PubMed1987

Pharmacokinetics of moricizine HCl.

Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of moricizine HCl. The bioavailability of moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when moricizine HCl is coadministered with digoxin. Because moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.

Anti-Arrhythmia Agents↗
PubMed1987

Efficacy and tolerance of Ethmozine (moricizine HCl) in placebo-controlled trials.

To investigate the tolerance and efficacy of moricizine HCl, single-blind placebo-controlled trials were conducted. The early protocols involved patients hospitalized for 14 days, and daily Holter monitoring was used to document efficacy and the degree of spontaneous variability of ventricular premature complexes (VPCs). Moricizine HCl was given orally from 2.9 to 15.3 mg/kg 3 times daily. Patients with lethal ventricular arrhythmias were excluded. Additional outpatient trials were conducted to define long-term efficacy and safety. A dose-response relation between moricizine HCl and the percentage of reduction in frequency of benign or potentially lethal ventricular arrhythmias was documented. Eighty-five percent of patients achieved a reduction in VPCs greater than 75% with daily dosages ranging from 10.1 to 15 mg/kg. This corresponded to a 95% decrease in mean frequency of VPCs. Long-term studies demonstrated no evidence of compromise in left ventricular function, and the proarrhythmic rate was only 2%. Symptomatic side effects were mild and usually well tolerated. Nausea, the most common, occurred in 11% of patients and dizziness in 9%. These results indicate that moricizine HCl is an effective and well-tolerated antiarrhythmic agent.

Anti-Arrhythmia Agents↗
PubMed1987

Antiarrhythmic effects of beta-adrenergic blocking agents in benign or potentially lethal ventricular arrhythmias.

Classification of ventricular arrhythmias into those that are benign, potentially lethal and lethal is based on their associated risk for producing sudden cardiac death. This classification system is useful in defining indications for the treatment of ventricular arrhythmias and predicting differential rates of antiarrhythmic drug efficacy and toxicity. Whether the reduction of potentially lethal ventricular arrhythmias will prevent sudden cardiac death remains to be determined. The class II antiarrhythmic agents--the beta-adrenergic blocking drugs--have been shown to reduce sudden cardiac death in postmyocardial infarction patients, but the precise mechanism of their effect has not been defined. beta blockers are efficacious in approximately 50% of patients with benign or potentially lethal ventricular arrhythmias. This response is comparable to that seen with the class IA agent disopyramide or the class IB agents tocainide and mexiletine. beta blockers have favorable side-effect profiles including a low incidence of proarrhythmia and a lack of organ toxicity such as hepatitis, pulmonary fibrosis or agranulocytosis, which are concerns with class I and class III antiarrhythmic drugs. The proper dosage of the beta blocker is critical in limiting adverse effects. In a study of 23 patients with benign or potentially lethal ventricular arrhythmias, 11 (48%) of the patients responded to nadolol with a reduction of greater than 75% in arrhythmia frequency, and several patients responded at nadolol dosages as low as 10 mg daily. Thus, it is plausible to consider beta blockers as first-choice antiarrhythmic therapy, even in patients with left ventricular dysfunction when sympathetic tone is not required to maintain cardiac compensation.

Adolescent↗