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PubMed1988

Ventricular Wenckebach after intravenous therapy with class I antiarrhythmic agents.

Two unusual cases of Wenckebach-like conduction block in the infranodal tissues which developed after an intravenous dose of a Class I antiarrhythmic drug are presented. The first case shows infra-Hisian Wenckebach during sustained atrioventricular nodal reentrant tachycardia. The second case demonstrates rate-dependent Wenckebach-like exit block between the pacing catheter and the right ventricular tissues during pacing.

Adult↗
PubMed1983

Physiological factors affecting drug toxicity.

Physiological factors that affect the fate of drugs in the body and thereby have effects on their pharmacology and toxicology involve the systems that control absorption, distribution, metabolism, and excretion. The main factors are disease, genetics, and age. Nutritional status, sex, hormonal status (e.g., the effects of pregnancy), and circadian rhythm have important influences. Maternal toxicity will affect the fetus. The absorption and excretion of drugs are frequently reduced by diseases. Excretion is reduced by impaired renal function, often found in the elderly, which may increase the toxic response. Distribution is affected by body weight and build, for example, the proportion of fat. The disposition of many drugs has been shown to be significantly influenced by circadian rhythms such that therapeutic doses may exhibit toxicity if administered at an inappropriate time of day. Metabolism is modified by environmental influences including previous food and drug experience, and various factors such as age, sex, and disease. Intersubject variations in drug disposition can be very great with possibly severe consequences for the individual; in this regard, knowledge of genetic polymorphism in drug metabolizing enzymes is rapidly increasing. The toxicology of a drug may be profoundly affected by a particular disease state, for example, the administration of a drug that might be a tumor promoter when a cancerous or precancerous condition exists. These effects are illustrated with examples from the literature and recent studies undertaken in the Bureau of Drug Research.

Acetylation↗
PubMed1984

Management of cardiac drug overdose.

Although overdoses from cardiac drugs are uncommon, these are compounds with narrow therapeutic indices and they may give rise to serious acute toxicity from accidental, deliberate or even iatrogenic overdosage. Through the National Poisons Information Service for England and the Poisons Unit laboratory, we monitor reports of serious toxicity from this group of drugs and use the information gained to assess our recommendations for treatment. This article reviews the toxicity and the management of overdosage with digoxin and representative drugs from each class of anti-arrhythmic drugs. From these observations, a general plan of management applicable to all cardiac drugs is proposed and its is suggested that this form of monitoring should be continued.

Adrenergic beta-Antagonists↗
PubMed1996

Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome.

OBJECTIVES: We examined the modulatory effects of autonomic nervous system and antiarrhythmic drugs on the ST segment in patients with Brugada syndrome to gain an insight into the mechanism of ST segment elevation. BACKGROUND: Right bundle branch block, ST segment elevation and ventricular tachyarrhythmias define a distinct clinical and electrocardiographic (ECG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown. METHODS: The study included four patients in whom structural heart or coronary artery disease was excluded by noninvasive and invasive tests. High take-off ST segment elevation of either the coved or saddle-back type in precordial leads V1, V2 and V3 was seen in all patients. Three patients experienced recurrent episodes of syncope or aborted sudden cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of antiarrhythmic drugs were performed during sinus rhythm while the 12-lead ECG was recorded. Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed. RESULTS: Beta-adrenoceptor stimulation by intravenous isoproterenol consistently reduced (> or = 0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alpha-adrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetylcholine or intravenous edrophonium or neostigmine augmented ST segment elevation without inducing coronary spasm in three of four patients. Class IA antiarrhythmic drugs also consistently augmented (three patients), whereas class IB drugs had no effect on (two patients) ST segment elevation. No abnormality was found on MIBG imaging or heart rate variability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segment in three control patients, suggesting that the ST segment elevation seen in patients with Brugada syndrome in response to the drugs is not a nonspecific response. CONCLUSIONS: ST segment elevation in patients with Brugada syndrome was augmented by selective stimulation of alpha-adrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor blockade. These responses might be explained by postulating the presence of an area of early repolarization or a local "depolarized" area in the ventricle causing ST segment elevation in this syndrome. Because only a small number of patients were studied, these possibilities need further evaluation.

Adult↗
PubMed1983

Unusual atrial potentials in a cardiac transplant recipient. Possible synchronization between donor and recipient atria.

It is usual to record independent activity from both the innervated recipient and the denervated donor atria in cardiac transplant recipients except for occasional, short-lived periods of entrainment that may occur during exercise. In this report a case is described in which, following orthotopic cardiac transplantation, the recipient and donor atria remained synchronized during a variety of physiological and non-physiological situations. Under no circumstances did the two sets of atria beat independently. The mechanisms that might be involved in this unique situation are discussed.

Adult↗
PubMed1984

Therapy with conventional antiarrhythmic drugs for ventricular arrhythmias.

Conventional antiarrhythmic drugs are an important tool for the clinical cardiologist for the treatment of ventricular arrhythmias. Knowledge of the different properties of these drugs will help decrease the incidence of adverse effects and increase the frequency of successful therapy.

Anti-Arrhythmia Agents↗