dothiepin-hydrochloride and Arrhythmias--Cardiac

Topics: Arrhythmias, Cardiac; Clinical Trials as Topic; Dibenzothiepins; Dothiepin; Electrocardiography; Heart; Heart Rate; Humans; Imipramine; Time Factors

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cardiology; Dothiepin; Electrocardiography; Female; Humans; Sodium Bicarbonate

QT interval dispersion (QTd) is conventionally interpreted as a result of repolarization heterogeneity in ventricular myocardium. However, another concept of QTd origin has been discussed recently, suggesting that different projections of the repolarization vector into individual ECG leads could be responsible for the differences in QT interval duration. Moreover, the reproducibility could be influenced by factors both electrocardiographic (T wave amplitude, U wave) and extracardiac (noise, ECG measures). In the presented study we have followed the QTd in two groups of patients with proved changes of an electric heart field.. Studied groups: 1. Control group, 2. Healthy pregnant women, 3. Patients treated with dosulepine. QT interval was measured from 80 unipolar chest leads used for body surface potential mapping. The QTd was significantly higher in both experimental groups in comparison with the control group (p < 0.001). Significant correlation was found between the QTd and dosulepine plasma level (p < 0.001). Also amplitude of the T wave loop was in both groups decreased and its width increased (both p < 0.001).. If appropriate procedure of measurement is used, the QTd is significantly increased in many physiological and pathological states. Clinical relevancy of borderline increased values has to be interpreted very carefully.

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Body Surface Potential Mapping; Dothiepin; Electrocardiography; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular

1. In order to clarify the arrhythmogenic effects of antidepressants, the authors examined the effects of dothiepin and amitriptyline on the ventricular activation time (VAT), effective refractory periods(ERP) and incidence of arrhythmias induced by programmed electrical stimulation(PES) in the dog heart in situ after myocardial infarction. 2. Myocardial infarction was produced by two-stage ligation of the left anterior descending coronary artery. Seven days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted and normal zones to apply an electrical stimulation or record ventricular activation. An electrical stimulation with coupling interval 250 or 180 ms was applied on the ventricular surface, and AT was measured. 3. Dothiepin at doses of 1-3 mg/kg increased the heart rate. The VAT of coupling interval 180 ms in the infarcted zone was increased by the administration of 3 mg/kg dosulepin. Dothiepin at 3 mg/kg increased the incidence of ventricular arrhythmias induced by PES. 4. Amitriptyline, at doses of 1-3 mg/kg, significantly increased the heart rate. Amitriptyline increased the VAT dose- and frequency-dependently(2,3 mg/kg zone), and prolonged the ERP and QT c interval. Amitriptyline at doses of 1-3 mg/kg increased the incidence of ventricular arrhythmias by PES. 5. These results indicate that dothiepin, 1-3 mg/kg, has lesser effects on cardiac delayed conduction produced by ventricular arrhythmia than amitriptyline.

Topics: Animals; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Dothiepin; Electric Stimulation; Heart Rate; Myocardial Infarction; Ventricular Function

Epidemiological studies have implicated dothiepin in a greater number of self-poisoning deaths than would be expected from its use. We have prospectively assessed the clinical toxicity of dothiepin and other tricyclic antidepressants (TCAs) in overdose. We followed-up consecutively admitted patients with TCA poisoning managed by our department between January, 1987, and August, 1992. 75 patients had taken dothiepin, 101 amitriptyline, 83 doxepin, and 61 other TCAs. Death after TCA poisoning is rare nowadays, so we used intermediate outcome measures--general seizures, tachyarrhythmias, sedation, and QRS width on the electrocardiogram. 15 patients had seizures and 7 tachyarrhythmias. When we excluded patients who had taken more than one TCA, general seizures were more likely after dothiepin than after other TCAs (9/67 vs 5/220) as were arrhythmias (4/67 vs 3/220). Rates of other complications were similar. The dothiepin group had ingested a larger dose, attributable to the larger average tablet strength, than patients who took other TCAs. The odds ratio for seizures with dothiepin versus other TCAs was 6.7 (95% Cl 2.2-20.7) unadjusted and 7.1 (2.2-23.2) after adjustment for sex, age, and ingested dose. The corresponding odds ratios for arrhythmias were 4.6 (1.0-21.1) and 3.4 (0.7-16.3). Dothiepin in overdose seems to be proconvulsant. Patients with only minor sedation and normal limb-lead QRS width may still have major complications. Consideration should be given to the use of other antidepressants in patients at risk of seizures or suicide. Regulatory authorities should review the need for a 75 mg strength tablet of any TCA.

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Dothiepin; Drug Overdose; Female; Humans; Male; Poisoning; Seizures

Topics: Arrhythmias, Cardiac; Bias; Dothiepin; Drug Overdose; Humans; Poisoning; Seizures

Topics: Adult; Arrhythmias, Cardiac; Blood Pressure; Dibenzothiepins; Dothiepin; Humans; Infusions, Intravenous; Male; Sodium Chloride

Topics: Amitriptyline; Animals; Arrhythmias, Cardiac; Dibenzothiepins; Dothiepin; Heart; Imipramine; Rats