Haemodynamic effects and kinetics of concomitant intravenous disopyramide and atenolol in patients with ischaemic heart disease

Abstract

The haemodynamic effects of concomitant intravenous administration of disopyramide (Norpace) and atenolol (Tenormin) were studied in a cross-over trial in 7 patients with ischaemic heart disease. Following 150 mg disopyramide i.v. the cardiac index (CI) and stroke volume index (SVI) decreased by 14% and 26%, respectively and the heart rate (HR) and preejection period index (PEPI) increased by 13% and 19%, respectively. A decrease in CI of 14% and HR of 21%, respectively were noted after intravenous administration of 7.5 mg atenolol; PEPI increased by 10% whereas SVI remained unchanged. The cardiac Index (CI) fell by 33% following the administration of both drugs. The effect on CI of the two drugs was additive. The effect of disopyramide and atenolol on HR, SVI and PEPI was not significantly modified by coadministration of the other drug. No change in blood pressure was observed after disopyramide or atenolol. A correlation (rho) of 0.540 and 0.387 was observed between the change in PEPI and the log free and total serum concentrations of disopyramide, respectively. Combined intravenous use of the two drugs in patients with incipient or overt heart failure is not recommended, unless it is due to the arrhythmia to be treated.

Antihypertensive therapy: special focus on drug interactions

“…Class I and III antiarrhythmic drugs Disopyramide [126] Amiodarone [132] Negative inotropism Impaired AV-conduction…”

Disposition Kinetics of Disopyramide in Human Healthy Volunteers Described by an Open Three Compartment Model

“…Due t o a concentration dependent plasma protein binding to a-1-acid glycoprotein within the therapeutic range (Bredesen & Kierulf 1984;Hinderling & Garrett 1976;Lima et al 1981;Bonde et al 1986) total elimination clearance of disopyramide increases with higher total drug concentration, while clearance of the unbound drug is constant (Bryson et al 1982).…”