Respiratory arrest as main determinant of toxicity due to overdose with different beta-blockers in rats

Propranolol, timolol and sotalol were compared regarding their toxicological effects on the cardiovascular and respiratory system. Each drug was administered intravenously to anaesthetized spontaneously breathing and artificially ventilated rats. After the start of infusion in spontaneously breathing rats each drug induced an expected decrease in arterial blood pressure and heart rate. An increase in PQ, QRS and QT interval was observed. From 5/8 of the survival time onwards these changes were accentuated. PaO2, pH and respiratory rate decreased and PaCO2 increased. The rats died as a result of respiratory arrest. Artificial ventilation of rats infused with the same doses increased the survival time significantly. The total doses administered before the animals died as a result of cardiovascular failure were significantly higher for each drug. The initial decreases in arterial blood pressure and heart rate were similar to those in spontaneously breathing rats. Thereafter, significantly smaller decreases were observed. The increases in PQ, QRS and QT interval were significantly less than in spontaneously breathing rats. Blood gases remained unchanged except for a decrease in pH in case of timolol.