Experimental investigations on the antidotal treatment of nifedipine overdosage

Rats anesthetized with pentobarbital and ventilated artificially were infused with 0.5 mg/kg X min nifedipine. They exhibited a sharp decline of blood pressure, heart rate, cardiac output and peripheral resistance and died after 62.3 +/- 5.3 min of infusion. In the ECG, sinus bradycardia followed by AV-dissociation and an escape rhythm originating from the AV-node or the bundle of His occurred. The survival time of nifedipine-infused rats increased by 100% and more upon additional infusion with calcium chloride, calcium gluconate, isoproterenol or dopamine and by 50% after prenalterol. Epinephrine, norepinephrine, angiotensin amide and the plasma expander polygeline were ineffective in this respect. All drugs prolonging the survival time elevated the cardiac output. Ca++ and dopamine also increased the blood pressure whereas isoproterenol accelerated the escape rhythm. Similar cardiovascular changes as in rats occurred in rabbits infused with 0.2 mg/kg X min nifedipine, the survival time without antidotal treatment amounting to 46.3 +/- 7.9 min. Calcium chloride more than doubled the survival time in rabbits, too, but isoproterenol and dopamine proved to be ineffective. Excess calcium did not overcome the inhibitory effects of nifedipine on pacemaker activity, atrioventricular conduction and peripheral resistance. The antidotal efficacy of calcium appears to be attributable to a reversal of the negative inotropic activity of nifedipine. In conclusion, Ca++ seems to be the drug of choice for the antidotal treatment of nifedipine intoxication.