PT  - JOURNAL ARTICLE
AU  - M Callaham
AU  - H Schumaker
AU  - P Pentel
TI  - Phenytoin prophylaxis of cardiotoxicity in experimental amitriptyline poisoning.
DP  - 1988 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 216--220
VI  - 245
IP  - 1
4099  - http://jpet.aspetjournals.org/content/245/1/216.short
4100  - http://jpet.aspetjournals.org/content/245/1/216.full
SO  - J Pharmacol Exp Ther1988 Apr 01; 245
AB  - Tricyclic antidepressants (TCA) are drugs with Type IA antiarrhythmic properties that cause severe cardiac conduction blocks, hypotension, and ventricular dysrhythmias at toxic levels. Phenytoin has been proposed as a prophylaxis and treatment of these dysrhythmias, since it is thought to improve conduction in this setting. Anesthetized dogs were given a loading dose of phenytoin, followed by constant amitriptyline infusion until death. Variables known to affect TCA toxicity, such as arterial pH, were carefully controlled. There were no significant differences between the phenytoin and control group in any physiologic parameter, including toxicity, drug levels, or dose to death. However, duration and frequency of episodes of ventricular tachycardia were dramatically increased in the phenytoin group. It is concluded that prophylactic phenytoin in this animal model provides no benefits and may in fact increase the severity of ventricular tachycardia and hypotension. In addition, it is speculated that similar adverse effects of phenytoin might be seen in other Type IA antiarrhythmics if the extremely toxic levels seen in this study with TCA were reached.