THE CARDIOTOXICITY OF TRICYCUC ANTIDEPRESSANT OVERDOSE AND EFFECTS OF PHYSOSTIGMINE ON IT

<正> Tricyclic antidepressant overdose(TCAs-OD)is now recognized as one of the most commonforms of acute life threatening self-poisoning,The major features of TCAs-OD includecardiac,neurologic and anticholinergic complications.However,the measures andantidotes recommended for the management of the cardiac complications have unfortunatelybeen based in large part on anecdotal reports and have been toplcs of considerablecontroversy,especially In the use of physostigmine(Phys).The purpose of our experiment isto study the effects of TCAs-OD on the cardio-vascular of rats and the factors that contributeto the lethality of it.The l.v.infusion of AMI in rats under artificial respiration produced deathdue to cardiovascular collapse.it Was characlerized by hypotension,bradycardia,depression of myocardial contractile force and intraventricular conduction delay.Studies onanesthetized spontaneously ventilated rat models given AMI(l.v.infusion)showed that afteran initial hypotensive response,pronounced respiratory depression invariably occurredpreceding critical changes in the heart with the incressing doses,respiration changed fromintercostal to abdominal,reducing both in rate and amplitude prior to amhythmlas and heartblock.The cardiac effects were followed by apnea.Supportive mechanical respirationdramatically reversed the toxic syndrome.Heart action toward normal and blood pressurewas restored.From the recovery and reversible nature of the cardiotoioxic signs,It appearsthat respiratory depression plays an important role in the toxicity of TCAs on the heart.Theeffects of Phys on TCAs-OD was also studied.it was found that Phys potentiates thetoxicity and lethality of two TCAs.AMI and clomipramine in mice.The LD50 of both thesedrugs was reduced 7.4% and 17.3% respectively when administered in conjunction with low,subtoxic dose of Phys(0.15mg/kg).Moreover,the influence of Phys in the treatment ofcardiotoxicity and respiratory amest caused by AMI,has been investigated in order toestablish its possible usefulcess in clinical practics.In experiment on rats.Phys wasineffective against the cardiovasular to further reduction of heart rate.the influence onrespiration was also unpredictable.We suggest that it is doubtful that Phys has any piace inthe routine management of TCAs-OD.