Toxic effects of some tricyclic antidepressant drugs on the heart: clinical and experimental study

ABSTRACT

This study was done due to increased potential risks of cardiotoxicity of acute tricyclic antidepressants intoxication in human. So this work was carried out to investigate the changes in SGOT, SGPT, CPK.MB, and electrocardiograms in human due to use of both imipramine hydrochloride and dothiepin hydrochloride in therapeutic and toxic doses. Also biochemical and histopathological changes that occur in rats receiving the same drugs in therapeutic and toxic doses. The human part was carried out on "100" persons [50 males and 50 females], the age ranges from 20-40 years. Biochemical analyses revealed that in comparing subjects received therapeutic doses of imipramine hydrochloride to the acutely intoxicated persons by the same drug, there was highly significant difference in SGOT, SGPT, CPK-MB levels. On the other hand, there was slight difference in the levels of SGOT, SGPT, CPK-MB in patient treated with dothiepin therapeutic doses and those received toxic doses of dothiepin hydrochloride where there was slight increase of enzyme levels in toxic doses more than therapeutic dose, but both still in normal range. On examination of electrocardiogram of persons that were treated with imipramine hydrochloride at therapeutic doses there were [30%] suffering from sinus tachycardia, [15%] presented with atrial extrasystole, and [5%] complains of atrial fibrillation. In those that were intoxicated with toxic doses of irnipramine hydrochloride, there were [80%] presented with sinus tachycardia, [40%] presented with atrial extrasystole, [15% ]suffering from atrial fibrillation, and there, were [10%] complained from ventricular tachycardia. Also there were [10%] with ventricular extrasystole and [5%] presented with ventricular fibrillation. Persons that were treated with dothiepin in therapeutic doses, only [20%] presented, with sinus tachycardia, and [10%] were presented with atrial extrasystole. While [50%] of subjects that were intoxicated with this drug presented with sinus tachycardia, [30%] presented with atrial extrasystole, [10%] suffering from atrial fibrillation, [5%] complained of ventricular tachycardia and [5%] presented with ventricular extrasystole. In comparison of animals that were injected with therapeutic doses of imipramine hydrochloride and that injected with toxic dose of imipramine hydrochloride group, there was a highly significant difference in SOOT, SGPT and CPK-MB levels. On the other hand the difference in the levels of SGOT, SGPT, CPK-MB in animals injected with dothiepin therapeutic doses and those injected with toxic doses of dothiepin hydrochloride was slight but both still in normal range. Histopathological examination of the heart of rats treated with therapeutic dose of imipramine revealed small areas of infarction. Histopathological examination of heart of rats treated with toxic dose of imipramine revealed massive infarction and the interstitial connective tissue was markedly infiltrated with lymphocytes, polymorphs, and histocytes. There are no histopathological changes in rats that treated with therapeutic doses of dothiepin hydrochloride while rats that treated with toxic doses of dothiepin hydrochloride showed moderate histopathological changes