Experimental amitriptyline intoxication: treatment of cardiac toxicity with sodium bicarbonate.
Overdose with amitriptyline and other tricyclic antidepressants can result in ventricular conduction abnormalities as well as severe ventricular arrhythmias. The arrhythmogenic effects of these compounds may be attributed to their direct local anesthetic actions in blocking sodium channels in cardiac membranes. Thus tricyclic-induced ventricular arrhythmias usually do not respond well to therapy with standard Class I antiarrhythmic drugs that also have the same direct local anesthetic action and may potentiate the adverse effects of tricyclic antidepressants. Cardiac toxicity was produced in dogs by the administration of amitriptyline, both orally and IV. At serum concentrations less than 2,000 ng/mL, sinus tachycardia occurred with widened QRS complexes. At higher concentrations, QRS duration became more markedly prolonged and was followed by ventricular tachyarrhythmias. Occurrence of ventricular tachyarrhythmias was associated with QRS durations of more than 0.11 second. Sodium bicarbonate (18 to 36 mEq) administered IV over either 30 seconds or two minutes rapidly converted ventricular tachycardia to normal sinus rhythm. Conversion was associated with abbreviation of the QRS complex and was accompanied by a rise in both systolic and diastolic pressures. The duration of sodium bicarbonate effect paralleled the duration of the changes in arterial pH and plasma bicarbonate concentrations. In vitro studies in cardiac Purkinje fibers suggested that reversal of amitriptyline-induced cardiac membrane effects by sodium bicarbonate may be attributed not only to alkalinization but also to increased in extracellular sodium concentration, diminishing the local anesthetic action of amitriptyline and resulting in less sodium channel block.(ABSTRACT TRUNCATED AT 250 WORDS)
D000639:Amitriptyline / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy; D001639:Bicarbonates / Q000627:therapeutic use*; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects; D011433:Propranolol / Q000627:therapeutic use; D012964:Sodium / Q000627:therapeutic use*; D017693:Sodium Bicarbonate; D013610:Tachycardia / Q000139:chemically induced* / Q000188:drug therapy
D001639:Bicarbonates; D000639:Amitriptyline; D017693:Sodium Bicarbonate; D012964:Sodium; D011433:Propranolol