Atropine as antidote Tricyclic s include Amitriptvline Clornipramine Imipramine Tricyclics act primarily by inhibiting serotonin and norepinephrine reuptake. It result in elevation of extracellular concentration of these drugs. The toxic effects of tricyclics are caused by four main phannacological propeies. a) Inhibition of norepinephrine reuptake at nerve terminals. b) Direct a adrenergic block c) Membrane stabilising or quinidine like effect on myocardium. d) Anticholinergic action The clinical feature of tricyclic overdose can be grouped according to their effects on the peripheral autonomic nervous system. Management of tricyclic overdose Assess and treat ABC as appropriate Examine for clinical features - Check urea and electrolytes -4 Look.for low potassium - Check aerial blood gases Look for acidosis Reducing absorption Consider gastric lavage only if within one hour of a potentially fatal overdose. -Lavage improves clinical condition only when given within one hour of ingestion of Amitriptylline. - "Activated charcoal" may reduce the absorption of TCA's and benefits of both simple and multiple doses have been described. - Emetic contraindicated. Alkalinisation Alkalinization with sodium bicarbonate seems to have beneficial effect. Alkalinization correct hypotension and arrhythmias. The mechanism of this effect is a subject of debate. - It is believed that plasma protein binding of amitriptylline increases with a more alkaline pH. - The protein bound .form is inactive. Non protein bound form is the active .fonn, this reduces the pharmacological active unbound fraction. The reduction in unbound. fraction also reduces the direct effect on myocardium. Give Sodium bicarbonate when: ? pH < 7.1 RS > .16 seconds Arryhthmias Hypotension Hypotension Give intravenous fluids Hypotension results from depression of myocardial contractility and peripheral vasodilatation. In cases refractory to the use of intravenous fluids inotropic agents may be required. Arryhthmias In general antiarryhthmic agents should be avoided and the correction of hypoxia, hypotension, acidosis, hypokalemia should be done to reduce the cardiotoxic effects of tricyclics. Seizures Seizures are usually self limiting but where t/t is necessary benzodiazepenes are the t/t of choice. Cardiac arrest Prolonged resuscitation may be required. Drug elimination Tricyclic specific antibody fragments have been developed and their effectiveness at reversing cardiovascular toxicity in animals has been demonstrated by several studies. However, experimental work has shown that extremely large amounts are required and at present the use of Fab fragments is limited by cost and possibility of renal toxic effects. Hemodialysis and hemoperfusion not effective.