Tricyclic antidepressants (TCA) Objective Understand metabolism of cyclic antidepressants overdose. Master the clinical presentation of TCA toxicity. Aware of TCA toxicity management. Use of HCO3 in TCA and managing its side effects. Zohair Al Aseri MD,FRCPC EM & CCM

Antidepressants PERSPECTIVE Including cyclic antidepressants (CAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and miscellaneous agents. Antidepressants can be classified based on structure or major mechanism of action. Zohair Al Aseri MD,FRCPC EM & CCM

CYCLIC ANTIDEPRESSANTS Principles of Disease Tricyclic antidepressant TCAs and the tetracyclic antidepressant have similar properties and are called CAs. well absorbed from the GI tract Peak plasma concentrations in 2 to 4 hs after therapeutic doses are reached. Absorption is prolonged in overdose Zohair Al Aseri MD,FRCPC EM & CCM

Principles of Disease So 6-hour observation period in management of CA overdose is appropriate CAs are highly lipophilic Extensively bound to plasma proteins Large volumes of distribution. CAs are metabolized predominantly by the liver. Zohair Al Aseri MD,FRCPC EM & CCM 4

MAJOR PHARMACODYNAMIC EFFECTS OF CYCLIC ANTIDEPRESSANTS Zohair Al Aseri MD,FRCPC EM & CCM

PERIPHERAL NERVOUS SYSTEM EFFECTS OF CYCLIC ANTIDEPRESSANTS Zohair Al Aseri MD,FRCPC EM & CCM

CENTRAL NERVOUS SYSTEM EFFECTS OF CYCLIC ANTIDEPRESSANTS Zohair Al Aseri MD,FRCPC EM & CCM

Clinical Features TCA toxicity should be considered in all patients with a decreased level of consciousness and prolonged QRS complex. Zohair Al Aseri MD,FRCPC EM & CCM

Diagnostic Strategies A dose greater than 10 mg/kg or 1000 mg in an adult should be considered life-threatening. Suspect CA poisoning in the following Patients who have an anticholinergic toxidrome Decreased level of consciousness, QRS prolongation (>100 msec) Rightward deviation of the terminal 40-msec QRS axis (R wave in aVR > 3 mm or R/SaVR ratio of >0.7) Zohair Al Aseri MD,FRCPC EM & CCM

Zohair Al Aseri MD,FRCPC EM & CCM

A ECG ventricular bigeminy, right axis deviation, wide QRS complex, long QTcinterval, and right deviation of terminal 40-msecQRS vector in limb leads,with prominent R wave in aVR. B,ECG of same patient after receiving bolus and continuous intravenous infusion of sodium bicarbonate shows sinus tachycardia, 90-degree axis, slight prolongation of QRS and QTc intervals, and persistent right axis deviation of terminal 40 msec in limb leads. C,ECG of same patient 25 hours after ingestion and 4 hours after termination of sodium bicarbonate infusion shows persistent but improved sinus tachycardia, normalization ofQRS axis and width, normalization of QTc interval, and resolution of prominent R wave in aVR. Zohair Al Aseri MD,FRCPC EM & CCM

TCA levels Neither serum toxicology tests nor laboratory tests are useful for clinical decision-making. Diagnosis, treatment, and disposition should be based on a clinical basis and with ECG and cardiac monitoring. Zohair Al Aseri MD,FRCPC EM & CCM

TCA Overdose Management CAB Endotracheal intubation for low level of consciousness. Zohair Al Aseri MD,FRCPC EM & CCM

TCA Overdose Management Gastric lavage & activated charcoal Within 60 minutes from time of ingestion Lethal amount Airway protection NO physostigmine in TCA Overdose, as it will cause Seizures Cardiac arrest Zohair Al Aseri MD,FRCPC EM & CCM

TCA Overdose Management Hypertension…………no treatment. Hypotension start with isotonic crystalloids. Sodium bicarbonate (NaHCO3) If QRS greater than 100 msec, awith hypotension or a dysrhythmia, or if the patient is acidemic,. If hypotension does not resolve, norepinephrine or dopamine is recommended. (high-dose) Seizures Usually respond to IV lorazepam or diazepam. Zohair Al Aseri MD,FRCPC EM & CCM

Algorithm for management of cyclic antidepressant overdose Algorithm for management of cyclic antidepressant overdose. (Modified from Cyclic antidepressant (CA) overdose. In Callaham M [ed]: Current Therapy in Emergency Medicine. Philadelphia, BC Decker, 1991.) Zohair Al Aseri MD,FRCPC EM & CCM

TCA Overdose Management Flumazenil is contraindicated, even if benzodiazepines are known coingestants. Flumazenil counteracts the anticonvulsant activity of the co-ingested benzodiazepines. Phenytoin is contraindicated in TCA Seizures. Zohair Al Aseri MD,FRCPC EM & CCM

TCA Overdose Management TCA induced Hyperthermia Best treated with control of seizures and neuromuscular blockade. A nondepolarizing neuromuscular blocker (e.g., rocuronium) is recommended if rhabdomyolysis and high K with ECG changes are present. Evaporative cooling should be used until core temperature reaches 38.5? C. Zohair Al Aseri MD,FRCPC EM & CCM

Disposition 6 hours of observation Patients may be discharged for psychiatric evaluation if they do not develop (1) Desaturation (2) QRS greater than 100 msec (3) sinus tachycardia (4) dysrhythmias (5) hypotension (6) decreased level of consciousness (7) seizures (8) abnormal or inactive bowel sounds. Zohair Al Aseri MD,FRCPC EM & CCM