EPIDEMIOLOGY TCA & MAOI first-generation antidepressant. Antidepressants third most common cause of drug-related fatalities . cyclic antidepressants the most commonly identified class of antidepressants to cause overdose-related deaths.!

PHARMACOKINETICS peak plasma levels : between 2 and 6 hours Tissue cyclic antidepressant levels : 10 to 100 times greater than plasma levels. Attempts to remove cyclic antidepressants by hemodialysis,hemoperfusion, peritoneal dialysis, or forced diuresis generally are unproductive.

The average half-life of cyclic antidepressants 24 hours (range, 6 to 36 hours).

TOXICITY patients at higher risk for cyclic antidepressant toxicity include who have medication such as: Cardiotoxic Sedative-hypnotic Geriatric patients, underlying heart or neurologic disease.

Desipramine Most potent sodium channel blocker Precipitate severe cardiotoxicity (e.g., wide QRS complex,hypotension) It is associated with a higher fatality rate than the other cyclic antidepressants

Amoxapine and maprotiline Associated with greater toxicity than other cyclic antidepressants, especially in regard to causing seizures.

CLINICAL FEATURES Mild antimuscarinic symptoms: (dry mouth and axillae,sinus tachycardia) Severe cardiotoxicity secondary to sodium channel blockade.

Most common symptom : Altered mental status. (GCS of <8 in the ED is a strong predictor of serious complications such as seizures and cardiac dysrhythmias) Most frequent dysrhythmia: Sinus tachycardia.

Serious toxicity within 6 hours of major cyclic antidepressant ingestion and consists of: coma cardiac conduction delays supraventricular tachycardia hypotension respiratory depression ventricular tachycardia seizures

Secondary complications Apiration pneumonia Anoxic encephalopathy Hyperthermia. Rhabdomyolysis. Pulmonary edema

Seizures Generalized and of brief duration. Exception : amoxapine and maprotiline (these agents can cause status epilepticus.)

DIAGNOSIS Urine tests Cannot differentiate between therapeutic and toxic levels. False positive results have been reported for a number of medications such as : carbamazepine. cetirizine, cyclobenzaprine. cyproheptadine. diphenhydramine, hydroxyzine. quetiapine. phenothiazines(e.g.• thioridazine).

ECG abnormalities The classic ECG with cyclic antidepressant toxicity: (sinus tachycardia, right axis deviation and prolongation of the PR,QRS. and QT intervals)

ECG abnormalities develop within 6 hours of ingestion and typically resolve over 36 to 48 hr. The identification of either QRS complex widening of >100 ms, right axis deviation of > 120 degrees, or a Brugada pattern warrants sodium bicarbonat therapy and admission to a ICU.

TREATMENT Evaluation for: alterations of consciousness. hemodynamic instability respiratory impairment. IV line Continuous cardiac rhythm monitoring Serial ECGs laboratory studies (electrolyte. creatinine. and glucose level) Serum acetaminophen level ABG

Antimuscarinic symptoms: urinary catheterization nasogastric tube Patients who are initially asymptomatic may deteriorate rapidly and therefore should be monitored closely for 6 hours.

GI DECONTAMINATION ipecac syrup cannot be recommended charcoal single 1 gram/kg dose. gastric lavage

• SODIUM BICARBONATE THERAPY: Indications: - Hypotension refractory to fluid hydration. -Cardiac conduction abnormalities (e.g., prolonged QRS duration or Brugada pattern), -Ventricular dysrhythmias.

SODIUM BICARBONATE THERAPY IV bolus of 1 to 2 mEq/kg. which can be repeated until patient improvement is noted or until blood pH equals 7.50 to 7.55

ALTERED LEVEL OF CONSCIOUSNESS Coma is rapid in onset and serves as a predictive factor for development of cardiotoxicity and/or seizures. Flumazenil Reassurance. decreased environmental stimulation. and benzodiazepines. Physostigmine

SEIZURES Seizures are generalized and of brief duration. Focal seizures are atypical and should prompt further neurologic evaluation. Seizures are common with maprotiline & amoxapine ingestions and require aggressive management. Because status epilepticus is frequently associated with them.

Benzodiazepines ( diazepam, lorazepam) are the anticonvulsants of choice to stop existing seizure activity Seizures resistant to benzodiazepine: Barbiturates(e.g .• phenobarbital) Endotracheal intubation and respiratory support are required when benzodiazepines are combined with barbiturates or propofol.

HYPOTENSION 1..Treated with isotonic crystalloid fluids in IV boluses 10 ml/kg. 2.. does not improve: sodium bicarbonate 3.. does not improve: vasopressor most effective:norepinephrine (1 microgram/min to 30 micrograms/min.)

CARDIAC CONDUGION ABNORMALITIES AND DYSRHYTHMIAS Asymptomatic patients with sinus tachycardia, isolated PR interval prolongation or first-degree atrioventTicular block do not require specific pharmacologic therapy.

Asymptomatic or mildly toxic patients with isolated QRS complex prolongation (QRS duration is > 100 milliseconds) should be treated with sodium bicarbonate therapy. Hyperventilation Hypertonic saline

Ventricular dysrhythmias: sodium bicarbonate second agent of choice: Lidocaine

Contraindicated medications all class Ia and Ic antiarrhythmic agents, B blockers Calcium channel blockers all class III antiarrhythmic agents.

Intravenous lipid emulsion: 20% lipid emulsion 100 mL IV bolus over 1 minute. followed by 400 mL IV over 20 minutes in patients with life-thTeatening cyclic antidepressant induced cardiotoxicity that is refractory to other measures

DISPOSITION AND FOLLOW-UP Asymptomatic after 6 hours of observation do not require hospital admission for toxicologic reasons. All symptomatic patients :hospital admission. signs of moderate to severe toxicity: ICU