2. 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.!

6. 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.

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

8. 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.

9. 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

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

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

12. 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.

13. 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

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

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

16. 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).

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

18. 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.

24. 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

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

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

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

28. 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

29. 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

30. 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.

31. 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.

32. 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.)

33. 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.

34. 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

35. Ventricular dysrhythmias: sodium bicarbonate
second agent of choice: Lidocaine

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

37. 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

38. 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