Tricyclic Antidepressants TCA It is the pharmacologic agents

Tricyclic Antidepressants (TCA) It is the pharmacologic agents used for treatment of endogenous and reactive depression. Overdose of these drugs are common and deadly. Classification of TCAs: i) First generation TCAs: a- Teriary amines: - imipramine (tofranil), amitrptyline (tryptizol). b- Secondary amines: - nortriptyline and desipramine. ii) Second generation TCAs: - amoxapine and tetracylic compounds.

iii) Newer antidepressants: - sertonin reuptake inhibitors such as fluoxetine (Prozac), and paroxetine. They have enjoyed substantial growth in popularity due to fewer side effects at therapeutic doses and less toxicity in overdose. Uses: For treatment of : *Depression *Panic attacks and phobia disorders *Nocturnal enuresis *Prophylaxis of migraine

Conditions of poisoning: 1 - Accidental (children and overdose) 2 - Suicidal Mechanism of action: They exert their action through: 1 - Neurotransmitter reuptake inhibition: resulting into increased neuronal synaptic concentrations of norepinephrine, dopamine and serotonin (ventricular arrhythmia). 2 -Receptor blockade: TCDs are competitive antagonist of cholinergic receptors (atropine like), alpha adrenergic receptors (peripheral vasodilatation) and histamine receptors.

3 - Myocardial membrane depressant effects: quinidine- like action predominantly due to Na channel blockage. Clinical presentation: I) CNS: *Depression of mental status and coma (may last as long as 3 days). *Delerium (central cholinergic blockage) *Seizures ( generalized, breif, and self limited). *Myoclonus (reduced serotonin reuptake) *Cerebellar and extrapyramidal signs (nystagmus, dysartheria, cholestasis and ataxia).

II) CVS: 1 -Arryhthmias: *Sinus tachycardia due to anticholinergic effect. *Conduction delays “quinidine-like action”, ECG showing prolonged PR intrerval and widened QRS complex and A-V block. *Ventricular arrhythmias: due to conduction delays, and ventricular tachycardia is the commonest and fibrillation is usually terminal. 2 - Initial transient hypertension: Increased catecholamine then hypotension.

3 -Anticholinergic effects: *Dry skin and mucosa *Dilated pupils *Decreased bowel sounds *Hyperthermia Investigations: 1 - Routine investigations 2 -Plasma drug level 3 -ECG Treatment: 1 -Supportive {ABCs}: Airway, Breathing, CNS and Cardiovascular support. 2 -GIT decontamination: *Gastric lavage *MDAC multiple dose activated charcoal due to enterohepatic circulation *Cathartic can initiate peristalsis on top of ilues produced by the drug.

3 -Elimination of the drug: *Diuresis, dialysis and hemoperfusion are largely ineffective due to: -Wide tissue distribution (large vd) -Tight binding of drug to plasma proteins - limited water solubility *Activated charcoal remains one of the most important therapeutic modalities. 4 - Treatment of conduction disturbances (arryhthmias): * Sodium bicarbonate (Na HCO 3) is the single most effective agent for treatment of conduction disturbances associated with TCAs. Mechanism: - both alkalinization and increased sodium concentration.

Dose= 1 -2 m. Eq/Kg bolus dose, followed by continuous IV infusion (100 -150 m. Eq Na Hco 3/ 1 L Dextrose) to maintain alkalinization. Serum PH should be maintained between 7. 45 and 7. 55. Lidocaine Physostigmine is contraindicated due to severe complications which will lead to death (HF). 5 - Symptomatic treatment: *Diazepam or barbiturates for convulsions *IV fluids

Thank you