**9. Cyclic antidepressants (CA) poisoning**

Cyclic antidepressants were used to depression, but now their use has reduced greatly because of the presences of more safe agents. Cyclic antidepressants were most common antidepressants associated with overdose-related deaths in 2013 [17].

#### **9.1. Mechanism of action**

CA has multiple pharmacologic effects.

#### **9.2. Antihistamine effects**

Cyclic antidepressants are inhibiting postsynaptic histamine receptors, causing sedation, decrease level of conscious and coma.

#### **9.3. Antimuscarinic effects**

Antimuscarinic effects are divided to central and peripheral. Inhibition central acetylcholine receptors cause agitation, delirium, confusion, hallucinations, slurred speech, ataxia and coma. Inhibition Peripheral acetylcholine receptors inhibition cause dilated pupils, tachycardia, hyperthermia, hypertension, dry skin, ileus, urinary retention, increased muscle tone and tremor [18].

#### **9.4. Inhibition of α-adrenergic receptors**

This effects cause sedation, orthostatic hypotension, tachycardia and pupillary constriction, but because of the antimuscarinic effects, this action usually offsets pupillary dilatation [18].

#### **9.5. Inhibition of amine reuptake**

This effect produces mydriasis, diaphoresis, tachycardia, early hypertension, myoclonus and hyperreflexia.

#### **9.6. Inhibition sodium channel block**

This effect produces decreased conduction velocity, increases the duration of repolarization and depressed myocardial contractility which lead to heart blocks, bradycardia and widening of the QRS complex [19].

#### **9.7. Inhibition potassium channel block**

This effect produces QT interval prolongation and rarely torsades de pointes can be seen [19].

#### **9.8. Clinical features**

when the nomogram is not applicable. Examples of such cases would be when the time of ingestion is unknown, when patients present more than 24 h after the ingestion and following ingestions that occur over many hours. In all of these cases NAC should be administered immediately. If aminotransferases (ALT, AST) are normal and APAP concentration is undetectable, the NAC may be discontinued. Otherwise, treatment with

N-acetylcysteine dose Oral 140 mg/kg loading dose 70 mg/kg q4 h × 17 doses or Intravenous 150 mg/kg loading dose 50 mg/kg over 4 h 100 mg/kg over 16 h [14–16] (**Figures 1** and **2**).

Cyclic antidepressants were used to depression, but now their use has reduced greatly because of the presences of more safe agents. Cyclic antidepressants were most common antidepres-

Cyclic antidepressants are inhibiting postsynaptic histamine receptors, causing sedation,

Antimuscarinic effects are divided to central and peripheral. Inhibition central acetylcholine receptors cause agitation, delirium, confusion, hallucinations, slurred speech, ataxia and coma. Inhibition Peripheral acetylcholine receptors inhibition cause dilated pupils, tachycardia, hyperthermia, hypertension, dry skin, ileus, urinary retention, increased muscle tone and tremor [18].

This effects cause sedation, orthostatic hypotension, tachycardia and pupillary constriction, but because of the antimuscarinic effects, this action usually offsets pupillary dilatation [18].

This effect produces mydriasis, diaphoresis, tachycardia, early hypertension, myoclonus and

NAC should be continued.

256 Essentials of Accident and Emergency Medicine

**9.1. Mechanism of action**

**9.2. Antihistamine effects**

**9.3. Antimuscarinic effects**

CA has multiple pharmacologic effects.

decrease level of conscious and coma.

**9.4. Inhibition of α-adrenergic receptors**

**9.5. Inhibition of amine reuptake**

hyperreflexia.

**9. Cyclic antidepressants (CA) poisoning**

sants associated with overdose-related deaths in 2013 [17].

Symptoms occur typically within 2 h of ingestion, which varies from mild antimuscarinic symptoms to severe cardio-toxicity. Patient may present with drowsiness, confusion, slurred speech, ataxia, sinus tachycardia, urinary retention, myoclonus and hyperreflexia. Serious toxicity is almost seen within 6 h of ingestion and patient present with: coma, cardiac conduction delays, supraventricular tachycardia, hypotension, respiratory depression, ventricular tachycardia and seizures [20, 21].

#### **9.9. ECG changes in cyclic antidepressant poisoning**


#### **9.10. Treatment**

Treatment starts with supportive management securing airway, bolus i.v fluid in case of hypotension, GI decontamination with activated charcoal within 1 h of ingestion.

Add vasopressors if hypotensive refractory to IV normal saline. Cardiac conduction abnormalities, ventricular dysrhythmias, or hypotension refractory to IV fluid are indicated to start blood alkalization by Sodium bicarbonate Keep blood pH 7.50–7.55. Seizures, treat with Benzodiazepines if seizure refractory use Phenobarbital 10–15 mg/kg, The medication contraindication in CA toxicity are: Class I antiarrhythmic (lidocaine, phenytoin, and flecainide), Class III antiarrhythmic (amiodarone, sotalol), Β-blockers, Ca channel blockers, Physostigmine and Flumazenil [22, 23].
