ACUTE POISONING OF ANTIDEPRESSANTS

TRICYCLIC ANTIDEPRESSANTS

They have been employed in drug therapy since the late 1950s.

Largest group of drug agents used for the treatment of depression.

Referred as “ tri cyclic ” compounds –three rings.

Due to both accidental and deliberate overdoses.

Life threatening ,high risk for suicide. Involve multiple ingestions – ethanol ,

diazepam, codeine. Toxicity due to rapid absorption , tight

binding to plasma proteins , low therapeutic margins.

TRICYCLIC ANTIDEPRESSANT DRUGS Secondary amines: -Amoxapine ,

Nortriptyline , Desipramine , Protriptyline. Tertiary amines:- Amitriptyline ,

Imipramine,Doxepin,Trimipramine.

Tetra cyclic:- Maprotiline.

Triazolopyridine :-Trazodone.

MECHANISM

Decreases the action of acetylcholine centrally and peripherally.

Enhances dopamine levels. Reduced serotonin uptake resultant

increase within the synapse. Respiratory dysfunction and

disturbances in body temp- respiratory center , thermoregulatory site.

CNS CARDIOVASCULAR

ANTICHOLINERGIC

HYPOTHERMIA VENTRICULAR RATE ≥120 BEATS/MIN

MYDRIASIS

RESPIRATORY DEPRESSION

ARRHYTHMIAS BLURRED VISION

SEIZURES BUNDLE BRANCH BLOCK

TACHYCARDIA

ABNORMAL TENDON REFLEXES

CARDIAC ARREST URINARY RETENTION

AGITATION HYPOTENSION VASODILATION

DISORIENTATION CIRCULATORY COLLAPSE

DECREASED GI MOTILITY

MYOCLONIC JERKS DECREASED BRONCHIAL SECREATIONS

COMA DRY MUCUS MEMBERANE AND SKIN

PYRAMIDAL SIGNS

CNS EFFECTS

Geriatric patients and alcoholics- confusion, agitation and nervousness.

Coma Elderly patients –memory deficit. Amitriptyline- acute dystonia and

extra pyramidal symptoms.

SEIZURES

Occur soon after admission. Lead to hypotension , cardiovascular

deterioration and death. Amoxapine , Maprotiline overdose.

PERIPHERAL NERVOUS SYSTEM

Amitriptyline overdose- peripheral neuropathies and polyradiculoneuropathy.

RHABDOMYOLYSIS Seizures and coma

PULMONARY EDEMA Develop between 5 & 48 hours after

ingestion. Respiratory distress syndrome and

pulmonary injury.

GASTRO INTESTINAL

Overdose in Elderly – acute intestinal pseudo obstruction ,fecal peritonitis.

WITHDRAWAL SYMPTOMS: Anorexia,nausea,emesis,diarrhoea,malaise , headache,chills,fatigue,anxiety,insomnia, parkinsonism and mania.

TREATMENT

Immediately evaluate the patient and administer oxygen.

Monitor vital signs. STABILISATION – Insert an intravenous

line and cardiac monitoring. Altered mental status- naloxone,

glucose and if indicated thiamine. Adequate ventilation ,prolonged

cardiac massage.

SUPPORT VITAL FUNCTIONS: Respiratory depression – intubation and hyperventilation

Hypotension- Nor epinephrine , Phenyl epinephrine. Sodium bicarbonate . Glucagon(10mg bolus followed by an infusion of 10 mg over 6 hours) . Dysrhythmias- sodium chloride.

REDUCE TCA ABSORPTION:- Ipecac or gastric lavage within 6

hrs. Activated charcoal (1g/kg) in all

cases. INCREASE TCA ELIMINATION:- Multiple doses of activated charcoal

(0.5-1.0 g/kg)

TREAT CONVULSIONS:- Diazepam(0.1 mg/kg iv). Phenytoin infusion (15 mg/kg iv) over

30 min . SEIZURES:- Benzodiazepines , Phenobarbital (15-20

mg/kg).

OBSERVE ECG CHANGES :- TREAT ARRHYTHMIAS – Sinus tachycardia-supportive measures only.Ventricular tachycardia – Alkalinize pH 7.45-7.5 . Lignocaine (1 mg/kg

iv bolus then infusion 2-4

mg/min). Isoprenaline

infusion(0.5- 5.0µg/min).

SUPRAVENTRICULAR ARRHYTHMIAS- Alkalinize pH 7.4-7.5 VENTRICULAR FIBRILLATION- Defibrillate. Sodium bicarbonate (1-3 mmol/kg). Hyperventilation pH 7.45-7.5 . 1:1000 Adrenaline (0.5-1.0 mg iv). Lignocaine . Beta blockers if these measures are

ineffective.

BRADYCARDIA : Alkalinize pH 7.4-7.5 Isoprenaline . Pacemaker. REFRACTORY CARDIAC ARREST: Basic and advanced life support for 1hr. Alkalinize pH 7.5 . VENTRICULAR ARRHYTHMIAS: Lidocaine , Magnesium sulphate infusion 3- 20mg/min , Magnesium 2g i.v .

ANTIDOTE:- Anti- Imipramine antibodies. Titrations with Fab. Anti -TCA monoclonal antibody. Combination of Anti - TCA Fab and

Sodium bicarbonate.

DISCHARGE CRITERIA

Observed for 6 hrs. If no abnormality in vital functions ,

discharged after a final dose of charcoal.

Persistent Tachycardia should be evaluated.

REFERENCES

1. MATHEW .J. ELLENHORN. ELLENHORNS MEDICAL TOXICOLOGY – DIAGNOSIS & TREATMENT OF POISONING, 2nd EDITION, WILLIAMS AND WILLKINS PUBLICATION, LONDEN, Pg No:626- 636.

2. PRINCIPLES OF CLINICAL TOXICOLOGY BY

THOMAS .A.GOSSEL & J.DOUGLAS BRICKER, 2nd EDITION, Pg No:301-303.