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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.