Acute poisoning of antidepressants

2. 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.

3.  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.

4. TRICYCLIC ANTIDEPRESSANT
DRUGS
 Secondary amines: -Amoxapine ,
Nortriptyline , Desipramine , Protriptyline.
 Tertiary amines:-Amitriptyline ,
Imipramine,Doxepin,Trimipramine.
 Tetra cyclic:- Maprotiline.
 Triazolopyridine :-Trazodone.

5. 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.

6. 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

7. CNS EFFECTS
 Geriatric patients and alcoholics- confusion,
agitation and nervousness.
 Coma
 Elderly patients –memory deficit.
 Amitriptyline- acute dystonia and extra
pyramidal symptoms.

8. SEIZURES
 Occur soon after admission.
 Lead to hypotension , cardiovascular
deterioration and death.
 Amoxapine , Maprotiline overdose.

9. 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.

10. 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.

11. 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.

12.  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.

13.  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)

14.  TREAT CONVULSIONS:-
Diazepam(0.1 mg/kg iv).
Phenytoin infusion (15 mg/kg iv) over 30 min .
SEIZURES:- Benzodiazepines ,
Phenobarbital (15-20 mg/kg).

15.  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).

16.  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.

17.  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 .

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

19. DISCHARGE CRITERIA
 Observed for 6 hrs.
 If no abnormality in vital functions ,
discharged after a final dose of charcoal.
 Persistent Tachycardia should be evaluated.

20. 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.