TRICYCLIC ANTIDEPRESSANT OVERDOSE

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TRICYCLIC ANTIDEPRESSANT OVERDOSE

• WILLEMIEN VAN DER WALT
• DEPARTMENT OF PHARMACOLOGY
• UNIVERSITY OF THE FREE STATE

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Chemical structure of TCAs
Common central structure of three rings. The
currently available tricyclic antidepressants
include Tertiary tricyclics
Amitriptyline, imipramine, doxepine,
clomipramine, dothiepine,
trimipramine,
lofepramine Secondary tricyclics Desipramine,
nortriptyline, protriptyline
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Mechanism of action
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CLINICAL CONSIDERATIONS

• The clinical presentation is non-specific.
• The clinical effects are caused by four main
• pharmacological properties
• - Inhibition of norepinephrine reuptake at
• nerve terminals.
• - Direct ? adrenergic block
• - A membrane stabilizing effect on the
• myocardium.
• - Anti-cholinergic action

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Clinical presentation

• CNS 6 48h post ingestion
• Confusion, seizures, delirium, coma
• Occurrence of seizures associated with
• prolonged QRS complex and a
• metabolic acidosis
• CVS Sinus tachycardia, hypotension or
• hypertension, QRS prolongation and
• ventricular dysrhythmias
• after 6 48h
• QRS prolongation also associated with
  a metabolic
• acidosis

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Other clinical effects

• Metabolic acidosis
• - pH lt 7.4 already too low
• - may increase the risk of
• seizures and arrythmia
• Other complications
• - ? CPK
• - ? temperature
• - ? liver transaminase
• - Hematological abnormalities

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Drug levels

• Confirmation of TCA ingestion.
• Drug level gt 300 nanogram/ml
• Method of analyses Immuno assay
• Confirmation Mass spectometry.
• Cross reactions

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MANAGEMENT OF A TCA OVERDOSE

• GASTRIC LAVAGE - up to 6h post ingestion
• ACTIVATED CHARCOAL - single dose or
  repeated administration
• - Mannitol 20 PO with multiple doses
• IVI FLUIDS - correcting electrolytes,
  hydration and acidosis
• ECG monitoring - continuously

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Metabolic acidosis treatment

• Correction to pH 7.45 - 7.5 with sodium
  bicarbonate.
• Advantages
• 1) Treatment of metabolic acidosis.
• 2) Reduces the blood pressure 3) Alleviates
  cardio-toxicity
• 4) Increased convulsion threshold

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Supportive and symptomatic treatment

• Early intubation in comatose patient
• Treatment of seizures with
• benzodiazepines
• Phenytoin and lignocaine

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CONCLUSION

• Tricyclic antidepressant overdose is
• common and potentially life threatening.
• As its presentation is non-specific and
• with multiple clinical and biochemical
• abnormalities, the role of the technologist is
• vital in the prompt and effective
• management of these patients.

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REFERENCES

• Linder MW, Keck PE, Standards of laboratory
  practice antidepressant drug
• monitoring. Clin Chem 1998441073-84
• Steimer W, Zöpf K, Amitriptyline or Not, That Is
  the Question. Clin Chem 200551376-385
• Micromedix, Tricyclic antidepressant overdose
• Kerr GW, McGuffie AC. Tricyclic antidepressant
  overdose a review. Emerg Med J 200118236-241