Management of tricyclic antidepressant overdose - Essay Example

Pathophysiology and treatment for tricyclic antidepressant overdose Tricyclic antidepressants were a chance discovery during the search for antihistamines, sedatives and antipsychotics during the late 1940s by Häfliger and Schindler (Goodman and Gilman’s, The Pharmacological Basis of Therapeutics, Eighth Edition, pg 405) and Imipramine was the first drug discovered in this class with remarkable anti depressant actions. This followed further research in the molecule which had three cyclic rings (hence the name) and a number of congeners namely Amitriptylene, Trimipramine, Doxepin, Desipramine, Nortriptylene, Protriptylene, Amoxapine and Maprotiline were developed.

The major use of the drugs belonging to this class has been of course as an antidepressant, but they have also found to be effective in controlling enuresis and attention deficit disorder in children and incontinence in the elderly. Other miscellaneous indications for use are Migraine, chronic pain, neuralgias, hiccups and irritable bowel syndrome. However the Therapeutic Index of these drugs has a narrow margin of safety i.e. the dose level between therapeutic and toxic level is very less. This accounts for several cases of adverse effects and acute toxicity with these compounds.

The toxicity is due to the same manner and mechanism of action in which the drug exerts its therapeutic action. Although poorly understood, the TCAs are hypothesized to exert their therapeutic action by preventing the reuptake of norepinephrine and serotonin by the presynaptic neuron. This results in an increased supply of these neurotransmitters in the synapse, which continues to stimulate the effector cells and organs. It is this constant stimulation that is believed to be responsible for the clinical improvement in depression (Baldessarini, 1989).

According to Richelson (1982) TCAs are also competitive antagonists of histamine H1 andH2 receptors. They also block muscarinic acetylcholine and alpha-one adrenergic receptors.The toxicity symptoms and presentations are manifested as central nervous system toxicity in the form of myoclonic seizures, cardiovascular complications like life threatening arrhythmias, asystole, ventricular tachycardia and ventricular fibrillation. The patient is usually presented with symptoms of orthostatic hypotension which is quite common with TCA use and is independent of the age factor and in some cases is followed by cardiac arrest.

Treatment is aimed at reversing the effects of the TCAs by specific antagonists, promoting elimination of the drug and its metabolites from the body and reestablishing cardiovascular function. The patient when reporting adverse effects or accidental or intentional over dosage should be monitored for at least six hours even if not exhibiting any symptoms. Continuous cardiac monitoring should be done and intubation done if there are signs of respiratory distress. Gastric lavage can be done to remove the unabsorbed drug.

Activated charcoal can be administered as it adsorbs TCAs. Diazepam is the drug of choice to control seizures and CNS toxicity. The dose has to be repeated in increments till the seizures are gone. However the total dose should not exceed the maximum permissible limits. Alkalinization is the first line treatment for TCA-induced conduction defects, arrhythmias, and hypotension, either by the administration of intravenous sodium bicarbonate or hyperventilation, if the patient is being artificially ventilated.

Ventricular ectopy or ventricular tachyarrhythmias that are refractory to alkalinization should be treated with Lidocaine. Occasionally pressor agents like Dopamine and Epi/Norepinephrine with direct alpha-adrenergic effects are preferred.References:1. Baldessarini RJ, Current status of antidepressants: Clinical pharmacology and therapy. 1989; 50:117-126.2. Goodman and Gilman’s, The Pharmacological Basis of Therapeutics, Eighth Edition, Chapter 18, Drugs and the treatment of Psychiatric Disorders.3. Richelson E.

Pharmacology of antidepressants in use in the United States. J. Clin Psych 1982; 43:4-11.