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Tricyclic antidepressant overdose is a significant
cause of fatal drug poisoning. The severe morbidity
and mortality associated with these drugs is well documented
and due to their cardiovascular and neurological toxicity.
Additionally, they are a serious problem in the pediatric
population due to their inherent toxicity and the availability
of these in the home when prescribed for bed wetting
and depression.
Symptoms
The central nervous system and heart are the two main
systems that are affected. Initial or mild symptoms
include drowsiness, a dry mouth, nausea, and vomiting.
More severe complications, include hypotension, cardiac
rhythm disturbances, hallucinations, and seizures. Electrocardiogram
(ECG) abnormalities are frequent and a wide variety
of cardiac dysrhythmias can occur, the most common being
sinus tachycardia and intraventricular conduction delay
(QRS prolongation). Seizures and cardiac dysrhythmias
are the most important life threatening complications.
Toxicity
Tricyclics have a narrow therapeutic index, i.e. the
therapeutic dose is close to the toxic dose. In the
medical literature the lowest reported toxic dose is
6.7 mg per kg body weight, ingestions of 10 to 20 mg
per kilogram of body weight are a risk for moderate
to severe poisoning, although doses ranging from 1.5
to 5 mg/kg may even present a risk. Most poison control
centers refer any case of TCA poisoning (especially
in children) to a hospital for monitoring. Factors that
increase the risk of toxicity include advancing age,
cardiac status, and concomitant use of other drugs.
Serum drug levels are not useful in tricyclic overdose.
Toxic mechanism
Most of the toxic effects of TCAs are caused by four
major pharmacological effects. TCAs have anticholinergic
effects, cause excessive blockade of norepinephrine
reuptake at the postganglionic synapse, direct alpha
adrenergic blockade, and importantly they block sodium
membrane channels with slowing of membrane depolarization,
thus having quinidine like effects on the myocardium.
Treatment
Initial treatment of an acute overdose includes gastric
decontamination of the patient. This is achieved by
administering activated charcoal which adsorbs the drug
in the gastrointestinal tract either orally or via a
nasogastric tube. Other decontamination methods such
as stomach pumps, ipecac induced emesis, or whole bowel
irrigation are not recommended in TCA poisoning.
Symptomatic patients are usually monitored in an intensive
care unit for a minimum of 12 hours, with close attention
paid to maintenance of the airways, along with monitoring
of blood pressure, arterial pH, and continuous ECG monitoring.
Supportive therapy is given if necessary, including
respiratory assistance, maintenance of body temperature,
and administration of sodium bicarbonate as an antidote.
Sodium bicarbonate is given intravenously and it has
been shown to be an effective treatment for resolving
the metabolic acidosis and cardiovascular complications
of TCA poisoning. If sodium bicarbonate therapy fails
to improve cardiac symptoms, conventional antidysrhythmic
drugs such as phenytoin and magnesium can be used to
reverse any cardiac abnormalities. However, no benefit
has been shown from lidocaine or other class 1a and
1c antiarrhythmic drugs; it appears they worsen the
sodium channel blockade, slow conduction velocity, and
depress contractility and should be avoided in TCA poisoning.
Hypotension is initially treated with fluids along with
bicarbonate to reverse metabolic acidosis (if present),
if the patient remains hypotensive despite fluids then
further measures such as the administration of epinephrine,
norepinephrine, or dopamine can be used to increase
blood pressure. Another potentially severe symptom is
seizures; often seizures resolve without treatment but
administration of a benzodiazepine or other anticonvulsive
may be required for persistent muscular overactivity.
There is no role for physostigmine in the treatment
of tricyclic toxicity as it may increase cardiac toxicity
and cause seizures.
Tricyclic antidepressants are highly protein bound
and have a large volume of distribution; therefore removal
of these compounds from the blood with hemodialysis,
hemoperfusion or other techniques are unlikely to be
of any significant benefit.
Epidemiology
Studies in the 1990s in Australia and the United Kingdom
showed that between 8 and 12% of drug overdoses were
following TCA ingestion. TCAs may be involved in up
to 33% of all fatal poisonings, second only to analgesics.
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