Tricyclic antidepressants poisoning with

Both accidental and intentional overdose are relatively frequent and pose difficult management problems. Particular concern has been expressed for children, either because they gain access to parents tablets or have been treated for enuresis. During one year a Melbourne hospital admitted 35 children poisoned with tricyclic antidepressants (147). In 1979 it was reported that tricyclic antidepressants had replaced salicylates as the most common cause of accidental death in English children under the age of five. Concern was expressed about this (148), and Swiss federal statistics raised similar worries (149). 

The literature on poisoning with tricyclic antidepressants has been reviewed and recommendations for the management of overdose proposed (SEDA-16, 8 156). In overdose, physostigmine can reverse life-threatening dysrhythmias, but its effect is short-lasting and it has adverse effects of its own it should be avoided (156). 

Thorstrand C. Cardiovascular effects of poisoning with tricyclic antidepressants. Acta Med Scand 1974 195(6) 505-14. 

Toxic Effects of Acute Overdoses Acute poisoning with tricyclic antidepressants or MAO inhibitors is potentially hfe-threatening. Fatalities are much less common since modern antidepressants have widely replaced these drugs however, suicide rates have not declined consistently as clinical usage of modern antidepressants has increased. Deaths have been reported with acute doses of 2 g of imipramine, and severe intoxication can be expected at doses >1 g, or about a week s supply. If a patient is severely depressed, potentially suicidal, impulsive, or has a history of substance abuse, prescribing a relatively safe antidepressant agent with close clinical follow-up is appropriate. If a potentially lethal agent is prescribed, it is best dispensed in small, sublethal quantities, with the risk that sustained adherence to recommended treatment may be compromised. 

Cardiac arrhythmia frequently accompanies poisoning, e.g. with tricyclic antidepressants, theophylline, P-adrenoceptor blockers. Acidosis, hypoxia and electrolyte disturbance are often important contributory factors the emphasis of therapy should be to correct these and to resist the temptation to resort to an antiarrhythmic drug. If arrhythmia leads... 

A wide variety of drugs and poisons can give ri.se to coma if taken in sufficient dose. In very few cases arc there specific clinical signs. Exceptions are the pinpoint pupils of opiate poisoning for which the specific antagonist naloxone is effective in restoring consciousness, and the divergent strabismus (Fig. 4) associated with tricyclic antidepressant... 

B. Toxicodynamics Toxicodynamics is a term used to denote the injurious effects of toxins, ie, their pharmacodynamics. A knowledge of toxicodynamics can be useful in the diagnosis and management of poisoning. For example, hypertension and tachycardia are typically seen in overdoses with amphetamines, cocaine, and antimuscarinic drugs. Hypotension with bradycardia occurs with overdoses of calcium channel blockers, beta-blockers, and sedative-hypnotics. Hypotension with tachycardia occurs with tricyclic antidepressants, phenothiazines, and theophylline. Hyperthermia is most frequently a result of overdose of drugs with antimuscarinic actions, the salicylates, or sympathomimetics. Hypothermia is more likely to occur with toxic doses of ethanol and other CNS depressants. Increased respiratory rate is often a feature of... 

A. Check blood pressure and pulse rate and rhythm. Perform cardiopulmonary resuscitation (CPR) if there is no pulse and perform advanced cardiac life support (ACLS) for arrhythmias and shock. Note that some ACLS drugs may be ineffective or dangerous in patients with dmg- or poison-induced cardiac disorders. For example, procainamide is contraindicated in patients with tricyclic antidepressant overdose, and atropine and isoproterenol are ineffective in patients with beta-blocker poisoning. 

B. Complications. QRS interval prolongation in patients with tricyclic antidepressant or similar drug poisonings is often accompanied by hypotension, AV block, and seizures. 

Sinus tachycardia and supraventricular tachycardia accompanied by QRS interval prolongation (eg, with tricyclic antidepressant poisoning) may have the appearance of ventricular tachycardia (see Figure 1-4). 

Although physostigmine was advocated in the past, it should not be routinely administered to patients with tricyclic antidepressant poisoning it may aggravate conduction disturbances, causing asystole, further impair myocardial contractility, worsening hypotension, and contribute to seizures. 

Thorstrand, C (1976) Clinical features in poisoning by tricyclic antidepressants with special reference to the ECG. Acta med. scand., 199, 337. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

Serafimovski N, Thorball N, Asmussen I, Lunding M. Tricyclic antidepressive poisoning with special reference to cardiac complications. Acta Anaesthesiol Scand Suppl... 

A survey of 100 cases of overdose with mianserin reported to the London Centre of the UK Poisons Information Service included 54 patients who took mianserin alone in amounts up to and in three cases in excess of 1000 mg (12). Plasma mianserin concentrations were 70-665 ng/1 (the usual mean target concentration is 50 ng/ 1). There were no reports of convulsions, cardiac dysrhythmias, or profound coma in any patient taking mianserin alone, but there were two deaths in patients who took multiple drugs. The authors concluded that in acute overdosage mianserin is less toxic than tricyclic antidepressants. 

The initial clinical review should include a search for known consequences of poisoning, which include impaired consciousness with flacddity (benzodiazepines, alcohol, trichloroethanol) or with hypertonia (tricyclic antidepressants, antimuscaiinic agents), hypotension, shock, cardiac arrhythmia, evidence of convulsions, behavioural disturbances (psychotropic drugs), hypothermia, aspiration pneumonia and cutaneous blisters, burns in the mouth (corrosives). 

Paracetamol plus dextropropoxyphene, the combination known as co-proxamol, is available as a prescription-only analgesic in many countries. Self-poisoning can be lethal, as respiratory depression can occur from an excessive dose of dextropropoxyphene. In England and Wales, co-proxamol alone accounts for 5% of all suicides, and overdose is more likely to result in death than overdose with paracetamol alone or tricyclic antidepressants (81). Furthermore, although it is often prescribed, it is no more effective than paracetamol for short-term relief of pain. It should not be prescribed without good... 

Poisoning and drug overdose with acetaminophen, anticholinesterase insecticides, calcium channel blockers, iron, and tricyclic antidepressants are the focus of the remainder of this chapter because they represent commonly encountered poisonings for which pharmacotherapy is indicated. These agents also were chosen because they represent common examples with different mechanisms of toxicity, and they illustrate the application of general treatment approaches as well as ... 

Tricyclic antidepressant poisoning is a common cause of death from drug overdose. The 2003 AAPCC-TESS report documented 12,710 patients with exposures to tricyclic antidepressants, of whom 62% were intentional overdoses. A total of 1373 people experienced... 

Patients with coexisting cardiovascular and pulmonary conditions (e.g., ARDS, pulmonary infection, pulmonary aspiration) may be more susceptible to the toxic effects or complications of tricyclic antidepressant poisoning. The influence of chronic exposure to tricyclic antidepressants on the risks of an acute overdose is unclear. Tricyclic antidepressants interact with other central nervous system depressant drugs, which together may lead to increased central nervous system and respiratory depression. 

Overdose of M blockers Poisoning most commonly follows excessive ingestion of over-the-counter (OTC) antihistamines and cold medications, or attempts to induce hallucinations. Note that M-blocking side effects (and possible toxicity) occur with both tricyclic antidepressants and phenothiazines. Management is largely symptomatic, although physostigmine can be seful and may counter both peripheral and central effects. 

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