Tricyclic antidepressants arrhythmia with

Tricyclic antidepressants are cardiotoxic, inducing tachycardias and an increased tendency for ventricular arrhythmias with high doses. This dose dependent cardiotoxicity gives these agents a low therapeutic index. Overdoses are characterized by cardiac conduction disturbances, hyperpyrexia, hypertension, confusion, hallucinations, seizures and coma and there is a high mortality rate in suicide attempts. Depressed patients should therefore not be given more than one week supply of these drugs. 

Toxic effects, such as seizures and arrhythmias, of other drugs taken in overdose, especially tricyclic antidepressants, may emerge with reversal of sedative effect of benzodiazepines,... 

Atropineintoxication is potentially lethal in children (see Chapter 8) and may cause prolonged severe behavioral disturbances and arrhythmias in adults. The tricyclic antidepressants, when taken in overdosage (often with suicidal... 

Adverse effects of flumazenil include agitation, confusion, dizziness, and nausea. Flumazenil may cause a severe precipitated abstinence syndrome in patients who have developed physiologic benzodiazepine dependence. In patients who have ingested benzodiazepines with tricyclic antidepressants, seizures and cardiac arrhythmias may follow flumazenil administration. 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly SSRIs and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia (see Chapter 16). 

Some of the tricyclic antidepressants also have the ability to block serotonin 2A receptors, which may contribute to the therapeutic actions of those agents with this property. Blockade of serotonin 2A receptors is discussed in Chapter 7. Tricyclic antidepressants also block sodium channels in the heart and brain, which can cause cardiac arrhythmias and cardiac arrest in overdose, as well as seizures. 

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. 

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). 

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... 

Adverse effects include constipation, dry mouth and insonmia which occur in > 10% of users. Less commonly, nausea, tachycardia, palpitations, raised blood pressure, anxiety, sweating and altered taste may occur. Blood pressure should be monitored closely throughout its use (twice weekly in the first 3 months). Contraindications include severe h3q>er-tension, peripheral occlusive arterial or coronary heart disease, cardiac arrhythmia, prostatic hypertrophy and those with severe hepatic or renal impairment. It should not be used to treat obesity of endocrine origin or those with a history of major eating disorder or psychiatric disease. Concomitant use with tricyclic antidepressants should be avoided (CNS toxicity). 

Clinical signs of toxicity most frequently seen include sedation, coma, seizures, extrapyramidal effects, and rarely hypotension and cardiac arrhythmias. Coma and seizures may develop rapidly following an exposure to loxapine. Cardiac effects include prolonged QRS, Q-T intervals, and mild hypotension however, the cardiac effects are less pronounced than those associated with tricyclic antidepressants. Anticholinergic effects, including dry mouth, blurred vision, and tachycardia, have been seen. Neuroleptic malignant syndrome has been reported after therapeutic use and acute intoxication. Hypokalemia has also been noted. 

Early signs of tricyclic antidepressant toxicity are due to anticholinergic effects and include tachycardia, mydriasis, dry mouth, low-grade fever, diminished bowel sounds, CNS excitation, and delirium. More serious toxicity is manifested by coma, respiratory depression, seizures, and cardiovascular toxicity including conduction disturbances, hypotension, ventricular arrhythmias, and asystole. Seizures cause hyperthermia, rhabdomyolysis, and metabolic acidosis. Clinical deterioration can be rapid and catastrophic in patients with tricyclic antidepressant overdose. Death most often occurs due to dysrhythmia and circulatory collapse. The typical therapeutic dose of a tricyclic antidepressant is 2-4 mg kg day Doses of 15-20 mg kg are potentially lethal. Therapeutic drug levels for most tricyclic antidepressants range from 100 to... 

Overdoses of tricyclic antidepressants can cause arrhythmias, such as prolonged QRS intervals and ventricular dysrhythmias, coma, respiratory depression, and seizures and are treated with symptomatic care and intravenous sodium bicarbonate. 

The antihypertensive effects of guanethidine may be partially or totally reversed by the mixed-acting sympathomi-metics. Halogenated hydrocarbon anesthetics may sensitize the myocardium to the effects of catecholamines. Use of vasopressors may lead to serious arrhythmias. MAO inhibitors, such as tranylcypromine, increase the pressor response to mixed-acting vasopressors. Possible hypertensive crisis and intracranial hemorrhage may occur. This interaction may also occur with furazolidone, an antimicrobial with MAO inhibitor activity. In obstetrics, if vasopressor drugs are used either to correct hypotension or are added to the local anesthetic solution, some oxytocics may cause severe persistent hypertension in the presence of mephenteramine. The pressor response of mephenteramine may be attenuated by tricyclic antidepressants, which block the uptake of norepinephrine. 

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