A method of monitoring drugs for adverse reactions II. Amitriptyline and cardiac disease

Coull, D.C.; Crooks, J.; Dingwall‐Fordyce, I.; Scott, Alwyn; Weir, Roy D.

doi:10.1007/bf00560292

Cited by 34 publications

(8 citation statements)

References 5 publications

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“…This high incidence was not found in cardiac patients on imipramine or noncardiac patients on amitriptyline. The imipramine group, however, contained more patients whose illnesses were chronic, stable and not acute (85)(86)(87). These results were not confirmed in a report from the Boston Collaborative Drug Surveillance Program, which found no increased risk of sudden death in 80 patients with cardiovascular disease receiving antidepressants (88).…”

Section: Sudden Deathmentioning

confidence: 91%

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

Jefferson

1975

Psychosomatic Medicine

227

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The tricyclic antidepressants have potent and complex effects on the cardiovascular system, both directly and through interactions with other drugs. Through a combination of anticholinergic activity, direct myocardial depressant activity and an effect on the adrenergic neuron, they can cause a combination of arrhythmias, blood pressure abnormalities and congestive heart failure. These changes, although most common with overdose, can occur at therapeutic levels. In addition a number of drug-drug interactions can occur between the tricyclics and agents used in the treatment of cardiovascular disease, as exemplified by tricyclic antagonism of the antihypertensive effect of guanethidine. Awareness of these factors is necessary to insure proper therapeutic utilization of the tricyclics as well as to treat effectively their toxicity.

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Section: Sudden Deathmentioning

confidence: 91%

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

Jefferson

1975

Psychosomatic Medicine

227

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“…Sudden death, myo cardial infarction and congestive cardiac fail ure have been reported [9,24,48], In a num ber of studies, the anti-arrhythmogenic prop erties of the tricyclic depressants have been emphasised [36,68], This effect may be re lated to their local anaesthetic and quinidinelike properties [11], The sequence of cardiotoxic events in overdose accidents includes sinus tachycardia, conduction defects, supra ventricular tachycardia, S-T T wave changes, ventricular arrhythmias, bradycardia and fi nally asystole [25,28], It often is difficult to tease out the various mechanisms involved in these complex changes of electrophysiological and haemo dynamic functions [16,72] (table IV).…”

Section: Discussionmentioning

confidence: 99%

“…35], at risk individ uals with a previous cardiovascular deficit [54,68] and interaction with other treatment regimens [29], Even the healthy are not to tally exempt from untoward effects, as clini cal and research reports have shown changes in cardiovascular status even within thera peutic dose range and plasma concentrations [10,36,56,69], Exercise and stress-related conditions may precipitate unexpected car diac effects [31], These factors illustrate the inherent difficulty for the clinician in the day-to-day use of antidepressant medication, but becomes more pronounced in overdose, accidently or otherwise, when it can lead to death due to cardiac asystole [6,8,23,70], Finally, to complicate matters further, one only has to look at the increased incidence of unexplained sudden death in the antidepres sant-treated group [24,52,72] to realise that we cannot, as yet, predict with any great cer tainty which individual will be prone to un wanted and unexpected cardiotoxic effects.…”

Section: Introductionmentioning

confidence: 99%

A Double-Blind Non-Crossover Placebo-Controlled Study between Group Comparison of Trazodone and Amitriptyline on Cardiovascular Function in Major Depressive Disorder

Silverstone

Si³

et al. 1984

Psychopathology

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The cardiovascular effects of trazodone (TZD), amitriptyline (AMT) and placebo were studied in out-patients with major depression. AMT was shown to have the expected effects on the electrocardiograph and on systolic time intervals consistent with its proven anticholinergic and quinidine-like properties. TZD, in contrast, had no quinidine-like effects and minor effects on systolic time intervals. However, it was not without any cardiovascular effects. Although TZD was shown to be a safer preparation than the reference drug AMT, long-term monitoring is needed to explain the minor effect on heart rate and T wave changes.

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“…A variety of side effects may occur during treatment with tricyclic antidepressant drugs, the most serious being the cardiac complications (Muller, Goodman & Bellet, 1961;Alexander & Nino, 1969;Coull, Crooks, Dingwall-Fordyce, Scott & Weir, 1970;Editorial 1971;Williams & Sherter, 1971). Electrocardiographic changes include sinus tachycardia, ventricular extrasystoles, prolongation of the PQ and QRS intervals and ST and T wave abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Plasma Concentrations and Cardiotoxic Effects of Desipramine and Protriptyline in the Rat

Bianchetti

Bonaccorsi

Chiodaroli

et al. 1977

British J Pharmacology

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Desipramine and protriptyline were administered to anaesthetized rats by two consecutive intravenous infusions in order to obtain a peak level (first infusion) followed by lower steady state concentrations (second infusion) (Wagner, 1974). Theoretical plasma level time courses were confirmed experimentally. Desipramine and protriptyline were measured in atria and ventricles. Increasing infusion rates led to proportional increases in plasma and atrial concentrations. The tissue/medium ratio ranged from 57 to 21 for desipramine and from 43 to 11 for protriptyline according to the time of determination during infusions. Heart rate changes, deviation of the electrical axis of the heart and prolongation of atrioventricular conduction were recorded at fixed times during infusion. Positive chronotropic effects were noted at plasma concentrations ranging from 0.035 to 0.1 μg/ml for desipramine and from 0.04 to 1.2 μg/ml for protriptyline. At higher plasma concentrations the positive chronotropic effect decreased and bradycardia developed. Both drugs induced right rotation of the electrical axis of the heart. Threshold plasma levels giving 40° rotation were 1.35 μg/ml (desipramine) and 1.75 μg/ml (protriptyline). Atrioventricular conduction was prolonged at threshold plasma concentrations of 2.2 μg/ml for desipramine and 3.6 μg/ml for protriptyline. Desipramine is more cardiotoxic than protriptyline. This difference is discussed in relation to the plasma and heart concentration of the two drugs.

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A method of monitoring drugs for adverse reactions II. Amitriptyline and cardiac disease

Cited by 34 publications

References 5 publications

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

A Double-Blind Non-Crossover Placebo-Controlled Study between Group Comparison of Trazodone and Amitriptyline on Cardiovascular Function in Major Depressive Disorder

Plasma Concentrations and Cardiotoxic Effects of Desipramine and Protriptyline in the Rat

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