Cardiovascular Abnormalities following Tricyclic Antidepressant Drug Overdosage

Zimmer R, Gieschke R, Fischbach R, Gasic S . Interaction studies with moclobemide. Acta Psychiatr Scand 1990: Suppl 360: 84-86.Drug interactions with moclobemide given to healthy subjects and depressed patients are reviewed. The drugs investigated for safety were antihypertensives, digoxin, oral contraceptives, anticoagulants and benzodiazepines. Cimetidine was studied for the pharmacokinetic effect, and possible interactions with alcohol (stimulation and/or sedation) were included. Finally, since inhibition of monoamine oxidase (MAO) can increase noradrenergic transmission, possible interaction with neuronal reuptake inhibitors such as tricyclic antidepressants (TCAs) was investigated. Whereas replacement of the older, irreversible MA0 inhibitors by a TCA was held to be dangerous and to require a therapy-free interval, the studies reviewed here provide evidence that amitriptyline can replace or be added to moclobemide without any sign of impaired tolerance, need for dose reduction or a therapy-free interval. Combined administration of moclobemide and desipramine was also tolerated well. Moclobemide did not interact with the direct-interacting sympathomimetics norepinephrine and isoproterenol and only to a negligible extent with phenylephrine. The combination of moclobemide with antihypertensive agents did not cause postural hypotension or an increase in other side effects. No clinically relevant interaction was observed between moclobemide and phenprocoumon, ghbenclamide, oral contraceptives, digoxin or benzodiazepines. Cimetidine increased the concentration of moclobemide in plasma after a single oral dose by about 100%. If moclobemide is to be used in a patient pretreated with cimetidine, treatment should therefore start with the lowest therapeutic dose and then be adjusted to clinical needs. Since moclobemide is devoid of anticholinergic effects, no interaction with alcohol was anticipated. High therapeutic doses (600 mglday) induced an effect similar to that of low doses of a TCA, but with 100-300 mg no interaction with alcohol was seen, even in elderly people. This article reviews the interaction studies with moclobemide performed in healthy volunteers and depressive patients. The drugs investigated for interaction were chosen according to safety criteria as well as the pharmacodynamic, pharmacokinetic and therapeutic properties of moclobemide. Thus, possible interactions with drugs that are frequently prescribed together with antidepressants or are hazardous if their effects are potentiated or eliminated, i.e., antihypertensive drugs, digoxin, oral contraceptives, phenprocoumon and benzodiazepines, were primarily investigated for safety reasons.The interaction with cimetidine was studied from a pharmacokinetic point of view, since cytochrome P-450 is probably involved in the metabolism of both cimetidine and moclobemide.

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“…In contrast, monoamine reuptake inhibitors are known to potentiate the action of directly acting sympathomimetics about %fold (5).…”

Section: Sympathomimeticsmentioning

confidence: 99%

Interaction studies with moclobemide

Zimmer

Gieschke

Fischbach

et al. 1990

Acta Psychiatr Scand

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“…Impaired atrioventricular conduction was observed in man only following drug overdosage by Vohra (1974), Thorstrand (1974) and by Spiker et al (1975).…”

Section: Resultsmentioning

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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“…(2) Specific antiarrhythmics have been advocated to combat the sympathomimetic and parasympatholytic effects of tricyclics. ~ blockade with practolol 5-10 mg intravenously has been found to be superior to the use of anticholinesterases such as neostigmine (Vohra 1974). Rapid tachycardia with wide QRS complexes is sometimes misdiagnosed as ventricular tachycardia.…”

Section: Tricyclic Antidepressantsmentioning

confidence: 99%

A Simple Plan for the Management of Drug Overdosage

1974

Anaesth Intensive Care

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Cardiovascular Abnormalities following Tricyclic Antidepressant Drug Overdosage

Cited by 19 publications

References 9 publications

Interaction studies with moclobemide

Interaction studies with moclobemide

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

A Simple Plan for the Management of Drug Overdosage

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