ECG‐Changes Induced by Phenothiazine Drugs in the Anaesthetized Rat

Langslet, A

doi:10.1111/j.1600-0773.1970.tb00552.x

Cited by 9 publications

(4 citation statements)

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“…The HR decay after exposure to the higher concentration was more pronounced. This finding is also in agreement with Langslet's results concerning a dose dependent decrease in cardiac impulse generation and conduction velocity induced by different phenothiazines among which perphenazine appeared to be one of the most efficient (Langslet 1970).…”

Section: Discussionsupporting

confidence: 82%

“…In agreement with data of Langslet (1969Langslet ( , 1970 we proved that higher concentration of perphenazine leads to significant prolongation of QT interval. In the present study, the direct changes of QT interval following exposure to nanomolar concentrations of perphenazine were similar to those characterized by Langslet at micromolar concentration.…”

Section: Discussionsupporting

confidence: 80%

“…The first group was exposed to the dose 3.10 -5 M of perphenazine similarly as by Langslet (1969Langslet ( , 1970. The second group was exposed to the dose 3.10 -8 M of perphenazine (plasma concentrations in treated patients; Omerov et al 1989).…”

Section: Experimental Groupsmentioning

confidence: 99%

“…Sensitivity of I Na and I to to perphenazine lies in the micromolar range, whereas the therapeutic plasma concentrations are in the nanomolar range (Bébarová et al 2009). In isolated rat hearts, perphenazine at concentrations highly above the clinically relevant range caused numerous ECG changes (Langslet 1970).…”

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confidence: 99%

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Effect of perphenazine on electrogram of rat isolated heart

et al. 2011

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The aim of this study was to clarify whether administration of antipsychotic perphenazine contributes to the electrophysiological changes of the isolated heart. Fourteen adult male Wistar rats were divided into two groups. Langendorff hearts were perfused with Krebs-Henseleit solution at constant pressure (85 mmHg) and 37 °C (CaCl 2 , 1.2 mM). The electrogram was recorded by touch-free method. The hearts of the first group were exposed to 3.10 -5 M perphenazine, the hearts of the second group to 3.10 -8 M perphenazine. The incidence of arrhythmias and the heart rate and QT interval changes were studied on electrogram during 30 min periods of control, the first perphenazine administration, washout, and the second drug administration.Perphenazine administration significantly prolonged QT (p < 0.001) and QTc (p < 0.05) in group 1. In group 2, QT and QTc prolongation was less pronounced (p < 0.05). A number of arrhythmias appeared, from single premature ventricular complexes to more severe ones in both groups. The heart rate changes were non-significant.We conclude that although phenothiazines are still medicaments of choice in certain psychoses, their cardiovascular side effects should be always taken in consideration. Phenothiazines, Langendorff heart, QT-interval, arrhythmiaCardiovascular system disorders are among the most common causes of morbidity and mortality in developed countries. Many of them are caused by side effects of noncardiovascular drugs whose nature and mode of action vary greatly. A typical example is psychotropic drugs, substances with reported high incidence of cardiovascular side effects, often expressed as various electrophysiological changes. Their representative perphenazine has been used as a psychotropic drug for several decades in therapy of certain psychiatric disorders. It has been reported to induce asymptomatic ECG changes, tachyarrhythmias, self-terminating arrhythmias, or even ventricular fibrillation resulting in the cardiac arrest, especially when overdosed. There are no reports that perphenazine affects electrophysiological properties of the cardiac tissue at therapeutic doses, but, certain ECG changes were observed during its administration in the presence of other potentially arrhythmogenic factors (Magorien et al. 1979).In isolated cardiomyocytes, the effects of perphenazine is functionally related to a variety of ion membrane currents. It reversibly blocks fast sodium current I Na and transient outward potassium current I to . Sensitivity of I Na and I to to perphenazine lies in the micromolar range, whereas the therapeutic plasma concentrations are in the nanomolar range (Bébarová et al. 2009). In isolated rat hearts, perphenazine at concentrations highly above the clinically relevant range caused numerous ECG changes (Langslet 1970).Perphenazine-triggered cardiovascular side effects may be of various severities. Prolonged QT interval is supposed to be a marker for the drug arrhythmogenic capacity. Therefore, L-QT is of major concern; however, there is growing evid...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 80%

Section: Experimental Groupsmentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of perphenazine on electrogram of rat isolated heart

et al. 2011

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Psychoactive Agents, Seizure Production, and Sudden Death in Epilepsy

Lipka

Lathers

1987

The Journal of Clinical Pharma

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Major tranquilizers as well as antidepressant agents have been associated with clinical seizures in patients administered these agents. The incidence of such seizures is generally low when these drugs are administered in therapeutic doses. However, administration of large doses of these agents has been associated with many cases of convulsion production. The effects that these drugs have on animal models of epilepsy have been examined. It appears that the phenothiazines act as convulsant agents at lower doses, whereas, at higher doses, they act as anticonvulsant drugs. Antidepressants, on the other hand, appear to exert an anticonvulsant effect at low doses and convulsant effects at high doses. The mechanism by which these agents alter the seizure threshold is not yet known. Clinically, drugs of lower seizure production potential should be substituted for those drugs with greater potential in treating epileptic patients for psychiatric ailments. The problem of sudden death in epileptic patients is one that must be confronted. Sudden death has most frequently been attributed to autonomic dysfunction and cardiac arrhythmia in these patients. The contribution of stress in sudden death production also must be taken into account. In addition, some psychoactive agents have been associated with sudden death as well as cardiac arrhythmia and seizure production. Thus, in light of the possible additivity of the factors involved in the production of sudden death, the administration of a psychoactive agent to an epileptic patient should be approached with caution. Those agents that do not alter cardiac rhythm or seizure threshold should be administered if a psychoactive agent is deemed necessary for the management of psychiatric illness in the epileptic patient.

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