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Cardiovascular effects of diethylcarbamazine citrate
Insights
Diethylcarbamazine citrate (DECC) causes initial hypotension and bradycardia by stimulating vagal receptors, followed by hypertension via sympathetic nervous system activation. These cardiovascular effects are dose-dependent and relevant to DECC
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Anesthesiology
Background:
- Diethylcarbamazine citrate (DECC) is an anthelmintic drug.
- Cardiovascular side effects of DECC require investigation.
Purpose of the Study:
- To investigate the cardiovascular effects of DECC in anesthetized cats.
- To elucidate the mechanisms underlying DECC-induced hemodynamic changes.
Main Methods:
- Intravenous administration of DECC (2.5-10 mg/kg) in pentobarbitone-anesthetized cats.
- Hemodynamic measurements including blood pressure, cardiac output, and ventricular contractility.
- Pharmacological blockade studies using vagotomy, hexamethonium, bethanidine, and phentolamine.
Main Results:
- DECC induced biphasic cardiovascular responses: initial transient hypotension and bradycardia, followed by secondary hypertension.
- Hypotension was linked to vagal receptor stimulation in the pulmonary vasculature.
- Hypertension involved sympathetic ganglial stimulation and noradrenaline release, as evidenced by blockade studies.
Conclusions:
- DECC exerts complex cardiovascular effects mediated by both vagal and sympathetic pathways.
- Findings provide insights into the mechanisms of DECC's cardiovascular side effects.
- DECC's inhibitory effect on prostaglandin F2alpha-induced bronchoconstriction may be relevant for asthma treatment.
Abstract:
1 The cardiovascular effects of the anthelmintic drug diethylcarbamazine citrate (DECC) were examined in cats anaesthetized with pentobarbitone. There were two quite distinct haemodynamic responses, an initial transient hypotension (occurring within 10 s of an intravenous injection) and a pronounced secondary hypertension which reached a peak 30-60 s after the injection. 2 Within 10 s of an intravenous injection of DECC (2.5 to 10 mg/kg) there was hypotension, bradycardia and there were reductions in left ventricular and carotid artery dP/dt max. These effects were most pronounced following injections into the pulmonary artery; they were not observed after bilateral vagotomy or after injections into the lumen of the left ventricle. It is suggested that DECC, like nicotine, stimulates vagal receptors in the pulmonary vascular bed. 3 The secondary phase was characterized by marked systemic and pulmonary hypertension, by contractions of the nictitating membrane and by increases in left ventricular dP/dt (at fixed isovolumic pressures), in cardiac output and in myocardial blood flow. All these effects were prevented, or markedly reduced, following the administration of hexamethonium or bethanidine and the pressor response was prevented by phentolamine. It is concluded that, in doses similar to those used in therapeutics, DECC stimulates sympathetic ganglia and releases noradrenaline. The relevance of this finding to the reported side effects of the drug are discussed. 4 DECC (5 or 10 mg/kg) significantly inhibited prostaglandin F2alpha-induced increases in peak inspiratory intra-tracheal pressure without modifying its pulmonary hypertensive effect. The possible relevance of this finding to the use of DECC in asthma is discussed.