Studies on the tissue distribution of d-propoxyphene

Emmerson, John L.; Welles, John S.; Anderson, Robert C.

doi:10.1016/0041-008x(67)90049-x

Cited by 24 publications

(4 citation statements)

References 1 publication

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“…Such high initial extractions suggest a rapid distribution of P to highly perfused tissues like the heart, and explains the rapid QRS prolongation. These observations are supported by the finding of high initial tissue concentrations in lung, heart and brain after intravenous injection of P in rats (Emmerson et al 1967). The rapid decrease in myocardial concentration seen a few min.…”

Section: Discussionsupporting

confidence: 59%

Cardio‐Respiratory Toxicity of Propoxyphene and Norpropoxyphene in Conscious Rabbits*

Lund-Jacobsen

1978

Acta Pharmacologica et Toxicologica

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Abstracl:The toxic effects of a-d-propoxyphene (P) and its primary metabolite a-d-norpropoxyphene (NP) were compared by intravenous infusions (100 min.) of equimolar doses of P and NP (80 pmol/kg equivalent to 30 mg/kg P HCI) in conscious rabbits. During P infusion severe respiratory depression and convulsions were seen in all the animals, and six of the nine animals died. During NP infusion, however, only minimal respiratory depression was seen and all the animals survived. Considerable prolongation of the QRS complex and cardiac arrhythmias like intermittent A-V block and ventricular extrasystoles were seen in the ECG during both P and NP infusion, while the arterial blood pressure was unchanged. In P injection experiments (6 mg/kg P HCI), ECG changes preceded reduction in respiratory rate and during NP infusion only minor changes were seen in arterial blood gases, demonstrating that the ECG changes produced by P and NP are independent of respiratory depression. The ECG changes were found to be similar to those reported in quinidine intoxication. The QRS prolongation was markedly correlated with plasma concentrations during and after P and NP infusions. The results of the present investigation favour the hypothesis that the contribution of NP to the toxicity of oral P overdosage in man is ascribed to its cardiotoxic action whereas P is responsible for the CNS toxicity (respiratory depression and convulsions) as well as cardiotoxicity.

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Section: Discussionsupporting

confidence: 59%

Cardio‐Respiratory Toxicity of Propoxyphene and Norpropoxyphene in Conscious Rabbits*

Lund-Jacobsen

1978

Acta Pharmacologica et Toxicologica

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“…Another possibility is saturation/desaturation of a myocardial receptor. Dextro-propoxyphene accumulates initially in highly perfused tissues.9 9 The peak concentration in the heart appears within 1-2 min of the administration of an i.v. bolus dose and rapidly declines (redistribution) after 5 min.…”

Section: Discussionmentioning

confidence: 99%

Dopamine and Dobutamine Reduce Myocardial d-Propoxyphene Content in Experimentally Intoxicated Rats

et al. 1991

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The effect of sympathomimetic intervention with dopamine or dobutamine on the myocardial uptake of d-propoxyphene was investigated experimentally in rats. The d-propoxyphene (19 mg kg-1 h-1) was continously infused, intravenously, over 45 min. After 20 min of infusion the rats were given either dopamine (12.5 ?g kg-1 min-1 or 25 ?g kg-1 min-1), dobutamine (25 ?g kg-1 min-1 or 45 ?g kg-1min-1) or normal saline (control). Each group consisted of eight rats. The myocardial d-propoxyphene content was significantly lower in the two groups given dopamine and in the group given dobutamine 45 ?g kg-1 min-1 than in the control group (P < 0.05). This finding indicates the benefit of early sympathomimetic intervention with either dopamine or dobutamine in d-propoxyphene intoxication.

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“…the plasma, skeletal muscles, brain and liver but lower than in the kidney. The low propoxyphene concentration in plasma and skeletal muscles is in accordance with findings in rats which were given 10 mg. kg-' of propoxyphene intravenously (20). The possible interference of prenalterol in the distribution of propoxyphene and norpropoxyphene in the different tissues is unknown.…”

Section: Discussionmentioning

confidence: 99%

Effects of prenalterol on central hemodynamics and myocardial metabolism in experimental propoxyphene‐induced shock

Häggmark

Strøm

Reiz

et al. 1987

Acta Anaesthesiol Scand

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The hemodynamic and cardiometabolic effects of prenalterol were evaluated in propoxyphene-induced circulatory shock in 10 pentobarbital-anesthetized pigs. Circulatory shock (i.e. a systolic arterial blood pressure below 60 mmHg (8 kPa) and/or a cardiac index of less than 2.0 1 X min-1 X m-2) was induced by intravenous propoxyphene chloride 15 mg X min-1. Circulatory shock occurred after 26 +/- 3 mg X kg-1 of propoxyphene. During continuous infusion of propoxyphene, consecutive doses of prenalterol 0.5, 1.0, 2.0 and 4.0 mg i.v. were injected with an interval between increments of 8 min. The maximum effect of prenalterol was seen following the 2 mg dose. Increases were observed in mean arterial blood pressure, cardiac index, stroke volume index, left ventricular stroke work index, right ventricular stroke work index, maximum rate of rise of ventricular pressure, and total body oxygen consumption. Decreases were observed in pulmonary artery occlusion pressure, mean right atrial pressure and systemic vascular resistance, whereas heart rate and pulmonary vascular resistance remained unchanged. The cardiometabolic parameters: coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and extraction, remained low. Due to profound vasodilation, normal perfusion pressures were not reestablished. In conclusion, prenalterol improved cardiac performance by a significant positive inotropic action. However, pure inotropic stimulation was not sufficient to counteract the circulatory shock state during severe propoxyphene intoxication.

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Studies on the tissue distribution of d-propoxyphene

Cited by 24 publications

References 1 publication

Cardio‐Respiratory Toxicity of Propoxyphene and Norpropoxyphene in Conscious Rabbits*

Cardio‐Respiratory Toxicity of Propoxyphene and Norpropoxyphene in Conscious Rabbits*

Dopamine and Dobutamine Reduce Myocardial d-Propoxyphene Content in Experimentally Intoxicated Rats

Effects of prenalterol on central hemodynamics and myocardial metabolism in experimental propoxyphene‐induced shock

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