ABSTRACT
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.
Subject(s)
Dextropropoxyphene/antagonists & inhibitors , Hemodynamics/drug effects , Myocardium/metabolism , Prenalterol/therapeutic use , Shock/drug therapy , Animals , Oxygen Consumption , Prenalterol/pharmacology , Shock/chemically induced , Shock/physiopathology , SwineSubject(s)
Acetaminophen/poisoning , Dextropropoxyphene/poisoning , Liver/drug effects , Acetaminophen/antagonists & inhibitors , Acetylcysteine/pharmacology , Cysteamine/pharmacology , Dextropropoxyphene/antagonists & inhibitors , Drug Combinations/antagonists & inhibitors , Drug Combinations/poisoning , HumansABSTRACT
The effects of propoxyphene, ethoheptazine, and azabicyclane, alone and in combination with 1 mg/kg naloxone, were studied in pigeons responding under a multiple fixed ratio, fixed interval schedule of food presentation. Low doses of pentobarbital (3, 5.6, and 10 mg/kg) attenuated the rate-decreasing effects produced by 20 mg/kg propoxyphene, ethoheptazine, and azabicyclane. Naloxone antagonized the rate-decreasing effects produced by 10 mg/kg azabicyclane but did not antagonize the rate-decreasing effects of propoxyphene or ethoheptazine.
Subject(s)
Analgesics, Opioid/pharmacology , Azepines/pharmacology , Bridged Bicyclo Compounds, Heterocyclic , Bridged Bicyclo Compounds/pharmacology , Bridged-Ring Compounds/pharmacology , Conditioning, Operant/drug effects , Dextropropoxyphene/pharmacology , Naloxone/pharmacology , Pentobarbital/pharmacology , Analgesics, Opioid/antagonists & inhibitors , Animals , Azepines/antagonists & inhibitors , Bridged Bicyclo Compounds/antagonists & inhibitors , Columbidae , Dextropropoxyphene/antagonists & inhibitors , Male , Reinforcement ScheduleABSTRACT
Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of opiate agonists, antagonists, and procaine on action potentials in frog sartorius muscles. Extracellular studies showed that morphine, methadone, propoxyphene, and procaine all depressed action potential production. Low concentrations of naloxone or naltrexone antagonized the excitability depression produced by the three opiate agonists but not the depression produced by procaine. Intracellular studies revealed that certain concentrations of the opiate agonists produced a biphasic decline in the stimulus-induced increase in sodium conductance (gNa). Naloxone or naltrexone antagonized only the second phase of this decline. These results show that part of the excitability depression produced by opiate agonists is due to an action on opiate drug receptors.
Subject(s)
Muscles/drug effects , Receptors, Opioid/metabolism , Action Potentials/drug effects , Animals , Anura , Dextropropoxyphene/antagonists & inhibitors , Dextropropoxyphene/pharmacology , In Vitro Techniques , Muscles/metabolism , Narcotic Antagonists/pharmacology , Narcotics/pharmacology , Potassium/metabolism , Procaine/antagonists & inhibitors , Procaine/pharmacology , Rana pipiens , Sodium/metabolismABSTRACT
Naloxone antagonized convulsions produced by tail vein infusions of d-propoxyphene, heroin, meperidine, normeperidine and thebaine in mice in a dose-related manner. Pretreatment with naloxone (60 mg/kg i.p.) produced a 200 percent increase of the dose of d-propoxyphene or heroin needed to produce a seizure. A 40 percent increase in the convulsant dose of meperidine was observed after naloxone pretreatment (30 mg/kg i.p.). Naloxone (15 mg/kg i.p.) produced a 30 percent increase in the convulsant dose of normeperidine; however, larger doses of naloxone did not produce any further increase in the convulsant dose of either normeperidine or meperidine. Larger doses of naloxone were needed to antagonize convulsions produced by thebaine. Heroin, d-propoxyphene and meperidine produced nonlethal clonic seizures, whereas normeperidine and thebaine produced tonic-clonic seizures which were followed by death. These data suggest that there may be two mechanisms by which narcotic analgesics and their congeners produce convulsions.
