morphinans and Coronary-Disease

The antiarrhythmic activities of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid receptor antagonists for delta, kappa and mu receptors, respectively, were examined during the 30 min following coronary artery occlusion in anaesthetised rats. The haemodynamic and electrocardiographic effects of the opioid receptor agonists [D-Ala2,D-Leu5]enkephalin (DADLE) (relatively selective for delta receptors), ICI-204448 (kappa) and glyol (mu) were also investigated over the 30-90 min post ligation period. When administered intravenously 5 min before ligation, M8008 (0.5 mg kg-1 and 2.5 mg kg-1) reduced the number of ventricular ectopic beats but had no effect on the incidence or duration of ventricular fibrillation. NBT and naltrexone were not antiarrhythmic at a dose of 0.5 mg kg-1 but at 2.5 mg kg-1 (a concentration at which both drugs block kappa receptors) the number of ventricular ectopic beats, the incidence of ventricular fibrillation and mortality were all reduced. All of the opioid receptor agonists caused a transient decrease in heart rate and in arterial blood pressure but none exhibited an arrhythmogenic effect. These studies suggest that the delta and kappa opioid receptor antagonists used may be antiarrhythmic as a result of blockade of the action of endogenously released peptides acting on these receptors or that they have a non-specific 'direct' antiarrhythmic action.

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Coronary Vessels; Electrophysiology; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Hemodynamics; Male; Morphinans; Naltrexone; Narcotic Antagonists; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu

The cardiac electrophysiological effects of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid antagonists for delta, kappa and mu receptors, respectively, were studied in paced (1.5 Hz) sheep Purkinje fibres in vitro. M8008 (1 ng ml-1-10 micrograms ml-1) caused a concentration-dependent reduction in the maximum rate of depolarisation of phase 0 (MRD) and in the action potential duration measured at 50% repolarisation, APD50. Neither NBT (10 ng ml-1-10 micrograms ml-1) nor naltrexone (1 ng ml-1-10 micrograms ml-1) produced any significant effect on the cardiac action potential. In the presence of a physiological salt solution modified to mimic some of the changes that occur during myocardial ischaemia (i.e. hypoxia, acidosis, hyperkalaemia), M8008 caused a more marked reduction in MRD and prolonged rather than shortened APD50. These results suggest that the reported antiarrhythmic activity of M8008, but not NBT or naltrexone, may be, at least in part, explained by a direct cardiac electrophysiological action.

Topics: Acidosis; Action Potentials; Animals; Coronary Disease; Hyperkalemia; Hypoxia; Morphinans; Naltrexone; Narcotic Antagonists; Purkinje Fibers; Sheep

Although the hemodynamic changes produced by small doses of nalbuphine given to patients with cardiac disease are minimal, the cardiovascular effects of large doses which have been used as supplements for general anesthesia have not been investigated. Cardiovascular variables were measured after incremental doses of nalbuphine, up to 2 or 3 mg/kg in fourteen patients with coronary artery disease with normal left ventricular function and in seven patients with mitral valve disease. No significant changes in cardiac index, stroke work index, mean arterial pressure, pulmonary diastolic or wedge pressure, heart rate, or central venous pressure occurred in the preoperative period. However, nalbuphine alone did not produce surgical anesthesia and the addition of diazepam, nitrous oxide, or halothane was required in all patients. The addition of halothane coupled with surgical stimulation significantly decreased cardiac and stroke indices, increased mean arterial and pulmonary wedge pressures, and increased systemic vascular resistance in patients with coronary artery disease. In patients with mitral valve disease, following surgical incision, there were small but significant decreases in cardiac index and left ventricular stoke work index, and increases in systemic vascular resistance. Despite its lack of deleterious hemodynamic effects, the place of nalbuphine in the armamentarium of the anesthesiologist must be limited to use as a premedicant, as an adjunct to balanced anesthesia, or for postoperative pain relief.

Topics: Adult; Aged; Anesthesia, General; Coronary Artery Bypass; Coronary Disease; Female; Heart Valve Diseases; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve; Morphinans; Nalbuphine

The hemodynamic effects of butorphanol, a potent synthetic narcotic-antagonist analgesic, were investigated and compared with those of morphine. A total of 20 patients were studied (8 butorphanol, 12 morphine) at the time of diagnostic cardiac catheterization. Butorphanol decreased pH, PCO2, and systemic artery pressure and increased PCO2, cardiac index, and pulmonary artery pressure. Morphine caused similar changes in pH, PO2, systemic artery pressure, and PCO2 but much smaller changes in cardiac index and no change in pulmonary artery pressure. The clinical implications and possible mechanisms are discussed.

Topics: Adult; Analgesics; Angina Pectoris; Coronary Disease; Female; Hemodynamics; Humans; Male; Middle Aged; Morphinans; Morphine; Narcotic Antagonists; Respiration; Time Factors

Topics: Adult; Aged; Anticoagulants; Arrhythmias, Cardiac; Atropine; Coronary Care Units; Coronary Disease; Diazepam; Digitalis Glycosides; Electrocardiography; Female; Humans; Intensive Care Units; Lidocaine; Male; Middle Aged; Morphinans; Myocardial Infarction; Pentazocine; Propranolol