Comparison of effect of morphine-like analgesics on transmurally stimulated guinea-pig ileum.

1. Morphine-like analgesic drugs caused depression of twitches of the isolated guinea-pig ileum in response to transmural electrical stimulation. The drugs tested were the narcotic analgesics codeine, diamorphine, fentanyl, morphine, morphine-N-oxide, normorphine, oxymorphone, pethidine, phenazocine and phenoperidine and the analgesic narcotic antagonists nalorphine and pentazocine.2. With the first application of one of these drugs the extent of depression of twitches was proportional to concentration. Except in the case of pethidine, there was no further depression when additional drug was added to the organ bath. With the second application of a drug after washing out the first dose, the depressant effect was less; that is, tolerance developed. With pethidine, the depression of twitches was proportional to concentration and tolerance could not be observed.3. When tolerance had been produced by cumulative addition of these drugs, a concentration was reached at which further addition resulted in increased activity of the ileum.4. With codeine, morphine and normorphine, the twitches were increased in height and regular.5. With diamorphine, fentanyl, oxymorphone, pentazocine, phenazocine and phenoperidine there were increased but irregular responses to transmural stimulation.6. Having reached the concentration at which these effects were observed, washout of the drug resulted in reduction of activity; the twitches became smaller or the irregular responses ceased.7. Readministration of a drug after activity of the ileum had been depressed by withdrawal of that drug resulted in restoration of activity, the ileum being dependent on the presence of the drug for its activity.8. Codeine and nalorphine did not produce as great an increase in activity on readministration to a dependent ileum as did morphine: they seem to act as partial agonists in producing this effect.9. In similar experiments with the isolated urinary bladder of the rat and guinea-pig, morphine was less active in depressing responses to stimulation than it was on the ileum, and tolerance to the drug and dependence on it did not occur.10. These observations have been discussed in relation to analgesic activity, tolerance and dependence in man.

Contemporary strategies to preserve renal function during cardiac and vascular surgery.

Mortality rates associated with perioperative acute renal failure (ARF) range from 60% to 90%. The major causes of ARF are prerenal factors that decrease renal blood flow; intrarenal factors that have a direct effect on tubules, interstitium, or glomeruli; and postrenal factors that obstruct urine outflow. Current strategies to provide perioperative renal protection include maintaining adequate renal O2 delivery, suppressing renovascular vasoconstriction, renovascular vasodilatation, maintaining tubular flow, decreasing renal cellular O2 consumption, and attenuating reperfusion injury. A study of patients undergoing elective repair of a thoracoabdominal aortic aneurysm (TAAA) found that the use of the selective dopamine-1 receptor agonist fenoldopam was associated with reductions in mortality, dialysis requirements, and lengths of stay in the hospital and intensive care unit. The study authors suggest that the improved patient outcomes and hospital-utilization data resulting from the use of fenoldopam were directly related to the protection of renal function during surgery and a reduction of postoperative renal complications.

The natural tolerance of the afghan pika (Ochotona rufescens) to morphine.

A lagomorph, the afghan pika, Ochotona rufescens showed no effect whatever following the subcutaneous injection of morphine in doses up to 50 mg per 100 g of body weight, i.e. 250 times the ED50 for the rat. Higher doses were toxic and induced convulsions. However, the pika is responsive to synthetic opiates such as etorphine, pentazocine and phenoperidine. Interestingly enough, morphine antagonized the opiate response elicited by those narcotics to which the animal is sensitive. Pharmacokinetic analysis demonstrated that morphine enters the pika's brain as readily as it does the rat's. In addition, opiate receptor sites, which are present in normal amounts in pika brain retained their high affinity for 3H-etorphine (KD = 0.3 nM), 3H-naloxone (KD = 1.2 nM) and morphine. Moreover, binding of morphine to pika brain homogenates was inhibited in the presence of sodium ions (agonist response). Therefore, the antagonism of phenoperidine action by morphine appeared not to occur at the opiate receptor site; the mechanism of the pika's natural tolerance to morphine may reside in molecular events that normally preceed (metabolism?) or follow (enzyme activation?) the interaction between the drug and its specific recognition sites.

Simultaneous determination of pethidine (meperidine), phenoperidine, and norpethidine (normeperidine), their common metabolite, by gas chromatography with selective nitrogen detection.

This article describes a selective gas chromatographic method for the resolution and quantification of phenoperidine and its two metabolites, pethidine (meperidine) and norpethidine (normeperidine). Drugs and SKF 525 A, the internal standard, are separated from plasma by solvent extraction under alkaline conditions. They are chromatographed on a 3% OV-17 Chromosorb Q glass column and detected with a nitrogen-phosphorous detector. Linearity is observed in the study range (5-200 ng/ml). No interference by endogenous substances is noted.

[Neuroleptic analgesia in the management of labor]. / La neuroleptanalgésie dans la direction majeure du travail.

Neuroleptic analgesia, which is used for the major part of the conduct of labour, has the advantage of abolishing the pain of uterine contractions without altering the mother's state of consciousness. A study of the effects of droperidol together with phenoperidine on the mother and the child has been carried out. Clinical results, the parameters of the intra-uterine pressure curves and the fetal heart rates as well as of the acid base balance and the pO2 of the mother and infant during dilatation of the cervix and the two first hours of life have been monitored. The conclusion is that neuroleptic analgesia does not cause neonatal depression and can be used as a method for conducting labour so long as very strict monitoring conditions are applied.

[Experimental study of the cerebrovascular effects of sodium nitroprusside in the baboon Papio papio. Its action on the experimental vasospasm]. / Etude expérimentale des effets cérébro-vasculaires du nitroprussiate de soude chez le babouin Papio papio. Son action sur le vasospasme expérimental

Sodium nitroprusside (SNP) has been suggested as hypotensive agent in the surgery of cerebral aneurysms. As a preliminary step to neurosurgery, a study of its cerebro-vascular and EEG action had been carried out in 42 papio-papio baboons. On the unanaesthetized analgesic-free animal, doses below 20 mumg/kg/min. induce only a moderate decrease of mean arterial blood pressure (MABP), a slight rise of intracranial pressure (ICP) and a neat fall of cerebro-vascular resistance (CVR) without EEG modifications. Doses above 50 mumg/kg/min. induce a neat fall of MABP with a rise of cerebral blood flow (CBF), of ICP and signs of poisoning with metabolic acidosis and prolonged EEG disturbances. Beyond 90 mumg/kg/min. irreversible hypotension occured accompanied by metabolic acidosis and progressive abolition of cerebral electrogenesis. The hypotensive action of SNP is potentiated by neuroleptanalgesic drugs (phenoperidine and dehydrobenzoperidol). Using this combination marked hypotension was achieved with non toxic doses of SNP (6 to 10 mumg/kg/min.). During those hypotensions cerebral auto-regulation was maintained up to a MABP of 50 mmHg. Deeper brief hypotensions up to a MABP of 25 to 45 mmHg induce a 23% fall of CBF (p less than 0, 05) but without major EEG alterations. During experimental arterial spasms induced by injection of blood in the cisterna magna or serotonin infusion, SNP has a vasodilating action. It induces a significant rise of CBF (p less than 0, 01) for doses between 8 and 19 mumg/kg/min.

[Hemodynamic parameters and blood-free surgical field with nitroglycerin in maxillofacial surgery]. / Paramètres hémodynamiques et exsanguinité du champ opératoire sous nitroglycérine en chirurgie maxillo-faciale.

73 oral facial surgery have been performed using controlled-hypotension induced with nitroglycerin (NTG) to reduce surgical bleeding. Surgical bleeding has been reduced in more than 45% of cases. But frequent lack of correlation between blood pressure, heart beat and bleeding might imply vascular reflex mechanisms induced by controlled-hypotension using NTG. Hemodynamic parameters such as blood pressure and heart rate seem to be insufficient to monitor controlled hypotension efficiency on surgical bleeding. The use of peroperative tissues blood flow monitoring may help for the better understanding of surgical bleeding during controlled-hypotension using NTG.