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At least 91 records · Page 5Linked to original sources
PubMed1979

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.

Animals↗
PubMed1984

Serum morphine levels. A comparison between continuous subcutaneous infusion and continuous intravenous infusion in postoperative patients.

A study was undertaken to compare continuous subcutaneous infusions of morphine with continuous intravenous infusions in patients whose lungs were mechanically ventilated for 24 hours postoperatively. Serum morphine levels were measured after the end of surgery and at 6, 12, 18 and 24 hours in nine patients receiving continuous subcutaneous morphine and in four patients receiving continuous intravenous morphine given at the same rate. At 6, 12, 18 and 24 hours the means of serum morphine levels in the intravenous group were 20 ng/ml, 17.75 ng/ml, 18.5 ng/ml and 18 ng/ml, respectively, the corresponding figures in the subcutaneous group being 23.2 ng/ml, 20 ng/ml, 20.7 ng/ml and 20 ng/ml. For the intravenous route the mean dose of supplementary analgesia was 14 mg of phenoperidine in the first 24 postoperative hours, whereas for the subcutaneous route the mean dose was 11.66 mg. The differences in the serum morphine levels and in the requirements of phenoperidine were not statistically significant. We conclude that a continuous subcutaneous infusion of morphine is a simple and effective means of achieving postoperative analgesia.

Humans↗
PubMed1976

The antagonist effect of naloxone hydrochloride after neuroleptanaesthesia during neurosurgery.

The effects of naloxone were studied in 82 patients undergoing intracranial surgery under general anaesthesia with fentanyl or phenoperidine. After the operation was finished the patients' alertness, sensitivity to pain, blood pressure, pulse rate, respiratory rate, tidal and minute volume were recorded parallel with arterial blood gas analyses prior to and immediately after the administration of varying amounts of naloxone i.v. in a single dose. These parameters were also repeatedly controlled for several hours in the postoperative period. The results show that a single i.v. naloxone dose of 1 mug/kg b.w. is effective in the rapid and definite reversal of the respiratory depression caused by the analgesics. This dose was neither correlated to the total amount of analgesics given, nor to the time period which elapsed between the last dose of the analgesic drug and the administration of naloxone. No side effects or complications were encountered when the indicated doses of naloxone were given. It is concluded that, even in a small single dose, naloxone effectively antagonises the respiratory depression caused by fentanyl and phenoperidine without totally eliminating the immediate postoperative analgesic effects of these agents.

Adolescent↗
PubMed1969

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.

Analgesics↗
PubMed1986

The effects of alfentanil and selected narcotic analgesics on the rate of action potential discharge of medullary respiratory neurones in anaesthetized rats.

The effects of intravenous injections of alfentanil, fentanyl, phenoperidine or morphine on respiratory and peak inspiratory air flow rate, the diaphragm electromyogram (EMG), the activity recorded extracellularly from respiratory neurones located in the ventral respiratory group and the cardiovascular system were examined in anaesthetized rats. Alfentanil produced dose-dependent changes in peripheral and central respiratory parameters, which were prevented by naloxone pretreatment. Minimal effects were produced on the cardiovascular system. The bradypnoea was principally due to a prolongation of the inspiratory phase and was accompanied by a comparable decrease in the peak inspiratory air flow rate. Alfentanil prolonged the discharge duration of inspiratory neurones such that it still maintained a strict phase correlation with the diaphragm EMG, but changes in firing frequency were inconsistent and negligible. The action on expiratory neuronal discharge was analogous to that on inspiratory neuronal discharge but delayed in onset. Hypotension produced by morphine limited the dose used but the respiratory responses to morphine and other selected narcotic analgesics were otherwise similar to that of alfentanil, differing mainly in time-course and magnitude. From the respiratory parameters assessed, the order of duration of effect was morphine greater than phenoperidine greater than fentanyl greater than alfentanil and the relative potencies were 0.1, 0.5, 2.5 and 1 respectively. The selective prolongation of inspiration and the immediate action on inspiratory neurones suggests that systemically administered narcotic analgesics may alter the mechanisms within the central respiratory rhythm generator which determine the cessation of inspiration.

Action Potentials↗
PubMed1978

[Pharmacology of morphine and its derivatives (review)].

Morphine, the principal alkaloid of "papaver somniferum" is the reference substance of central analgesics, the parmacodynamic constants of which are: analgesia and the possibility of addiction. Respiratory depression is, for many of them, a grave side-effect. At the present time, no substance in this category is fully satisfactory and all may result in dependence. Equi-analgesic doses of dextromoramide, phenoperidine and Fentanyl are less than those of morphine, whilst those of pethidine and pentazocine are higher. Study of the pharmacokinetics of these various substances indicates no common elements, and it is difficult to consider that the analgesic action is proportional to blood levels. Clinical assessment of the mean duration of action makes it possible to divide morphine derivatives into substances with a very short action (20 to 45 minutes) such as Febtanyl and phenoperidine, and those with a longer action (1 to 4 hours) which includes the majority of the other substances. The analgesic activity of Methoadone lasts for 4 to 6 hours. Morphine antagonists such as Methadone, nalophine, naloxone and naltrexone possess specific problems in terms of their utilization. Pharmacological data concerning theses substances are described.

Biotransformation↗
PubMed1980

[Induction of anaesthesia. Haemodynamic incidence in patients with ischaemic myocardiopathy (author's transl)].

Haemodynamic incidence of induction of anaesthesia was evaluated in four groups of 10 patients in general surgery: patients without heart disease (gr. I), patients with ischaemic myocardiopathy (gr. II, gr. IV), patients with ischaemic heart disease who were digitalized before anaesthesis (gr. III). An anaesthetic technique comprising a combination of phenoperidine, thiopentone, suxamethonium, pancuronium, N2O/O2 was used in groups I, II, III and patients of group IV were anaesthetized with a protocol of narconeuroleptanalgesia (phenoperidine, droperidol, thiopentone, pancuronium, N2O/O2). Induction of anaesthesia in patient with ischaemic myocardiopathy leads to haemodynamic changes with a predominant decrease of mean arterial pressure. But the haemodynamic changes are less important with neuroleptanalgesia than with balanced anaesthesia. With neuroleptanalgesia decrease of mean arterial pressure is rather less important than with balanced anaesthesia and it is not coupled with a significant decrease of cardiac index but only with a decrease of total peripheral resistances. On contrary with balanced anaesthesia decrease of mean arterial pressure is connected with a significant decrease of cardiac index related to a decrease of systolic index. Pre-operative digitalization do not attenuate cardiac and haemodynamic changes occurring after induction and balanced anaesthesia. Though neuroleptanalgesia appears to be a safe technique in patients with ischaemic heart disease.

Abdomen↗
PubMed1979

Neuroleptanesthesia for the guinea pig. An ideal anesthetic procedure for long-term physiological studies of the cochlea.

The guinea pig is notoriously difficult to anesthetize with conventional agents. Cardiorespiratory depression by general depressant anesthetic agents can render the cochlea abnormal. I report a technique that uses the specific neuroleptic and analgesia properties of the agents droperidol and phenoperidine, respectively, in combination with small doses of pentobarbital sodium, which is required only to produce unconsciousness. These agents can be given intraperitoneally, intramuscularly, or intravenously. The regimen allows performance of substantial surgery (including intracranial) and long-term (minimum, six to ten hours) physiological studies, such as those on the cochlea, with excellent cardiorespiratory stability. The method has been in continuous use in this laboratory since 1974 for single-fiber recordings from the cochlear nerve of normal and kanamycin-treated guinea pigs. This method has proved to be substantially more effective than use of pentobarbital, thiopental sodium, urethan, chloralose, or ketamine alone.

Animals↗
PubMedDate not supplied

[Study of recovery and the post-anaesthetic period (author's transl)].

The authors compare recovery and the post-anaesthetic period in 45 patients anaesthetised with a combination of either pentothal, nitrous oxide, fluothane and dolosal (group 1, 24 subjects), or of pentothal, nitrous oxide and phenoperidine (group 2, 21 subjects). The quality of recovery was judged at the end of anaesthesia by determining of occurrence of the first response to 3 types of stimulation (calling the name, noise and pain) and the density of these responses during each minute. During the post-anaesthetic period the respective percentages of wakefulness and sleep were calculated. In this way the authors demonstrate a significant (P less than 0.01) shortening in recovery time for group 2, reactivity to own name occurring first in both groups, and a very significant (P less than 0.001) increase in the percentage of physiological sleep in subjects of group 2 during the post-anaesthetic stage.

Adolescent↗