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[Hemodynamic effects of equipotent doses of phenoperidine and fentanyl in man].

The haemodynamic effects of phenoperidine and fentanyl were studied in ten patients with craniocerebral trauma who presented no surgical indications. They were all mechanically ventilated with a constant tidal volume and rate and their cardiovascular state was stable. The patients were given 5 gamma/kg of fentanyl intravenously; the haemodynamic measurements were performed at two mn interval for 20 mn. Three hours later, the patients were given 30 gamma/kg of phenoperidine intravenously and the haemodynamic measurements were performed similarly. Phenoperidine and fentanyl had the same effects: a significant fall in heart rate, mean arterial pressure and cardiac index without any change in pulmonary wedge pressure. These changes do not dangerously alter the haemodynamic condition of the patients and thus are not a contra-indication to the general use of phenoperidine and fentanyl in anaesthetic practice and in intensive care.

Adult

[Anesthesia with continuous infusion of alfatesine and phenoperidine. Uses in anesthesia of aged subjects in visceral surgery].

Anaesthesia was administered to one hundred and fifty eight patients by continuous infusion of a mixture of Alfatesine and phenoperidine. The patients were divided on two groups: group A consisted in 96 patients undergoing abdominal surgery and group B of 62 cases of various types of surgery, mainly orthopedics. The average age was 63 years (range 16-96). The operative risk scored 6 or more in 71 cases. The length of operation averaged 151 minutes (S.D. +/- 15). The mixture made of alfadione 25 ml and phenoperidine 5 mg in a glucose 5 per cent 250 ml solution was administered by mechanical pump. The induction dose was 50 ml of the mixture for patients under 50 years (rate 10 ml per minute), 40 ml per patients from 50 to 70 years (5 ml per minute), and 30 ml for patients over 70 years (5 ml per minute). The maintenance dose was adjusted to weight and age and ranged from 0,11 to 0,15 ml/kg/h for alfadione and from 0,022 to 0,030 mg/kg/h for phenoperidine. Routine tracheal intubation and artificial ventilation were performed in group A. The results are studied in relation to the effectiveness of the anaesthesia mixture, its side effects and influence on recovery. Generally, the results are good and emphasize the value of the technic in abdominal surgery for elderly patients. The methods of application are discussed in terms of medical background.

Adult

Influence of anaesthetic technique on postoperative pain. A comparison of anaesthetic supplementation with halothane and with phenoperidine.

Fifty male patients undergoing elective surgery for duodenal ulcer received either phenoperidine or halothane 0.5% for the supplementation of anaesthesia. The patients in the phenoperidine group required the first postoperative dose of analgesic later and had lower pain scores in the first 2 h after operation. In the course of the 1st, 2nd and 3rd days, the two groups of patients showed a similar pattern after operation with regard to pain scores, vital capacity impairment and oxygen tension measurements.

Adolescent

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. II. Comparative study on the epileptoid activity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The experimental design, described in part I, was again used here. The electrocortical activity was registered with an EEG amplifier using a bipolar derivation of needle electrodes fixed in the scalp of a dog in the fronto-occipital position. In this situation the convlusion threshold for the 8 substances is as follows: pethidine 20 mg.kg-1 I.V., piritramide 30, morphine 180, phenoperidine 4, R 39 209 5, fentanyl 4, sufentanil 4 and R 34 995 10 mg.kg-1 I.V. Comparing the I.V. doses producing severe convulsions with the doses necessary for deep surgical analgesia a safety margin of neurological toxicity was calculated. This was for pethidine 2.2, for piritramide 6.6, for phenoperidine 16, for R 39 209 62.5, for morphine 72, for fentanyl 160, for sufentanil 1 000 and for R 34 995 10 000. It is concluded that for pure narcotics there exists an inverse relationship between analgesic potency and neurological toxicity which is always accompanied by a hyperactivity of the automatic nervous system. Factors modifying the convulsive level of the narcotics are still under investigation. In the meanwhile it can be stated that the association of a strong narcotic with flunitrazepam, droperidol or etomidate will increase the convulsion threshold of the morphinomimetics.

Acidosis

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.

Cholinesterase Inhibitors

[Neuroplegia and extracorporeal circulation. Comparison between combinations of droperidol-phenoperidine and chlorprothixene-dextromoramide in cardiac surgery].

After a quick review of the physiopathology of extra-corporeal circulation, the value of the use of neuroplegic drugs in cardiac surgery is recalled by means of pharmacological arguments. The experimental differences existing between the combinations droperidol - phenoperidine and chlorportixene - dextromoramide, on the rate of flow and on the pressure of the perfusion, and on the esophago-rectal thermic gradients during E.C.C. is then demonstrated. Statistic calculation confirmed the superiority of chlorprotixene in the realm of tissue perfusion during E.C.C. under hypothermia.

Adult

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. III. Comparative study of the acute metabolic toxicity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The I.V. administration in dogs of high and massive doses of narcotics produced an acute rise in CO2 consumption, a rise of plasma catecholamines and other slight biochemical and metabolic perturbances. A general trend towards metabolic acidosis and hypermetabolism was noticed but important differences appeared according the drugs and doses chosen. The safety margin for metabolic toxicity (ratio between IV doses producing severe metabolic side-effects and doses necessary for deep surgical analgesia) were calculated for each narcotic and found as follows: 1 for pethidine, 3.3 for piritramide, 13 for morphine and phenoperidine, 12.5 for R 39 209, 60 for fentanyl, 800 for sufentanil and 4 000 for R 34 995. Drug associations may decrease or increase the metabolic safety margin of the narcotics. Beneficial associations with morphinomimetics are found with droperidol, etomidate and flunitrazepam.

Acidosis

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

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