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Biomedical subjects

F Reynolds

Publications and source records attributed to F Reynolds.

At least 145 records · Page 8Linked to original sources
PubMed1986

Transfer of fentanyl across the rabbit placenta. Effect of umbilical flow and concurrent drug administration.

The transfer of fentanyl has been studied in the perfused in situ rabbit placenta. Does were infused with fentanyl and, subsequently, with fentanyl plus bupivacaine and pethidine. Antipyrine was infused throughout as an index of materno-fetal exchange. The fetal side of one placenta was perfused artificially with Krebs buffer containing dextran, and the effluent collected from the umbilical vein (uv). Drug concentrations were measured in maternal arterial blood (ma) and uv. Maternal plasma protein binding was also measured. Transfer of fentanyl was intermediate between that of pethidine and bupivacaine (Cuv:Cma for fentanyl was 0.25, for bupivacaine, 0.11 and for pethidine was 0.44), while placental clearance (Cuv X umbilical flow/Cma) increased with umbilical flow between 0.5 and 4.0 ml min-1 for all drugs. When clearances of unbound drugs were calculated, those of bupivacaine, pethidine and antipyrine were similar, but that of fentanyl was higher. The clearance of fentanyl was not affected by the presence of bupivacaine and pethidine.

Analgesics↗
PubMed1986

Extracorporeal circuit sequestration of fentanyl and alfentanil.

Fentanyl or alfentanil, in doses approximating to those used in clinical practice, was added to the priming fluid of an extracorporeal circuit before the institution of cardiopulmonary bypass (CPB). The concentrations of both drugs in the priming fluid were measured over a 20-min period. The concentration of fentanyl decreased at neutral or high pH values, suggesting drug adsorption to the circuit. The concentration of alfentanil was unaffected. The administration of fentanyl to the priming fluid may produce lower anaesthetic concentrations than anticipated.

Adsorption↗
PubMed1986

Phenytoin kinetics during pregnancy and the puerperium.

During pregnancy changes in maternal physiology and plasma composition may alter drug binding and dose requirements. We have measured plasma unbound and total phenytoin, and saliva concentrations at intervals in 11 pregnant epileptics. Plasma albumin concentrations were also measured in pregnant and non-pregnant women. Saliva phenytoin correlated closely with the plasma unbound concentrations (r = 0.98). The saliva:plasma (S:P) ratio, reflecting the free fraction, was variable during pregnancy but tended to increase to maximal values at delivery and return to non-pregnant values within 2-8 weeks thereafter. Plasma albumin concentrations correlated poorly with phenytoin binding. Binding in umbilical cord plasma appeared higher than that in maternal plasma and total fetal concentrations correlated closely with maternal plasma concentrations at delivery. No ill effects of phenytoin were detected in the newborn infant. During the third trimester phenytoin dose increments were necessary to maintain therapeutic concentrations. After delivery maternal saliva phenytoin concentrations rose, and dose reductions were necessary to avoid clinical symptoms of toxicity. It is therefore appropriate to monitor saliva phenytoin concentrations regularly both during pregnancy and the puerperium.

Adult↗
PubMed1985

Comparison of the antiemetics metoclopramide and promethazine in labour.

A double blind trial was conducted in 477 mothers in labour to compare the antiemetics metoclopramide 10 mg and promethazine 25 mg and placebo when added to the first dose of pethidine. Metoclopramide and promethazine were equally effective, and both better than placebo, in reducing the incidence of nausea and vomiting after the administration of pethidine. Seventy seven per cent of mothers were drowsy, and 8% slept in the hour after the pethidine injection, with no difference between the groups. The sedative effect was more persistent in the promethazine group, 66% of whom were still drowsy after delivery. One third of the mothers in each group needed further analgesia, with 77% of these ultimately requesting an epidural. The reduction in pain half an hour and one hour after pethidine, assessed by a visual analogue scale, were, respectively, 22% and 22% for placebo; 26% and 23% for metoclopramide; 13% and 9% for promethazine. Analgesia after metoclopramide was significantly better than that after promethazine in terms of pain score, duration of first injection, and need for Entonox. Metoclopramide is therefore to be preferred to promethazine as an antiemetic in labour.

Clinical Trials as Topic↗
PubMed1985

Comparison of the vasoactivity of amide and ester local anaesthetics. An intradermal study.

The vascular effects and duration of action of two ester-linked local anaesthetics, procaine and amethocaine, and four amide-linked local anaesthetics, cinchocaine, lignocaine, mepivacaine and prilocaine, were investigated in 10 volunteers by intradermal injection using a double-blind technique. Procaine and amethocaine produced marked vasodilatation; weal formation was observed at 80% of the amethocaine injection sites. Mepivacaine had a marked vasoconstrictor effect; the other three agents produced more variable vasoactivity. Duration of action was concentration-dependent for all six drugs, the slopes of the log dose--duration plots reflecting the observed vasoactivity.

Adult↗
PubMed1985

Epidural fentanyl in labour. An evaluation of the systemic contribution to analgesia.

In a randomized double-blind trial in the first stage of labour, 20 patients given fentanyl 80 micrograms in the epidural test dose of bupivacaine, were compared with 20 patients receiving an intravenous infusion designed to produce comparable plasma fentanyl concentrations, at the same time as their epidural test dose. Despite slightly higher plasma fentanyl concentrations in the intravenous fentanyl group, epidural fentanyl produced analgesia which was more complete, more rapid in onset and slightly longer lasting. Supplementary doses of bupivacaine were needed to produce analgesia in 75% of the intravenous and 30% of the epidural fentanyl group. It is clear that epidural fentanyl produces satisfactory pain relief when added to the epidural test dose, but that the presence of fentanyl in the systemic circulation makes a negligible contribution to analgesia.

Adult↗
PubMed1985

Placental transfer of bupivacaine, pethidine and lignocaine in the rabbit. Effect of umbilical flow rate and protein content.

The factors determining the placental transfer of drugs used in labour were studied in the rabbit placenta perfused in situ with Krebs bicarbonate buffer. During concurrent maternal intravenous infusion of bupivacaine, lignocaine, pethidine and antipyrine, drug concentrations were measured in maternal arterial plasma and placental effluent perfusate, the flow rate and protein content of which were varied. Protein binding and content were also measured. Placental clearance of antipyrine, which is unbound, was unaltered by perfusate protein content, and increased with umbilical perfusate flow up to 2 ml/min. Clearance of lignocaine and pethidine, which were 20-30% protein bound, increased to a small extent with perfusate protein, and were flow-dependent up to the maximum perfusate flow of 4 ml/min. Clearances of bupivacaine, which was greater than 80% bound, increased markedly with perfusate protein but, though flow-dependent, was one-tenth to one-fifth that of the other drugs. Fetal binding and glycoprotein content were less than maternal, hence the equilibrium fetal: maternal ratio is predictably lower for the highly bound bupivacaine than for lignocaine or pethidine. Measured fetal: maternal ratios of bupivacaine were, however, only one-half to one-third of the predicted equilibrium values, suggesting that bupivacaine does not unbind readily in a single transit through the rabbit placenta. Thus, though bupivacaine crosses the placenta more slowly than the other drugs, the fetal dose of all these drugs will be greatest in healthy babies with good placental blood flows and high plasma proteins.

Animals↗
PubMed1984

The place of saliva in antiepileptic drug monitoring.

It has previously been shown that saliva phenytoin concentration bears a constant relationship to plasma free concentration whether protein binding of phenytoin is normal or disturbed by other drugs, pregnancy, renal failure, or hypoalbuminaemia. The present work examines the relationship between saliva (S), plasma free (F), and plasma total (P) concentrations of other anticonvulsants in 100 epileptic patients. Mean S/P ratios were for phenobarbitone 0.37 (r = 0.95), primidone 0.95 (r = 0.87), and carbamazepine 0.27 (r = 0.94). A highly significant correlation of S with F was found for these drugs, more significant than the correlation of S with P for carbamazepine in patients receiving multiple anticonvulsant drugs. Saliva valproate, however, had no predictive value for P or F. No binding to saliva proteins was demonstrated for any drug. Data for in vitro binding to plasma proteins was in good agreement with ex vivo data. Saliva is therefore a valid medium for monitoring treatment with phenobarbitone, primidone, and carbamazepine, as well as phenytoin.

Adolescent↗
PubMed1984

Epidural analgesia and instrumental delivery.

In patients given epidural analgesia who had singleton vertex vaginal deliveries the normal delivery rate was 57%, compared to 80% in all this group. The increase in instrumental delivery rate could partly be accounted for by parity (primigravidae are over-represented in the epidural group), by obstetric and medical indications for epidurals, and by the need for sitting top-ups to relieve perineal pain. There remained a small population of patients in whom epidurals may have contributed to the need for instrumental delivery.

Anesthesia, Epidural↗
PubMed1984

Do saliva concentrations predict plasma unbound theophylline concentrations? A problem re-examined.

On the assumption that plasma unbound drug concentrations are therapeutically active, the value of saliva concentrations in predicting plasma unbound theophylline concentrations was investigated in 25 ambulatory adults (aged 27 to 84 years) receiving theophylline (225-1350 mg aminophylline daily) for asthma or chronic bronchitis. Plasma samples from all patients were ultrafiltered, and the plasma unbound theophylline (F) concentrations were compared with the corresponding total plasma (P), citric acid stimulated saliva (S) and non-stimulated saliva (Ns) theophylline concentrations. Plasma unbound theophylline concentrations correlated significantly with P (r = 0.97) and S (r = 0.973), but less well with Ns (r = 0.883), emphasising the benefit of saliva stimulation. The ability of S to predict F theophylline concentrations was assessed using the mean ratio of 0.7297. In 92% of the patients, predicted F concentrations were within +/- 1 microgram/ml of the measured concentrations. Similarly, using the mean F/P ratio of 0.418, predicted P were within +/- 1 microgram/ml of obtained P in 84% patients, and using the mean S/P ratio of 0.568, predicted P were within +/- 1 microgram/ml of obtained P in 81%. An accuracy of +/- 1 microgram/ml in estimating F from S concentrations would be sufficient to indicate appropriate dose adjustments, and we therefore advocate the use of stimulated saliva samples for routine monitoring of theophylline therapy.

Adult↗
PubMed1983

Epidural versus intramuscular fentanyl. Analgesia and pharmacokinetics in labour.

In a randomised double blind trial, 36 patients in the first stage of labour received either epidural or intramuscular fentanyl at the same time as the epidural test dose of bupivacaine. Analgesia was more rapid in onset and more complete in the epidural fentanyl group. Supplementary doses of bupivacaine were required within the first hour in 62% of the intramuscular fentanyl group compared with only 16% in the epidural group. Plasma fentanyl concentrations showed wide interindividual variation, but after epidural fentanyl the peak occurred earlier. There was no correlation between analgesia and plasma fentanyl concentration, and epidural fentanyl produced superior analgesia but a systemic contribution to this effect cannot be ruled out.

Adult↗
PubMed1983

Epidural analgesia in labour and maternal posture.

The effect of maternal position in the period immediately following epidural administration on analgesia and side effects was examined during labour. Patients were randomly allocated to two groups and were either turned from left to right lateral position within 5 minutes of bupivacaine administration (n = 35), or kept in the supine position, modified as appropriate, until pain relief or side effects indicated a change (n = 35). There was no significant difference between the two groups in onset or duration of analgesia, the need for supplements or in absorption of bupivacaine. Circulatory disturbances, all mild and transient, were seen in 14 patients (eight lateral, six supine). There was no significant difference between the two groups either in the frequency of hypotension (four lateral, five supine) or of fetal heart deterioration (four lateral, three supine). However motor block occurred in 15 of the lateral group and five supine (p less than 0.02). Such differences are not thought sufficient to counterbalance the potential circulatory disadvantage of the supine position.

Adult↗