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Biomedical subjects

B J Pleuvry

Publications and source records attributed to B J Pleuvry.

At least 19 recordsLinked to original sources
PubMed2000

Behavioural measurement of postoperative pain after oral surgery.

The amount and type of postoperative analgesia prescribed depends on the clinician's judgement of the patient's need. Among other factors, this judgement is likely to be based on the patient's behaviour. The primary aim of this study was to investigate the validity of using behavioural measures to provide information about a patient's experience of pain during the early stages of recovery from oral surgery under general anaesthesia. Behavioural measures were not valid measures of acute postoperative pain, which suggests that while clinicians may build a better picture of a patient's experience of pain by including behavioural observation in their range of assessments, they should not rely on them when judging a patient's need for analgesia. The results also show differences between the sexes in their reaction to pain. Significantly more women than men showed signs of pain, despite little difference in self-rating pain scores.

Acetaminophen↗
PubMed2000

Treatment of postoperative pain in oral and maxillofacial surgery.

We questioned 75 patients after inpatient oral and maxillofacial operations to find out how satisfied they were with the extent to which their pain had been controlled. Seventy (93%) had had postoperative pain. In 33 (47%), it was moderate and in 24 (34%), severe. Analgesic drugs were not given immediately to 6 of the 24 patients who requested them. Seventeen (24%) reported that the pain was worse than they had expected, but 74 of the 75 patients were satisfied with the pain control they received. We conclude that patients' expectations of pain control are low and that questions about satisfaction should not be used in isolation.

Acetaminophen↗
PubMed1996

Biochemical aspects of chronic pain and its relationship to treatment.

This review presents an overview of the neurotransmitters and neuromodulators involved in acute and chronic pain. Although there is little evidence that the neuronal pathways differ in the two types of pain, it is clear that different transmitters or receptor types are involved in hyperalgesia and chronic pain. While most attention has been focussed on spinal processes, it is apparent that some types of chronic pain have both a peripheral and a supraspinal component. The presently available drugs are probably adequate for acute pain, but the treatment of chronic pain may need to be tailored to the individual patient.

Acute Disease↗
PubMed1995

Interactions involving new antiepileptic drugs.

The advent of new antiepileptic drugs (AED) has increased the opportunities for interaction. Clinicians seek therapeutic interactions in which two AED together have greater efficacy than either drug alone; there are case reports of such, but few prospective studies. Interactions must also be suspected when the adverse effects of a new AED differ according to the co-medication. The basis can be pharmacodynamic, but more frequently it is pharmacokinetic. Inhibition of cytochrome P450 enzymes by the new drugs is more common than induction. There are important implications for the design of clinical trials and the planning of treatment changes in patients.

Anticonvulsants↗
PubMed1995

Interactions between opioid drugs and propofol in laboratory models of seizures.

Propofol (i.v. and i.p.) exhibited anticonvulsant activity in three models of seizure in the mouse, induced by bicuculline, kainic acid and N-methyl-DL-aspartic acid (NMDLA). Morphine, pethidine and fentanyl, which showed a biphasic dose-response relationship with respect to seizure modulation, abolished the anticonvulsant activity of propofol to exhibit their own intrinsic activity in proconvulsant doses. This occurred with very low doses of fentanyl and pethidine (15 micrograms kg-1 and 0.5 mg kg-1, respectively) in the NMDLA model. Thus it appears that propofol has anticonvulsant activity only when a convulsion is elicited directly; it does not prevent the actions of compounds that lower seizure threshold to convulsant stimuli. The anticonvulsant doses of morphine and fentanyl did not summate with the anticonvulsant activity of propofol. However, there was some evidence of summation of anticonvulsant activity between pethidine and propofol in the NMDLA model.

Analgesics, Opioid↗
PubMed1994

The activity of opioid analgesics in seizure models utilizing N-methyl-DL-aspartic acid, kainic acid, bicuculline and pentylenetetrazole.

Morphine, fentanyl and pethidine exhibited a biphasic dose response relationship with respect to their effects on seizure thresholds to bicuculline, pentylenetetrazole, N-methyl-DL-aspartate (NMDLA) and kainic acid in mice. The usual pattern was for low doses to be anticonvulsant and higher doses to be proconvulsant. However this pattern was reversed for fentanyl and pethidine when NMDLA was used to induce seizures. The low dose effects of all three opioid drugs was sensitive to 1 mg kg-1 naloxone in all seizure models. The responses to high doses of pethidine were unaffected or enhanced by this dose of naloxone. Naloxone reversed the effects of the higher doses of morphine and fentanyl in all models except bicuculline induced seizures.

Analgesics, Opioid↗
PubMed1993

Protective effect of flunarizine and nifedipine alone and in combination with anticonvulsant drugs against PTZ-induced seizures in mice.

The anticonvulsant effect of flunarizine has been compared to that of nifedipine in the pentylenetetrazole (PTZ)-induced seizure incidence/latency test and the PTZ seizure threshold test in mice. Nifedipine was found to have anticonvulsant activity in both models but flunarizine only had an anticonvulsant effect in the PTZ seizure incidence/latency test. Interactions with commonly used anti-epileptic drugs were also examined. In both models, the anticonvulsant effects of small doses or carbamazepine and phenytoin were enhanced by flunarizine and the effects of small doses of ethosuximide were enhanced by nifedipine. The effects of large doses of the anti-epileptic drugs were not further enhanced by either flunarizine or nifedipine. It is possible that these findings in mice are relevant to the variability of the responses to calcium antagonists as add-on therapy for epilepsy in man.

Animals↗
PubMed1993

Impairment of psychomotor function at modest plasma concentrations of carbamazepine after administration of the liquid suspension to naive subjects.

1. The influence of pharmaceutical formulation on the plasma drug concentration-time curve and the psychomotor responses to 400 mg carbamazepine has been assessed in 12 healthy male volunteers; three formulations and placebo were compared in a randomised, blind, crossover study. 2. The plasma concentration of carbamazepine rose to a maximum of 3-7 mg l-1 by 2-3 h after administration of the liquid suspension. Conventional and controlled release tablet formulations gave lower peaks at about 8 and 32 h, respectively. From 32 h onwards the plasma concentrations from the three formulations were indistinguishable. 3. Significant impairment of psychomotor function was observed after the liquid suspension only; subjective sedation was significant at 1 and 2 h and the critical flicker fusion frequency threshold was lowered at 1-8 h. Digit-symbol substitution, choice reaction time and body sway gave less conclusive evidence of impairment. 4. The results do not support the hypothesis that a psychomotor effect from carbamazepine is a threshold phenomenon with a critical plasma drug concentration at about 8 mg l-1. 5. A second hypothesis that rate of rise of plasma carbamazepine concentration has an important influence on psychomotor effect fits the observations. This interpretation is tentative since the use of a fixed dose of carbamazepine meant that differences due to rate of rise of drug concentration were confounded with differences due to peak height.

Adult↗
PubMed1992

Tolerance to the anticonvulsant effects of clobazam in mice.

Tolerance to the anticonvulsant effects of clobazam has been studied in three murine models of epilepsy: pentylenetetrazole- and N-methyl-D,L-aspartic acid-induced seizures and audiogenic-induced seizures in the DBA/2 strain. Tolerance occurred most rapidly in the pentylenetetrazole model but the development of tolerance could be reduced by increasing the dose interval. Tolerance to the protective effects of clobazam occurred more readily to the first tonic seizure than to the full tonic clonic seizure. The development of tolerance could not be attributed to smaller concentrations of clobazam in brain or to increasing concentrations of the metabolite. Although slower to develop, tolerance to clobazam did occur in the N-methyl-D,L-aspartate model. However, tolerance to the protection from the full tonic clonic seizure in DBA/2 mice could not be detected, even when the dose of clobazam was reduced to the smallest dose that acutely protected most of the mice. In contrast, the protection given by clobazam to the induction of the wild-run in DBA/2 mice, did exhibit tolerance. Studies on the mechanism of tolerance to the anticonvulsant activity of benzodiazepines must take account of the seizure model used and the dose and interval between doses.

Acoustic Stimulation↗
PubMed1991

Relationship between analgesia and respiratory depression for mu opioid receptor agonists in mice.

The relationship between analgesic activity, measured as the hot plate reaction time, and respiratory depression, measured as ventilatory frequency, was investigated in mice for a variety of mu opioid receptor agonists with differing selectivities for mu receptors compared with delta receptors. There was a weak correlation between analgesia and respiratory depression for opioids with the greatest selectivity for mu opioid receptors compared with delta receptors, such as alfentanil. The strength of the correlation increased for opioids which had greater delta receptor activity, such as morphine and fentanyl. Etorphine, which has almost equal affinity for mu, delta and, incidentally, kappa receptors, showed a strong correlation between analgesia and respiratory depression. We conclude that the predictability of the degree of respiratory depression produced by a given analgesic dose of an opioid appears to decrease with its selectivity for mu opioid receptors, at least in the mouse.

Analgesics, Opioid↗
PubMed1991

Modification by drugs used in anaesthesia of CNS stimulation induced in mice by laudanosine and strychnine.

We have investigated in mice the effects of several drugs which may be administered as part of an anaesthetic technique on the convulsive threshold to laudanosine and to strychnine, which is reported to have a similar mechanism of action. I.v. administered propofol, thiopentone and midazolam increased the dose of convulsant necessary to produce seizure when administered 2 min before the convulsive stimulus. In contrast, methohexitone and etomidate exhibited a proconvulsant effect, although with the latter this was significant only in laudanosine-treated mice. Pethidine was proconvulsant in both laudanosine- and strychnine-treated mice, but morphine was proconvulsant only in strychnine-treated mice. The effects of morphine, but not pethidine, were antagonized by naloxone 1 mg kg-1. Laudanosine, but not strychnine caused arousal from anaesthesia in subconvulsive doses. This and other evidence suggests that the mechanism of the CNS excitation produced by strychnine and laudanosine are not the same.

Analgesics↗
PubMed1990

Respiratory and sedative effects of clobazam and clonazepam in volunteers.

1. The respiratory and psychomotor effects of two benzodiazepines used mainly as anticonvulsants were compared in healthy volunteers, using a double-blind placebo controlled design. 2. Clobazam (10 and 20 mg) produced significantly fewer psychomotor side effects than clonazepam (0.5 and 1 mg). Neither drug at either dose affected the ventilatory response to CO2. 3. Although clonazepam produced significant effects on psychomotor performance, these did not correlate with plasma drug concentration. 4. Our studies provide further evidence that at the doses chosen clobazam is considerably less sedating than clonazepam. Further investigation is required into the tolerance profile of both drugs in patients.

Adult↗
PubMed1989

Effect of oral doxapram on morphine-induced changes in the ventilatory response to carbon dioxide.

A double-blind crossover volunteer trial has been carried out to determine if oral doxapram reduces the respiratory depression caused by morphine 0.12 mg kg-1 i.m. Doxapram was given to the subjects 90 min before the morphine and significantly reduced the displacement of the ventilatory response to carbon dioxide caused by the morphine. This occurred despite the fact that the plasma concentrations of doxapram were significantly lower when the subject had been given morphine than when a placebo injection had been administered. Doxapram alone in doses of 300 mg and 600 mg did not alter significantly the respiratory variables measured in this study.

Administration, Oral↗
PubMed1989

Doxapram and the neuromuscular junction.

We have studied the action of doxapram on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Doxapram augmented neuromuscular transmission in a dose-related manner when a threshold concentration of 5 x 10(-5) mol litre-1 had been exceeded. The activity of the acetylcholinesterase in rat diaphragm has been examined also in the presence of doxapram. No inhibitory effect was seen in the concentration range which augmented neuromuscular transmission, thus excluding cholinesterase inhibition as the underlying mechanism. In contrast, in the presence of partial neuromuscular block, a dose-related depression of neuromuscular transmission with doxapram was revealed. This was greatest when the neuromuscular blocking agents possessed significant presynaptic activity (beta-bungarotoxin and tubocurarine). In this situation any facilitatory action of doxapram was severely reduced or abolished. In contrast, the facilitatory effects of doxapram were apparent in the presence of partial block produced by agents with less or no presynaptic activity (pancuronium and alpha-bungarotoxin). This study suggests that doxapram has a presynaptic facilitatory action at the neuromuscular junction. In the presence of partial neuromuscular block, an inhibitory action is revealed which may be post-junctional. The concentrations of doxapram at which these effects appear are approximately five times greater than those reached in plasma after a standard clinical dose.

Acetylcholinesterase↗
PubMed1989

An in-vitro study of the interactions between intravenous induction agents and the calcium antagonists verapamil and nifedipine.

Thiopentone, propofol and etomidate inhibit the contractions of the rat isolated atria and portal vein. The actions of thiopentone and propofol summate with those of verapamil and nifedipine. Verapamil potentiates the action of etomidate on both preparations. The depressant actions of thiopentone and propofol on the portal vein are associated with a reduced response to calcium. Etomidate does not reduce the response to calcium in this preparation.

Anesthetics↗