Search PubMed⌕ Search

Biomedical subjects

M D Rawlins

Publications and source records attributed to M D Rawlins.

At least 37 records · Page 2Linked to original sources
PubMed1994

The efficacy of locally applied morphine in post-operative pain after bilateral third molar surgery.

1. Recent evidence has hinted at a peripheral site of action of morphine analgesic efficacy. 2. Previous studies by the same authors have developed a model for testing local analgesic efficacy by placing drugs into tooth sockets after third molar surgery. 3. The present studies test the hypothesis of local morphine activity at two dosage concentrations, 100 ng ml-1 and 100 micrograms ml-1 after third molar surgery. 4. No significant analgesic efficacy was found at either dose when compared with placebo.

Administration, Oral↗
PubMed1993

Are systemic levels of non steroidal anti inflammatory drugs relevant to acute upper gastrointestinal haemorrhage?

It is uncertain as to the extent which gastrointestinal (GI) haemorrhage related to NSAIDs is due to a local, topical effect or to an action related to systemic absorption. We hypothesised that, should systemic drug concentrations be of importance, plasma levels of NSAIDs might be higher in patients who had developed GI haemorrhage, from controls who had not. Ten patients with GI haemorrhage, who had ingested piroxicam (and no other NSAID), within the preceding 64 h, at the same dosage and on no new medication for the past 14 days, had blood taken at presentation for measurement of piroxicam concentrations. Plasma piroxicam concentrations were measured in 19 community dwelling controls, matched for age +/- 8 years, gender, daily piroxicam dosage, and time from last dose as their respective index case. All had been taking piroxicam for at least 3 months, and none had experienced GI adverse effects. Median plasma piroxicam concentrations in patients at 8.27 micrograms/l, was higher than in controls at 5.06 micrograms/l. These results suggest that a systemic component, at least with piroxicam, may play a significant (though not necessarily exclusive) role in causing major gastrointestinal haemorrhage.

Acute Disease↗
PubMed1993

United Kingdom Product Licence applications involving new active substances, 1987-1989: their fate after appeals.

1. The overall fate of Product Licence applications for new active substances considered by the Committee on the Safety of Medicines between 1987 and 1989 is described. 2. Fifty-one applications were the subject of appelate procedures and 44 (86%) were successful. In 19 (43%) of the latter, applicants sought either decreased dosage regimens, substantially reduced indications, or (once) topical rather than systemic treatment. 3. Overall 57% of Product Licence applications considered between 1987 and 1989 either do not reach the market (23%) or only with substantial restrictions on dosage or indications (34%). Drug regulation, in the United Kingdom, thus plays a significant role in promoting public health rather than merely delaying the entry of new products to the market. 4. The number of volunteers and patients exposed to new active substances at the time of marketing varied widely within and between therapeutic classes. The median number of patients (1528) available for the assessment of safety underlies the importance of postmarketing safety surveillance.

Drug Approval↗
PubMed1992

Review of company postmarketing surveillance studies.

OBJECTIVES: To review postmarketing surveillance studies sponsored by the pharmaceutical industry since the introduction of voluntary guidelines in 1987 and to evaluate their contribution to monitoring drug safety. DESIGN: Retrospective analysis of the information submitted to the Medicines Control Agency on postmarketing surveillance studies. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Study designs, projected and actual sample sizes, provision of interim and final reports, number of suspected serious adverse reactions reported, identification of new drug safety hazards. RESULTS: 31 studies had been conducted under the guidelines, of which 27 were prospective and four retrospective. Nine studies had at least one comparator group, the remainder were uncontrolled. The median projected sample size for the studies was 5600 patients. Only five studies had achieved at least 75% of the projected sample size. 11 studies had been abandoned, predominantly because of difficulties in recruitment, and 15 were ongoing. One study had identified an important new safety hazard. CONCLUSIONS: Company postmarketing surveillance studies have made only a limited contribution to the assessment of drug safety, principally because of weak study designs and difficulties in recruitment. The guidelines require modification to take this experience into account.

Drug Industry↗
PubMed1992

Influence of probenecid and paracetamol (acetaminophen) on zidovudine glucuronidation in human liver in vitro.

The effects of probenecid and paracetamol on zidovudine glucuronidation were investigated, in vitro, using human liver microsomal preparations. The presence of probenecid in the incubation medium significantly reduced the maximum reaction velocity for zidovudine glucuronide formation by more than 60 per cent, and the Km was reduced by 47 per cent, suggesting an uncompetitive inhibition of zidovudine glucuronidation. In contrast, paracetamol had no significant effect on zidovudine glucuronidation. The maximum reaction velocity for zidovudine glucuronide formation and the Km were unchanged when paracetamol (5 mM) was present in the incubation medium. The effects of probenecid and paracetamol on zidovudine metabolism in vitro correlates closely with those observed in vivo. The in vitro system of human liver microsomes may have a useful role in predicting the possible interaction of other drugs with zidovudine metabolism.

Acetaminophen↗
PubMed1992

Dose proportionality study of loperamide following oral administration of loperamide oxide.

The pharmacokinetics of loperamide, after oral administration of increasing doses (1 to 16 mg) of loperamide oxide, has been investigated in 10 healthy male volunteers, using a randomised cross-over design. Comparison of the maximum plasma loperamide concentration and AUC demonstrated that the bioavailability of loperamide was proportional to the dose of loperamide oxide administered.

Administration, Oral↗
PubMed1992

The effects of two different local anaesthetic solutions administered for oral surgery on plasma potassium levels in patients taking kaliuretic diuretics.

The effects of two different dental local anaesthetic solutions, administered for oral surgery, on the plasma potassium levels of patients taking non-potassium sparing diuretics has been investigated. There was a significant reduction in plasma potassium concentration in eight subjects who received 4.4 ml of 2% lignocaine with 1:80,000 adrenaline; the mean reduction from baseline being 0.30 mmol.l-1 10 min following intraoral extravascular injection of the local anaesthetic. There was no significant difference from the pre-treatment plasma potassium concentration 10 min following similar injections of 3% prilocaine with 0.03 IU.ml-1 felypressin in 8 patients; the mean change in these subjects being -0.05 mmol.l-1. It is suggested that the use of adrenaline-free local anaesthetics would seem to be appropriate in patients receiving kaliuretic diuretics.

Aged↗
PubMed1992

Absence of withdrawal effects of ritanserin following chronic dosing in healthy volunteers.

The possible development of withdrawal symptoms following abrupt discontinuation of ritanserin after chronic administration of 10 mg daily for 8 weeks was investigated in a placebo controlled trial in 40 healthy subjects. The study consisted of two phases. In the first phase, under single blind conditions, all subjects received placebo for 2 weeks followed by a single daily dose of ritanserin (10 mg) for 8 weeks. In the second phase, under double blind conditions, subjects were randomised to receive either placebo or to continue on ritanserin (10 mg) for a further 4 weeks. Psychological assessments were performed at the start of and at intervals throughout the study. Levels of anxiety, concentration, quality of sleep and morning vigilance were measured throughout by daily visual analogue scales. No significant changes were detected in any of the measures in the group of subjects who received ritanserin compared to the group who received placebo during the second phase of the study. Ritanserin discontinuation following chronic dosing in healthy volunteers does not appear to be associated with withdrawal symptoms.

Adolescent↗
PubMed1992

The efficacy of locally applied aspirin and acetaminophen in postoperative pain after third molar surgery.

This study evaluated the efficacy of and investigated the site of action of aspirin and acetaminophen placed directly into tooth sockets after bilateral third molar surgery under local anaesthesia. On completion of surgery, 12 patients received in random, blind order either a suspension of aspirin in a methyl cellulose gel (100 mg/ml) in their tooth sockets and an oral placebo or the methyl cellulose alone in their sockets and an oral dose of aspirin (50 mg). The remaining 12 patients were treated in the same fashion with use acetaminophen. Patients were asked to record their pain, at intervals, over an 8-hour period on a 10 cm visual analog scale. Significantly less pain (p less than 0.05) was recorded throughout the 8-hour investigation period after both locally placed drugs than after placebo. There was no adverse effect on healing. The peripheral activity of aspirin is confirmed, and our findings suggest that acetaminophen has a significant peripheral effect in mediating its analgesic properties in postoperative pain after third molar surgery.

Acetaminophen↗
PubMed1992

The pharmacokinetics and effects of prochlorperazine in elderly female volunteers.

The pharmacokinetics and effects of prochlorperazine (PCZ) have been studied in six healthy elderly female volunteers in a double-blind placebo-controlled study of 3.125 mg intravenous (IV) and 25 mg oral PCZ. The pharmacokinetics of IV PCZ in elderly subjects appear similar to those previously obtained in young subjects, with a terminal half-life of 7.5 +/- 1.8 h after intravenous dosing. Oral bioavailability was low (14.7 +/- 1.5%). The pharmacological actions of prochlorperazine in elderly people appear to include antidopaminergic (prolactin rise) and anticholinergic (reduced salivary flow) effects. At the dose of PCZ used in this study, no significant haemodynamic or psychomotor changes were observed though there was a trend to prolongation of the movement component of the reaction time.

Administration, Oral↗
PubMed1992

The association of age with the activity of alcohol dehydrogenase in human liver.

Ethanol is principally oxidized in the liver by the cytosolic enzyme alcohol dehydrogenase (ADH). We have examined the effect of age and sex on alcohol dehydrogenase activities in human liver obtained from 16 healthy subjects, age range 45-88 years. There was no correlation between ADH activity, whether expressed as activity per mg cytosolic protein or per gram wet weight liver, and age. Activities were similar in men and women. These results suggest that, in common with activities of other hepatic drug metabolizing enzymes, age has no effect upon the activity of ADH in human liver.

Aged↗
PubMed1992

The effect of pirenzepine on gastric emptying and salivary flow rate: constraints on the use of saliva paracetamol concentrations for the determination of paracetamol pharmacokinetics.

1. The effects of pirenzepine on gastric emptying, salivary flow and saliva paracetamol concentrations were investigated in healthy volunteers. 2. Pirenzepine significantly reduced the area under the saliva flow-time curves (7.29 +/- 3.30 g min-1 h without pirenzepine; 4.19 +/- 2.59 g min-1 h with pirenzepine, P less than 0.01). Pirenzepine had no significant effect on plasma paracetamol Cmax (17.5 +/- 7.8 micrograms ml-1 without pirenzepine; 12.6 +/- 7.7 micrograms ml-1 with pirenzepine), plasma tmax (0.2 h (0.2-0.8 h) without pirenzepine; (0.2 h 0.2-0.8 h) with pirenzepine) and plasma AUC(0.6 h) (32.3 +/- 7.2 micrograms ml-1 h without pirenzepine; 30.3 +/- 6.5 micrograms ml-1 h with pirenzepine). 3. Mean ratios of saliva:plasma paracetamol AUC (1.06 +/- 0.24 without pirenzepine; 1.84 +/- 0.48 with pirenzepine, P less than 0.001) and saliva:plasma paracetamol Cmax (1.7 +/- 1.0 without pirenzepine; 6.5 +/- 2.7 with pirenzepine, P less than 0.01) were significantly increased by pirenzepine pretreatment, but there was a poor correlation between the percentage change in the area under the saliva flow-time curve and the percentage change in saliva paracetamol AUC (r = 0.47, P = 0.21). 4. The findings suggest that a) pirenzepine is a more selective antagonist of the muscarinic receptors in salivary glands than those in gastric smooth muscle and b) caution is required when using saliva paracetamol concentrations to determine the pharmacokinetics of the drug in the presence of other agents which may influence salivary flow rate.

Acetaminophen↗
PubMed1992

Incidence and severity of phenytoin-induced gingival overgrowth in epileptic patients in general medical practice.

This investigation examines the incidence of phenytoin-induced gingival overgrowth in a population of epileptic patients who attend General Medical Practices for treatment of their epilepsy and compares the gingival changes with an otherwise healthy group of patients. The plaque score, gingival index, and gingival overgrowth did not differ significantly between the two groups (P > 0.05). A significant correlation was observed between plaque score and gingival overgrowth in the phenytoin-treated patient, but in this group there was no correlation between gingival overgrowth and salivary concentration of the drug. The overall incidence of clinically significant overgrowth (13%) is considerably less than in other studies.

Adolescent↗
PubMed1992

Attitudes to adverse drug reaction reporting in the Northern Region.

1. The attitudes and knowledge of doctors in the Northern Region to reporting of adverse drug reactions were assessed using a postal questionnaire to all doctors in two, previously identified, high reporting and two low reporting health districts. Comparisons were made of the attitudes and knowledge within professional groups (GPs, Consultants and Junior Hospital Doctors), and between the amalgamated doctor groups. 2. 1181 of 1600 doctors (74%) responded. Despite being selected on the basis of previous adverse drug reaction reporting patterns, GPs and consultants from high and low reporting districts perceived they had sent a similar number of ADR reports, and there were few differences in opinion and attitude within these two groups. 3. Most differences within doctor groups were found for junior doctors, with those from low reporting districts indicating they had sent significantly less yellow cards than those in high reporting districts. There were also significant differences in the estimates junior doctors made with a frequency of adverse drug reactions, the existing documentation on adverse drug reactions, and the purposes of the adverse reaction scheme. 4. General Practitioners in low reporting areas stated they wrote more prescriptions (P < 0.02), consultants spent more time in clinical contact (P < 0.01) and junior doctors did both (P < 0.01), all of which suggest different workloads may effect reporting of adverse drug reactions. 5. When given clinical examples, or asked about the CSMs black triangle scheme, all doctor groups performed poorly. 6. The number of reports stated as being sent increased with time from qualification for 10 years, then seemed to plateau.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗