Search PubMed⌕ Search

Biomedical subjects

S Dawling

Publications and source records attributed to S Dawling.

At least 55 records · Page 3Linked to original sources
PubMed1984

A comparison of diazepam and midazolam as sedatives for minor oral surgery.

Diazepam in propylene glycol (Valium, Roche) and midazolam (Hypnovel, Roche) were compared as sedatives in 40 patients undergoing minor oral surgery. Twenty patients received each drug. The cardiovascular effects, the acceptability of the drugs to patients and dentists and the incidence of anterograde amnesia and adverse venous sequelae were investigated. Serum benzodiazepine levels were measured and recovery studied by six psychomotor tests repeated over five hours. Both drugs provided safe and acceptable sedation. More amnesia was reported in the midazolam group and more adverse venous sequelae by the diazepam patients. The recovery tests showed that the time taken to return to pre-sedation scores varied with the tests used and there was no significant evidence of the midazolam group recovering more quickly. In particular, significant impairment of delayed memory recall persisted in both groups throughout the investigation period.

Adolescent↗
PubMed1983

Gradual withdrawal of diazepam after long-term therapy.

41 outpatients who were long-term consumers of diazepam in therapeutic dosage were gradually withdrawn from the drug over 3 months by stepwise reduction. In a double-blind procedure half the patients began withdrawal immediately and half after 8 weeks. Of 36 patients who completed treatment, 16 (44.4%) experienced true withdrawal phenomena on reducing their drugs, but 8 other patients had pseudo-withdrawal reactions at a time when their drug treatment was unchanged. The pseudo-withdrawal reactions consisted of an increase in anxiety symptoms only, whereas true withdrawal symptoms also included perceptual changes and psychotic symptoms. Examination of pharmacological and clinical predictors of withdrawal phenomena and later relapse showed that personality factors were the most important, patients with passive-dependent traits having a significantly greater prevalence of withdrawal reactions.

Adult↗
PubMed1983

Activated charcoal in tricyclic antidepressant poisoning: pilot controlled clinical trial.

1 A randomised clinical trial was carried out to assess the effects of activated charcoal in the management of suspected tricyclic antidepressant poisoning. 2 Forty-eight patients entered the study, twenty receiving supportive care plus activated charcoal (10 g) and twenty-eight supportive care alone. 3 Drug screening showed that only seventeen patients had taken tricyclic antidepressants alone. 4 Activated charcoal had no effect on either the rate of lightening of coma or the fall in plasma antidepressant concentration in the 'pure' tricyclic antidepressant poisoning group. 5 No serious side-effects of activated charcoal were reported.

Adolescent↗
PubMed1983

In vitro and in vivo evaluation of two preparations of activated charcoal as adsorbents of aspirin.

1 The adsorptive capacities of two preparations of activated charcoal have been studied both in vitro and in vivo using aspirin as a test compound. 2 The in vitro adsorptive capacities of the charcoal preparations were 477 mg of acetylsalicylic acid/g effervescent charcoal ('Medicoal'); 359 mg/g untreated standard charcoal ('Norit-A') and 482 mg/g reheated charcoal ('Norit A'). 3 In vivo both charcoal preparations significantly reduced peak salicylate concentrations and salicylate availability, to a similar extent (analysis of variance P less than 0.001). 4 Both charcoal preparations have similar capacities for adsorbing aspirin both in vitro and in vivo.

Adsorption↗
PubMed1982

Monitoring of tricyclic antidepressant therapy.

During the three-year period 1978-1980, 2141 plasma samples from 1055 patients receiving therapy with amitriptyline (77%) or nortriptyline (23%) were analysed using GLC with nitrogen selective detection. Compared to the recommended therapeutic ranges, wild inter-individual differences were observed in plasma drug concentration, even when corrections for dosage were made. Concentrations ranged from below the limit of sensitivity of the assay (5 microgram.1(-1)) to greater than 1 mg.1(-1). The reporting of toxic symptoms subjective side-effects) was found not to reliably predict high drug concentrations. Serious complications, however, were associated with high plasma drug concentrations. Neither nortriptyline nor amitriptyline displayed dose-dependent pharmacokinetics over the concentration ranges studied. Treatment with either drug produced age-related increases in drug concentration, which were more pronounced in female patients. With amitriptyline therapy, there was an age-related decrease in the plasma nortriptyline:amitriptyline ratio, suggesting that demethylation may be more influenced by increasing age than hydroxylation. Plasma drug monitoring of tricyclic antidepressant therapy is the only reliable means of ensuring that all patients receive a fair opportunity to benefit from these drugs.

Adolescent↗
PubMed1982

Nortriptyline metabolism in chronic renal failure: metabolite elimination.

Single oral dose kinetics of nortriptyline and of tis two major metabolites, conjugated and unconjugated 20-hydroxynortriptyline, were studied in eight healthy subjects and 15 patients with chronic renal failure, five of whom were being treated with hemodialysis. Nortriptyline kinetics were unaltered, but the elimination of the metabolites was reduced in both groups of patients. In chronic renal failure the excretion of nortriptyline metabolites appeared to be the rate-limiting step in nortriptyline elimination. Three depressed hemodialysis patients were treated with nortriptyline (75 mg at night) for 6 wk. The ratios of the steady-state plasma concentrations of unconjugated 10-hydroxynortriptyline to nortriptyline (0.74 to 2.30) were in the same range as those in a control group of depressed patients with adequate renal function (0.53 to 4.08) who were also receiving nortriptyline. Conjugated 10-hydroxynortriptyline in renal failure patients was slow to reach steady-state concentrations and these were 10 to 20 times as high as those of the control depressed patients. Conjugated 10-hydroxynortriptyline in dialysis fluid during treatment showed that a mean 43 +/- 7% (SD) of the dose was removed by a 10-hr dialysis. Dialysis clearance of conjugated 10-hydroxynortriptyline was 58 +/- 8 (SD) ml min-1, but nortriptyline and unconjugated 10-hydroxynortriptyline were not appreciably removed by dialysis. Hemodialysis is not likely to be of value in the management of acute nortriptyline poisoning.

Adolescent↗
PubMed1982

Prediction of steady-state plasma concentrations and individual dosage regimens of tricyclic antidepressants from a single test dose.

Inappropriate plasma drug concentrations may be one major reason why many patients fail to show a satisfactory clinical response or experience side-effects to treatment with tricyclic antidepressants. One way of improving the situation is to try to reduce the variability in plasma concentrations by individualising drug dosage regimens as early as possible in treatment. This could be done if it were possible to predict the steady-state plasma concentrations that would be achieved by patients on any given dosage regimen. Our own studies, as well as those of other groups, have demonstrated that it is possible to make such predictions from simple measurements of drug plasma concentrations after administration of a single test dose of antidepressant. The test is best carried out in addition to therapeutic monitoring and is a simple means of selecting the optimum starting dose. The clinical advantages of a simple tolerance test are (1) ensuring that an appropriate dosage is prescribed, (2) reducing the number of dosage alterations, (3) reducing the risk of toxicity, and (4) checking patient compliance when used in combination with routine therapeutic monitoring.

Antidepressive Agents, Tricyclic↗
PubMed1982

The effect of desipramine upon central adrenergic function in depressed patients.

Eleven drug free patients meeting Research Diagnostic Criteria for Major Depressive Disorder have been treated with desipramine and given a clonidine infusion after 0, 1 and 3 weeks of treatment. The sedative and hypotensive effects of clonidine were significantly inhibited after three weeks of treatment with desipramine: a similar interaction was seen after one week of treatment although this just failed to reach statistical significance. The growth hormone (GH) response to clonidine was initially impaired, but increased significantly after one week of treatment. A significant reduction in the GH response occurred during the second and third weeks of treatment with desipramine. This last finding is interpreted as evidence of adaptive change of alpha 2 adrenoceptors: the other changes can be explained by the known ability of desipramine to block the re-uptake of noradrenaline.

Adult↗
PubMed1982

Liquid-chromatographic measurement of nitrazepam in plasma.

In this simple and rapid "high-performance" liquid-chromatographic method for determining nitrazepam in plasma, serum, or whole blood, the sample at pH 7.4 is extracted into diethyl ether with an internal standard (prazepam), chromatographed, and detected at 280 nm with a fixed-wavelength ultraviolet detector. A specimen, together with standards and a quality control, can be analyzed in duplicate within 90 min. The limit of sensitivity is 5 micrograms/L (nitrazepam and 7-acetamidonitrazepam) and 50 micrograms/L (7-aminonitrazepam), and no interferents have been found. This method has the advantages of a small sample requirement and complete resolution of nitrazepam and the above-mentioned major metabolites. We have used this method for analysis of therapeutic and overdose concentrations of nitrazepam, and to investigate the stability of the drug in blood.

Chromatography, High Pressure Liquid↗
PubMed1981

Comparison of the serum protein binding of maprotiline and phenytoin in uraemic patients on haemodialysis.

The serum protein binding of maprotiline and phenytoin has been compared in a group of 22 uraemic patients receiving haemodialysis. Determination of protein binding was carried out in vitro using equilibrium dialysis at 37 degrees C and 14C-labelled drug. The mean percentage unbound maprotiline found in patients (10.0%, SD 2.5) was not significantly different from that obtained in healthy volunteers (mean 10.5%, SD 1.0). However, there was a significantly increased variability in binding in patients compared with healthy subjects. The mean percentage unbound phenytoin in the same patients (22.2%, SD 3.3) was significantly greater than that obtained in healthy control subjects (12.5%, SD 0.6). Although there was no correlation between maprotiline and phenytoin binding and serum concentrations of alpha 1-acid glycoprotein, there was a significant correlation between percentage unbound maprotiline and serum albumin concentrations. The findings indicate that the binding of this tricyclic antidepressant is essentially normal in uraemia, although there may be increased interindividual variability in the free fraction of drug.

Adolescent↗
PubMed1981

A pilot study of the mechanism of action of desipramine.

To test the hypothesis the desipramine alters alpha adrenoceptor function in depressed patients, the effects of clonidine upon growth hormone sedation and blood pressure have been measured in depressed patients before and after treatment with desipramine. After three weeks of treatment the hypotensive and sedative effects of clonidine were inhibited in all patients even though plasma desipramine concentrations at this time varied from 42 to 560 micrograms/l. Growth hormone responses to clonidine were enhanced in five of the six patients but this effect was not statistically significant. These findings are consistent with the hypothesis that in these patients desipramine altered alpha adrenoceptor function: other explanation are discussed.

Adult↗
PubMed1981

Nortriptyline therapy in elderly patients: dosage prediction from plasma concentration at 24 hours after a single 50 mg dose.

Ten depressed elderly female patients in hospital (mean age 82 years) received a single oral dose of 50 mg nortriptyline prior to commencing treatment with this drug. The nortriptyline concentration in a plasma sample obtained 24 hours afterwards was used to predict the daily dose required to achieve a steady-state concentration within the range of 50-150 micrograms. l-1. The mean daily dose prescribed was 50 mg (range 20-100 mg). These dosage regimes provided a mean observed steady-state nortriptyline concentration of 104 micrograms. l-1, with a range of 76-180 microgram. l-1 (S.D. 30 microgram. l-1). Use of this prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success.

Aged↗