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Biomedical subjects

S Dawling

Publications and source records attributed to S Dawling.

16 recordsLinked to original sources
PubMed1992

Toxicity and deaths from 3,4-methylenedioxymethamphetamine ("ecstasy")

The risk of adverse reactions to 3,4-methylenedioxymethamphetamine (MDMA), more commonly known as "ecstasy", is now widely known in both the USA and UK, but the patterns of illness remain varied. We report our experience during 1990 and 1991. There has been a recent increase in cases of severe toxicity following recreational misuse of small amounts of MDMA. Among 7 fatalities, the pattern of toxicity included fulminant hyperthermia, convulsions, disseminated intravascular coagulation, rhabdomyolysis, and acute renal failure. Until now, there have been few reports of this type of toxicity from MDMA, which may be related both to the potential of the drug to alter thermoregulation and to the circumstances of misuse. In addition, we have monitored 7 cases of hepatotoxicity and suspect that the frequency of this complication is increasing; a history of MDMA misuse should be sought in young people presenting with unexplained jaundice or hepatomegaly. We also describe 5 subjects involved in road traffic accidents in whom MDMA was identified. Misuse of MDMA can have severe acute toxic effects; few data are available concerning long-term morbidity, and this deserves close monitoring in future.

3,4-Methylenedioxyamphetamine↗
PubMed1992

Noradrenaline uptake inhibition increases melatonin secretion, a measure of noradrenergic neurotransmission, in depressed patients.

Eight patients with endogenous depression who had received no antidepressant treatment for the previous year were treated with the noradrenaline (NA) uptake inhibitor, desipramine (DMI). Pre-treatment plasma melatonin concentrations were normal. After one day of DMI treatment plasma melatonin concentrations were increased but the response was impaired compared to normal subjects. The acute effect of DMI on plasma melatonin persisted after six weeks of treatment. These findings question the hypothesis that beta adrenoceptors are supersensitive in depression and that antidepressant drugs act by down-regulating these receptors.

Adult↗
PubMed1992

Accidental ingestion of 'Ecstasy' (3,4-methylenedioxymethylamphetamine).

There is no report of the effects of 'Ecstasy' (3,4-methylenedioxymethylamphetamine) poisoning in childhood. The case of a 13 month old boy who ingested one capsule of Ecstasy is reported. Neurological and cardiovascular side effects predominated, which responded well to treatment with a chlormethiazole infusion.

3,4-Methylenedioxyamphetamine↗
PubMed1992

Predicting severity of tricyclic antidepressant overdose.

The measurement of plasma concentration, a prolonged QRS interval, and level of consciousness have all been recommended as useful indicators of toxicity following tricyclic antidepressant overdose. The aims of this study were firstly, to determine the relative prognostic value of each of these indicators and secondly, to assess when a patient can be discharged safely from the intensive care unit. Data were evaluated on 67 patients with tricyclic antidepressant overdose from four centers. Plasma tricyclic antidepressant concentrations were measured, coma grade was evaluated using the Matthew-Lawson Coma Scale and a ECG was obtained from 23 patients on admission. Complications such as convulsions, hypotension, arrhythmias, and need for intubation and ventilation were recorded. Thirty patients developed complications and no patient died. Coma grade was the best predictor of outcome. The development of serious complications is unlikely in patients whose level of consciousness is grade II or less and who are admitted to hospital more than 6 h after overdose. Plasma tricyclic antidepressant concentration was of no additional value in predicting toxic complications or deciding when the patient could leave the intensive care unit. Our study suggests that an alert and orientated patient with a QRS duration less than 100 ms is the best indicator for safe transfer to a medical or psychiatric ward.

Adolescent↗
PubMed1978

Effect of delayed administration of activated charcoal on nortriptyline absorption.

Activated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, 'Medicoal' was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charcoal may therefore be useful in the treatment of tricyclic antidepressant poisoning even if a delay of several hours ensues before medical help is sought.

Adult↗
PubMed1978

Simplified method for monitoring tricyclic antidepressant therapy using gas--liquid chromatography with nitrogen detection.

A simplified gas chromatographic method for the rapid measurement of tricyclic antidepressant drugs in plasma using a nitrogen-sensitive detector is described. All drugs are extracted and chromatographed under identical conditions. Tertiary amines are separated from their secondary amine metabolites, which are determined simultaneously without the need for derivatisation. The lower limit of accurate determination for most drugs is 10 microgram/1. The method has been applied to the routine measurement of amitriptyline and nortriptyline in plasma from patients receiving antidepressant treatment. Large and important interindividual differences in plasma concentrations in the patients investigated have been found, and the significance of these results is discussed.

Antidepressive Agents, Tricyclic↗
PubMed1978

High plasma nortriptyline levels in the treatment of depression. I.

Following a 3-day single-dose kinetic study, 21 moderate to severely depressed inpatients were treated with 100 mg of nortriptyline nightly. Eighteen patients completed the 4-wk trial. The severity of depression was measured by weekly Hamilton Rating Scale and global rating. Blood for plasma nortriptyline estimation was taken at weekly intervals 12 h following the nighttime dose. There was a 6-fold variation in mean plasma nortriptyline levels, ranging from 120 microgram/L to 681 microgram/L. Patients with high plasma levels (greater than 200 microgram/L) showed significantly poorer clinical responses than those with levels in routine treatment, high plasma nortriptyline levels are significantly less effective than intermediate levels. Single-dose pharmacokinetic data obtained on the same patients showed a highly significant correlation with mean steady-state plasma levels obtained, which themselves correlated with clinical response. The value of predicting high plasma nortriptyline levels which are associated with poor response is discussed.

Adult↗
PubMed1978

Measurement of plasma nortriptyline concentrations: radioimmunoassay and gas-chromatography compared.

We compared measurement of plasma nortriptyline by a recently developed radioimmunoassay technique with values obtained by traditional gas chromatography. The coefficient of correlation (r) was 0.98 for 84 samples from 21 controlled patients; for a separate series of 45 samples from 34 patients who were receiving in addition other medication, r was 0.96. Use of radioimmunoassay in the routine determination of plasma nortriptyline concentration is discussed.

Chromatography, Gas↗
PubMed1977

Effect of activated charcoal on absorption of nortriptyline.

The ability of 'Medicoal', a new effervescent, activated charcoal preparation, to adsorb nortriptyline, has been investigated both in vitro and in vivo. A single dose of the effervescent charcoal 30 min after a dose of 75 mg nortriptyline produced a 60% mean reduction in both peak plasma levels and nortriptyline availability in healthy volunteers. Multiple doses of the effervescent charcoal produced 70% mean reduction in peak nortriptyline levels and availabiltiy. Activated charcoal is recommended for the treatment of tricyclic antidepressant poisoning. In in-vitro tests, a 10 g packet of the effervescent preparation containing 5 g activated charcoal) had an adsorptive capacity of approximately 3000 mg nortriptyline, a dose not usually exceeded in most cases of trycyclic antidepressant overdose.

Absorption↗
PubMedDate not supplied

Dosage adjustment from simple nortriptyline spot level predictor tests in depressed patients.

20 routine patients with endogenous depression were investigated in a kinetic and 4 week treatment study. Steady-state plasma nortriptyline concentrations above 200 microgram/L were associated with a highly significant poorer therapeutic outcome. The correlations between the 24, 48 and 72 hour concentrations and steady-state concentration were very good (r = 0.81, 0.97, 0.94; p less than 0.0001) and better than the correlation between half-life and steady-state (r = 0.65; p less than 0.01). The Spearman rank correlations (Rs) between amelioration of depression measured by the Hamilton Rating Scale (HRS) and the 24, 48 and 72 hour concentrations were highly significant (Rs = 0.74, 0.79, 0.79; p less than 0.001) but for half-life (Rs = 0.33) the correlation was not significant. The single 48 hour plasma nortriptyline concentration following a single oral dose is recommended as a reliable simplified monitoring test suitable for a busy clinic. The test is useful for dosage adjustment to maximise antidepressant action and minimise toxicity. A tentative dosage adjustment schedule for individualising antidepressant treatment with nortriptyline based on the 48 hour or the 24 hour plasma concentration is proposed.

Clinical Trials as Topic↗