Search PubMed⌕ Search

Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

At least 163 records · Page 9Linked to original sources
PubMed1981

Methods of assessment of antiepileptic drugs.

Epilepsy is a symptom with protean manifestations and as such it is a difficult disease in which to carry out a therapeutic trial. The methods available to research workers for the assessment of new antiepileptic drugs are hampered by the fact that epilepsy is a fluctuant condition. Although it is a chronic disorder open to study using cross-over trials and within-patient comparisons, accurate assessment cannot be easily made at any one point in time. Research workers are therefore automatically placed at a time factor disadvantage and this is especially so for those searching for quick methods of evaluating new compounds. The need for a quick and reliable method of assessing a new antiepileptic drug has long been appreciated. This article will discuss the methods currently available and we will begin by considering the most commonly used method of assessment with particular reference to some of the problems involved in conducting a controlled clinical trial in epilepsy.

Anticonvulsants↗
PubMed1981

The relationship between peak velocity of saccadic eye movements and serum benzodiazepine concentration.

1 Six healthy male volunteers received single oral doses of 10 mg diazepam, 20 mg temazepam, 15 mg flurazepam, 5 mg nitrazepam, 10 mg desmethyl-diazepam and placebo in a double-blind randomized fashion. 2 Peak velocity of saccadic eye movements, serum benzodiazepine concentration, and subjective ratings of wakefulness and co-ordination were measured at intervals up to 12 h after drug administration. 3 All active treatments produced a statistically significant decrease in peak saccadic velocity. The effect of temazepam and diazepam was generally more pronounced than that of flurazepam, nitrazepam and desmethyl-diazepam. 4 There were log-linear correlations between peak saccadic velocity and serum benzodiazepine concentration after ingestion of temazepam, diazepam and nitrazepam. 5 These results demonstrate a clear relationship between serum benzodiazepine concentration and its effect on a convenient measure of brainstem reticular formation function.

Adult↗
PubMed1981

Pharmacokinetics of diazepam in epileptic patients and normal volunteers following intravenous administration.

1 The pharmacokinetics of diazepam following intravenous administration have been investigated in six normal volunteers and nine epileptic patients receiving chronic antiepileptic drug therapy. 2 After intravenous administration, serum diazepam levels declined biexponentially in all subjects. The elimination half-life was significantly shorter and the plasma clearance significantly higher in the patients than in the normal volunteers. 3 Serum N-desmethyldiazepam levels were higher and the time to peak serum concentration was earlier in the epileptic patients than in the controls. 4 It is suggested that the metabolism of diazepam is induced in patients treated with enzyme inducing antiepileptic drugs, although a protein binding interaction between valproic acid and diazepam may contribute to the higher plasma clearance in the epileptic patients taking sodium valproate.

Adult↗
PubMed1981

Anticonvulsant-induced status epilepticus in Lennox-Gastaut syndrome.

A 22-year-old woman with the Lennox-Gastaut syndrome developed serial apnoeic-tonic seizures with concomitant bursts of repetitive spikes at 16-20/sec, after receiving therapeutic doses of chlormethiazole, clonazepam, and diazepam for the treatment of serial tonic-clonic generalized seizures. There was a direct relationship between dose of chlormethiazole and frequency of apnoeic-tonic seizures. Since these tonic seizures have been noted during natural sleep and after sleep induced by various sedative drugs in patients with slow spike-wave in EEG, it is likely that the reduction in level of consciousness induced by sedative drugs is the causative factor.

Adolescent↗
PubMed1981

Rectal diazepam in the treatment of absence status: a pharmacodynamic study.

Rectal administration of diazepam is highly effective in terminating absence status as judged by reduction of spike-wave activity in the EEG. Pharmacokinetic studies indicate that diazepam can have antiepileptic properties at serum levels well below those previously reported as being necessary to achieve a therapeutic effect.

Adult↗
PubMed1981

Phenylethylmalonamide in essential tremor. A double-blind controlled study.

A randomised double-blind placebo-controlled trial of phenylethylmalonamide, the major metabolite of primidone was performed in eight patients with essential tremor. Phenylethylmalonamide was given in a daily dose of 400 mg for one week and 800 mg for a second week. The compound had no statistically significant effect on the amplitude of tremor assessed by an accelerometric method, tests of performance, clinical evaluation and patient self assessment. No side effects occurred. Serum levels of phenylethylmalonamide on a daily dose of 400 mg were 11-27 micrograms/ml and on 800 mg daily were 16-48.5 micrograms/ml.

Adult↗
PubMed1981

Metoprolol and propranolol in essential tremor: a double-blind, controlled study.

Single oral doses of propranolol (120 mg), metoprolol (150 mg) and placebo were given in a randomised, double-blind fashion to 23 patients with essential tremor. Both beta blockers were significantly more effective than placebo in reducing the magnitude of tremor. The decrease in tremor produced by metoprolol (47, sem 9%, n = 23) was not significantly different from that observed propranolol (55, sem 5%, n = 23). Tachycardia on standing was antagonised by both drugs to a similar extent. These findings suggest that metoprolol may represent a valuable alternative to propranolol in the treatment of essential tremor. The data is consistent with the hypothesis that the tremorolytic effect of beta blockers in these patients may be unrelated to peripheral beta-2 adreno-receptor blockade, being possibly mediated by other central or peripheral modes of action of these drugs. However, it cannot be excluded that at the dose used, metoprolol had lost its relative cardio-selectivity and that the reduction in tremor was mediated by competitive antagonism at beta-2 receptor sites in skeletal muscle.

Adult↗
PubMed1981

Genetic markers in epilepsy: a survey.

In a study of genetic markets in patients with epilepsy, 30 genetic systems have been tested and the results compared with all previously published studies on this subjects. Only one marker, Ss + ss/SS in the MNSs blood group system showed a statistically highly significant difference (p below 0.001) in the epileptic patients compared with a control group. A previously reported difference in the Pc gene of the red cell acid phosphatase system was not confirmed in the present study. The basis for an association between the S antigen and epilepsy is difficult to understand at present and will need to to be confirmed by studies on other groups of epileptic patients and in the aetiologically different groups before being accepted. This is especially so as the Chalfont patients are the only group so far studied for this blood group system.

Blood Group Antigens↗
PubMed1981

Altered drug binding to serum proteins in pregnant women: therapeutic relevance.

The binding of diazepam, phenytoin and valproic acid to serum proteins in vitro has been compared in pregnant women of different gestational ages and in controls. The unbound fraction of each of three drugs was elevated during pregnancy (particularly during the last 8 weeks) probably due, at least in part, to a fall in serum albumin concentration. These findings may provide a partial explanation for the increase in the clearance of certain drugs during pregnancy and need to be taken into account when interpreting serum drug levels in clinical practice.

Adult↗
PubMed1981

Drug interactions with phenytoin.

Drug interactions with phenytoin are a frequent occurrence, although their clinical relevance has often been overemphasised. Probably the most important of such interactions are those resulting in inhibition of phenytoin metabolism: due to the saturable nature of phenytoin biotransformation even minor degrees of inhibition can produce disproportionate changes in both steady-state serum concentration and the magnitude of pharmacological effect. Phenytoin has marked enzyme-inducing properties and can stimulate the metabolism of many concurrently administered drugs, thereby reducing their therapeutic efficacy. Clinically important examples of such interactions include a reduction of the anticoagulant effect of dicoumarol, a decrease in the prophylactic efficacy of the contraceptive pill and failure of response to various corticosteroid agents when administered therapeutically or diagnostically. Unless complicated by additional mechanisms, plasma protein binding interactions with phenytoin are seldom of clinical significance. However, they may alter considerably the relationship between serum drug concentration and clinical response, a possibility which needs to be taken into account when interpreting serum phenytoin levels in clinical practice.

Anticonvulsants↗