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Biomedical subjects

D Chadwick

Publications and source records attributed to D Chadwick.

At least 109 records · Page 6Linked to original sources

Comparison of monotherapy with valproate and other antiepileptic drugs in the treatment of seizure disorders.

Comparative data strongly suggest that valproate is the drug of choice for patients with primary and secondarily generalized epilepsies and that it is as effective as other antiepileptic drugs in the treatment of less clearly defined or partial epilepsies beginning in adult life. In simple absence epilepsy, several studies found no significant difference in efficacy between valproate and ethosuximide. In all primary generalized epilepsies, valproate has in many studies produced an excellent response, with one comparative study showing that valproate was as effective as phenytoin. Infantile spasms responded as well to valproate as to adrenocorticotropic hormone in several studies, while valproate produced fewer side effects. More long-term studies designed to compare the efficacy of monotherapy with valproate with that of other antiepileptic drugs are needed, and several are underway in both Europe and the United States.

Anticonvulsants↗

Drug withdrawal and epilepsy. When and how?

While 80% of patients who develop epilepsy will enter prolonged remissions with drug therapy, there is no agreement about who can safely be withdrawn from treatment without the risk of relapse. In light of the fact that seizure recurrence often has very important social implications, the final decision about drug withdrawal must be made by the patient and their family after full consultation with their physician about possible risks and benefits.

Anticonvulsants↗

The modern treatment of epilepsy.

Epilepsy is a varied condition. For some patients it is a disorder that afflicts them for a short part of their life while for others it may be a chronic condition demanding life-long treatment. The most difficult decisions in treating the patient with epilepsy are when to start treatment, which drug to choose, when to stop therapy and how to manage chronic epilepsy. This short review considers each of these areas.

Abnormalities, Drug-Induced↗

Gabapentin as an antiepileptic drug in man.

Gabapentin, 1-(aminomethyl) cyclohexane acetic acid, is a GABA analogue whose antiepileptic properties were tested in a double blind cross-over trial design as add-on therapy in a dose ranging study which compared 300 mg, 600 mg, and 900 mg/day (each dose given for 2 months) in 25 patients with severe partial and generalised epilepsies. A dose related antiepileptic effect was observed. All three doses were well tolerated and no psychometric impairment was noted. No significant drug interactions were seen. The drug appears worthy of further assessment.

Acetates↗

The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids.

Patients taking anticonvulsants such as phenobarbitone, phenytoin and carbamazepine together with their oral contraceptive steroid may suffer contraceptive failure because of the enzyme-inducing properties of these anticonvulsants. We have examined, in six women, the effect of sodium valproate, an effective broad spectrum anticonvulsant, on the area under the plasma concentration versus time profile (AUC) of ethinyloestradiol (EE2) and levonorgestrel (Ng). Prior to sodium valproate therapy the mean AUC for EE2 was 880 +/- 109 pg/ml X h (+/- S.E.) and for levonorgestrel it was 29.1 +/- 2.9 ng/ml X h (n = 4). Between two and four months after sodium valproate therapy the mean AUC figures had not changed significantly, the figure for EE2 being 977 +/- 130 pg/ml X h and for levonorgestrel 29.2 +/- 1.9 ng/ml X h (p greater than or equal to 0.1 in each case). We conclude that sodium valproate in the dose used (200 mg b.d.) does not interact with oral contraceptive steroids.

Adolescent↗

A comparative study of progabide, valproate, and placebo as add-on therapy in patients with refractory epilepsy.

A three way single blind cross-over comparison of progabide, valproate and placebo, as adjunctive therapy, was undertaken in 64 patients with therapy-resistant partial and generalised seizures. The study was not completed because of the incidence of elevated hepatic enzymes on progabide. Analysis of efficacy showed progabide to be inferior to valproate against all seizure types, particularly against tonic-clonic seizures. Valproate was superior to placebo against all seizure types, partial and tonic-clonic seizures. Progabide did not differ significantly from placebo in any instance. In addition progabide caused elevation of hepatic enzymes which was symptomatic in one case, and was associated with an interaction with phenytoin which resulted in symptoms of intoxication in some cases.

Adolescent↗

When do epileptic patients need treatment? Starting and stopping medication.

Decisions about when to start and stop antiepileptic treatment have important implications for patients with epilepsy. Clinical practice varies and is determined more by dogmatic teaching than by knowledge of either the clinical course of epilepsy or the influence of the drugs. A review of the available evidence shows the need for further studies on the effects of starting and withdrawing treatment on the clinical course and prognosis of epilepsy.

Anticonvulsants↗

The comparative efficacy of antiepileptic drugs for partial and tonic-clonic seizures.

Studies of the efficacy of anticonvulsant drugs are difficult to undertake and historically have been of poor quality. Randomised comparisons of drugs are few in number, and have failed to detect significant differences between drugs. This is surprising in view of the strong feelings that many clinicians have about the relative efficacy of the drugs they use. A review of the literature emphasises the need for further studies in this field.

Anticonvulsants↗

D-penicillamine-induced myasthenia gravis in primary biliary cirrhosis.

A 62-yr-old woman with recently diagnosed primary biliary cirrhosis was started on D-penicillamine, 250 mg twice daily. Within 9 mo, she developed myasthenia gravis, associated with elevated antiacetylcholine receptor antibody titers and abnormalities of single-fiber electromyography. The D-penicillamine was withdrawn and pyridostigmine bromide was prescribed. The latter drug was slowly reduced, and at the end of 6 mo stopped, after a full recovery by the patient. The clinical response was paralleled by a fall in the antiacetylcholine receptor antibody titer into the normal range and reversal of the previously abnormal single-fiber electromyographic findings. The human leukocyte antigen type of the patient was not that typically associated with classic myasthenia gravis. It is suggested that D-penicillamine-induced myasthenia gravis is due to an independent effect of the drug on the immune system rather than to the unmasking of subclinical myasthenia gravis.

Autoantibodies↗