Anticonvulsant drugs phenobarbitone

While regular monitoring of plasma phenytoin levels can result in improved seizure control, the benefit derived from measuring other commonly prescribed anticonvulsant drugs is difficult to assess. Phenobarbitone, primidone, and carbamazepine will be discussed briefly. 

Anticonvulsant action In anaesthetic dose all barbiturates e.g. phenobarbitone, mephobarbitone possess anticonvulsant action. Phenobarbitone is drug of choice for the treatment of grandmal epilepsy (details are given in chapter Antiepileptic drugs ). 

Fig. 5. Folate levels in patients receiving anticonvulsant drugs. P, phenobarbitone M, Mysoline D, Dilantin. [From Davis and Woodliff (D3), 1969, Tbe Medical Journal of Australia, reprinted with permission.]...

Callaghan N, Feeley M, Du an F, O Callaghan M, Seldrup J. The effect of anticonvulsant drugs which induce liver microsomal enzymes on derived and ingested phenobarbitone levels. Acta Neurol Scand (1977) 56, 1-6. 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

The relation between the drug levels and seizure control is not clear, and opinion is divided whether primidone exerts anticonvulsant activity solely as the metabolite phenobarbitone (B15, 06) or as native primidone, as suggested by experimental (Gl) and clinical (B7, B17) studies. 

Drugs acting on GABA/glutamate - hypnotics/anxiolytics barbiturates, benzodiazepines, chlormethiazole, chloral derivatives, baclofen - anticonvulsants phenobarbitone, primidone, phe-nytoin, sodium, valproate, carbamazepine - alcohol, phencyclidine, ketamine... 

The anticonvulsants are metabolized in the liver by the microsomal oxidative pathway, although some drugs, such as phenobarbitone and... 

Phenobarbitone is the oldest anticonvulsant in common use but suffers from a high incidence of behavioural and cognitive effects, particularly in children. While tolerance may develop to the sedative effects of the drug, high blood levels are associated with a measurable deterioration in motor performance, and learning difficulties are likely to occur in children as a... 

The antiepileptic (anticonvulsant) effect of primidone is attributed to both the parent drug and its principal metabolite, phenobarbitone. 

High Pressure Liquid Chromatography. In serum methylphenobarbitone, phenobarbitone and other anticonvulsants, sensitivity 500 ng/ml, UV detection—P. M. Kabra et al., J. analyt. Toxicol., 1978, 2, 127-133. In urine the metabolites phenobarbitone, p-hydroxyphenobarbitone and p-hydroxyme-thylphenobarbitone, detection limit 500 ng/ml for each compound, UV detection—H. E. Kunze et al., Ther. Drug Monit.,... 

Windorfer A, Sauer W. Drug interactions during anticonvulsant Iher y in childhood diphe-nylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipro-pylacetate. Neuropadiatrie (1977) 8, 29-41. 

Therapeutic drug monitoring Anticonvulsants Carbamazepine Phenytoin Ethosuximide Primidone Phenobarbitone Valproic acid... 

Anticonvulsants Anticonvulsants were one of the first groups of drugs for which TDM was indicated. The common anticonvulsants encountered in clinical practice are phenobarbitone, primidone (metabolized to phenobarbitone), phenytoin, carbamazepine, ethosuximide, and valproate. The majority of assays for these drugs are immunoassays these days as 24 h availability of measurements of these drugs has become the general expectation. 

Calcium absorption was studied in 28 adult male epileptics on chronic anticonvulsant therapy. In 16 patients on phenytoin alone calcium absorption was abnormal in 9. In 12 patients on both phenytoin and phenobarbitone calcium absorption was abnormal in 3. Hypocalcaemia (<8.5 mg/ 100 ml) occurred in only 2 patients, while serum alkaline phosphatase was elevated in 7 patients. The findings support the suggestion that rickets and osteomalacia reported in patients on chronic anticonvulsant therapy results from reduced calcium absorpion. The effect of these drugs appear to be the increased metabolism of vitamin D via enzyme induction, and an increase in the excretion of polar metabolites 25-hydroxycholecalciferol and 1,25-dihy-droxycholecalciferol which are necessary for normal calcium absorption (40 ). 

Antinuclear antibodies were found in 14 of 70 children on ethosuximide and/or phenytoin, and in 5 of 23 on phenobarbitone alone. On frequent surveillance, none developed clinical signs of systemic lupus erythematosus. It is probably unnecessary therefore to discontinue the drugs in children with antinuclear antibodies, but careful observation is required. Five children with clinical systemic lupus-like disease were observed. In each case, symptoms appeared within 1 —6 months of starting ethosuximide. The syndrome included fever, malar rash, lymphadenopathy, arthropathy, pleural effusions, myocarditis and pericarditis (43 ). Scleroderma has also been attributed to ethosuximide therapy (51 ). All these cases were on other anticonvulsants as well, but ethosuximide seemed to be the precipitating drug. 

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