This study set out to assess the effect of non-pharmacological conservative (NPC) interventions as alternatives to antiepileptic pharmacotherapy. A prospective follow-up cohort study was conducted in an outpatient seizure clinic of a referral center for epilepsy. Twenty-five patients (nine males, 16 females) aged 16-45, with at least two well-described epileptic seizures, were included who had rejected antiepileptic pharmacotherapy. Twelve had idiopathic generalized epilepsy, 11 had symptomatic or cryptogenic localization-related epilepsy, and two had epilepsy with generalized and focal signs. Twenty-three of the patients were followed for more than 2 years. The patients were treated with arrest after focal seizure onset (2 cases), sensory protection against reflex seizures (3 cases), avoidance of non-specific seizure-precipitating factors ('life hygiene', 16 cases), and/or miscellaneous interventions (8 cases). The main outcome measures were complete seizure control (more than 2 years) or sufficient improvement to continue with NPC treatment alone. Eight of the 23 patients were completely seizure free for more than 4 years, and three were sufficiently improved to continue NPC treatment without drugs. Trends were observed for patients with idiopathic generalized epilepsies with less than seven convulsive seizures, and with only one seizure type to respond better to NPC treatment. The duration of epilepsy, and the finding of generalized epileptiform discharge in the EEG had no influence on the outcome. Rational NPC treatments which are aimed at specific factors in the precipitation and development of epileptic seizures can be useful therapeutic alternatives for patients with milder forms of epilepsy. Apart from photosensitive patients, those most likely to profit are patients with idiopathic generalized epilepsy, a maximum of six generalized tonic-clonic seizures which were precipitated by lack of sleep or excessive alcohol intake, and with no or rare concomitant absences. In such cases, NPC treatment may be as effective as pharmacotherapy and gives the patient a positive experience of regained self-control.
The interaction of carbamazepine and promethazine in rabbits has been investigated. The influence of this interaction on the processes of biotransformation in the liver was revealed. The drugs were administered as single oral doses (100 mg of each drug) as well as simultaneously with an interval of 15 min. The sequence of administration of the drugs was varied. The influence of promethazine on the pharmacokinetics of carbamazepine is expressed by: (a) strong suppression of carbamazepine's level in plasma and appearance of multiple peaks of carbamazepine; (b) suppression of biotransformation of carbamazepine into carbamazepine-10,11-epoxide at the initial stages and its increase in the intermediate stages. These data are explained by the active capture of carbamazepine by liver at its primary transferal through the liver and sufficient presystem elimination of carbamazepine in the presence of promethazine. The character of kinetic curves of promethazine varies substantially under the influence of carbamazepine. However, this change is not as strong as in case of carbamazepine. The concentration of promethazine in plasma varies slightly and multiple peaks are not observed. The rate of terminal elimination of promethazine varies and abrupt prolonged segments of elimination appear at the initial and terminal stages of the process in return. These data perhaps indicate the induction of biotransformation of promethazine in the presence of carbamazepine-an inductor of microsomal liver enzymes. The changes of kinetics of promethazine and carbamazepine by simultaneous administration as compared with their administration separately, as well as a comparative consideration of pharmacokinetics of promethazine and carbamazepine by simultaneous administration show the existence of competition in the elimination between these drugs and the periodic saturation of liver for their biotransformation.
The interaction of carbamazepine and phenobarbital in rabbits was investigated. The drugs were administered to the rabbit orally as a single dose. By simultaneous administration the sequence of drugs was varied, with an interval between doses of 15 min. The doses of carbamazepine and phenobarbital were 100 and 25 mg, respectively. It was established that phenobarbital appears to be an inductor for carbamazepine independently sequence of administration of the drugs. Carbamazepine reveals inductive properties for phenobarbital in the case where phenobarbital enteres in the organism first. It was ascertained also that, by simultaneous administration, these drugs reduce absorption of each other in plasma.
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