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Clinically relevant anti-epileptic drug interactions.
No full textAnti-epileptic drugs frequently interact due to pharmacokinetic features (induction or inhibition of metabolism, production of active metabolites, low therapeutic indices) and the need for prolonged treatment with possible addition of other drugs to treat concomitant diseases. The most important pharmacokinetic interactions are those that inhibit phenytoin, carbamazepine and phenobarbitone metabolism and thus increase their toxicity. Drugs inhibiting metabolism include antibiotic macrolides, chloramphenicol, isoniazide, some sulphonamides, propoxyphene, cimetidine, valproic acid and sulthiame. Anti-epileptic drugs can induce hepatic microsomal enzymes and, therefore, may increase metabolism of corticosteroids, oral contraceptives, oral anticoagulants, cardiovascular agents, antibiotics, chemotherapeutic agents, psychotropic drugs and non-opiate analgesics, thereby reducing their efficacy. Advantageous pharmacodynamic interactions include synergism of ethosuximide plus valproic acid and of carbamazepine plus valproic acid. A pharmacodynamic mechanism may be responsible for the reduced sensitivity of chronically treated epileptics to some neuromuscular blockers
[Effects of amantadine on the electric activity of the brain during sleep in patients with Parkinsonism]
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The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction
No full textPURPOSE: To assess the comparative therapeutic value of valproate (VPA), lamotrigine (LTG), and their combination in patients with complex partial seizures resistant to other established antiepileptic drugs (AEDs).
METHODS: After a 3-month prospective baseline, 20 adults with refractory complex partial seizures not exposed previously to VPA and LTG were scheduled to receive three consecutive add-on treatments with VPA, LTG, or their combination, according to an open, response-conditional, crossover design. Each period consisted of a 6- to 12-week dose optimization followed by 3-month evaluation at stabilized serum drug levels. Only patients not responding to one phase proceeded to the next.
RESULTS: A >50% reduction in seizure frequency was observed in three of 20 patients given VPA and in four of 17 patients given LTG. Of the remaining 13 patients, four became seizure free, and an additional four experienced seizure reductions of 62-78% when VPA and LTG were given in combination. Mild tremor was observed in three patients receiving VPA and in all patients taking the VPA--LTG combination. In patients responding to combination therapy, optimized dosages and peak serum levels of both VPA and LTG were lower than those during separate administration.
CONCLUSIONS: A considerable proportion of patients who failed to respond to VPA and LTG separately improved when the two drugs were combined, although serum levels of both agents were lower during combination therapy. Despite methodologic limitations in the nonrandomized treatment sequence, these findings suggest that VPA and LTG exhibit a favorable pharmacodynamic interaction in patients with refractory partial epilepsy. The dosage of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects
[Electrophysiological findings during treatment of the parkinsonian syndrome with amantadine]
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Effects of the antidepressant drug viloxazine on oxcarbazepine and its hydroxylated metabolites in patients with epilepsy.
No full textThe effects of Viloxazine (VLX, 100 mg b.i.d. for 10 days) on the steady-state plasma concentrations of Oxcarbazepine (OXC), its active metabolite 10, 11-dihydro-10-hydroxy-carbazepine (MHD) and the corresponding diol (DHD) were studied in a randomized, double-blind cross-over placebo-controlled trial in 6 epileptic patients stabilized on a fixed dosage of OXC. Administration of VLX resulted in an 11% increase in the plasma concentration of MHD (p = 0.003) associated with a 31% fall in DHD levels (p = 0.0001). Plasma concentrations of unchanged OXC were unaffected by VLX. No changes in seizure frequency nor signs of drug toxicity were observed during the study. Although VLX may inhibit the conversion of MHD to the inactive diol, the interaction is unlikely to be of clinical significance
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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