. Pharmacotherapy, 2007, 278: 1202-1205. Mancl E.E., Gidal B.E.: The effect of carbapenem antibiotics on plasma concentrations of valproic acid. Ann. Pharmacother., 2009, 43: 2082-2087. Omoda K., Murakami T., Yumoto R., Nagai J., Maeda Y., Kiribayashi Y., Takano M.: Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human. J. Pharm. Sci., 2005, 8: 1685-1693. Park M.K., Lim K.S., Kim T.E., Han H.K., Yi S.J., Shin K.H. et al.: Reduced valproic acid serum
Tapani Keränen and Hanna Kuusisto
Walter Fröscher, Timo Kirschstein and Johannes Rösche
(Anticonvulsant therapy for brain tumor-related epilepsy). Fortschr. Neurol. Psychiat., 2014, 82: 678-690. Gefroh-Grimes H.A., Gidal B.E.: Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and pharmacokinetics. Acta Neurol. Scand., 2016, 133: 4-16. Gerstner T., Teich M., Bell N., Longin E., Dempfle C.-E., Brand J. et al.: Valproate-associated coagulopathies are frequent and variable in children. Epilepsia, 2006, 47: 1136-1143. Glantz M.J., Cole B.F., Forsyth P.A., Recht L.D., Wen P.Y., Chamberlain M.C. et
Mirosław Jasiński, Magdalena Chrościńska-Krawczyk and Stanisław J. Czuczwar
Background. Adenosine is regarded as an endogenous anticonvulsant and its agonists have been proved to affect the anticonvulsant activity of a number of antiepileptic drugs (AEDs) in animal models of seizures.
Aim. To evaluate effects of adenosine agonists on carbamazepine (CBZ) and valproate (VPA) in mouse model of generalized tonic-clonic convulsions.
Methods. The following adenosine receptor agonists were used: A1 – cyclohexyladenosine, A2A – CGS 21 680, A3 – N6-benzyl-NECA and A1 (preferentially) and A2 – 2-chloroadenosine. Their possible anticonvulsant effects were studied in a threshold electroconvulsive test for maximal electroconvulsions. The protective activity of AEDs alone or in combinations with adenosine agonists was evaluated in the form of their respective ED50 values necessary to protect 50% of mice against tonic extension of the hind limbs, following maximal electroshock, delivered through ear electrodes. The specificity of interactions between AEDs and adenosine agonists was challenged with an adenosine receptor A1 and A2 antagonist, aminophylline (5 mg/kg). The effects of AEDs alone or with adenosine agonists were tested for the occurrence of adverse effects (AE) (impairment of motor coordination) in a chimney test. All combinations with an enhancement the protective activity of CBZ or VPA were verified with the free plasma or brain concentration of these AED.
Results. Adenosine receptor agonists (cycloheksyladenosine up to 4 mg/kg; CGS 21 680 – 8 mg/kg; N6-benzyl-NECA – 1 mg/kg; 2-chloroadenosine – 2 mg/kg) did not significantly affect the threshold for maximal electroconvulsions. Cycloheksyladenosine (1 mg/kg), N6-benzyl-NECA (0.5 and 1 mg/kg) and 2-chloroadenosine (1 mg/kg) potentiated the anticonvulsant activity of CBZ. Valproate’s protective action was enhanced by one adenosine agonist – cycloheksyladenosine (1 mg/kg). Only the combination of CBZ + N6-benzyl-NECA (1 mg/kg) was resistant to aminophylline (5 mg/kg). Pharmacokinetic interactions were evident in case of the combination of CBZ + N6-benzyl-NECA (1 mg/kg) and resulted in an increased free plasma concentration of this CBZ. Interestingly, total brain concentration of CBZ confirmed the pharmacokinetic interaction as regards CBZ + N6-benzyl-NECA (1 mg/kg).
Conclusion. The best profile was shown by the combination of CBZ + 2-chloroadenosine which involved no AE or a pharmacokinetic interaction. The remaining positive combinations in terms of anticonvulsant activity were associated with general profound AE and pharmacokinetic interactions in some of them.
Background. Monotherapy is the choice regimen to treat newly diagnosed epilepsies. However, if it fails, several strategies may be followed.
Aim. To discuss the treatment options when an initial monotherapy regimen fails.
Methods. We reviewed the relevant literature on the topic by using PubMed.
Review and Discussion. Approximately 64% of people with epilepsy (PWE) de novo are free of seizures with the first appropriate antiepileptic drug (AED) in monotherapy. The type (first versus second generation) of the first AED to use depends on the physician's personal choice provided that it is a first-line AED. There is a tendency to prefer a substitution rather than a combination of a failed first AED when it was produced associated with an idiosyncratic reaction, was poorly tolerated at a moderate dose, or produced no improvement in seizure control. In contrast, there is some evidence to prefer secondary polytherapy whenever the PWE tolerate its first AED but with a suboptimal response. In this case, and particularly mainly if a first generation AED was used as a first-line treatment, I prefer to choose a new generation AED given their more favourable pharmacokinetic and pharmacodynamic profiles. A very often used strategy is transitional polytherapy between two regimens of monotherapy.
Conclusion. Any therapeutic decision should take into account factors such as seizure type or syndrome, possibility of drug side effects, comorbidities, comedications, age, teratogenic potential, and compliance. Whatever the option to be taken, the PWE, his family or the caregivers should take part in the decision making.
Pavel Vlasov, Vladimir Karlov, Irina Zhidkova, Aleksandr Chervyakov, Oleg Belyaev, Iosif Volkov, Diana Dmitrenko, Antonina Karas, Tatiana Kazennykh, Olga Miguskina, Anna Moskvicheva, Elena Paramonova and Irina Ponomareva
effects of adjunctive perampanel for partial-onset seizures: A randomized trial. Epilepsia, 2016, 57: 243-251. Mula M., Kanner A.M., Schmitz B., Schachter S.: Antiepileptic drugs and suicidality: An expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology. Epilepsia, 2013, 54: 199-203. Patsalos P.N.: Drug Interactions With the Newer Antiepileptic Drugs (AEDs) - Part 1: Pharmacokinetic and Pharmacodynamic Interactions Between AEDs. Clinical Pharmacokinetics, 2013a, 52: 927
Walter Fröscher and Alois Rauber
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Mirosław Zagaja, Barbara Miziak, Katarzyna Załuska, Paweł Marzęda, Bartłomiej Drop, Karolina Załuska-Patel, Grażyna Ossowska, Stanisław J. Czuczwar and Jarogniew J. Łuszczki
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Magdalena Chrościńska-Krawczyk, Magdalena Wałek, Bożydar Tylus and Stanisław J. Czuczwar
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