Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Selection of antiepileptic drug polytherapy based on mechanisms of action:The evidence reviewed
Autore:
Deckers, CLP; Czuczwar, SJ; Hekster, YA; Keyser, A; Kubova, H; Meinardi, H; Patsalos, PN; Renier, WO; Van Rijn, CM;
Indirizzi:
Univ Nijmegen, Med Ctr, Inst Neurol, Nijmegen, Netherlands Univ Nijmegen Nijmegen Netherlands , Inst Neurol, Nijmegen, Netherlands Univ Nijmegen, Med Ctr, Dept Clin Pharm, Nijmegen, Netherlands Univ Nijmegen Nijmegen Netherlands pt Clin Pharm, Nijmegen, Netherlands Lublin Med Univ Sch, Dept Pharmacol & Toxicol, Lublin, Poland Lublin Med Univ Sch Lublin Poland t Pharmacol & Toxicol, Lublin, Poland Acad Sci Czech Republ, Inst Physiol, Lab Dev Epileptol, Prague, Czech Republic Acad Sci Czech Republ Prague Czech Republic tol, Prague, Czech Republic Inst Neurol, Dept Clin Neurol, Pharmacol & Therapeut Unit, London WC1N 3BG, England Inst Neurol London England WC1N 3BG apeut Unit, London WC1N 3BG, England Univ Nijmegen, Dept Psychol, NICI, NL-6500 HE Nijmegen, Netherlands Univ Nijmegen Nijmegen Netherlands NL-6500 HE 0 HE Nijmegen, Netherlands
Titolo Testata:
EPILEPSIA
fascicolo: 11, volume: 41, anno: 2000,
pagine: 1364 - 1374
SICI:
0013-9580(200011)41:11<1364:SOADPB>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
NMDA RECEPTOR ANTAGONISTS; GAMMA-AMINOBUTYRIC-ACID; VALPROIC ACID; INTRACTABLE EPILEPSY; SODIUM VALPROATE; ABSENCE SEIZURES; PHARMACODYNAMIC INTERACTION; CARBAMAZEPINE MONOTHERAPY; ANTICONVULSANT ACTIVITY; MAXIMAL ELECTROSHOCK;
Keywords:
isobologram; mechanism of action; methodology; polytherapy;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
82
Recensione:
Indirizzi per estratti:
Indirizzo: Meinardi, H Leiden Univ, Med Ctr, Dept Physiol, POB 9604, NL-2300 RC Leiden, Netherlands Leiden Univ POB 9604 Leiden Netherlands NL-2300 RC etherlands
Citazione:
C.L.P. Deckers et al., "Selection of antiepileptic drug polytherapy based on mechanisms of action:The evidence reviewed", EPILEPSIA, 41(11), 2000, pp. 1364-1374

Abstract

Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried in an attempt to improve effectiveness by improving efficacy, tolerability, or both. We reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be selected for combination therapy based on their mechanisms of action, and if so, which combinations are associated with increased effectiveness. Because variousdesigns and methods of analysis were used in these studies, it was also necessary to evaluate the appropriateness of these approaches. Methods: Published papers reporting on AED polytherapy in animals or humans were identified by Medline search and by checking references cited in these papers. Results: Thirty-nine papers were identified reporting on two-drug AED combinations. Several combinations were reported to offer improved effectiveness, but no uniform approach was used in either animal or human studies for the evaluation of pharmacodynamic drug interactions; efficacy was often the only end point. Conclusions: There is evidence that AED polytherapy based on mechanisms ofaction may enhance effectiveness. In particular, combining a sodium channel blocker with a drug enhancing GABAergic inhibition appears to be advantageous. Combining two GABA mimetic drugs or combining an AMPA antagonist withan NMDA antagonist may enhance efficacy, but tolerability is sometimes reduced. Combining two sodium channel blockers seems less promising. However, given the incomplete knowledge of the pathophysiology of seizures and indeed of the exact mechanisms of action of AEDs, an empirical bur rational approach for evaluating AED combinations is of fundamental importance. This would involve appropriate testing of all possible combinations in animal models and subsequent evaluation of advantageous combinations in clinical trials. Testing procedures in animals should include the isobologram method, and the concept of drug load should be the basis of studies in patients with epilepsy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 11:32:46