Best mulig behandling med antiepileptika for den enkelte pasient!

Hensikt «Best mulig behandling med antiepileptika for den enkelte pasient!» er et avgjørende mål for behandling av pasienter med epilepsi, men også for stadig nye pasientgrupper som bruker antiepileptika. Hensikten med artikkelen er å gi en oppdatert oversikt over metoder og anvendelse av klinisk farmakologi for antiepileptika, med fokus på populasjons- og pasientaspekter. Materiale og metoder Artikkelen er basert på erfaring og et utvalg av litteratur fra forfatternes forskningsbakgrunn. Resultater Det er fokusert på to tilnærminger for å studere klinisk farmakologi av antiepileptika. Endring i bruk av antiepileptika ved epilepsi og andre indikasjoner (smerte og psykiatri), polyterapi og psykiatrisk komorbiditet kan undersøkes ved farmakoepidemiologiske studier, for eksempel ved bruk av Reseptregisteret. Slike studier kan være til hjelp også i behandling av den enkelte pasient. Farmakokinetisk variabilitet hos enkeltpasienter og i spesielle pasientgrupper som barn, gravide og eldre kan studeres ved bruk av data fra terapeutisk legemiddelmonitorering. Dermed kan dosen bedre tilpasses individuelt for optimalisering av behandlingen. Utfordringer inkluderer aldersrelaterte endringer i farmakokinetikk, interaksjoner, farmakogenetisk variasjon, stor bivirkningsbelastning og varierende etterlevelse. Konklusjon Kunnskap om bruk og oppfølging av antiepileptika i hele populasjonen og i spesielle pasientgrupper er viktig for å oppnå en best mulig behandling for den enkelte pasient

Legemidler og pasientsikkerhet – fokus på eldre

Fagartikkel som beskriver utfordringer knyttet til legemiddelbruk hos eldre.Hensikt: eldre står for en stor andel av det totale legemiddelbruket og bruker ofte flere ulike legemidler samtidig. Legemiddelbruk hos eldre er dermed et stort og viktig område. Hensikten med denne oversiktsartikkelen er å peke på utfordringer relatert til legemiddelbruk hos eldre og vise hvordan feil legemiddelbruk kan oppstå og mer optimal behandling kan tilstrebes. Materiale og metode: artikkelen favner bredt og dekker ulike fagområder som samfunnsfarmasi, galenisk farmasi, farmakologi og legemiddelanalyse. Den er basert på utvalgte forskningsartikler publisert i internasjonale eller norske vitenskapelige tidsskrifter. Egen forskning er trukket frem særskilt. Resultater: sannsynligheten for feil og uhensiktsmessig bruk av legemidler øker hos pasienter med høy alder. Høy alder medfører også ofte polyfarmasi, noe som øker sannsynligheten for feil ytterligere. Fysiologiske endringer kan føre til endret farmakokinetikk, svelgevansker, og at det blir vanskeligere for pasienten å sette seg godt inn i sin egen medikamentelle behandling for dermed å kunne oppdage eventuelle feil. Ulike utfordringer følger av dette, og kan relateres til forskrivningssituasjonen, utfordringer relatert til skifte mellom ulike omsorgsnivå, legemiddelhåndtering og etterlevelse. Konklusjon: optimal legemiddelbruk hos eldre er en utfordrende problemstilling. Valg av indikasjon og legemiddel, formulering, dosering, behov for informasjon og hvorvidt legemiddellistene er samstemte bør vurderes kritisk. En god balanse mellom effekt og tolerabilitet og total legemiddelbelastning bør tilstrebes

Decreased serum concentrations of antiseizure medications in children with drug resistant epilepsy following treatment with ketogenic diet

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A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.info:eu-repo/semantics/publishedVersio

Pharmacology and drug interactions of cannabinoids

Cannabinoids include a variety of substances, of which cannabidiol (CBD) is the main substance investigated for the treatment of epilepsy, and this will be the focus in the present review. CBD preparations exist in various forms. There are significant differences in quality control regarding content and reproducibility for an approved drug versus herbal preparations. Cannabidiol has challenging pharmacological properties, and pharmaceutical and pharmacokinetic aspects will depend on the formulation or preparation of a certain product. This article will focus on the characteristics, pharmacokinetic challenges, and interactions of standardised CBD-containing drugs based on evidence from clinical and pharmacokinetic studies

Drug interactions involving the new second- and third-generation antiepileptic drugs

During the period 1989-2009, 14 new antiepileptic drugs (AEDs) were licensed for clinical use and these can be subdivided into new second- and third-generation AEDs. The second-generation AEDs comprise felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. The third-generation AEDs comprise eslicarbazepine acetate and lacosamide. The interaction propensity of AEDs is very important because all new AEDs are licensed, at least in the first instance, as adjunctive therapy. The present review summarizes the interactions (pharmacokinetic and pharmacodynamic) that have been reported with the newer AEDs. The pharmacokinetic interactions include those relating to protein-binding displacement from albumin in blood, and metabolic inhibitory and induction interactions occurring in the liver. Overall, the newer AEDs are less interacting because their pharmacokinetics are more favorable and many are minimally or not bound to blood albumin (e.g., eslicarbazepine, felbamate, gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) and are primarily renally excreted or metabolized by noncytochrome P450 or uridine glucoronyl transferases (e.g., gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) as opposed to hepatic metabolism which is particularly amenable to interference. Gabapentin, lacosamide, levetiracetam, pregabalin and vigabatrin are essentially not associated with clinically significant pharmacokinetic interactions. Of the new AEDs, lamotrigine and topiramate are the most interacting. Furthermore, the metabolism of lamotrigine is susceptible to both enzyme inhibition and enzyme induction. While the metabolism of felbamate, tiagabine, topiramate and zonisamide can be induced by enzyme-inducing AEDs, they are less vulnerable to inhibition by valproate. Noteworthy is the fact that only five new AEDs (eslicarbazepine, felbamate, oxcarbazepine, rufinamide and topiramate) interact with oral contraceptives and compromise contraception control. The most clinically significant pharmacodynamic interaction is that relating to the synergism of valproate and lamotrigine for complex partial seizures. Compared with the first-generation AEDs, the new second- and third-generation AEDs are less interacting, and this is a desirable development because it allows ease of prescribing by the physician and less complicated therapeutic outcomes and complications for patients