Samenvatting van alle hoorcolleges, werkcolleges en zelfstudies van de cursus Algemene Farmacologie Thema 1: Farmacokinetiek (BMW30405)
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Course
Algemene Farmacologie (BMW30405)
Institution
Universiteit Utrecht (UU)
Book
Rang
Deze gedetailleerde samenvatting behandelt alles wat aan bod is gekomen tijdens de hoorcolleges, werkcolleges en zelfstudies van Thema 1: Farmacokinetiek van de cursus Algemene Farmacologie aan de Universiteit Utrecht (BMW30405). Hierdoor bevat het alle informatie die nodig is voor het deeltentamen...
,Inhoudsopgave
Absorptie en metabolisme van medicijnen............................................................................................3
Farmacokinetiek.................................................................................................................................4
Primaire en secundaire farmacokinetische parameters.................................................................4
Concentratie-tijd curve.......................................................................................................................6
Toedieningsroutes..............................................................................................................................6
Orale toediening.............................................................................................................................7
Oromucosale toediening (sublinguaal of buccaal)..........................................................................8
Rectale toediening..........................................................................................................................9
Dermale toediening (cutaan)..........................................................................................................9
Nasale toediening (neusspray).......................................................................................................9
Inhalatie..........................................................................................................................................9
Injectie............................................................................................................................................9
Absorptie van geneesmiddelen........................................................................................................13
Toedieningsvorm..........................................................................................................................13
Grootte.........................................................................................................................................13
pH en ionisatie..............................................................................................................................14
Lipofiliteit......................................................................................................................................15
Transportmechanismen....................................................................................................................17
Carrier-mediated transport..........................................................................................................18
Organische kation- en aniontransporters.....................................................................................19
P-glycoproteïne transporters........................................................................................................19
Plasma-eiwitten en verdeling van medicijnen..............................................................................20
Metabolisme (biotransformatie)......................................................................................................21
Fase I reacties...............................................................................................................................21
Fase II reacties..............................................................................................................................24
Enterohepatische circulatie..............................................................................................................25
Absorptie en metabolisme van alcohol................................................................................................26
Farmacokinetiek...............................................................................................................................26
Alcohol dehydrogenase pathway..................................................................................................27
Microsomal ethanol-oxidizing system (MEOS).............................................................................28
Aceetaldehyde metabolisme........................................................................................................28
Interactie tussen alcohol en medicijnen...........................................................................................29
Distributie en eliminatie van medicijnen..............................................................................................30
Distributie.........................................................................................................................................30
1
, Verdelingsvolume.........................................................................................................................32
Binding aan plasma-eiwitten........................................................................................................34
Verdeling in lichaamsvet en andere weefsels...............................................................................35
Excretie.............................................................................................................................................37
Hepatische klaring........................................................................................................................37
Glomerulaire filtratie en renale klaring.........................................................................................41
Relatie tussen totale klaring en verdelingsvolume.......................................................................46
Farmacogenetica..................................................................................................................................47
Medische genetica............................................................................................................................47
Genen en allelen...........................................................................................................................47
Fenotype en genotype..................................................................................................................47
Markers........................................................................................................................................47
Polymorfismen..............................................................................................................................48
Genotypering................................................................................................................................48
Linkage studies.............................................................................................................................48
Associatiestudies..........................................................................................................................49
Farmacogenetica van fase I metabolisme.........................................................................................49
P-glycoproteïnen en farmacokinetiek...................................................................................................52
Drug-drug interacties........................................................................................................................52
P-glycoproteïnen (P-gps)..................................................................................................................52
Interactie tussen loperamide en quinidine...................................................................................52
Absorptie......................................................................................................................................53
Distributie.....................................................................................................................................53
Eliminatie......................................................................................................................................53
Drug-drug interacties....................................................................................................................53
Integratie van ADME processen...........................................................................................................55
Farmacokinetiek...............................................................................................................................55
Single-compartment model..............................................................................................................56
Nulde-orde kinetiek......................................................................................................................57
Eerste-orde kinetiek.....................................................................................................................57
Two-compartment model.................................................................................................................58
Toedieningsvormen..........................................................................................................................59
Intraveneuze bolusinjectie............................................................................................................60
Eenmalige orale toediening..........................................................................................................61
Intraveneuze infusie.....................................................................................................................62
Meerdere orale toedieningen.......................................................................................................66
Absorptie en metabolisme van medicijnen
Een geneesmiddel kan om drie redenen gebruikt worden:
Genezen van een ziekte
Voorkomen van een ziekte
Diagnose vaststellen
Daarnaast kunnen geneesmiddelen in twee groepen onderverdeeld worden, namelijk:
Conventionele geneesmiddelen (small molecules):
250-500 dalton
Niet zo selectief
Meestal een voorspelbare relatie tussen dosis en effect
Toediening vaak oraal
Halfwaardetijden meestal uren tot dagen
Drug-drug interacties komen vaak voor
Zelden sprake van immunogeniteit
Biologische geneesmiddelen (biologicals):
150.000 dalton
Zeer selectief
Meestal geen voorspelbare relatie tussen dosis en effect
Halfwaardetijden meestal weken tot maanden
Drug-drug interacties komen nauwelijks voor
Soms sprake van immunogeniteit
De meeste geneesmiddelen zijn conventionele geneesmiddelen. De biologische geneesmiddelen
daarentegen zijn lichaamseigen stoffen, zoals eiwitten, aminozuren, antilichamen, et cetera.
3
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