Samenvatting van alle hoorcolleges, werkcolleges en zelfstudies van de cursus Algemene Farmacologie Thema 1: Farmacokinetiek (BMW30405)

Samenvatting algemene
farmacologie
Thema 1 - Farmacokinetiek


Biomedische Wetenschappen
2020-2021




Door Nicole (studente BMW)

,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

2

, Chronisch nierfalen...........................................................................................................................69
Levercirrose......................................................................................................................................71
Lineaire vs. niet-lineaire kinetiek......................................................................................................72
Delayed release medicijnen..............................................................................................................73

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.




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