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Samenvatting farmaco 1E ZIT GEHAALD
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Volledige samenvatting van farmacokinetiek en dynamiek
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2023ALGEMENE
FARMACOLOGI
E
FARMACOKINETIEK EN FARMACODYNAMIEK
,Inhoudsopgave
Introductie..............................................................................................................................................5
Voorstelling van PK Parameters..........................................................................................................5
Fysicochemische eigenschappen en permeabiliteit...............................................................................6
Dissolutie............................................................................................................................................6
Absorptie van geneesmiddelen in de pens.....................................................................................6
Fysicochemische eigenschappen........................................................................................................7
Ionisatiegraad en pH.......................................................................................................................7
Polariteit.........................................................................................................................................7
Permeabiliteit.....................................................................................................................................8
Passief transport.............................................................................................................................8
Carrier-gemedieerd transport........................................................................................................9
Pinocytose/endocytose..................................................................................................................9
BCS classificatie................................................................................................................................10
ADME....................................................................................................................................................11
Absorptie of resorptie.......................................................................................................................11
Parenterale toedieningsroute.......................................................................................................11
Enterale toedieningsroute............................................................................................................11
Fysiologie van GI en belang bij absorptie......................................................................................12
Beïnvloeding maaglediging...........................................................................................................12
Distributie.........................................................................................................................................13
Permeabiliteit en perfusie............................................................................................................13
Schijnbaar verdelingsvolume V.....................................................................................................14
Eiwit/weefselbinding....................................................................................................................15
Metabolisme.....................................................................................................................................16
First pass effect.............................................................................................................................17
Niet-lineaire kinetiek....................................................................................................................17
Klaring...........................................................................................................................................17
Geneesmiddelinteracties..............................................................................................................18
Excretie.............................................................................................................................................19
Renaal...........................................................................................................................................19
Gal................................................................................................................................................20
Farmacokinetische modellen................................................................................................................21
PK parameters..................................................................................................................................21
Niet-compartimentele analyse.........................................................................................................22
, PK modellen......................................................................................................................................22
Empirisch......................................................................................................................................22
Compartimenteel..........................................................................................................................22
Fysiologisch...................................................................................................................................22
Verschil 0e en 1e orde kinetiek..........................................................................................................22
1e orde kinetiek.................................................................................................................................22
1-compartiment model.................................................................................................................23
2-compartiment model.................................................................................................................24
Orale dosering = absorptiemodel.....................................................................................................25
0e orde kinetiek.................................................................................................................................26
Oorzaken van niet-lineaire kinetiek..............................................................................................27
Interspecies schaling.........................................................................................................................27
Allometrie.....................................................................................................................................27
Meervoudige toediening en infuus...................................................................................................27
PK/PD evaluatie....................................................................................................................................28
Indeling concentratie-effect relaties.................................................................................................28
Direct............................................................................................................................................29
Indirect.........................................................................................................................................29
Modellen concentratie-effect relaties..............................................................................................29
Direct link model..........................................................................................................................30
Indirect Link model (= Effect compartiment model).....................................................................31
indirect reversibel effect (turnover model)..................................................................................32
Indirect respons model.................................................................................................................32
Optreden van tolerantie...................................................................................................................34
Counter regulatoir effect: Nifedipine............................................................................................34
Receptor down- of upregulatie: Tolerantie..................................................................................35
Depletie precursoren: tolerantie nitraten....................................................................................35
Waarde van PK/PD...........................................................................................................................35
Voorbeeld van 2 NSAIDs: COX1 en COX2......................................................................................36
Vergelijking PD verschillende GM.................................................................................................36
Inleiding................................................................................................................................................38
Weinig specifiek................................................................................................................................38
Specifiek...........................................................................................................................................39
Biologische specificiteit................................................................................................................39
Chemische specificiteit.................................................................................................................39
Aangrijpingspunten geneesmiddelen – voorbeelden...........................................................................39
, Maagzuurklachten............................................................................................................................39
H2 antagonisten...........................................................................................................................40
Protonpomp inhibitor (PPI)...........................................................................................................40
Ischemisch herseninfarct..................................................................................................................41
Virchow’s triad..............................................................................................................................42
Stollingscascaderemmers.............................................................................................................42
Plaatjesremmers...........................................................................................................................42
Adrenerg system...............................................................................................................................43
Gladde spiercel.............................................................................................................................44
Hartspiercel..................................................................................................................................44
Biologische selectiviteit................................................................................................................45
Cardiovasculaire geneesmiddelen................................................................................................45
Adrenerge effecten.......................................................................................................................46
Reuma/Reumatoïde arthritis (RA)....................................................................................................47
Geneesmiddelen bij reumatoïde arthritis.....................................................................................47
Receptoren...........................................................................................................................................48
Geneesmiddel-receptor interacties..................................................................................................49
Agonist..........................................................................................................................................49
Two-state receptor model............................................................................................................49
Allosterische modulatie................................................................................................................50
Antagonist....................................................................................................................................50
Adaptatie en therapeutische index...............................................................................................52
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