Samenvatting van "partim II" als onderdeel van het vak 'Farmacologie' gegeven door prof. De Meyer G. in de 2e Bachelor Geneeskunde aan de UA. Samenvatting gebaseerd op slides, lesnotities én cursus.
Inhoudstafel
Hypolipemiërende farmaca........................................................................................................................... 7
Lipoproteïnetransport in het bloed........................................................................................................7
Stoornissen in het lipidenmetabolisme = dyslipidemie............................................................. 7
Atherogenese (slagaderverkalking) en atherotrombose...................................................................... 7
Stabiele atherosclerose............................................................................................................ 8
Instabiele atherosclerose..........................................................................................................9
Hypolipemiërende farmaca.................................................................................................................. 9
Statines (bv. simvastatine)........................................................................................................9
Fibraten (bv. fenofibraat).........................................................................................................11
Inhibitie van cholesterol (her)opname in de darm...................................................................11
Visoliederivaten = omega-3 vetzuren ethylesters...................................................................12
PCSK9-inhibitoren.................................................................................................................. 12
Bempedoïnezuur.................................................................................................................... 13
Farmacologie van het hart.......................................................................................................................... 15
Farmaca die de hartfunctie beïnvloeden............................................................................................ 15
Antiaritmica.........................................................................................................................................15
Ritmestoornissen....................................................................................................................15
Vaughan-Williams classificatie van anti-aritmica.................................................................... 17
Nevenwerkingen.....................................................................................................................19
Klinische toepassingen...........................................................................................................19
Inotrope stoffen (oa. hartglycosiden).................................................................................................. 20
Hartcontractie......................................................................................................................... 20
Inotropica................................................................................................................................23
Hartglycosiden........................................................................................................................23
Inhibitoren van PDE-III (bv. milrinon)...................................................................................... 25
Autonome neurotransmitters en verwante stoffen..............................................................................25
1-receptoren in het hart.......................................................................................................... 25
M2-receptoren in het hart....................................................................................................... 25
Anti-anginosa..................................................................................................................................... 26
Zuurstofverbruik door het myocard en coronaire flow............................................................ 26
Classificatie van ischemische hartziekten.............................................................................. 26
Anti-anginosa farmaca............................................................................................................27
NO-donoren............................................................................................................................27
-blokkers................................................................................................................................. 29
Calcium-antagonisten.........................................................................................................................29
Voltage-gated Ca2+-kanalen.................................................................................................. 29
Effecten.................................................................................................................................. 29
Klinische indicaties................................................................................................................. 30
Neveneffecten........................................................................................................................ 30
Farmacologie van het vasculair systeem.................................................................................................. 32
Regulatie van gladde spiercellen....................................................................................................... 32
Contractie van GSC................................................................................................................32
Relaxatie van GSC................................................................................................................. 32
Rol van endotheel in regulatie van de tonus van vasculaire GSC..........................................33
, Vasoconstrictoren............................................................................................................................... 33
Endothelinen (ET-1, ET-2, ET-3)............................................................................................ 33
Angiotensine II........................................................................................................................34
Vasopressine = antidiuretisch hormoon (ADH).......................................................................35
Klinische toepassingen van vasoconstrictoren.......................................................................35
Vasodilatoren: directe......................................................................................................................... 35
Toename van cAMP............................................................................................................... 36
Toename van cGMP............................................................................................................... 36
Hydralazine.............................................................................................................................36
Vasodilatoren: indirecte...................................................................................................................... 37
Clonidine.................................................................................................................................37
Moxonidine............................................................................................................................. 37
Inhibitie van RAAS..................................................................................................................38
Ziektebeelden waarbij vasoactieve geneesmiddelen worden gebruikt.............................................. 38
Hypertensie............................................................................................................................ 38
Hartfalen (HFrEF)................................................................................................................... 39
Hartfalen................................................................................................................................. 41
Angina pectoris.......................................................................................................................41
Ziekte van Raynaud................................................................................................................42
Pulmonaire hypertensie..........................................................................................................42
Farmacologie van de nier............................................................................................................................43
Functie van niertubuli......................................................................................................................... 43
Transport in de proximale tubulus.......................................................................................... 43
Transport in lus van Henle......................................................................................................43
Transport in de distale tubulus................................................................................................43
Transport in de ductus colligens............................................................................................. 44
Diuretica............................................................................................................................................. 44
Lisdiuretica (bv. furosemide)...................................................................................................45
Thiazidediuretica (bv. hydrochloorthiazide)............................................................................ 46
Kaliumsparende diuretica....................................................................................................... 46
Osmotische diuretica (bv. Mannitol)....................................................................................... 46
Koolzuuranhydraseremmers.............................................................................................................. 46
CASUS: diabetes............................................................................................................................... 47
Farmacologie van het ademhalingsstelsel................................................................................................ 48
Regulatie van de luchtwegen............................................................................................................. 48
Astma................................................................................................................................................. 48
Bronchiale hyperreactiviteit.................................................................................................... 49
Mediatoren..............................................................................................................................49
Geneesmiddelen bij astma.................................................................................................................50
2-receptor agonisten (bv. salbutamol, salmeterol, formoterol)............................................... 50
Theofylline.............................................................................................................................. 50
M-antagonisten.......................................................................................................................51
CysLT-receptor antagonisten..................................................................................................51
Glucocorticoïden.....................................................................................................................52
Natriumcromoglicaat...............................................................................................................52
Farmacologie van het maagdarmstelsel....................................................................................................53
, Secretie van maagzuur, mucus en bicarbonaat................................................................................. 53
Anti-ulcerosa...................................................................................................................................... 54
Antacida..................................................................................................................................54
H2-antihistaminica.................................................................................................................. 54
Protonpompinhibitoren........................................................................................................... 55
Prostaglandine E1-analogen.................................................................................................. 55
Rol van NSAID bij peptische ulcera........................................................................................56
Behandeling van H. pylori.......................................................................................................56
Anti-emetica....................................................................................................................................... 56
Braken.................................................................................................................................... 56
Anticholinergica (bv. scopolamine)......................................................................................... 57
H1-antagonisten..................................................................................................................... 57
Neuroleptica / antipsychotica..................................................................................................58
Gastrokinetica.........................................................................................................................58
5-HT3-antagonisten (bv. Ondansetron).................................................................................. 59
Cannabinoïden....................................................................................................................... 59
Dexamethason....................................................................................................................... 59
Neurokinine-1 antagonisten (bv. aprepitant)...........................................................................59
Laxativa.............................................................................................................................................. 59
Obstipatie............................................................................................................................... 59
Laxativa met lubrifiërende werking......................................................................................... 60
Contactlaxativa....................................................................................................................... 60
Osmotische laxativa............................................................................................................... 61
Zwelmiddelen......................................................................................................................... 62
Antidiarreïca....................................................................................................................................... 62
Orale rehydratiezouten (ORS)................................................................................................62
Secretie- en motiliteitsinhibitoren............................................................................................62
Spasmolytica...................................................................................................................................... 63
Farmacologie van het centraal zenuwstelsel............................................................................................ 64
Chemische transmissie in het CZS.................................................................................................... 64
Aminozuren als transmitters...............................................................................................................64
Exciterende aminozuren (EAA).............................................................................................. 64
Inhiberende aminozuren.........................................................................................................66
Klassieke neurotransmitters............................................................................................................... 67
Noradrenaline......................................................................................................................... 67
Dopamine............................................................................................................................... 67
Serotonine.............................................................................................................................. 68
Acetylcholine.......................................................................................................................... 69
Andere transmitters en modulatoren.................................................................................................. 69
Histamine................................................................................................................................70
Purines................................................................................................................................... 70
Melatonine.............................................................................................................................. 70
NO.......................................................................................................................................... 70
Neurodegeneratieve aandoeningen........................................................................................................... 71
Foutieve opvouwing van proteïnen.................................................................................................... 71
Excitotoxiciteit en oxidatieve stress....................................................................................................71
Dementie en ziekte van Alzheimer.....................................................................................................72
Opioïden......................................................................................................................................................100
Pijnperceptie.....................................................................................................................................100
Nociceptie vs. pijn.................................................................................................................100
Nociceptieve pijn vs. neuropathische pijn.............................................................................100
Nociceptief circuit............................................................................................................................. 101
1. Polymodale nociceptoren (PMN)......................................................................................101
2. Nociceptieve afferente zenuwvezels in dorsale hoorn van ruggenmerg.......................... 102
Hyperalgetische en plasticiteitsveranderingen die volgen op acute weefselschade............ 103
Samenvatting........................................................................................................................103
Analgetica.........................................................................................................................................104
Morfinomimetica (opioïden)..............................................................................................................104
Modulatie van pijntransmissie.............................................................................................. 105
Opioïdreceptoren..................................................................................................................106
Indeling opioïde analgetica...................................................................................................108
Farmacologische effecten.................................................................................................... 109
Farmaca........................................................................................................................................... 109
Morfine..................................................................................................................................109
Buprenorfine......................................................................................................................... 110
Methadon.............................................................................................................................. 110
Codeïne................................................................................................................................ 110
Tramadol (Contramal ®, Dolzam ®, Tradonal ®).................................................................. 111
Fentanyl................................................................................................................................ 111
Opioïden gebruik en misbruik............................................................................................... 111
Opioïd antagonisten..............................................................................................................112
Samenvatting....................................................................................................................................112
Lokale anesthetica..................................................................................................................................... 114
Werkingsmechanisme...................................................................................................................... 114
Use-dependency...................................................................................................................114
Farmacokinetiek............................................................................................................................... 115
Ongewenste effecten........................................................................................................................115
Gebruik van lokale anesthetica........................................................................................................ 115
Toedieningswijze...................................................................................................................115
Farmacologie van diabetes....................................................................................................................... 117
Diabetes........................................................................................................................................... 117
Type 2 DM............................................................................................................................ 117
Complicaties......................................................................................................................... 118
,Hypolipemiërende farmaca
Lipoproteïnetransport in het bloed
vervoer van lipiden in het plasma onder de vorm van lipoproteïnen
● chylomicronen: transport van triglyceriden en cholesterol
vanuit GI-tractus naar weefsels
○ lipoproteïne lipase (LPL) splitst triglyceriden in
glycerol + vrije vetzuren die in spier- en vetweefsel
worden opgenomen
○ chylomicron remnants worden in lever opgenomen
■ secreteren in gal
■ oxideren tot galzuren
■ opstapelen
■ synthese van VLDL
● VLDL: transport van cholesterol en nieuw gesynthetiseerde
triglyceriden naar weefsels
○ lipoproteïne lipase (LPL): triglyceriden → vrije
vetzuren + LDL
● LDL: hoog cholesterolgehalte waarvan een deel wordt opgenomen door weefsels en een deel door
de lever (LDL-receptoren, endocytose)
○ = slechte cholesterol = pro-atherogene cholesterol
● HDL: cholesterol uit weefsels en arteriën opnemen en transfereren naar VLDL en LDL
○ = goede cholesterol = anti-atherogene cholesterol
Stoornissen in het lipidenmetabolisme = dyslipidemie
primaire stoornis: 6 fenotypes, afhankelijk van welk type lipoproteïnepartikel is gestegen
→ genetisch bepaald
secundaire stoornis: in aansluiting op een veralgemeende aandoening (bv. obesitas, diabetes mellitus,
hypothyroïdie)
⇒ hoe hoger de plasmaspiegel van LDL en hoe lager de concentratie HDL, hoe groter het risico op
ischemische hartziekte
● LDL ↑ en/of HDL ↓ → atherosclerose
● hoog triglyceridegehalte → verlaagde HDL
streefwaarden voor LDL-cholesterol afhankelijk van het risico
Atherogenese (slagaderverkalking) en atherotrombose
, = focale (lokale) aandoening van de intima van (middel)grote arteriën
pathogenese
● sluipend: verloopt over verschillende decennia, met weinig klinische symptomen
● ziekteverschijnselen wijzen meestal op een vergevorderd stadium
○ coronaire hartziekten: angina pectoris (hartkramp), hartinfarct
○ cerebrovasculaire ziekten: TIA (transient ischemic attack), herseninfarct (beroerte)
○ perifeer arterieel vaatlijden: claudicatio intermittens (etalagebenen)
⇒ hart- en vaatziekten (België): > ⅓ van het aantal sterfgevallen
Stabiele atherosclerose
1. LDL dringt door tot in de subendotheliale structuren (intima) waar het wordt geoxideerd tot oxLDL
● vooral bij patiënten met hypercholesterolemie
● oxLDL: immunogeen, door het lichaam als vreemd ervaren
2. oxLDL activeert endotheelcellen die adhesiemoleculen (bv. VCAM = vascular cell-adhesion
molecule) tot expressie brengen
● monocyten blijven kleven en transmigreren doorheen het endotheel naar
intima, waar ze worden omgevormd tot geactiveerde macrofagen
● geactiveerde macrofagen fagocyteren oxLDL via scavenger receptoren op
een ongecontroleerde wijze → schuimcellen
3. oxLDL trekt T-lymfocyten aan
● schuimcellen en T-lymfocyten vormen vetstrepen = fatty streaks (merker voor eerste stadia
van atheroomletsels)
4. bloedplaatjes, macrofagen en endotheelcellen zetten cytokines (INF-γ) en groeifactoren vrij →
migratie en proliferatie van GSC vanuit tunica media naar tunica intima, waar ze extracellulaire
matrix (oa. collageen) produceren → bindweefselvorming
5. ontstekingsreactie: vorming van een fibreus kapsel (collageen) die de necrotische kern (lipiden +
weefseldebris) afschermt van het lumen
● collageen: trekvaste koorden waardoor de plaque niet kan openscheuren
● fibroatheromateus letsel: atheroom = atheroomplaque = plaque
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