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Samenvatting Farmacologie partim II

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Samenvatting van het volledige 2e (& 3e) deel van farmacologie. Dit deel wordt gegeven samen met de studierichting farmacie. Op de eerste 3 pagina's is de inhoudstafel terug te vinden. Op het einde van het document zitten zowel de voorbeeldvragen als antwoorden die klassikaal beantwoord werden. Ik...

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  • August 30, 2024
  • 94
  • 2023/2024
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Inhoudstafel
Inhoudstafel ............................................................................................................................................................................. 1

1) Hypolipemiërende farmaca ................................................................................................................................................... 4
Lipoproteïnetransport in het bloed................................................................................................................................................. 4
Stoornissen in het lipidenmetabolisme (dyslipidemie) ................................................................................................................... 4
Atherosclerose .......................................................................................................................................................................... 4
Hypolipemierende farmaca ............................................................................................................................................................ 7
Statines ...................................................................................................................................................................................... 7
Fibraten ..................................................................................................................................................................................... 8
Harsen die galzuren binden ....................................................................................................................................................... 8
Remmer van de cholesterolopname in de darm ....................................................................................................................... 9
Visoliederivaten ......................................................................................................................................................................... 9
PCSK9-inhibitoren ...................................................................................................................................................................... 9
Bempedoïnezuur ..................................................................................................................................................................... 10

2) Farmacologie van het hart .................................................................................................................................................. 11
Effecten van GM op het hart ........................................................................................................................................................ 11
Farmaca die de hartfunctie beïnvloeden ...................................................................................................................................... 11
Anti-artimica ............................................................................................................................................................................ 11
Hartglycosiden ......................................................................................................................................................................... 14
Autonome neurotransmitters en verwante stoffen ................................................................................................................ 17
Anti-anginosa........................................................................................................................................................................... 18
Calciumantagonisten ............................................................................................................................................................... 20

3) Farmacologie van het vasculair systeem ............................................................................................................................. 23
Gladde spiercellen ........................................................................................................................................................................ 23
Vasoconstrictoren ........................................................................................................................................................................ 24
Endotheline ............................................................................................................................................................................. 24
Angiotensine II ......................................................................................................................................................................... 24
Vasopressine = ADH ................................................................................................................................................................ 25
Klinische toepassingen ............................................................................................................................................................ 25
Vasodilatoren ............................................................................................................................................................................... 26
Directe vasodilatoren .............................................................................................................................................................. 26
Indirecte vasodilatoren ........................................................................................................................................................... 27
Geneesmiddelen ........................................................................................................................................................................... 28
GM bij hypertensie .................................................................................................................................................................. 28
GM bij hartfalen met een gereduceerde ejectiefractie ........................................................................................................... 29
GM bij angina pectoris............................................................................................................................................................. 31
GM bij de ziekte van Raynaud ................................................................................................................................................. 32
GM bij pulmonale hypertensie ................................................................................................................................................ 32

4) Farmacologie van de nier .................................................................................................................................................... 33
Inleiding ........................................................................................................................................................................................ 33
Transportprocessen ...................................................................................................................................................................... 33
Diuretica ....................................................................................................................................................................................... 34
Aangrijpingspunten diuretica .................................................................................................................................................. 34
Lisdiuretica .............................................................................................................................................................................. 35
Thiazidediuretica ..................................................................................................................................................................... 35
Kaliumsparende diuretica........................................................................................................................................................ 36
Osmotische diuretica ............................................................................................................................................................... 36
Koolzuuranhydrase remmers .................................................................................................................................................. 36
Werking ACE-remmers bij nier problematiek in context van diabetes ......................................................................................... 37

,5) Farmacologie van het respiratoir en GI stelsel ..................................................................................................................... 38
Farmacologie van het ademhalingsstelsel ................................................................................................................................... 38
Regulatie van de luchtwegen .................................................................................................................................................. 38
Astma ........................................................................................................................................................................................... 38
Geneesmiddelen...................................................................................................................................................................... 39
Farmacologie van het maagdarmstelsel ...................................................................................................................................... 42
Secretie van maagzuur, mucus en bicarbonaat....................................................................................................................... 42
Anti - ulcerosa.......................................................................................................................................................................... 42
Braken ..................................................................................................................................................................................... 44
Obstipatie / constipatie ........................................................................................................................................................... 46
Diarree: anti-diarreïca ............................................................................................................................................................. 47
Spasmolytica............................................................................................................................................................................ 48

6) Farmacologie van het CZS ................................................................................................................................................... 49
Geneesmiddelen ........................................................................................................................................................................... 49
Neurotransmitters ........................................................................................................................................................................ 49
Aminozuren ............................................................................................................................................................................. 49
Noradrenaline in het CZS ......................................................................................................................................................... 51
Dopamine in het CZS ............................................................................................................................................................... 51
5-HT (serotonine) in het CZS.................................................................................................................................................... 52
Acetylcholine in het CZS .......................................................................................................................................................... 53
Histamine ................................................................................................................................................................................ 53
Purines ..................................................................................................................................................................................... 53
Melatonine .............................................................................................................................................................................. 53
NO............................................................................................................................................................................................ 54
Neurodegeneratieve aandoeningen ............................................................................................................................................. 54
Oorzaken ................................................................................................................................................................................. 54
Ziekte van Alzheimer ............................................................................................................................................................... 55
Ziekte van Parkinson................................................................................................................................................................ 55
Antipsychotica .............................................................................................................................................................................. 57
Schizofrenie ............................................................................................................................................................................. 58
Werkingsmechanisme ............................................................................................................................................................. 58
Typische antipsychotica........................................................................................................................................................... 59
Atypische antipsychotica ......................................................................................................................................................... 60
Ziekte van Parkinson................................................................................................................................................................ 61
Antidepressiva .............................................................................................................................................................................. 61
Affectieve stoornissen ............................................................................................................................................................. 61
Monoamine-theorie van depressie ......................................................................................................................................... 61
Pathofysiologie van depressie ................................................................................................................................................. 62
Werkingsmechanismen ........................................................................................................................................................... 62
Stemmingsstabilisatoren ......................................................................................................................................................... 65
Anxiolytica en hypno-sedativa...................................................................................................................................................... 66
Benzodiazepines ...................................................................................................................................................................... 66
Barbituraten ............................................................................................................................................................................ 67
Andere ..................................................................................................................................................................................... 68
Anti-epileptica .............................................................................................................................................................................. 68
Epilepsie .................................................................................................................................................................................. 68
Anti-epileptica ......................................................................................................................................................................... 69

7) Opioïden ............................................................................................................................................................................. 71
Definitie van pijn .......................................................................................................................................................................... 71
Soorten pijn .................................................................................................................................................................................. 71
Nociceptieve pijn ..................................................................................................................................................................... 71
Analgetica: opioïden..................................................................................................................................................................... 73
Werkingsmechanisme ............................................................................................................................................................. 74
Opioïde receptoren ................................................................................................................................................................. 75

,8) Lokale anesthetica .............................................................................................................................................................. 79
Werkingsmechanisme .................................................................................................................................................................. 79
Gebruik ......................................................................................................................................................................................... 80

Farmacologie van diabetes ..................................................................................................................................................... 81
Symptomen ............................................................................................................................................................................. 81
Screening ................................................................................................................................................................................. 81
Classificatie van diabetes: 4 klinische klassen .............................................................................................................................. 81
Type 1-diabetes mellitus ......................................................................................................................................................... 81
Type 2-diabetes mellitus ......................................................................................................................................................... 82
Andere specifieke types diabetes ............................................................................................................................................ 82
Zwangerschapsdiabetes .......................................................................................................................................................... 82
Complicaties ................................................................................................................................................................................. 82
Geneesmiddelen: anti-diabetica................................................................................................................................................... 83
Insuline .................................................................................................................................................................................... 83
Metformine ............................................................................................................................................................................. 85
Sulfonylurea............................................................................................................................................................................. 86
Gliniden ................................................................................................................................................................................... 87
Incretines ................................................................................................................................................................................. 87
Gliflozinen................................................................................................................................................................................ 89
Glitazonen (TZDS) .................................................................................................................................................................... 89
Glucagon .................................................................................................................................................................................. 90

Voorbeeldvragen .................................................................................................................................................................... 93

, 1) Hypolipemiërende farmaca

Lipoproteïnetransport in het bloed
Chylomicronen
- Bevatten triglyceriden en cholesterolesters: brengen het vd GI-tractus naar de weefsels
- LPL (lipoproteinelipase) zet triglyceriden om naar glycerol en vrije vetzuren --> brengen naar de spieren &
vetweefsel
- Het gene dat overblijft = chylomicronen remnants kan opgestapeld w, gescrecreteerd w tot gal, geoxideerd w
of gebruiken voor VLDL-partikels

VLDL
- Bevat cholesterol met nieuw gesynthetiseerde
triglyceriden --> transport naar weefsels
- Via LPL omzetting tot vrije vetzuren --> LDL partikel met
cholesterolester blijft over (= oorzakelijke
factoratherosclerose)

LDL
- W deels opgenomen door de weefsels maar ook door de
lever via endocytose mbv specifieke LDL-receptoren
- Bevat hoog gehalte cholesterol
- Oorzakelijke factor van atherosclerose

HDL
- Neemt cholesterol op vanuit weefsels (celturnover), ook
uit arteriën! --> VLDL en LDL
- = goede cholesterol


Stoornissen in het lipidenmetabolisme (dyslipidemie)
Primair
- Genetisch bepaald
- 6 fenotypes afhankelijk van welk type lipoproteïnepartikel is gestegen

Secundair
- In aansluiting op een veralgemeende aandoening: bv tgv overgewicht, diabetes mellitus, hypothyroïdie
ð Hoe hoger de plasmaspiegel van het LDL-cholesterol en hoe lager de concentratie van het HDL-cholesterol, hoe
groter het risico is op het tot stand komen van ischemische hartziekte

Frederickson / WHO classificatie hyperlipoproteïnemie
- Type 1: geen behandeling voor
- Type 2A: LDL toegenomen
o Hoog risico voor atherosclerose
- Type 2B: LDL en VDL toegenomen --> cholesterol &
triglyceriden gestegen
o Hoog risico voor atherosclerose


Atherosclerose
Cholesterol
- Hoog triglyceridengehalte is gecombineerd met laag HDL-C (cholesterol)
- LDL-C ↑ en/of HDL-C ↓ --> atherosclerose

, = slagaderverkalking = atherotrombose (want kan trombus bij betrokken zijn)
- Is focale aandoening van de intima van grote en middelgrote arterien
- Thv coronaire arterien: hartkramp (angina pectoris), hartinfarct
- Cerebrovasculaire ziekten: TIA (transient ischemic attack: nog geen volledige verstopping, maar O2 toevoer is
verminderd), beroerte (herseninfarct: volledige occlusie)
- Perifeer arterieel vaatlijden: claudicatio intermittens (etalagebenen: mensen hebben veel pijn bij stappen -->
zullen stilstaan om pijn te verminderen)
ð Heel groot aandeel van het aantal sterfgevallen

Atherogenese
= ontstaan van atherosclerose
- Is aandoening vd binnenwand (intima) van grote en middelgrote arteriën
- Pathogenese duurt enkele decennia: tijdens weinig klinische symptomen
- Na tijd wel ziekteverschijnselen: wijst op vergevorderd stadia
- O2 tekort thv coronairen --> angina pectoris
- O2 tekort thv perifere bloedvaten --> claudicatie intermittens
- Foto:
o Links: doorsneden bloedvat bij geboorte: endotheel is enige
laag cellen vd intima
o 2e: rond 20 jaar: plakkenvorming, maar nog relatief klein en
bloedvat vrij doorgankelijk
§ !! het is niet omdat plak klein is dat het niet gevaarlijk
kan zijn: als die onstabiel is bv
o 3e: rond 40 jaar: plak groeit en komen plakken bij, kunnen al
symptomen zijn
o Rechts: heel weinig doorgankelijk: symptomen zichtbaar

Pathogenese:
- Vooral bij patienten met hypercholesterolemie dringt het LDL door tot in de subendotheliale structuren -->
geoxideerd tot oxLDL
o Is immunogeen, wordt door het lichaam als vreemd ervaren
o Trekt T lymfocyten aan
o Zendt signalen uit naar het endotheel dat adhesiemoleculen tot expressie brengt (oa VCAM) waaraan
monocyten blijven kleven die de bloedbaan verlaten en worden omgevormd tot geactiveerde macrofagen
- Hypercholesterolemie (teveel LDL) --> LDL wordt
opgenomen in de intima --> wordt geoxideerd naar
oxLDL --> endotheelcellen worden geactiveerd -->
adhesiemoleculen tot expressie --> monocyten
blijven kleven aan adhesiemoleculen --> eens in
intima w ze omgevormd tot macrofagen -->
macrofagen willen geoxideerde LDL opruimen:
fagocyteren het via scavenger receptor op een
ongecontroleerde wijze ==> vormen zich om tot
‘foamcels’ (schuimcellen)
g Ondertussen zullen ook T lymfocyten in intima binnenkomen, IFN𝛾 produceren ->
macrofaag geactiveerd
o Schuimcellen tesamen met T lymfocyten vormen “vetstrepen’ of fatty streaks (->)
die de 1ste stadia vh atheroomletsel uitmaken
g Ook GSC migreren en prolifereren vanuit media naar intima --> produceren extracellulaire matrix: oa
collageen --> vormt soort van kap op de plak: lipide,
necrotische kern afschermen van het lumen
o Fibroatheromateus letsel = atheroom,
atheroomplaque, plaque
g Bloedplaatjes zullen cytokines en groeifactoren
vrijstellen --> vorming BW, proliferatie & migratie GSC
g = stabiele plak

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