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Samenvatting Farmacologie Deel 4 - 2025

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Samenvatting voor Farmacologie (Deel 4) aan KU Leuven, gericht op geneesmiddelen met betrekking tot het cardiovasculair stelsel, docent Minne Casteels. Het document behandelt diuretica (koolzuuranhydrase-inhibitoren, thiaziden, lisdiuretica), het werkingsmechanisme in de nieren, bijwerkingen en klinische indicaties, evenals anti-aritmische middelen zoals amiodaron voor voorkamerfibrillatie.

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FARMACOLOGIE DEEL 4
GENEESMIDDELEN IN VERBAND MET HET CARDIOVASCULAIR STELSEL




MINNE CASTEELS




Inhoudsopgave
H1: DIURETICA...............................................................................................2
KOOLZUURANHYDRASE-INHIBITOREN.........................................................................................3
THIAZIDEN.......................................................................................................................... 4
LISDIURETICA....................................................................................................................... 5
KALIUMSPARENDE DIURETICA..................................................................................................7
OSMOTISCHE DIURETICA........................................................................................................ 8
ALGEMENE OPMERKINGEN....................................................................................................... 9

H2: ARTERIËLE HYPERTENSIE........................................................................10
DIURETICA........................................................................................................................ 11
SS-RECEPTOR BLOKKERS...................................................................................................... 11
ACE-INHIBITOREN.............................................................................................................. 12
ANGIOTENSINE II RECEPTORANTAGONISTEN..............................................................................14
ANDERE VASODILATOREN..................................................................................................... 14
CENTRAAL WERKENDE ANTIHYPERTENSIVA................................................................................17
ALFA1-BLOKKERS............................................................................................................... 17
H3: HARTFALEN............................................................................................ 18
ALGEMEEN........................................................................................................................ 18
Symptomen van hartfalen..........................................................................................18
Compensatiemechanismen........................................................................................18
mortaliteit en genezing..............................................................................................19
POSITIEVE INOTROPICA........................................................................................................ 20
Digitalisglycosiden..................................................................................................... 20
Bipyridines................................................................................................................. 22
ß-agonisten................................................................................................................ 22
DIURETICA........................................................................................................................ 23
ACE-INHIBITOREN EN ANGIOTENSINEII-RECEPTORANTAGONISTEN.................................................23
COMBINATIE SACUBITRIL EN VALSARTAN..................................................................................24
ANDERE VASODILATOREN..................................................................................................... 24
SS-BLOKKERS..................................................................................................................... 24
SGLT2 INHIBITORS............................................................................................................. 24
BEHANDELING CHRONISCH HARTFALEN....................................................................................25
H4: ISCHEMISCH HARTLIJDEN........................................................................26

, BEHANDELING.................................................................................................................... 27
Hygiënische maatregelen........................................................................................... 27
Plaatsjesaggregatie-remmers.....................................................................................27
Organische nitraten.................................................................................................... 27
ß-blokkers.................................................................................................................. 29
ivabradine (ter info)................................................................................................... 29
calciumkanaalblokkers............................................................................................... 29
samenvatting............................................................................................................. 31
H5: HYPERLIPIDEMIE....................................................................................33
VETTRANSPORT IN DE CIRCULATIE.......................................................................................... 36
HYPERLIPOPROTEÏNEMIEËN................................................................................................... 38
THERAPEUTISCHE BENADERING.............................................................................................. 39
HYPOLIEMIËRENDE FARMACA................................................................................................. 39
Fibraten...................................................................................................................... 39
harsen........................................................................................................................ 40
Statines...................................................................................................................... 41
Ezetimibe................................................................................................................... 42
PCSK9-inhibitoren....................................................................................................... 42
Inclisiran..................................................................................................................... 43
bempodoïnezuur........................................................................................................ 43
H6: BLOEDSTOLLING.....................................................................................43
VKA............................................................................................................................ 45
DOAC.......................................................................................................................... 47
Injecteerbare anticoagulantia.....................................................................................48
THROMBOCYTENAGGREGATIEREMMERS – ANTI-AGGREGANTIA.......................................................50
Aspirine...................................................................................................................... 50
Perorale P2Y12-remmers............................................................................................50
Glycoprotein IIb/IIIa inhibitoren..................................................................................51
FIBRINOLYTISCHE STOFFEN................................................................................................... 51
Streptokinase............................................................................................................. 51
Urokinase................................................................................................................... 52
(r)t-PA......................................................................................................................... 52
anti-fibrinolytica......................................................................................................... 52
INDICATIES ANTI-COAGULANTIA, ANTI-AGGREGANTIA EN THROMBOLYTICA.......................................52
PRAKTISCHE RICHTLIJNEN EN PROBLEMEN MET ORALE ANTICOAGULANTIA........................................54
GEHEUGENSTEUNTJE: ANTI-COAGULANTIA.................................................................................54

H7: VOORKAMERFIBRILLATIE........................................................................56




H1: DIURETICA

 Verhogen urinevolume
 Verhogen netto verlies van oplossingen/H2O
 ALLE diuretica, BEHALVE spironolacton bereiken apicale transportlocaties via
tubulaire vloeistof (filtratie en secretie)
 ALLE diuretica, BEHALVE osmotische diuretica, worden actief gesecreteerd door
proximale tubulus in tubulaire vloeistof
 Gezonde volwassene

, o Renale blood flow = 1200 ml/min
o GFR = 125 ml/min




Impact op proximaal  ook gevolgen voor segmenten die meer distaal zijn

Elke factor die hogerop ervoor zorgt dat er minder Na+ gereabsorbeerd wordt en er dus
meer Na+ in tubulair vocht blijft  groter K+ verlies in urine (hypokaliëmie)

Bij thiaziden, KZA-inhibitoren en lisdiuretica  verhoogd K+ en H+ verlies

KOOLZUURANHYDRASE-INHIBITOREN

 Koolzuuranhydrase (KZA)
o Doel: H2CO3 reabsorptie in proximale tubulus  geen H2CO3 in urine
o Waar
 Overal: oog (oogvocht), pancreas, CZS
 Vooral nier
o Mechanisme:
 Basolaterale Na+/K+ pomp maakt Na+ gradiënt (Na+ naar
interstitium, K+ naar lumen)
 Apicale Na/H+ uitwisselaar gebruikt gradiënt om Na+ uit te wisselen
tegen H+ (Na+ en H+ naar lumen)
 H+ vormt met HCO3-netto H2CO3
 KZA zet H2CO3 om tot H2O en CO2
 CO2 naar cel (lipofiel)
 KZA zet CO2 terug om tot H2CO3
 Dissociatie tot HCO3- en H+  proton terug beschikbaar voor
Na+/H+ uitwisselaar
 Koolzuuranhydrase INHIBITOR (KZA-I)

, o = sulfonamidederivaten (niet meer als diureticum gebruikt)
o Netto effect: beperkt en zelf-limiterend
 minder transport NaHCO3 van lumen naar interstitium (minder
totale lichaamsbicarbonaat)
 Minder beweging van H2O naar interstitium
 Lichaam: acidose (bij lang gebruik)
 Urine: alkalose
o Product: acetazolamide
o farmacokinetiek
 Goede absorptie na perorale opname
 Stijging urinaire pH: na 30 min
 Maximaal effect: na 2h
 Effectduur: 12h
 Renale excretie: dosisaanpassing nodig bij nierinsufficiëntie
o Specifieke indicaties
 Openhoek-glaucoom
 Acuut gedecompenseerd hartfalen: samen met lisdiuretica
 Metabole alkalose tgv diureticagebruik bij ernstig hartfalen
 Alkalinisatie van urine
 Acute mountain sickness (hoogteziekte): off label gebruik 
productie en pH van cerebrospinaal vocht verlagen
o Toxiciteit (gevolg van alkalinisatie urine en metabole acidose)
 Verergeren metabole/respiratoire acidose doordat urine alkaliseert
 Nierstenen die minder oplosbaar zijn in alkalische urine
 Hypokaliëmie via hetzelfde mechanisme als thiazide en lisdiuretica
 Encefalopathie (meer ammoniak in systeemcirculatie)
 Dus: contra-indicatie: LEVERCIRROSE
 Overgevoeligheidsreacties
 Want < sulfonamiden
 Slaperigheid en paresthesieën (bij hoge dosis)

THIAZIDEN

 NCC-transporter
o Elektroneutraal
o = Apicaal in distale kronkelbuisje
o Functie
 Na+ van lumen naar interstitium
 Cl- van lumen naar interstitium
o Uiteindelijk: K+ naar lumen (K+ secretie)
o Hoe meer vocht, hoe meer K+ secretie
 Thiazide
o = INHIBITIE NCC-transporter
  NaCl blijft in lumen
  Chronisch: minder Ca2+ excretie
o Farmacokinetiek
 Enkel peroraal
 In competitie met urinezuur
 Diuretisch maar ook zwak vasodilaterend
 Typisch onderhoudsbehandeling
 NIET wanneer GFR > 30 ml/min

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