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Samenvatting Farmacologie - deel 4
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Dit document bevat alle hoofdstukken van deel 4 Farmacologie. Dit vak werd gegeven door prof. de Hoon en prof. Casteels.
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INHOUDDEEL 4 ..................................................................................................................................................................... 6
Hoofdstuk 1: diuretica............................................................................................................................................. 6
Koolzuuranhydrase-inhibitoren .......................................................................................................................... 6
Werking ........................................................................................................................................................... 6
Producten ........................................................................................................................................................ 6
Farmacokinetiek .............................................................................................................................................. 6
Klinisch gebruik ............................................................................................................................................... 6
Toxiciteit .......................................................................................................................................................... 7
Thiaziden ............................................................................................................................................................. 7
Werking ........................................................................................................................................................... 7
Farmacokinetiek .............................................................................................................................................. 7
Indicaties ......................................................................................................................................................... 7
Bijwerkingen/ongewenste effecten ................................................................................................................ 8
Lisdiuretica .......................................................................................................................................................... 8
Werking ........................................................................................................................................................... 8
Producten ........................................................................................................................................................ 8
Farmacokinetiek .............................................................................................................................................. 8
Indicaties ......................................................................................................................................................... 9
Bijwerkingen/ongewenste effecten ................................................................................................................ 9
Kaliumsparende diuretica ................................................................................................................................... 9
Spironolacton en epleneron............................................................................................................................ 9
Inhibitoren van Na-kanalen in nierepitheel .................................................................................................... 9
Indicaties ....................................................................................................................................................... 10
Bijwerkingen en interacties........................................................................................................................... 10
Contra-indicaties ........................................................................................................................................... 10
Osmotische diuretica ........................................................................................................................................ 10
Product .......................................................................................................................................................... 10
Klinisch gebruik ............................................................................................................................................. 10
Indicaties ....................................................................................................................................................... 10
Bijwerkingen/ongewenste effecten .............................................................................................................. 11
Hoofdstuk 2: farmacotherapie van arteriële hypertensie .................................................................................... 12
Inleiding............................................................................................................................................................. 12
Diuretica ............................................................................................................................................................ 13
Effecten ......................................................................................................................................................... 13
β-receptor blokkers ........................................................................................................................................... 13
1
, Bijwerkingen/ongewenste effecten .............................................................................................................. 13
ACE-inhibitoren ................................................................................................................................................. 13
Producten ...................................................................................................................................................... 14
Farmacokinetiek ............................................................................................................................................ 14
Effecten ......................................................................................................................................................... 14
Angiotensine II receptorantagonisten (sartanen, ARB) .................................................................................... 15
Producten ...................................................................................................................................................... 15
Andere vasodilatoren ........................................................................................................................................ 15
Calcium-kanaal-blokkers (CCB) ..................................................................................................................... 15
Producten .................................................................................................................................................. 15
Farmacokinetiek ........................................................................................................................................ 15
Werkingsmechanisme ............................................................................................................................... 15
Effecten ..................................................................................................................................................... 15
Nitroprusside................................................................................................................................................. 17
Indicaties ................................................................................................................................................... 17
Bijwerkingen/ongewenste effecten .......................................................................................................... 17
Centraal werkende antihypertensiva ................................................................................................................ 17
Clonidine ....................................................................................................................................................... 17
Neuronblokkers ............................................................................................................................................. 17
α1-blokkers ........................................................................................................................................................ 17
Overzicht specifieke condities........................................................................................................................... 18
Hoofdstuk 3: farmacotherapie van hartfalen ....................................................................................................... 19
Inleiding............................................................................................................................................................. 19
Positieve inotropica .......................................................................................................................................... 20
Digitalis-glycosiden........................................................................................................................................ 20
Indicaties ................................................................................................................................................... 20
Farmacokinetiek ........................................................................................................................................ 20
Effecten ..................................................................................................................................................... 20
DOsering.................................................................................................................................................... 20
Interacties ................................................................................................................................................. 21
Behandeling bij intoxicatie ........................................................................................................................ 21
Bipyridines..................................................................................................................................................... 21
Effecten ..................................................................................................................................................... 21
Geneesmiddelen met β-agonistische activiteit ............................................................................................. 21
Diuretica ............................................................................................................................................................ 22
ACE-inhibitoren en Ang II-receptor antagonisten (sartanen) ........................................................................... 22
Combinatie sacubitril en valsartan.................................................................................................................... 22
2
, Andere vasodilatoren ........................................................................................................................................ 22
β-blokkers ......................................................................................................................................................... 22
SGLT-inhibitoren ............................................................................................................................................... 22
Behandeling chronisch hartfalen en therapeutische efficaciteit ...................................................................... 22
Hoofdstuk 4: farmacotherapie van ischemisch hartlijden .................................................................................... 24
Inleiding............................................................................................................................................................. 24
Behandeling ...................................................................................................................................................... 24
Levensstijl maatregelen ................................................................................................................................ 24
Plaatjesaggregatie-remmers ......................................................................................................................... 25
Organische nitraten ...................................................................................................................................... 25
Werkingsmechanisme ............................................................................................................................... 25
Farmacokinetiek ........................................................................................................................................ 25
Cardiovasculaire effecten.......................................................................................................................... 25
Andere effecten ........................................................................................................................................ 25
Mechanisme van therapeutisch effect bij angor ...................................................................................... 25
Bijwerkingen/ongewenste effecten .......................................................................................................... 25
Tolerantie .................................................................................................................................................. 26
Klinisch gebruik ......................................................................................................................................... 26
Fosfodiesterase-type V inhibitoren ............................................................................................................... 26
β-blokkers in onderhoudstherapie................................................................................................................ 26
Effecten ..................................................................................................................................................... 26
Ivabradine ..................................................................................................................................................... 26
Indicaties ................................................................................................................................................... 27
Bijwerkingen/ongewenste effecten .......................................................................................................... 27
Interacties ................................................................................................................................................. 27
Calciumkanaalblokkers.................................................................................................................................. 27
Overzicht angor (angina pectoris)-behandeling ................................................................................................ 27
Hoofdstuk 5: farmacotherapie van hyperlipidemie .............................................................................................. 28
Inleiding............................................................................................................................................................. 28
Vettransport in circulatie .................................................................................................................................. 28
Hyperlipoproteïnemieën ................................................................................................................................... 30
Therapeutische benadering .............................................................................................................................. 31
Hypolipemiërende farmaca .............................................................................................................................. 31
Fibraten ......................................................................................................................................................... 31
Producten .................................................................................................................................................. 31
Werkingsmechanisme ............................................................................................................................... 31
Effect op plasmalipiden en lipoproteïnen ................................................................................................. 31
3
, Farmacokinetiek ........................................................................................................................................ 32
Bijwerkingen/ongewenste effecten .......................................................................................................... 32
Interacties ................................................................................................................................................. 32
Indicaties ................................................................................................................................................... 32
Anionenuitwisselaars (galzuurbindende harsen) .......................................................................................... 32
Scheikunde ................................................................................................................................................ 32
Werkingsmechanisme ............................................................................................................................... 32
Effect op plasmalipiden en lipoproteïnen ................................................................................................. 32
Bijwerkingen/ongewenste effecten .......................................................................................................... 32
Interacties ................................................................................................................................................. 33
Indicaties ................................................................................................................................................... 33
Inhibitoren van 3-hydroxy-3-methylglutaryl-CoA reductase: statines .......................................................... 33
Producten .................................................................................................................................................. 33
Werkingsmechanisme ............................................................................................................................... 33
Effect op plasmalipden en lipoproteïnen .................................................................................................. 33
Farmacokinetiek ........................................................................................................................................ 34
Bijwerkingen/ongewenste effecten .......................................................................................................... 34
Interacties ................................................................................................................................................. 34
Indicaties ................................................................................................................................................... 34
Ezetimibe....................................................................................................................................................... 35
Farmacokinetiek ........................................................................................................................................ 35
PCSK9-inhibitoren: add on bij statines .......................................................................................................... 35
Inclisiran ........................................................................................................................................................ 35
Bempedoïnezuur ........................................................................................................................................... 35
Hoofdstuk 6: geneesmiddelen in verband met bloedstolling ............................................................................... 36
Anticoagulantia ................................................................................................................................................. 36
Vitamine K-antagonisten (VKA) of coumarines ............................................................................................. 36
Producten .................................................................................................................................................. 36
Werkingsmechanisme ............................................................................................................................... 36
Effecten ..................................................................................................................................................... 36
Farmacokinetiek ........................................................................................................................................ 36
Interacties ................................................................................................................................................. 37
Behandeling .............................................................................................................................................. 37
Directe orale anticoagulantia (DOAC) ........................................................................................................... 38
Vergelijkingen............................................................................................................................................ 38
Contra-indicaties ....................................................................................................................................... 38
Interacties ................................................................................................................................................. 38
4
, Injecteerbare anticoagulantia ....................................................................................................................... 39
Producten .................................................................................................................................................. 39
Werkingsmechanisme ............................................................................................................................... 39
Effecten ..................................................................................................................................................... 39
Anti-aggregantia................................................................................................................................................ 40
Aspirine (acetylsalicylzuur)............................................................................................................................ 40
Ticlopidine/clopidogrel/prasugrel ................................................................................................................. 40
Glycoprotein IIb/IIIa-inhibitoren ................................................................................................................... 40
Fibrinolytische stoffen....................................................................................................................................... 40
Streptokinase ................................................................................................................................................ 40
Urokinase ...................................................................................................................................................... 40
Tissue plasminogen activator (t-PA).............................................................................................................. 41
Anti-fibrinolytica ........................................................................................................................................... 41
Indicaties anticoagulantia, anti-aggregantia, thrombolytica ............................................................................ 41
Veneuze thrombose ...................................................................................................................................... 41
Arteriële thrombose...................................................................................................................................... 42
Gebruik anti-aggregantia .............................................................................................................................. 42
Praktische richtlijnen en problemen met orale anticoagulantia....................................................................... 42
Peri-operatieve aanpak van antistollingstherapie ........................................................................................ 42
Overdreven antistolling................................................................................................................................. 43
Hoofdstuk 7: farmacotherapie van voorkamerfibrilatie (VKF) .............................................................................. 44
Bijzondere aandacht ......................................................................................................................................... 44
Amiodarone ...................................................................................................................................................... 44
5
,FARMACOLOGIE
DEEL 4
HOOFDSTUK 1: DIURETICA
KOOLZUURANHYDRASE-INHIBITOREN
- Proximale tubulus
WERKING
Koolzuuranhydrase (CA) speelt een rol in absorptie van NaHCO3
- Aanwezig in nefron, oog, CZS, pancreas, RBC
- Basolaterale membraan: Na-gradiënt door Na/HCO3-cotransporter (Na en HCO3 naar buiten)
- Apicale membraan: Na/H-uitwisselaar (Na naar binnen, H naar buiten)
o H in lumen samen met HCO3- (gefilterd) → H2CO3 → H2O + CO2 (CA)
Koolzuuranhydrase-inhibitoren (sulfonamide-derivaten)
- Inhibitie van omzetting H2CO3 naar H2O + CO2 in lumen
- Inhibitie van omzetting H2O + CO2 naar H2CO3 in cel → terug dissociatie tot H en HCO3- voor opnieuw
- Netto-effect: minder transport NaHCO3 van lumen naar interstitium (minder buffer HCO3- en minder
weghalen H) → acidose cel (systemisch), alkalisch urine
PRODUCTEN
- Acetazolamide
FARMACOKINETIEK
- Goede absorptie na inname PO
- Max effect na 2 uur
- Renale excretie
KLINISCH GEBRUIK
- Openhoek-glaucoom (acuut + onderhoud): minder productie oogvocht → daling oogdruk
- Alkalinisatie van urine: beter oplossen van zuren (moeilijker zouten)
- Metabole alkalose: compensatie door acetazolamide, want zout niet mogelijk toedienen voor herstel
ECV (patiënten met hartfalen met diuretica)
- Acute mountain sickness: productie en pH verlagen van CSV → symptomen verminderen
- Niet bij levercirrose (NH3)
6
, TOXICITEIT
Door gevolg van alkalinisatie van urine en metabole acidose
- Verergeren metabole of respiratoire acidose
- Nierstenen (Ca-zouten minder oplosbaar in alkalische urine)
- Hypokaliëmie (verlies K via nier)
- Ammoniak (NH3) in systeemcirculatie vanuit urine → kans op encefalopathie
- Overgevoeligheidsreacties
- Slaperigheid en paresthesieën (hoge dosis)
THIAZIDEN
- Distale tubulus
WERKING
- Inhibitie Na/Cl-cotransporter
- Apicaal: NCC (Na en Cl naar binnen)
- Basolateraal: Na-kanaal, Cl-kanaal (Na, Cl naar buiten)
- Minder Na-reabsorptie → minder H2O-reabsorptie → meer vochtsecretie (in lumen, urine) → meer K-
secretie in distale segmenten
- Chronische toediening thiaziden: verminderen Ca-excretie
o Meer Ca-reabsorptie proximaal
o Meer Ca-reabsorptie DCT
Verband tussen alkalose en hypokaliëmie
- Ernstige K-depletie → K naar buiten (bloed aanvullen), uitwisseling met Na en H (naar binnen cel) voor
elektroneutraliteit → extracellulaire alkalose (H binnen)
- Maar ook contractie-alkalose
FARMACOKINETIEK
- PO inname
- Secretie thiaziden door secretiemechanismen voor organische zuren → competitie met urinezuur (thv
renale tubulus)
INDICATIES
- Hypertensie (1e lijn)
o Vasodilatatie → effectief bij matige essentiële hypertensie
o Combinatie zoutbeperking PO → meer effect vasodilatatie → minder K-verlies
- Congestief hartfalen (onderhoud)
- Nefrolithiase door hypercalciurie: vermindering calciurie, combinatie met zoutbeperking
- Nefrogene diabetes insipidus: vermindering polyurie en polydipsie
o Reductie plasmavolume (meer in lumen) → daling GFR → stijging reabsorptie NaCl en H2O
proximaal → minder volume secretie (urine)
7
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