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Samenvatting boek 3 farmacologie geneeskunde
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Volledige samenvatting boek 3 farmacologie. Met lesnotities. Met glans geslaagd in eerste zit.
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DEEL 3: GENEESMIDDELEN DIEINWERKEN OP HET CENTRAAL
ZENUWSTELSEL
1. Farmacotherapie van depressie.............................................................................................................. 5
1.3 De neurobiologische oorzaak van depressie .................................................................................... 5
1.4 Indeling en structuur van antidepressiva ......................................................................................... 5
1.5 Werkingsmechanisme van antidepressiva ....................................................................................... 7
1.6 Farmacokinetische eigenschappen................................................................................................... 8
1.7 Indicaties en bijzondere aspecten van de behandeling ................................................................... 8
1.8 Bijwerkingen ...................................................................................................................................... 9
Tricyclische antidepressiva ................................................................................................................. 9
Antidepressiva direct werkend op neuroreceptoren ....................................................................... 10
SSRI’s.................................................................................................................................................. 10
SNRI’s ................................................................................................................................................. 10
1.9 Contra-indicaties ............................................................................................................................. 10
1.10 Antidepressiva en zwangerschap en lactatie ............................................................................... 11
1.11 Interacties...................................................................................................................................... 11
2. Farmacotherapie van psychose en manie: antipsychotica en lithium ................................................. 12
2.1 Behandeling bipolaire stoornis ....................................................................................................... 12
2.2 Antipsychotica ................................................................................................................................. 12
Chemie van antipsychotica: klassen op basis van structuur ............................................................ 12
Werkingsmechanisme van antipsychotica ....................................................................................... 12
Farmacokinetiek van antipsychotica ................................................................................................ 13
Farmacodynamiek van antipsychotica ............................................................................................. 13
Indicaties ........................................................................................................................................... 14
Bijwerkingen ...................................................................................................................................... 14
Contra-indicaties en risicopopulaties ............................................................................................... 15
Interacties.......................................................................................................................................... 15
De praktijk: opstarten van een antipsychoticum ............................................................................. 16
2.3 Lithium ............................................................................................................................................. 16
Werkingsmechanisme van lithium ................................................................................................... 16
Farmacokinetiek ................................................................................................................................ 16
Bijwerkingen ...................................................................................................................................... 17
1
, Contra-indicaties ............................................................................................................................... 17
Interacties.......................................................................................................................................... 17
Intoxicatie .......................................................................................................................................... 18
Alternatieven voor LI+ bij de behandeling van bipolaire stoornis ................................................... 18
3. Farmacotherapie van epilepsie ............................................................................................................. 19
3.1 Inleiding ........................................................................................................................................... 19
3.2 Werkingsmechanisme van anti-epileptica ..................................................................................... 20
3.4 Anti-epileptica die werken via een blokkering van Na+ kanalen .................................................... 21
Fenytoïne........................................................................................................................................... 21
Carbamazepine en oxcarbazepine .................................................................................................... 22
Lamotrigine ....................................................................................................................................... 23
Topiramaat ........................................................................................................................................ 24
Valproaat ........................................................................................................................................... 24
3.5 Anti-epileptica die werken via GABA .............................................................................................. 25
Fenobarbital en primidon ................................................................................................................. 25
Benzodiazepines: midazolam, diazepam, lorazepam....................................................................... 26
Tiagabine, vigabatrine, gabapentine en pregabaline ....................................................................... 26
3.6 Anti-epileptica die werken via T-type Ca2+ kanalen ........................................................................ 27
3.7 Andere anti-epileptica..................................................................................................................... 27
Levetiracetam en brivaracetam ........................................................................................................ 27
Lacosamide ........................................................................................................................................ 28
3.8 Algemene bemerkingen bij het gebruik van anti-epileptica .......................................................... 28
3.9 Bijkomende indicaties van anti-epileptica ...................................................................................... 28
4. Farmacotherapie van de ziekte van Parkinson en parkinsonisme ....................................................... 29
Inleiding ................................................................................................................................................. 29
4.1 Farmacokinetiek .............................................................................................................................. 30
Plasmahalfwaardetijd........................................................................................................................ 30
Resorptie ........................................................................................................................................... 31
Interacties.......................................................................................................................................... 31
4.2 Efficaciteit en indicaties .................................................................................................................. 31
4.3 Bijwerkingen .................................................................................................................................... 32
L-DOPA .............................................................................................................................................. 32
D2-agonisten ..................................................................................................................................... 33
COMT inhibitoren .............................................................................................................................. 33
MAO-B inhibitoren ............................................................................................................................ 33
Antimuscarinica ................................................................................................................................. 33
2
, Apomorfine ....................................................................................................................................... 34
Andere behandelingen...................................................................................................................... 34
5. Farmacotherapie van andere bewegingsstoornissen .......................................................................... 35
5.1 Tremor ............................................................................................................................................. 35
5.2 Medicatie-geïnduceerde dyskinesie/dystonie ............................................................................... 35
5.3 Restless-legs syndroom ................................................................................................................... 35
6. SkeletspierrelaxantiA............................................................................................................................. 36
6.1 Diazepam ......................................................................................................................................... 36
6.2 Baclofen ........................................................................................................................................... 36
6.3 Dantroleen ...................................................................................................................................... 36
6.4 Botulinetoxine ................................................................................................................................. 36
7. Farmacotherapie van de ziekte van Alzheimer .................................................................................... 38
7.1 Inleiding ........................................................................................................................................... 38
7.2 Neurobiologisch mechanisme bij de ziekte van Alzheimer en mogelijke therapeutische targets 38
7.3 ACh-E-inhibitoren ............................................................................................................................ 39
7.4 NMDA-antagonist: memantine ....................................................................................................... 39
8. Farmacotherapie van pijn ..................................................................................................................... 40
8.1 Opioïde analgetica .......................................................................................................................... 40
Structuur en indeling van de opioïden ............................................................................................. 40
Werkingsmechanisme ....................................................................................................................... 41
Farmacokinetiek ................................................................................................................................ 43
Zuivere opioïd-agonisten: prototype morfine .................................................................................. 43
Partiële opioïd agonisten en gemengde agonist-antagonisten ....................................................... 49
Opioïd antagonisten: naloxon, naltrexon en methylnatrexon ......................................................... 49
8.2 Lokale anesthetica........................................................................................................................... 50
Stoffen en structuur .......................................................................................................................... 50
Werkingsmechanisme ....................................................................................................................... 50
Farmacokinetiek ................................................................................................................................ 51
8.3 Farmacotherapie van kankerpijn: WHO richtlijnen ........................................................................ 52
8.4 Farmacotherapie van neuropathische pijn .................................................................................... 53
Verbeter je inzicht ................................................................................................................................. 54
9. Hypnotica – Anxiolytica ......................................................................................................................... 55
9.1 Benzodiapzepines ........................................................................................................................... 55
Structuur ........................................................................................................................................... 55
Werkingsmechanisme ....................................................................................................................... 55
Farmacologische effecten ................................................................................................................. 56
3
, Ongewenste effecten........................................................................................................................ 56
Farmacokinetiek ................................................................................................................................ 59
Therapeutische indicaties van benzodiazepines .............................................................................. 60
Relatieve contra-indicaties van benzodiazepines ............................................................................ 61
Bijzonderheden ivm benzodiazepine-therapie ................................................................................ 61
Besluit ................................................................................................................................................ 61
9.2 Stoffen met werking analoog aan deze van benzodiazepines (z-drugs)........................................ 62
9.3 Benzodiazepine-antagonist............................................................................................................. 62
9.4 Beta-Blokkers .................................................................................................................................. 62
9.5 Histamine H1-R blokkers ................................................................................................................. 62
9.6 Antidepressiva ................................................................................................................................. 62
9.7 Fytotherapeutica ............................................................................................................................. 63
9.8 Melatonine ...................................................................................................................................... 63
9.9 Barbituraten .................................................................................................................................... 63
4
, 1. FARMACOTHERAPIE VAN DEPRESSIE
1.1 definitie -> nk
1.2 socio-economische aspecten van depressie -> nk
1.3 DE NEUROBIOLOGISCHE OORZAAK VAN DEPRESSIE
• Geen consensus
• Hypothese = mono-amine deficiëntie
o Reserpine (A-HT) induceerde depressies -> door depletie van monoamino-NT
• Werkingsmechanisme van bijna alle antidepressiva -> verhogen concentratie monoamino-NT
(dopamine, serotonine en/of noradrenaline) in de synaptische spleet
o Heropname remmen zoals TCA
o Afbraak inhiberen zoals MAO-I
• à noradrenerge en/of serotonerge transmissie verhogen
o à verstoorde balans van noradrenerge en/of serotonerge transmissie in CZS
waarschijnlijk basis van depressie
o Maar: niet-selectieve heropnameremming van NA en 5-HT door TCA’s of SSRI’s is
onmiddellijk, maar therapeutisch effect pas na enkele weken (2-6 weken) ->
bijkomende moleculaire of structurele wijzigen treden op als gevolg van
heropnameremming
1.4 INDELING EN STRUCTUUR VAN ANTIDEPRESSIVA
• Indeling op basis van werkingsmechanisme
• Selectieve heropnameremmers: SSRI en selectieve NA-heropname remmers
Niet-selectieve heropnameremmers: TCA, SNRI en NA- en dopamine heropnameremmers
• Enzyme inhibitoren: MAO
Directe werking op verschillende neuroreceptoren
• Oudere producten: TCA en MAO
Nieuwere producten: zelfde klinische efficiaciteit als TCA’s, maar betere tolerantie dankzij
minder nevenwerkingen, toegenomen veiligheid en kleinere kans op klinisch relevante
interacties
MAO- INHIBITOREN
• Inhiberen monoamineoxidase -> remmen afbraak natuurlijk voorkomende mono-aminen
• Niet-selectieve MAO-A en MAO-B inhibitoren zijn niet meer op de Belgische markt
• Selectieve, reversibele MAO-A inhibitie (moclobemide) enkel nog voor zware depressie
TRI CYCLI SCHE ANTI DEPRESSI VA
• Afgeleid van imipramine (gelijkaardige structuur aan amitriptyline)
• Prototype: clomipramine
• Niet-selectieve inhibitie van de heropname van NA en 5-HT
SELECTIEVE SEROTONINE REUPTAKE INHIBITOREN (SSRI’S)
5
, • Eerste keuze behandeling voor matige tot ernstige depressie
• Relatief selectieve blokkering van SERT (serotonine reuptake transporter) tov NET
(noradrenaline reuptake transporter)
o ‘selectieve’ blokkering heel variabel
• Fluvoxamine, paroxetine, (es)citalopram, sertraline en fluoxetine (prototype)
• Werken evengoed als TCA’s, maar veel minder nevenwerkingen
SELECTIEVE NORADRENALINE REUPTAKE INHIBITOREN
• Inhibitie NET
• Reboxetine (antidepressivum) en atomoxetine (behandeling ADHD en narcolepsie)
DUAL REUPTAKE INHIBITOREN = SEROTONINE EN NORADRENALINE REUPTAKE INHIBITOREN
(SNRI ’S)
• Venlafaxine en duloxetine
• Laatste jaren enorm aan populariteit gewonnen
Andere
• Bupropion
o NA- en dopamine reuptake inhibitor
o Antidepressivum en hulpmiddel bij rookstop
• Naltrexon + bupropion
o Behandeling obesitas
o Beperkte gewichtsdaling, onduidelijk of effect na verloop van tijd blijft -> geen eerste
keuze voor behandeling obesitas
• Mianserine, mirtazepine, trazondon en agomelatine
o Niet primair actief als heropnameremmer, maar werken vooral thv neuroreceptoren
o Mianserine
§ Oorspronkelijk anti-allergicum
§ Toevallig ontdekt als antidepressivum (blokkeert presynaptische a2-
receptoren
§ Slaapmiddel door antihistaminerge werking
o Mirtazapine
§ Antagonist presynaptische a2-receptoren
§ Inhibeert postsynaptische serotonine en H1-histaminereceptoren
o Trazodon
§ Rechtstreeks blokkeren van 5-HT2A en a1-receptoren.
o Agomelatine
§ Melatonerge agonist: stimuleert melatonine receptoren MT1 en MT2 die
normaal door endogeen melatonine worden gestimuleerd
§ 5-HT2C antagonist: R wordt normaal door endogeen serotonine geactiveerd
§ Heel weinig gegevens over werkzaamheid en veiligheid onzeker
• Vortioxetine
o Moduleert serotoninereceptoractiviteit en remt SERT
o Moduleren dopamine en noradrenaline
o Geen meerwaarde tov andere antidepressiva en veiligheid op lange termijn niet
gekend
• Sint-Janskruid
o Evidentie niet eenduidig
6
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