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Samenvatting praktische psychofarmacologie (2023-24)

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  • Course
  • Praktische psychofarmacologie (002275)
  • Institution
  • Vrije Universiteit Brussel (VUB)

Dit is een uitgebreide samenvatting van het vak 'Praktische Psychofarmacologie' gedoceerd door Prof. Dr. Ilse Smolders in het academiejaar aan de VUB. Het bevat uitgebreide notities vanuit de hoorcolleges, afbeeldingen en de powerpoint gebruikt door de prof. Succes!

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Document information

  • May 18, 2024
  • 168
  • 2023/2024
  • Summary

Subjects

  • hypnotica
  • middelen adhd
  • antidepressiva
  • antipsychotica
  • psychedelica
  • anti epileptica
  • stemmingsstabilisatoren
  • aan middelen gebonden stoornissen

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  • Vrije Universiteit Brussel (VUB)
  • Psychologie
  • Praktische psychofarmacologie (002275)
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PRAKTISCHE PSYCHOFARMACOLOGIE
INHOUDSOPGAVE

Hoofdstuk 1: Inleiding ..................................................................................................................................... 8
1. Hersenen: Anatomie en functies van de hersenen .......................................................................................... 8
1.1. Cerebrum (telencephalon) – grote hersenen ........................................................................................... 8
1.1.1. Cortex cerebri .............................................................................................................................. 8
1.1.2. Prefrontale cortex ....................................................................................................................... 9
1.1.3. Primaire motorische cortex ......................................................................................................... 9
1.1.4. Secundaire motorische schors................................................................................................... 10
1.1.5. Primaire sensorische cortex ...................................................................................................... 10
1.1.6. Secundaire sensorische schors .................................................................................................. 10
1.1.7. Visuele cortex ............................................................................................................................ 11
1.1.8. Auditieve cortex ........................................................................................................................ 11
1.1.9. Gnostisch centrum .................................................................................................................... 11
1.2. Diencephalon .................................................................................................................................... 11
1.3. Hersenstam ....................................................................................................................................... 12
1.4. Cerebellum (kleine hersenen) ........................................................................................................... 12

2. Ruggenmerg .......................................................................................................................................... 12
2.1. Sensibel systeem voor zintuiglijke waarnemingen ........................................................................... 12
2.2. Motorisch systeem voor beweging ................................................................................................... 13
2.3. Limbisch systeem voor emotioneel gedrag ....................................................................................... 13
2.4. Nucleus accumbens of ventraal stratium .......................................................................................... 13
3. Neurotransmissie................................................................................................................................... 14
3.1. Klassieke anterograde neurotransmissie .......................................................................................... 14
3.1.1. Hoe communiceren zenuwcellen? ............................................................................................ 14
3.1.2. De actiepotentiaal ..................................................................................................................... 15
3.2. Synaptische neurotransmissie ........................................................................................................... 16
3.3. De klassieke neurotransmitters......................................................................................................... 16
3.4. Retrograde neurotransmissie (e.g. endocannabinoïden).................................................................. 17
3.5. Extrasynaptische neurotransmissie ................................................................................................... 17
4. Aangrijpingspunten voor psychofarmaca.............................................................................................. 18
4.1. Receptoren ........................................................................................................................................ 20
4.1.1. Affiniteit & intrisnsieke activiteit ............................................................................................... 22
4.2. Ionkanalen ......................................................................................................................................... 23
4.3. Enzymen ............................................................................................................................................ 24
4.4. Carriers of transporters ..................................................................................................................... 25
5. Mechanismen van neuromodulatie ....................................................................................................... 25
5.1. Desensitisatie .................................................................................................................................... 26
5.2. Down-regulatie .................................................................................................................................. 26
5.3. Up-regulatie....................................................................................................................................... 26

1

, 5.4. Supersensitiviteit ............................................................................................................................... 26

6. Neurotransmitters ................................................................................................................................. 27
6.1. Noradrenaline ................................................................................................................................... 28
6.1.1. Adrenaline (AD) ......................................................................................................................... 29
6.1.2. Adrenerge receptoren ............................................................................................................... 29
6.1.3. Signaaltransductie-mechanismen van adrenerge receptoren (GPCRs) ..................................... 30
6.1.4. Beëindiging van de effecten van NAD – (Re)Uptake ................................................................. 31
6.1.5. Re-uptake transporters voor monoamines NET, DAT en SERT .................................................. 32
6.1.6. Beëindiging van de effecten van NAD & adrenaline – Metabolisatie........................................ 32
6.1.7. NAD & adrenaline metabolisatie ............................................................................................... 33
6.1.8. Centrale adrenerge banen......................................................................................................... 33
6.1.9. Centrale NAD-erge banen vanaf de locus coeruleus ................................................................. 33
6.2. Dopamine .......................................................................................................................................... 34
6.2.1. dopaminerge zenuwbanen ........................................................................................................ 35
6.3. Serotonine (5HT) ............................................................................................................................... 36
6.3.1. Serotoninerge neurotransmissie ............................................................................................... 36
6.3.2. 5HTerge banen vanaf de raphe nucleus .................................................................................... 37
6.3.3. Serotonine receptoren overzicht .............................................................................................. 38

Hoofdstuk 2: Antidepressiva ......................................................................................................................... 39

1. Majeure depressie ......................................................................................................................................... 39
1.1. Symptomen ............................................................................................................................................ 39
1.2. In de hersenen........................................................................................................................................ 39
1.2.1. Serotoninerge neurotransmissie ..................................................................................................... 41
1.2.2. Noradrenerge neurotransmissie ..................................................................................................... 42
1.3. Neurobiologie van majeure depressie ................................................................................................... 43
1.3.1. Problemen met neuronale netwerkactiviteiten en monoaminerge neurotransmissie thv de
prefrontale cortex ..................................................................................................................................... 43
1.3.2. Problemen met hyperactiviteit van limbische regio’s zoals amygdala............................................ 43
1.3.3. Verminderde neurogenese en neuroplasticiteit ............................................................................. 44
1.3.4. Neuroinflammatie; inflammatiemediatoren zoals IL1b, TNFa beïnvloeden monoaminerge en
glutamaterge neurotransmissie en neuronale plasticiteit ........................................................................ 45
1.4. Behandeling van een depressie .............................................................................................................. 46
2. Behandeling van unipolaire majeure depressie met monoaminerge farmaca.............................................. 46
2.1. Heropnameremmers van noradrenaline, serotonine, dopamine .......................................................... 47
2.1.1. Niet-selectieve heropnameremmers .............................................................................................. 48
2.1.2. Selectieve heropnameremmers voor serotonine = SSRI’s .............................................................. 50
2.1.3. NRI’s = Selectieve noradrenaline reuptake inhibitor....................................................................... 55
2.2. Antidepressiva direct werkend op de receptoren .................................................................................. 56
2.2.1. Trazodon Nestrolan® ....................................................................................................................... 57
2.2.2. Mirtazapine, mianserine ................................................................................................................. 57
2.2.3. Agomelatine Valdoxan® .................................................................................................................. 57
2.2.4. Vortioxetine Brintellixâ (10 mg een maal per dag).......................................................................... 58
2.3. Mono-amine-oxidase-inhibitoren .......................................................................................................... 58
3. Behandeling Glutamaterge middelen bij een unipolaire majeure depressie ................................................. 60
3.1. Werkingsmechanisme esketamine......................................................................................................... 61
3.1.1. Neveneffecten esketamine ............................................................................................................. 61

2

, 4. Middelen bij een unipolaire milde depressie: Sint-Janskruid ......................................................................... 62
4.1. Hypericum perforatum Hyperiplant® ..................................................................................................... 62
5. Plaatsbepaling antidepressiva....................................................................................................................... 62

6. Conclusie folia BCFI juli 2018 & Meta-analyse Capriani et al. (2018) The Lancet 391, 1357-66 ................... 63
7. Zwangerschap ....................................................................................................................................... 63
8. Interacties .............................................................................................................................................. 64

Hoofdstuk 3: Antipsychotica ......................................................................................................................... 65
1. Psychotische stoornissen & Schizofrenie ....................................................................................................... 65
1.1. Neurobiologie van schizofrenie ......................................................................................................... 66
1.1.1. Oorzaken ................................................................................................................................... 66
1.1.2. Positieve symptomen ................................................................................................................ 70
1.1.3. Negatieve symptomen .............................................................................................................. 71
2. Conventionele of typische antipsychotica ............................................................................................. 72
2.1. D2 receptor antagonisme: de effecten en neveneffecten ................................................................ 73
2.2. Antipsychotica met verlengde werking ............................................................................................. 74
3. Atypische of nieuwere antipsychotica ................................................................................................... 75
3.1. Serotonine-dopamine antagonist...................................................................................................... 76
3.1.1. Sertonine-dopamine antagonist – SDA ..................................................................................... 79
3.2. Andere atypische mechanismen ....................................................................................................... 80
3.2.1. De rol van 5-HT1A receptor ....................................................................................................... 80
3.2.2. Atypische antipsychotica en verbetering van negatieve symptomen ........................................... 81
3.3. Doeltreffendheid atypische antipsychotica....................................................................................... 81
3.4. Ongewenste effecten atypische antipsychotica ................................................................................ 82
4. Indicaties en contra-indicaties antipsychotica ...................................................................................... 82
4.1. Indicaties ........................................................................................................................................... 82
4.2. Contra-indicaties ............................................................................................................................... 83
5. Zwangerschap en borstvoeding............................................................................................................. 84
6. Interacties .............................................................................................................................................. 84

Hoofdstuk 4: Hypnotica (mineure tranquilisers) ............................................................................................ 85
1. Neurobiologie van slaapstoornissen.............................................................................................................. 85
1.1. Alertheid ............................................................................................................................................ 85
1.2. Slaap-waak switch ............................................................................................................................. 87
1.3. Slapeloosheid .................................................................................................................................... 88
1.4. GABAerge neurotransmissie ............................................................................................................. 88
1.4.1. Synthese en metabolisatie van het aminozuur GABA ............................................................... 89
2. Benzodiazepines .................................................................................................................................... 90
2.1. Effecten van benzodiazepine ............................................................................................................ 92
2.2. Farmacokinetiek benzodiazepines .................................................................................................... 92
2.3. Benzodiazepine full agonisten indicaties .......................................................................................... 93
2.4. Neveneffecten ................................................................................................................................... 94
2.5. Addendum – bezodiazepine antagonist ............................................................................................ 95


3

, 3. Andere GABAA receptor positieve allosterische modulatoren = zolpidem, zopiclon ............................. 96
3.1. Z drugs neveneffecten ....................................................................................................................... 96
4. Melatonine ............................................................................................................................................ 97

5. Valeriaanextracten ................................................................................................................................ 98
6. Diverse middelen ................................................................................................................................... 99
7. Aanpak slapeloosheid – kernboodschap ............................................................................................... 99

Hoofdstuk 5: Anxiolytica ............................................................................................................................. 100
1. Neurobiologie van angst- en stressstoornissen ........................................................................................... 100
1.1. Soorten angst- en stressstoornissen .................................................................................................... 100
1.2. Neurobiologie ....................................................................................................................................... 101
2. Anxiolyse ..................................................................................................................................................... 103
2.1. aniolyse Door benzodiazepines ............................................................................................................ 103
2.2. Anxiolyse door antidepressiva............................................................................................................. 103
2.3. Diversen................................................................................................................................................ 103
3. Aanpak bij angst- en stressstoornissen ....................................................................................................... 104
3.1. Aanpak van gegeneraliseerde angststoornissen (GAS) ........................................................................ 104
3.2. Aanpak van paniekstoornissen ............................................................................................................. 104
3.3. Aanpak van fobie .................................................................................................................................. 105
3.4. Aanpak van sociale angststoornissen ................................................................................................... 105

Hoofdstuk 6: Stemmingsstabilisatoren ........................................................................................................ 106
1. Bipolaire stoornis ......................................................................................................................................... 106
1.1. Symptomen van manie.................................................................................................................... 106
2. Behandeling van bipolaire stoonrissen ................................................................................................ 107

3. Lithiumzouten ...................................................................................................................................... 108
4. Andere mood stabilisers ...................................................................................................................... 109
4.1. bepaalde anti-epileptica .................................................................................................................. 109
4.2. atypische antipsychotica bij manie ................................................................................................. 109

Hoofdstuk 7: Anti-epileptica ....................................................................................................................... 110

1. Wat is epilepsie?.......................................................................................................................................... 110
1.1. Soorten epileptische aanvallen ............................................................................................................ 110
1.2. Soorten epileptische aanvallen & diagnose ......................................................................................... 111
1.3. Status epilepticus ................................................................................................................................. 111
1.4. Epilepsiesyndromen ............................................................................................................................. 111
1.5. Epilepsie incidentie, oorzaken .............................................................................................................. 112
1.6. Epilepsy spectrum disorder .................................................................................................................. 112
1.7. Behandeling epilepsie .......................................................................................................................... 113
1.8. Plaatsbepaling ...................................................................................................................................... 113
1.9. Pathofysiologie van epilepsie ............................................................................................................... 114
2. Indeling volgens werkingsmechanisme ....................................................................................................... 116
3. Indeling volgens werkingsspectrum ............................................................................................................ 119

4

, 3.1. Anti-epileptica met een breder spectrum ............................................................................................ 119
3.1.1. Valproïnezuur – natriumvalproaat ................................................................................................ 119
3.1.2. Lamotrigine ................................................................................................................................... 121
3.1.3. Levetiracetam en analogen ........................................................................................................... 121
3.1.4. Topiramaat .................................................................................................................................... 122
3.1.5. Perampanel ................................................................................................................................... 123
3.2. Anti-epileptica met een nauwer spectrum........................................................................................... 123
3.2.1. Carbamazepine en oxcarbazepine ................................................................................................ 124
3.2.2. Gabapentine en pregabaline ......................................................................................................... 125
3.2.3. Fenobarbital en primidon .............................................................................................................. 126
3.2.4. Fenytoïne en natriumfenytoïne .................................................................................................... 126
3.2.5. Tiagabine ....................................................................................................................................... 127
3.2.6. Lacosamide .................................................................................................................................... 127
3.3. Andere anti-epileptica .......................................................................................................................... 128
3.3.1. Felbamaat ...................................................................................................................................... 128
3.3.2. Vigabatrin ...................................................................................................................................... 128
3.3.3. Ethosuximide ................................................................................................................................. 128

4. Behandeling................................................................................................................................................. 129
4.1. Stoppen van de anti-epileptische behandeling ................................................................................... 129
4.2. Behandeling van vrouwelijke epilepsiepatiënten ................................................................................ 129

Hoofdstuk 8: Aan middelen gebonden stoornissen en hun behandeling...................................................... 131
1. Verslaving .................................................................................................................................................... 131
1.1. Mesolimbische dopaminerge baan medieert “rewarding” ............................................................. 131
1.2. Neurobiologie van verslaving ............................................................................................................... 132
1.3. Hersengebieden en neuromediatoren betrokken in verslaving........................................................... 132

2. Opoïden en middelen bij opoïdeverslaving.................................................................................................. 133
2.1. Opoïden ................................................................................................................................................ 133
2.2. Medicatie bij opoïdeverslaving ............................................................................................................ 134
3. Alochol en middelen bij alcholmisbruik ....................................................................................................... 135
3.1. Alcoholverslaving ................................................................................................................................. 136
3.2. Middelen bij alcoholmisbruik ............................................................................................................... 137
3.2.1. alcoholontwenning ........................................................................................................................ 137
3.2.2. Terugvalpreventie ......................................................................................................................... 137
3.3. Interacties tussen geneesmiddelen en alcohol .................................................................................... 138

4. Nicotine en middelen bij tabakmisbruik ...................................................................................................... 138
5. Cannabinoïden ............................................................................................................................................ 140
5.1. CB1 receptor agonisten: klinisch gebruik ............................................................................................. 140
5.2. Middelen bij cannabisafhankelijkheid .................................................................................................. 141
6. Dissociatieve anesthetica ............................................................................................................................ 141
6.1. PCP, ketamine en dextromethorphan ............................................................................................. 141

7. Centrale stimulantia ............................................................................................................................ 142
7.1. Amfetamine en -derivaten .............................................................................................................. 142
7.1.1. Re-uptake transporters NET, DAT en SERT .............................................................................. 142
7.1.2. Amfetamine effecten algemeen .............................................................................................. 143

5

, 7.1.3. Amfetamine neveneffecten..................................................................................................... 143
7.2. Cocaïne ............................................................................................................................................ 144
7.3. Middelen bij verslaving aan centrale stimulantia............................................................................ 144

8. Hallucinogenen (verwant met monoamines) ...................................................................................... 144
8.1. Effecten van LSD .............................................................................................................................. 145
8.2. Werkingsmechanisme hallucinogenen = partieel 5HT 2A agonisme. ............................................. 145

Hoofdstuk 9: Middelen bij ADHD ................................................................................................................ 146
1. ADHD aandacht – hersenregio’s.................................................................................................................. 146
2. ADHD hyperactiviteit en impulsiviteit – hersenregio’s ................................................................................ 146

3. ADHD bij volwassenen ................................................................................................................................. 148
4. Behandeling van ADHD ............................................................................................................................... 149
4.1. Methylfenidaat ..................................................................................................................................... 149
4.2. Lis-dexamfetamine ............................................................................................................................... 150
4.3. Atomoxetine .................................................................................................................................... 150
4.4. Guanfacine ...................................................................................................................................... 151
4.5. Addendum ....................................................................................................................................... 151
4.6. Plaatsbepaling – behandeling.......................................................................................................... 152

Hoofdstuk 10: Psychedelica als geneesmiddel? ........................................................................................... 153
1. Inleiding ....................................................................................................................................................... 153

2. Kan je psychedelica gebruiken als medicatie? ............................................................................................. 154
3. OVer welk soort onderzoek gaat het? ......................................................................................................... 156
4. Enkele voorbeelden – psychedelica bij mentale aandoeningen .................................................................. 156
4.1. MDMA voor post-tramuatische stressstoornis .................................................................................... 156
4.1.1. Tijdslijn .......................................................................................................................................... 156
4.1.2. MDMA-assisted psychotherapy .................................................................................................... 156
4.1.3. Typische therapeutische effecten ................................................................................................. 157
4.1.4. Neveneffecten ............................................................................................................................... 158
4.1.5. Wat mag dat kosten? .................................................................................................................... 158
4.1.6. Wat is het onderliggende werkingsmechanisme?......................................................................... 158
4.2. (Es)ketamine voor therapieresistente depressie ................................................................................. 160
4.2.1. Tijdslijn .......................................................................................................................................... 160
4.2.2. Typische therapeutische effecten ................................................................................................. 160
4.2.3. Is het therpaeutische effect geassocieerd met het psychedelisch/ dissociatieve effect?............. 162
4.2.4. Effecten op bewustzijn en gemoed ............................................................................................... 162
4.2.5. Hebben R-ketamine of andere niet- dissociatieve NMDA-receptor antagonisten therapeutische
effecten in depressie? ............................................................................................................................. 163
4.2.6. Wat zou de onderliggende onderliggende neurobiologische basis zijn? ...................................... 163
4.3. Psilocybine voor TRD ............................................................................................................................ 165
4.3.1. Tijdslijn .......................................................................................................................................... 165
4.3.2. Typische therapeutische effecten ................................................................................................. 165
4.3.3. Werkt het beter dan andere antidepressiva? ............................................................................... 166
4.3.4. Wat zou de onderliggende neurbiolosiche basis zijn? .................................................................. 167
4.3.5. Een reset van het brein met betere flexibiliteit en minder pieken? ............................................. 168

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