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Zusammenfassung Vorlesung G2 Psychopharmakologie
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Einführung ................................................................................................................................... 8Grundlegende Begriffe ........................................................................................................................ 8
Resorption, Distribution und Elimination............................................................................................ 9
Pharmakokinetik .......................................................................................................................... 9
Applikation von Pharmaka .................................................................................................................. 9
Metabolismus und Elimination ......................................................................................................... 13
Blut-Hirn-Schranke ............................................................................................................................ 14
Depletionsexperimente ................................................................................................................. 14
Zusammenfassung: pharmakokinetische Kenngrößen ..................................................................... 15
Klassifikation der Neuropsychopharmaka......................................................................................... 15
Informationsquellen .......................................................................................................................... 16
Pharmakodynamik ..................................................................................................................... 17
Dosis-Wirkungsbeziehung ................................................................................................................. 17
Pharmakodynamik: Kennwerte ......................................................................................................... 18
Pharmakokinetische Interaktionen ................................................................................................... 19
Ebene der Resorption .................................................................................................................... 19
Ebene der Verteilung ..................................................................................................................... 19
Ebene des Metabolismus .............................................................................................................. 20
Ebene der Ausscheidung ............................................................................................................... 21
Pharmakodynamische Interaktionen ................................................................................................ 22
Transmittersysteme ................................................................................................................... 23
Wirkungsmechanismen der Transmitter........................................................................................... 25
Interaktionen an Rezeptoren ........................................................................................................ 27
Rezeptorbindung und -wirkung ..................................................................................................... 27
Pharmakawirkungen auf Transmittersysteme .................................................................................. 28
Angriffspunkte der Psychopharmaka ............................................................................................ 28
Neurotransmitter .............................................................................................................................. 29
Glutamat ........................................................................................................................................ 29
GABA.............................................................................................................................................. 31
Acetylcholin ................................................................................................................................... 32
Cholinerges System ........................................................................................................................... 32
Rezeptorbeeinflussung im cholinergen System ............................................................................ 34
Neuromodulatoren............................................................................................................................ 35
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, Monoaminerge Systeme ................................................................................................................... 35
Noradrenalin/ Norepinephrine ..................................................................................................... 36
Serotonin (5-HT) ............................................................................................................................ 36
Monoamine (Dopamin) .............................................................................................................. 38
dopaminerge System(e) .................................................................................................................... 38
Dopaminsynthese und -metabolismus.............................................................................................. 38
Elimination..................................................................................................................................... 39
Dopaminrezeptoren .......................................................................................................................... 39
Dopaminerge Synapse im Kortex .................................................................................................. 41
Aktivitätsmodi dopaminerger Zellen ............................................................................................. 42
Dopaminkonzentration im PFC vs. Striatum ..................................................................................... 42
Dopamin im präfrontalen Kortex (PFC) ......................................................................................... 42
Zwei-Zustandsmodell der DA-Wirkung im PFC ............................................................................. 43
Dopamin und Lernen ......................................................................................................................... 44
phasisches DA & Verstärkungslernen............................................................................................ 44
Vorhersagefehler ........................................................................................................................... 44
Temporal difference learning ........................................................................................................ 45
DA und Belohungsvorhersage ....................................................................................................... 46
VTA / SNc in humans ..................................................................................................................... 46
error-related negativity (ERN, Ne)................................................................................................. 46
Dopamin und Handlungsüberwachung ............................................................................................. 47
Dopamin und Entscheidung .............................................................................................................. 48
DA in den Basalganglien ................................................................................................................ 48
Probabilistische Wahlaufgabe ....................................................................................................... 49
DRD2 / ANKK1 TAQ IA Polymorphism ............................................................................................... 50
DRD2 und probabilistische Wahlaufgabe ...................................................................................... 50
Zusammenfassung Dopamin ............................................................................................................. 51
Antipsychotika ........................................................................................................................... 52
Geschichte ......................................................................................................................................... 52
Schizophrenie .................................................................................................................................... 53
Entwicklung schizophrener Psychosen.............................................................................................. 54
Risikofaktoren................................................................................................................................ 54
Vulnerabilitäts-Stress-Modell ........................................................................................................ 54
Genetische Befunde ...................................................................................................................... 55
Neurotransmitterhypothesen der Schizophrenie ............................................................................. 55
Dopaminhypothese ....................................................................................................................... 55
2
, revidierte Dopaminhypothese ...................................................................................................... 55
Glutamat ........................................................................................................................................ 56
Serotonin ....................................................................................................................................... 56
Befund von Metaanalysen und PET-Studien ................................................................................. 56
Antipsychotika-Einteilung nach chemischer Struktur ....................................................................... 56
Konventionelle vs. Atypische Antipsychotika (KAP/AAP) .............................................................. 57
Rezeptorbindungen: D2-artige Rezeptoren .................................................................................. 58
Unerwünschte Wirkungen der Antipsychotika ................................................................................. 58
Zeitlicher Verlauf der Therapie...................................................................................................... 61
Affektive Störungen ................................................................................................................... 62
Endogene Depression........................................................................................................................ 62
Hypothesen zur Neurobiologie der Depression ................................................................................ 62
Neurotransmitterhypothesen ....................................................................................................... 63
Neuroendokrinologische Hypothesen........................................................................................... 64
Antidepressiva ................................................................................................................................... 64
Allgemeine Therapiekonzepte........................................................................................................... 66
Trizyklische Antidepressiva ............................................................................................................... 68
Biochemische Wirkungen .............................................................................................................. 68
Anticholinerge Nebenwirkungen .................................................................................................. 68
Antihistaminerge Nebenwirkungen .............................................................................................. 68
Selektive Serotonin-Wiederaufnahmehemmer (SSRI) ...................................................................... 69
Allgemeine Nebenwirkungen ........................................................................................................ 69
Monoaminoxidasehemmer (MAOH) ................................................................................................. 70
Neuartige Antidepressiva .................................................................................................................. 70
Agomelatin .................................................................................................................................... 70
Johanniskraut ................................................................................................................................ 71
Ketamin ......................................................................................................................................... 71
Vergleich von Antidepressiva ............................................................................................................ 71
Phasenprophylaxe mit Lithium.......................................................................................................... 71
Wirkmechanismen......................................................................................................................... 72
Kontraindikation ............................................................................................................................ 72
Lithiumintoxikation ....................................................................................................................... 72
Antikonvulsiva in der Phasenprophylaxe .......................................................................................... 73
Angst- und Zwangsstörungen ...................................................................................................... 73
Zwang ................................................................................................................................................ 73
Prävalenz /Verlauf ......................................................................................................................... 74
3
, Evidenz für genetische Faktoren bei OCD ..................................................................................... 74
Risikogene/ –allele für die Zwangsstörung ................................................................................... 74
Genetische Tiermodelle der Zwangsstörung................................................................................. 75
Neurobiologie ................................................................................................................................ 75
Pharmakotherapie ......................................................................................................................... 75
experimentelle Therapieansätze ................................................................................................... 76
Angst .................................................................................................................................................. 76
Lebenszeitprävalenz ...................................................................................................................... 77
lerntheoretische Erklärung ............................................................................................................ 77
Modell der 2-Faktoren-Theorie ..................................................................................................... 78
Komorbidität ................................................................................................................................. 78
Bereichsspezifische Ängste und ihr evolutionärer Hintergrund ................................................... 78
Neurobiologie ................................................................................................................................ 79
Pharmakologische Therapie der Angststörungen ......................................................................... 80
Stufenschema der Pharmakotherapie........................................................................................... 80
Wahl der Psychopharmaka bei Angststörungen ........................................................................... 80
Benzodiazepine ............................................................................................................................. 81
GABA-Rezeptoren .......................................................................................................................... 81
GABAA-Rezeptor und Liganden...................................................................................................... 82
Andere Anxiolytika ........................................................................................................................ 82
Sucht ......................................................................................................................................... 83
Definitionen ....................................................................................................................................... 83
Riskanter Konsum .......................................................................................................................... 83
Missbrauch / schädlicher Gebrauch .............................................................................................. 83
Abhängigkeit .................................................................................................................................. 83
Wirkung und Wirkorte einiger Suchtmittel ....................................................................................... 84
Neurobiologie .................................................................................................................................... 84
Suchtentwicklung .............................................................................................................................. 85
Toleranz ......................................................................................................................................... 85
Akute und repetitive Wirkung ....................................................................................................... 86
Entzugssymptome ............................................................................................................................. 86
Alkohol............................................................................................................................................... 87
Alkoholabhängigkeit: Therapieprinzipien...................................................................................... 87
Akute Intoxikation mit Alkohol ...................................................................................................... 87
Alkoholentzugssyndrom ................................................................................................................ 88
Therapie des Alkoholentzugssyndroms......................................................................................... 88
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