Inhoudsopgave psychofarmacologie
1. History of psychofarmacology (part 1) .................................................................................................... 3
1.1. Ancient history ..................................................................................................................................... 3
1.2. Influences from psychology .................................................................................................................. 4
1.2.1. Experimental psychology ................................................................................................................ 4
1.2.2. Comparative psychology ................................................................................................................. 6
1.2.3. Behavioural psychology................................................................................................................... 6
1.3. Example hebbian learning .................................................................................................................... 7
1.3.1. Explaining classical conditioning ..................................................................................................... 8
1.3.2. Explaining the Placebo Effect ........................................................................................................ 10
1.3.3. Application: placebo-controlled dose reduction (PCDR) ............................................................... 10
2. History of psychopharmacology (part 2) ............................................................................................... 12
2.1. Influences from psychiatry ................................................................................................................. 12
2.1.1. Early pharmacotherapy ................................................................................................................. 12
2.1.2. Experimenting with hallucinogenics.............................................................................................. 13
2.1.3. The first ‘antidepressant’ .............................................................................................................. 14
2.1.4. The revolutionary decade ............................................................................................................. 15
2.2. In conclusion....................................................................................................................................... 17
3. Behavioral neuroscience ....................................................................................................................... 19
3.1. Anatomy & organization of the nervous system ................................................................................ 19
3.1.1. Different nervous systems ............................................................................................................ 19
3.1.2. What are cells made of? ................................................................................................................ 21
3.1.3. Neurons: specialized cells ............................................................................................................. 22
3.2. Origin of signals ................................................................................................................................. 23
3.2.1. What makes our brain tick? .......................................................................................................... 23
3.3. Neural communication ....................................................................................................................... 24
3.3.1. Situating biochemical signal processing ........................................................................................ 24
3.3.2. Membrane potentials .................................................................................................................... 24
4. Behavioral neuroscience (part 2)........................................................................................................... 27
4.1. Neural communication ....................................................................................................................... 27
4.1.1. Synaptic communication ............................................................................................................... 27
4.1.2. Endocrinergic communication ...................................................................................................... 30
5. Pharmacokinetics .................................................................................................................................. 33
5.1. General framework ............................................................................................................................ 33
5.2. Pharmacokinetics ............................................................................................................................... 34
5.2.1. Routes of administration ............................................................................................................... 34
5.2.2. Absorption & distribution ............................................................................................................. 37
5.2.3. Depot binding ................................................................................................................................ 39
5.2.4. Inactivation & biotransformation .................................................................................................. 39
5.2.5. Excretion........................................................................................................................................ 41
6. Pharmacodynamics ............................................................................................................................... 42
6.1. Drug categorization ........................................................................................................................... 42
1
, 6.2. From synaptic activity… ..................................................................................................................... 42
6.2.1. Drugs as ligands ............................................................................................................................. 43
6.2.2. Physiological responses of receptors ............................................................................................ 44
6.2.3. Dynamic reactions ......................................................................................................................... 47
6.3. To behavioral effects (niet kennen, geen examenvragen over) ......................................................... 49
6.3.1. From drug actions to drug effects ................................................................................................. 49
7. Drug abuse, addicition and dependency ............................................................................................... 52
7.1. Characteristics .................................................................................................................................... 52
7.2. Biopsychosocial mechanisms ............................................................................................................. 53
7.2.1. Mesolimbic DA-pathway (reward mechanisms) ........................................................................... 53
7.2.2. Cravings & operant conditioning ................................................................................................... 57
7.2.3. Social network hypothesis............................................................................................................. 57
7.3. Therapeutic actions ............................................................................................................................ 57
7.4. Drug scheduling systems & policies ................................................................................................... 58
8. Therapy adherence (zelfstudie) ............................................................................................................. 60
8.1. Defining therapy (non)adherence ...................................................................................................... 60
8.2. Factors related to therapy (non)adherence ....................................................................................... 61
8.3. Societal problems related to therapy (non)adherence ....................................................................... 62
8.4. The case of Scott Martin .................................................................................................................... 62
8.4.1. Getting to know Scott ................................................................................................................... 62
8.4.2. Treatment adherence: a new hope ............................................................................................... 63
8.4.3. The short-term effects of Lithium ................................................................................................. 63
8.4.4. The 6-week follow-up.................................................................................................................... 63
8.4.5. Putting strain on Scott’s treatment adherence ............................................................................. 63
8.4.6. Remarkable effects come in small packages ................................................................................. 63
8.5. How to improve therapy adherence ................................................................................................... 64
9. Repercussions of Medicalization: a topical discussion on other factors influencing therapy
(non)adherence.............................................................................................................................................. 65
9.1. Ethical marketing ............................................................................................................................... 66
9.1.1. Selling products with medical labels ............................................................................................. 66
9.1.2. Implications for Pharma industry .................................................................................................. 67
9.1.3. Ethical correct reporting ............................................................................................................... 67
9.2. Use, misuse and abuse ....................................................................................................................... 69
9.2.1. Antidepressants on the rise… ........................................................................................................ 69
10. From (pre)clinical research to pharmacy........................................................................................... 71
10.1. Research cycle .................................................................................................................................... 71
10.1.1. Preclinical research ................................................................................................................... 71
10.1.2. Clinical research, phase I, II and III ........................................................................................... 72
10.1.3. FDA assessment ........................................................................................................................ 74
10.1.4. Post-marketing research, phase IV ........................................................................................... 74
10.2. Topical discussions on… ..................................................................................................................... 74
10.2.1. Animal research ethics ............................................................................................................. 74
10.2.2. Fast-track research ................................................................................................................... 75
2
,Psychofarmacologie
1. History of psychofarmacology (part 1)
1.1. Ancient history
Periode voor experimentele psychologie (19e eeuw), begin van evidence-based medicine: 3
mannen gingen experimenteren (op zichzelf) met medicatie
- Pierre-Alexandre Charvet
- Jacques-Joseph Moreau de Tours
- Paolo Mantegazza
Jean-Baptise Charvet:
- Opium crisis: recreatief gebruik zorgde voor maatschappelijke impact
o Uitwisseling in verschillende landen, gebruik vooral voor pijnstilling en
relaxatie
- Interesseveld: opium/heroïne/morfine > effect op mensen en dieren
- Eerste systematische, farmacologische studies: gebruik condities, observaties, …
o Gedrag > fysiologie
o Systematisch testen op dieren (honden, duiven en konijnen)
o Zelf-experimenten: hij geloofde dat opium veel potentie kon hebben in de
medicatiewereld voor de maatschappij
▪ Effecten van euforie, pijnstilling en sufheid
Jacques-Joseph Moreau de Tours
- Van engelen-en-demonen naar humanistische aanpak
o Opsluiten >< behandelen
- Interesseveld: hasj
o Onderzoek van effecten die hij bij zichzelf en anderen vaststelde
o Mensen die hier veel van innamen kregen ‘psychotic craziness’ of werden
‘delusional’
▪ Effecten van hasj waren gelijkaardig aan psychotische episodes van
patiënten met schizofrenie
- Eerste op stoffen gebaseerde model van psychische aandoeningen
o Gedragsmatige vergelijking
o Hypothese over het central zenuwstelsel
DR. Philippe Pinel: mentaal zieke patiënten werden eerst geïsoleerd uit de maatschappij, hij
begreep dat dit niet de oplossing was en deze mensen ook gewoon mensen waren en deze
hulp moesten krijgen.
Paolo Mantegazza
- Antroplogische exploitaties in Zuid-Amerika
o Stammen en het gebruik van cocabladeren (Inca’s)
- Interesseveld: effecten cocaïne/cocabladeren op zichzelf en anderen
- Zelfexperimenten (werd verslaafd), maar kan voordelig zijn voor maatschappij in
mate
o Opbeurende eigenschappen van coca
o Link met ‘psychotische gekte’
3
, o Enthousiaste supporter van coca, was te progressief want hij haalde vooral de
positieve effecten aan en negeerde de negatieve verslavende effecten > kreeg
veel kritiek in de toekomst
▪ Je bent heel productief onder invloed van coca, maar werk is minder
kwaliteitsvol
- Eerste poging tot classificatiesysteem
o Gebaseerd op psychoactieve planten en plantextracten
1.2. Influences from psychology
1.2.1. Experimental psychology
Wundt: psychologie als wetenschappelijke discipline
Kraepelin: gedragsmatige uitkomsten linken aan dosis die de persoon innam: de hoeveelheid
dat men inneemt heeft een effect op het gedrag
- Classificatie van mentale stoornissen (vandaag nogsteeds gebruikt met andere
namen + meer differentiatie)
o Twee hoofdcategorieën: dementia praecox (psychose) en manisch-
depressieve waanzin (bipolaire stoornis)
o Ontstaan van diagnostische criteria
4
1. History of psychofarmacology (part 1) .................................................................................................... 3
1.1. Ancient history ..................................................................................................................................... 3
1.2. Influences from psychology .................................................................................................................. 4
1.2.1. Experimental psychology ................................................................................................................ 4
1.2.2. Comparative psychology ................................................................................................................. 6
1.2.3. Behavioural psychology................................................................................................................... 6
1.3. Example hebbian learning .................................................................................................................... 7
1.3.1. Explaining classical conditioning ..................................................................................................... 8
1.3.2. Explaining the Placebo Effect ........................................................................................................ 10
1.3.3. Application: placebo-controlled dose reduction (PCDR) ............................................................... 10
2. History of psychopharmacology (part 2) ............................................................................................... 12
2.1. Influences from psychiatry ................................................................................................................. 12
2.1.1. Early pharmacotherapy ................................................................................................................. 12
2.1.2. Experimenting with hallucinogenics.............................................................................................. 13
2.1.3. The first ‘antidepressant’ .............................................................................................................. 14
2.1.4. The revolutionary decade ............................................................................................................. 15
2.2. In conclusion....................................................................................................................................... 17
3. Behavioral neuroscience ....................................................................................................................... 19
3.1. Anatomy & organization of the nervous system ................................................................................ 19
3.1.1. Different nervous systems ............................................................................................................ 19
3.1.2. What are cells made of? ................................................................................................................ 21
3.1.3. Neurons: specialized cells ............................................................................................................. 22
3.2. Origin of signals ................................................................................................................................. 23
3.2.1. What makes our brain tick? .......................................................................................................... 23
3.3. Neural communication ....................................................................................................................... 24
3.3.1. Situating biochemical signal processing ........................................................................................ 24
3.3.2. Membrane potentials .................................................................................................................... 24
4. Behavioral neuroscience (part 2)........................................................................................................... 27
4.1. Neural communication ....................................................................................................................... 27
4.1.1. Synaptic communication ............................................................................................................... 27
4.1.2. Endocrinergic communication ...................................................................................................... 30
5. Pharmacokinetics .................................................................................................................................. 33
5.1. General framework ............................................................................................................................ 33
5.2. Pharmacokinetics ............................................................................................................................... 34
5.2.1. Routes of administration ............................................................................................................... 34
5.2.2. Absorption & distribution ............................................................................................................. 37
5.2.3. Depot binding ................................................................................................................................ 39
5.2.4. Inactivation & biotransformation .................................................................................................. 39
5.2.5. Excretion........................................................................................................................................ 41
6. Pharmacodynamics ............................................................................................................................... 42
6.1. Drug categorization ........................................................................................................................... 42
1
, 6.2. From synaptic activity… ..................................................................................................................... 42
6.2.1. Drugs as ligands ............................................................................................................................. 43
6.2.2. Physiological responses of receptors ............................................................................................ 44
6.2.3. Dynamic reactions ......................................................................................................................... 47
6.3. To behavioral effects (niet kennen, geen examenvragen over) ......................................................... 49
6.3.1. From drug actions to drug effects ................................................................................................. 49
7. Drug abuse, addicition and dependency ............................................................................................... 52
7.1. Characteristics .................................................................................................................................... 52
7.2. Biopsychosocial mechanisms ............................................................................................................. 53
7.2.1. Mesolimbic DA-pathway (reward mechanisms) ........................................................................... 53
7.2.2. Cravings & operant conditioning ................................................................................................... 57
7.2.3. Social network hypothesis............................................................................................................. 57
7.3. Therapeutic actions ............................................................................................................................ 57
7.4. Drug scheduling systems & policies ................................................................................................... 58
8. Therapy adherence (zelfstudie) ............................................................................................................. 60
8.1. Defining therapy (non)adherence ...................................................................................................... 60
8.2. Factors related to therapy (non)adherence ....................................................................................... 61
8.3. Societal problems related to therapy (non)adherence ....................................................................... 62
8.4. The case of Scott Martin .................................................................................................................... 62
8.4.1. Getting to know Scott ................................................................................................................... 62
8.4.2. Treatment adherence: a new hope ............................................................................................... 63
8.4.3. The short-term effects of Lithium ................................................................................................. 63
8.4.4. The 6-week follow-up.................................................................................................................... 63
8.4.5. Putting strain on Scott’s treatment adherence ............................................................................. 63
8.4.6. Remarkable effects come in small packages ................................................................................. 63
8.5. How to improve therapy adherence ................................................................................................... 64
9. Repercussions of Medicalization: a topical discussion on other factors influencing therapy
(non)adherence.............................................................................................................................................. 65
9.1. Ethical marketing ............................................................................................................................... 66
9.1.1. Selling products with medical labels ............................................................................................. 66
9.1.2. Implications for Pharma industry .................................................................................................. 67
9.1.3. Ethical correct reporting ............................................................................................................... 67
9.2. Use, misuse and abuse ....................................................................................................................... 69
9.2.1. Antidepressants on the rise… ........................................................................................................ 69
10. From (pre)clinical research to pharmacy........................................................................................... 71
10.1. Research cycle .................................................................................................................................... 71
10.1.1. Preclinical research ................................................................................................................... 71
10.1.2. Clinical research, phase I, II and III ........................................................................................... 72
10.1.3. FDA assessment ........................................................................................................................ 74
10.1.4. Post-marketing research, phase IV ........................................................................................... 74
10.2. Topical discussions on… ..................................................................................................................... 74
10.2.1. Animal research ethics ............................................................................................................. 74
10.2.2. Fast-track research ................................................................................................................... 75
2
,Psychofarmacologie
1. History of psychofarmacology (part 1)
1.1. Ancient history
Periode voor experimentele psychologie (19e eeuw), begin van evidence-based medicine: 3
mannen gingen experimenteren (op zichzelf) met medicatie
- Pierre-Alexandre Charvet
- Jacques-Joseph Moreau de Tours
- Paolo Mantegazza
Jean-Baptise Charvet:
- Opium crisis: recreatief gebruik zorgde voor maatschappelijke impact
o Uitwisseling in verschillende landen, gebruik vooral voor pijnstilling en
relaxatie
- Interesseveld: opium/heroïne/morfine > effect op mensen en dieren
- Eerste systematische, farmacologische studies: gebruik condities, observaties, …
o Gedrag > fysiologie
o Systematisch testen op dieren (honden, duiven en konijnen)
o Zelf-experimenten: hij geloofde dat opium veel potentie kon hebben in de
medicatiewereld voor de maatschappij
▪ Effecten van euforie, pijnstilling en sufheid
Jacques-Joseph Moreau de Tours
- Van engelen-en-demonen naar humanistische aanpak
o Opsluiten >< behandelen
- Interesseveld: hasj
o Onderzoek van effecten die hij bij zichzelf en anderen vaststelde
o Mensen die hier veel van innamen kregen ‘psychotic craziness’ of werden
‘delusional’
▪ Effecten van hasj waren gelijkaardig aan psychotische episodes van
patiënten met schizofrenie
- Eerste op stoffen gebaseerde model van psychische aandoeningen
o Gedragsmatige vergelijking
o Hypothese over het central zenuwstelsel
DR. Philippe Pinel: mentaal zieke patiënten werden eerst geïsoleerd uit de maatschappij, hij
begreep dat dit niet de oplossing was en deze mensen ook gewoon mensen waren en deze
hulp moesten krijgen.
Paolo Mantegazza
- Antroplogische exploitaties in Zuid-Amerika
o Stammen en het gebruik van cocabladeren (Inca’s)
- Interesseveld: effecten cocaïne/cocabladeren op zichzelf en anderen
- Zelfexperimenten (werd verslaafd), maar kan voordelig zijn voor maatschappij in
mate
o Opbeurende eigenschappen van coca
o Link met ‘psychotische gekte’
3
, o Enthousiaste supporter van coca, was te progressief want hij haalde vooral de
positieve effecten aan en negeerde de negatieve verslavende effecten > kreeg
veel kritiek in de toekomst
▪ Je bent heel productief onder invloed van coca, maar werk is minder
kwaliteitsvol
- Eerste poging tot classificatiesysteem
o Gebaseerd op psychoactieve planten en plantextracten
1.2. Influences from psychology
1.2.1. Experimental psychology
Wundt: psychologie als wetenschappelijke discipline
Kraepelin: gedragsmatige uitkomsten linken aan dosis die de persoon innam: de hoeveelheid
dat men inneemt heeft een effect op het gedrag
- Classificatie van mentale stoornissen (vandaag nogsteeds gebruikt met andere
namen + meer differentiatie)
o Twee hoofdcategorieën: dementia praecox (psychose) en manisch-
depressieve waanzin (bipolaire stoornis)
o Ontstaan van diagnostische criteria
4
