INHOUD
DEEL 3 ..................................................................................................................................................................... 8
Hoofdstuk 1: depressie ........................................................................................................................................... 8
Neurobiologische oorzaak van depressie ........................................................................................................... 8
Antidepressiva..................................................................................................................................................... 8
Indeling en structuur ....................................................................................................................................... 8
Werkingsmechanisme ..................................................................................................................................... 9
Farmacokinetiek ............................................................................................................................................ 10
Indicaties en bijzondere aspecten van behandeling ..................................................................................... 10
Bijwerkingen/ongewenste effecten .............................................................................................................. 11
Tricyclische antidepressiva (TCA) .............................................................................................................. 11
Antidepressiva inwerkend op neuroreceptoren ....................................................................................... 11
SSRI ............................................................................................................................................................ 11
SNRI ........................................................................................................................................................... 11
Contra-indicaties ........................................................................................................................................... 11
Zwangerschap en lactatie ............................................................................................................................. 11
interacties ..................................................................................................................................................... 12
Hoofdstuk 2: psychose en manie .......................................................................................................................... 13
Inleiding............................................................................................................................................................. 13
Antipsychotica ................................................................................................................................................... 14
Structuur ....................................................................................................................................................... 14
Werkingsmechanisme ................................................................................................................................... 14
Farmacokinetiek ............................................................................................................................................ 15
Farmacodynamiek ......................................................................................................................................... 15
Indicaties ....................................................................................................................................................... 15
Bijwerkingen/ongewenste effecten .............................................................................................................. 15
Cardiovasculair, cerebrovasculair ............................................................................................................. 15
Neurologisch ............................................................................................................................................. 15
Metabool, endocrien................................................................................................................................. 16
Hematologisch .......................................................................................................................................... 16
Gastro-intestinaal, hepatisch .................................................................................................................... 16
Andere ....................................................................................................................................................... 16
Contra-indicaties ........................................................................................................................................... 16
Interacties ..................................................................................................................................................... 16
Praktijk: opstarten van antipsychotica .......................................................................................................... 16
Lithium .............................................................................................................................................................. 17
1
, Werkingsmechanisme ................................................................................................................................... 17
Farmacokinetiek ............................................................................................................................................ 17
Bijwerkingen/ongewenste effecten .............................................................................................................. 17
Contra-indicaties ........................................................................................................................................... 17
Interacties ..................................................................................................................................................... 17
Intoxicatie...................................................................................................................................................... 18
Alternatief bij bipolaire stoornis ................................................................................................................... 18
Hoofdstuk 3: epilepsie .......................................................................................................................................... 19
Inleiding............................................................................................................................................................. 19
Anti-epileptica ................................................................................................................................................... 19
Structuur ....................................................................................................................................................... 19
Werkingsmechanisme ................................................................................................................................... 19
Via blokkering Na-kanalen ................................................................................................................................ 20
Fenytoïne ...................................................................................................................................................... 20
Farmacokinetiek ........................................................................................................................................ 20
Bijwerkingen/ongewenste effecten .......................................................................................................... 20
Interacties ................................................................................................................................................. 20
Carbamazepine en oxcarbazepine ................................................................................................................ 20
Werkingsmechanisme ............................................................................................................................... 21
Farmacokinetiek ........................................................................................................................................ 21
Therapeutische concentraties ................................................................................................................... 21
Bijwerkingen/ongewenste effecten .......................................................................................................... 21
Interacties ................................................................................................................................................. 21
Lamotrigine ................................................................................................................................................... 21
Werkingsmechanisme ............................................................................................................................... 21
Farmacokinetiek ........................................................................................................................................ 21
Bijwerkingen/ongewenste effecten .......................................................................................................... 22
Interacties ................................................................................................................................................. 22
Topiramaat .................................................................................................................................................... 22
Valproaat ....................................................................................................................................................... 22
Werkingsmechanisme ............................................................................................................................... 22
Farmacokinetiek ........................................................................................................................................ 22
Therapeutische concentraties ................................................................................................................... 22
Bijwerkingen/ongewenste effecten .......................................................................................................... 23
Contra-indicaties ....................................................................................................................................... 23
Interacties ................................................................................................................................................. 23
Via GABA ........................................................................................................................................................... 23
2
, Fenobarbital en primidon ............................................................................................................................. 23
Werkingsmechanisme ............................................................................................................................... 23
Farmacokinetiek ........................................................................................................................................ 23
Bijwerkingen/ongewenste effecten .......................................................................................................... 23
Interacties ................................................................................................................................................. 23
Benzodiazepines (midazolam, diazepam, lorazepam) .................................................................................. 24
Werkingsmechanisme ............................................................................................................................... 24
Farmacokinetiek en bijwerkingen ............................................................................................................. 24
Tiagabine, vigabatrine, gabapentine, pregabaline ........................................................................................ 24
Via T-type Ca-kanalen ....................................................................................................................................... 24
Ethosuximide................................................................................................................................................. 24
Werkingsmechanisme ............................................................................................................................... 24
Farmacokinetiek ........................................................................................................................................ 25
Bijwerkingen/ongewenste effecten .......................................................................................................... 25
Andere anti-epileptica....................................................................................................................................... 25
Levetiracetam en brivaracetam .................................................................................................................... 25
Werkingsmechanisme ............................................................................................................................... 25
Farmacokinetiek ........................................................................................................................................ 25
Bijwerkingen/ongewenste effecten .......................................................................................................... 25
Lacosamide.................................................................................................................................................... 26
Werkingsmechanisme ............................................................................................................................... 26
Farmacokinetiek ........................................................................................................................................ 26
Bijwerkingen/ongewenste ........................................................................................................................ 26
Algemene bemerkingen .................................................................................................................................... 26
Hoofdstuk 4: ziekte van parkinson en parkinsonisme .......................................................................................... 27
Inleiding............................................................................................................................................................. 27
L-DOPA .............................................................................................................................................................. 27
Farmacokinetiek ............................................................................................................................................ 27
Interacties ..................................................................................................................................................... 27
Efficaciteit ..................................................................................................................................................... 28
Indicaties ....................................................................................................................................................... 28
Bijwerkingen/ongewenste effecten .............................................................................................................. 28
D2-agonisten...................................................................................................................................................... 28
Farmacokinetiek ............................................................................................................................................ 28
Interacties ..................................................................................................................................................... 29
Efficaciteit ..................................................................................................................................................... 29
Indicaties ....................................................................................................................................................... 29
3
, Bijwerkingen/ongewenste effecten .............................................................................................................. 29
Amantadine ....................................................................................................................................................... 29
Farmacokinetiek ............................................................................................................................................ 29
Interacties ..................................................................................................................................................... 29
Efficaciteit ..................................................................................................................................................... 29
Indicaties ....................................................................................................................................................... 29
COMT-inhibitoren ............................................................................................................................................. 30
Farmacokinetiek ............................................................................................................................................ 30
Interacties ..................................................................................................................................................... 30
Bijwerkingen/ongewenste effecten .............................................................................................................. 30
MAO-B inhibitoren ............................................................................................................................................ 30
Farmacokinetiek ............................................................................................................................................ 30
Interacties ..................................................................................................................................................... 30
Efficaciteit ..................................................................................................................................................... 30
Indicaties ....................................................................................................................................................... 31
Bijwerkingen/ongewenste effecten .............................................................................................................. 31
Antimuscarinica................................................................................................................................................. 31
Farmacokinetiek ............................................................................................................................................ 31
Interacties ..................................................................................................................................................... 31
Efficaciteit ..................................................................................................................................................... 31
Indicaties ....................................................................................................................................................... 31
Bijwerkingen/ongewenste effecten .............................................................................................................. 31
Apomorfine ....................................................................................................................................................... 31
Farmacokinetiek ............................................................................................................................................ 31
Interacties ..................................................................................................................................................... 32
Efficaciteit ..................................................................................................................................................... 32
Indicaties ....................................................................................................................................................... 32
Bijwerkingen/ongewenste effecten .............................................................................................................. 32
Andere behandelingen ...................................................................................................................................... 32
Hoofdstuk 5: andere bewegingsstoornissen ......................................................................................................... 33
Tremor .............................................................................................................................................................. 33
Medicatie-geïnduceerde dyskinesie/dystonie .................................................................................................. 33
Restless legs syndroom ..................................................................................................................................... 33
Hoofdstuk 6: skeletspierrelaxantia ....................................................................................................................... 34
Inleiding............................................................................................................................................................. 34
Diazepam .......................................................................................................................................................... 34
Baclofen ............................................................................................................................................................ 34
4
, Dantroleen ........................................................................................................................................................ 34
Botulinetoxine ................................................................................................................................................... 34
Hoofdstuk 7: ziekte van Alzheimer ....................................................................................................................... 35
Inleiding............................................................................................................................................................. 35
Neurobiologisch mechanisme ........................................................................................................................... 35
Ach-esterase-inhibitoren .................................................................................................................................. 36
Farmacokinetiek ............................................................................................................................................ 36
Indicaties ....................................................................................................................................................... 36
Bijwerkingen/ongewenste effecten .............................................................................................................. 36
NMDA-antagonist (memantine)........................................................................................................................ 36
Farmacokinetiek ............................................................................................................................................ 36
Indicaties ....................................................................................................................................................... 36
Bijwerkingen/ongewenste effecten .............................................................................................................. 36
Hoofdstuk 8: pijn ................................................................................................................................................... 37
Inleiding............................................................................................................................................................. 37
Opioïde analgetica ............................................................................................................................................ 37
Structuur en indeling..................................................................................................................................... 37
Werkingsmechanisme ................................................................................................................................... 38
Farmacokinetiek ............................................................................................................................................ 39
Zuivere opioïd-agonisten (prototype morfine) ............................................................................................. 39
Farmacodynamiek ..................................................................................................................................... 40
Bijwerkingen/ongewenste effecten .......................................................................................................... 40
Tolerantie .................................................................................................................................................. 40
Afhankelijkheid en misbruik ...................................................................................................................... 40
Contra-indicaties ....................................................................................................................................... 41
Morfine ..................................................................................................................................................... 41
Hydromorfon............................................................................................................................................. 41
Oxycodon .................................................................................................................................................. 42
Piritramide ................................................................................................................................................ 42
Fentanyl en andere fenylpiperidines ........................................................................................................ 42
Methadon.................................................................................................................................................. 42
Loperamide ............................................................................................................................................... 42
Zwakkere opioïden ........................................................................................................................................ 42
Codeïne ..................................................................................................................................................... 42
Tramadol ................................................................................................................................................... 43
Tilidine ....................................................................................................................................................... 43
Tapentadol .................................................................................................................................................... 43
5
, Partiële opioïd-agonisten en gemengde agonist-antagonisten .................................................................... 43
Buprenorfine ............................................................................................................................................. 43
Opioïd-antagonisten ..................................................................................................................................... 43
Naloxon ..................................................................................................................................................... 43
Naltrexon................................................................................................................................................... 43
Methylnaltrexon........................................................................................................................................ 44
Lokale anesthetica (LA) ..................................................................................................................................... 44
Stoffen en structuur ...................................................................................................................................... 44
Werkingsmechanisme ................................................................................................................................... 44
Farmacokinetiek ............................................................................................................................................ 44
Gebruik ...................................................................................................................................................... 45
Systeemeffecten: local anesthetic systemic toxicity (LAST) ...................................................................... 45
Kankerpijn ......................................................................................................................................................... 46
Neuropathische pijn .......................................................................................................................................... 46
Algemene bemerkingen .................................................................................................................................... 47
Hoofdstuk 9: hypnotica – anxiolytica .................................................................................................................... 48
Inleiding............................................................................................................................................................. 48
Benzodiazepines ............................................................................................................................................... 48
Structuur ....................................................................................................................................................... 48
Werkingsmechanisme ................................................................................................................................... 48
Effecten ......................................................................................................................................................... 49
Psychotrope effecten ................................................................................................................................ 49
Motorische effecten .................................................................................................................................. 50
Tolerantie .................................................................................................................................................. 50
Afhankelijkheid en misbruik ...................................................................................................................... 51
Toxiciteit .................................................................................................................................................... 52
Andere ....................................................................................................................................................... 52
Farmacokinetiek ............................................................................................................................................ 52
Snelheid..................................................................................................................................................... 52
Duur .......................................................................................................................................................... 52
Interacties ................................................................................................................................................. 52
Indicaties ....................................................................................................................................................... 52
Slapeloosheid ............................................................................................................................................ 53
Angststoornis ............................................................................................................................................ 53
Pre-operatieve sedatie .............................................................................................................................. 53
Epilepsie .................................................................................................................................................... 53
Spierspasmen en spastische toestanden .................................................................................................. 53
6
, Delirium tremens ...................................................................................................................................... 53
Relatieve contra-indicaties............................................................................................................................ 54
Ademhalingsstoornis ................................................................................................................................. 54
Zwangerschap ........................................................................................................................................... 54
Andere ....................................................................................................................................................... 54
bijzonderheden ............................................................................................................................................. 54
Besluit............................................................................................................................................................ 54
Stoffen met analoge werking (z-drugs) ............................................................................................................. 54
Benzodiazepine-antagonist (flumazenil) ........................................................................................................... 54
Indicaties ....................................................................................................................................................... 55
β-blokkers ......................................................................................................................................................... 55
H1-receptor blokkers ......................................................................................................................................... 55
Antidepressiva................................................................................................................................................... 55
Fytotherapeutica ............................................................................................................................................... 55
Melatonine ........................................................................................................................................................ 55
Barbituraten ...................................................................................................................................................... 56
Eigenschappen .............................................................................................................................................. 56
Indicaties ....................................................................................................................................................... 56
7
,FARMACOLOGIE
DEEL 3
HOOFDSTUK 1: DEPRESSIE
Depressie = chronische terugkerende en potentieel levensbedreigende aandoening met een incidentie van 20%
wereldwijd
NEUROBIOLOGISCHE OORZAAK VAN DEPRESSIE
Ontdekking reserpine (antihypertensiva): depletie van mono-amino NT in centrale en perifere neuronen door
inhibitie van opname en opslag van NT in vesikels van zenuwuiteinden
➔ Verstoorde balans van noradrenerge of serotonerge transmissie in CZS ligt aan de basis van depressie
Werking antidepressiva: verhogen concentratie van mono-amino NT in synaptische spleet (SS)
- Remmen heropname NT (bv TCA)
- Remmen afbraak NT (bv monoamine-oxidase remmers)
➔ Verhogen noradrenerge of serotonerge transmissie (of beide)
Opm: niet-selectieve heropname remming treedt onmiddellijk op, terwijl maximale therapeutische werking pas
te zien is na enkele weken
ANTIDEPRESSIVA
INDELING EN STRUCTUUR
Selectieve heropnameremmers
- Selectieve serotonine reuptake inhibitors (SSRI): bv fluoxetine, fluvoxamine, paroxetine, citalopram,
sertraline
o Selectieve inhibitie serotonine reuptake transporter (SERT)
o
- Selectieve noradrenaline reuptake inhibitors: bv reboxetine, (atomoxetine) (behandeling ADHD,
narcolepsie)
o Selectieve inhibitie noradrenaline reuptake transporter (NET)
Niet-selectieve heropnameremmers
- Tricyclische antidepressiva (TCA): bv clomipramine, amitriptyline, imipramine, dosulepine, maprotiline
o Niet-selectieve inhibitie heropname NA en 5-HT
o Bijwerkingen geassocieerd met inhibitie van histaminerge, muscarinerge, adrenerge
receptoren
- Serotonine en noradrenaline reuptake inhibitors (SNRI, dual reuptake inhibitoren): bv venlafaxine,
duloxetine
- Noradrenaline en dopamine reuptake inhibitors (NET en DAT): bv bupropion (ook rookstop)
8
, Enzyme-inhibitoren
- Monoamine-oxidase inhibitoren (MAO-inhibitoren, reversibele MAO-A)
o MAO-A: voorkeur NA, 5-HT (niet-specifiek dopamine, tyramine), bv moclobemide, fenelzine
o MAO-B: voorkeur fenylethylamines (niet-specifiek dopamine, tyramine), bv selegiline
Directe werking op verschillende neuroreceptoren
- Bv mianserine, mirtazapine, trazodon, agomelatine
o Mirtazapine
▪ Antidepressief: antagonist PRE α2-receptoren, inhibitie POST serotonine en H1-
receptoren
▪ Verbetert slaap en eetlust
o Trazodon
▪ Minder antidepressiva, verbetert slaap
o Agomelatine
▪ Melatonerge agonist: stimulatie MT1 en MT2-receptoren (normaal endogeen
melatonine)
▪ 5-HT2C-antagonist: stimulatie 5-HT2C-receptoren (normaal endogeen serotonine)
- Betere tolerantie
- Toegenomen veiligheid bij overdosis
- Kleinere kans op interacties
➔ Beginnen met nieuwere producten en later met 1e generatie (TCA, MAO-inhibitoren)
Andere antidepressiva
- Vortioxetine
o Regulatie serotonine receptor activiteit, inhibitie SERT
o Regulatie dopamine, noradrenaline
- Esketamine
o Niet-selectief, niet-competitieve antagonist van N-methyl-D-aspartaat (NMDA) receptor
o Bij majeure depressie
o Combinatietherapie met SSRI of SNRI (na falen van 2 andere behandelingen)
o Bijwerkingen: abusus (misbruik), hypertensie, dissociatie
- Sint-Janskruid
o Bij milde tot matige depressie
o Potente pan-inductor van CYP2C9, CYP2C19, CYP3A4 en P-gp
o Bijwerkingen: doorbraakbloedingen, ongewenste zwangerschap (bij combinatie
anticonceptie), verminderde werkzaamheid VKA
WERKINGSMECHANISME
Werking door inhibitie van noradrenaline- of serotonine-reuptake transporter (NET, SERT)
- Uitz MAO-inhibitoren en direct werkend op neuroreceptoren
- Membraaneiwitten: transport van NA, serotonine, dopamine tegen concentratiegradiënt in
→ heropname uit SS (inhibitie door antidepressiva)
Blokkeren van NET of SERT is niet voldoende voor de antidepressieve werking → ook aanpassingen in
signaaltransductie van PRE en POST serotonine-receptoren
9
DEEL 3 ..................................................................................................................................................................... 8
Hoofdstuk 1: depressie ........................................................................................................................................... 8
Neurobiologische oorzaak van depressie ........................................................................................................... 8
Antidepressiva..................................................................................................................................................... 8
Indeling en structuur ....................................................................................................................................... 8
Werkingsmechanisme ..................................................................................................................................... 9
Farmacokinetiek ............................................................................................................................................ 10
Indicaties en bijzondere aspecten van behandeling ..................................................................................... 10
Bijwerkingen/ongewenste effecten .............................................................................................................. 11
Tricyclische antidepressiva (TCA) .............................................................................................................. 11
Antidepressiva inwerkend op neuroreceptoren ....................................................................................... 11
SSRI ............................................................................................................................................................ 11
SNRI ........................................................................................................................................................... 11
Contra-indicaties ........................................................................................................................................... 11
Zwangerschap en lactatie ............................................................................................................................. 11
interacties ..................................................................................................................................................... 12
Hoofdstuk 2: psychose en manie .......................................................................................................................... 13
Inleiding............................................................................................................................................................. 13
Antipsychotica ................................................................................................................................................... 14
Structuur ....................................................................................................................................................... 14
Werkingsmechanisme ................................................................................................................................... 14
Farmacokinetiek ............................................................................................................................................ 15
Farmacodynamiek ......................................................................................................................................... 15
Indicaties ....................................................................................................................................................... 15
Bijwerkingen/ongewenste effecten .............................................................................................................. 15
Cardiovasculair, cerebrovasculair ............................................................................................................. 15
Neurologisch ............................................................................................................................................. 15
Metabool, endocrien................................................................................................................................. 16
Hematologisch .......................................................................................................................................... 16
Gastro-intestinaal, hepatisch .................................................................................................................... 16
Andere ....................................................................................................................................................... 16
Contra-indicaties ........................................................................................................................................... 16
Interacties ..................................................................................................................................................... 16
Praktijk: opstarten van antipsychotica .......................................................................................................... 16
Lithium .............................................................................................................................................................. 17
1
, Werkingsmechanisme ................................................................................................................................... 17
Farmacokinetiek ............................................................................................................................................ 17
Bijwerkingen/ongewenste effecten .............................................................................................................. 17
Contra-indicaties ........................................................................................................................................... 17
Interacties ..................................................................................................................................................... 17
Intoxicatie...................................................................................................................................................... 18
Alternatief bij bipolaire stoornis ................................................................................................................... 18
Hoofdstuk 3: epilepsie .......................................................................................................................................... 19
Inleiding............................................................................................................................................................. 19
Anti-epileptica ................................................................................................................................................... 19
Structuur ....................................................................................................................................................... 19
Werkingsmechanisme ................................................................................................................................... 19
Via blokkering Na-kanalen ................................................................................................................................ 20
Fenytoïne ...................................................................................................................................................... 20
Farmacokinetiek ........................................................................................................................................ 20
Bijwerkingen/ongewenste effecten .......................................................................................................... 20
Interacties ................................................................................................................................................. 20
Carbamazepine en oxcarbazepine ................................................................................................................ 20
Werkingsmechanisme ............................................................................................................................... 21
Farmacokinetiek ........................................................................................................................................ 21
Therapeutische concentraties ................................................................................................................... 21
Bijwerkingen/ongewenste effecten .......................................................................................................... 21
Interacties ................................................................................................................................................. 21
Lamotrigine ................................................................................................................................................... 21
Werkingsmechanisme ............................................................................................................................... 21
Farmacokinetiek ........................................................................................................................................ 21
Bijwerkingen/ongewenste effecten .......................................................................................................... 22
Interacties ................................................................................................................................................. 22
Topiramaat .................................................................................................................................................... 22
Valproaat ....................................................................................................................................................... 22
Werkingsmechanisme ............................................................................................................................... 22
Farmacokinetiek ........................................................................................................................................ 22
Therapeutische concentraties ................................................................................................................... 22
Bijwerkingen/ongewenste effecten .......................................................................................................... 23
Contra-indicaties ....................................................................................................................................... 23
Interacties ................................................................................................................................................. 23
Via GABA ........................................................................................................................................................... 23
2
, Fenobarbital en primidon ............................................................................................................................. 23
Werkingsmechanisme ............................................................................................................................... 23
Farmacokinetiek ........................................................................................................................................ 23
Bijwerkingen/ongewenste effecten .......................................................................................................... 23
Interacties ................................................................................................................................................. 23
Benzodiazepines (midazolam, diazepam, lorazepam) .................................................................................. 24
Werkingsmechanisme ............................................................................................................................... 24
Farmacokinetiek en bijwerkingen ............................................................................................................. 24
Tiagabine, vigabatrine, gabapentine, pregabaline ........................................................................................ 24
Via T-type Ca-kanalen ....................................................................................................................................... 24
Ethosuximide................................................................................................................................................. 24
Werkingsmechanisme ............................................................................................................................... 24
Farmacokinetiek ........................................................................................................................................ 25
Bijwerkingen/ongewenste effecten .......................................................................................................... 25
Andere anti-epileptica....................................................................................................................................... 25
Levetiracetam en brivaracetam .................................................................................................................... 25
Werkingsmechanisme ............................................................................................................................... 25
Farmacokinetiek ........................................................................................................................................ 25
Bijwerkingen/ongewenste effecten .......................................................................................................... 25
Lacosamide.................................................................................................................................................... 26
Werkingsmechanisme ............................................................................................................................... 26
Farmacokinetiek ........................................................................................................................................ 26
Bijwerkingen/ongewenste ........................................................................................................................ 26
Algemene bemerkingen .................................................................................................................................... 26
Hoofdstuk 4: ziekte van parkinson en parkinsonisme .......................................................................................... 27
Inleiding............................................................................................................................................................. 27
L-DOPA .............................................................................................................................................................. 27
Farmacokinetiek ............................................................................................................................................ 27
Interacties ..................................................................................................................................................... 27
Efficaciteit ..................................................................................................................................................... 28
Indicaties ....................................................................................................................................................... 28
Bijwerkingen/ongewenste effecten .............................................................................................................. 28
D2-agonisten...................................................................................................................................................... 28
Farmacokinetiek ............................................................................................................................................ 28
Interacties ..................................................................................................................................................... 29
Efficaciteit ..................................................................................................................................................... 29
Indicaties ....................................................................................................................................................... 29
3
, Bijwerkingen/ongewenste effecten .............................................................................................................. 29
Amantadine ....................................................................................................................................................... 29
Farmacokinetiek ............................................................................................................................................ 29
Interacties ..................................................................................................................................................... 29
Efficaciteit ..................................................................................................................................................... 29
Indicaties ....................................................................................................................................................... 29
COMT-inhibitoren ............................................................................................................................................. 30
Farmacokinetiek ............................................................................................................................................ 30
Interacties ..................................................................................................................................................... 30
Bijwerkingen/ongewenste effecten .............................................................................................................. 30
MAO-B inhibitoren ............................................................................................................................................ 30
Farmacokinetiek ............................................................................................................................................ 30
Interacties ..................................................................................................................................................... 30
Efficaciteit ..................................................................................................................................................... 30
Indicaties ....................................................................................................................................................... 31
Bijwerkingen/ongewenste effecten .............................................................................................................. 31
Antimuscarinica................................................................................................................................................. 31
Farmacokinetiek ............................................................................................................................................ 31
Interacties ..................................................................................................................................................... 31
Efficaciteit ..................................................................................................................................................... 31
Indicaties ....................................................................................................................................................... 31
Bijwerkingen/ongewenste effecten .............................................................................................................. 31
Apomorfine ....................................................................................................................................................... 31
Farmacokinetiek ............................................................................................................................................ 31
Interacties ..................................................................................................................................................... 32
Efficaciteit ..................................................................................................................................................... 32
Indicaties ....................................................................................................................................................... 32
Bijwerkingen/ongewenste effecten .............................................................................................................. 32
Andere behandelingen ...................................................................................................................................... 32
Hoofdstuk 5: andere bewegingsstoornissen ......................................................................................................... 33
Tremor .............................................................................................................................................................. 33
Medicatie-geïnduceerde dyskinesie/dystonie .................................................................................................. 33
Restless legs syndroom ..................................................................................................................................... 33
Hoofdstuk 6: skeletspierrelaxantia ....................................................................................................................... 34
Inleiding............................................................................................................................................................. 34
Diazepam .......................................................................................................................................................... 34
Baclofen ............................................................................................................................................................ 34
4
, Dantroleen ........................................................................................................................................................ 34
Botulinetoxine ................................................................................................................................................... 34
Hoofdstuk 7: ziekte van Alzheimer ....................................................................................................................... 35
Inleiding............................................................................................................................................................. 35
Neurobiologisch mechanisme ........................................................................................................................... 35
Ach-esterase-inhibitoren .................................................................................................................................. 36
Farmacokinetiek ............................................................................................................................................ 36
Indicaties ....................................................................................................................................................... 36
Bijwerkingen/ongewenste effecten .............................................................................................................. 36
NMDA-antagonist (memantine)........................................................................................................................ 36
Farmacokinetiek ............................................................................................................................................ 36
Indicaties ....................................................................................................................................................... 36
Bijwerkingen/ongewenste effecten .............................................................................................................. 36
Hoofdstuk 8: pijn ................................................................................................................................................... 37
Inleiding............................................................................................................................................................. 37
Opioïde analgetica ............................................................................................................................................ 37
Structuur en indeling..................................................................................................................................... 37
Werkingsmechanisme ................................................................................................................................... 38
Farmacokinetiek ............................................................................................................................................ 39
Zuivere opioïd-agonisten (prototype morfine) ............................................................................................. 39
Farmacodynamiek ..................................................................................................................................... 40
Bijwerkingen/ongewenste effecten .......................................................................................................... 40
Tolerantie .................................................................................................................................................. 40
Afhankelijkheid en misbruik ...................................................................................................................... 40
Contra-indicaties ....................................................................................................................................... 41
Morfine ..................................................................................................................................................... 41
Hydromorfon............................................................................................................................................. 41
Oxycodon .................................................................................................................................................. 42
Piritramide ................................................................................................................................................ 42
Fentanyl en andere fenylpiperidines ........................................................................................................ 42
Methadon.................................................................................................................................................. 42
Loperamide ............................................................................................................................................... 42
Zwakkere opioïden ........................................................................................................................................ 42
Codeïne ..................................................................................................................................................... 42
Tramadol ................................................................................................................................................... 43
Tilidine ....................................................................................................................................................... 43
Tapentadol .................................................................................................................................................... 43
5
, Partiële opioïd-agonisten en gemengde agonist-antagonisten .................................................................... 43
Buprenorfine ............................................................................................................................................. 43
Opioïd-antagonisten ..................................................................................................................................... 43
Naloxon ..................................................................................................................................................... 43
Naltrexon................................................................................................................................................... 43
Methylnaltrexon........................................................................................................................................ 44
Lokale anesthetica (LA) ..................................................................................................................................... 44
Stoffen en structuur ...................................................................................................................................... 44
Werkingsmechanisme ................................................................................................................................... 44
Farmacokinetiek ............................................................................................................................................ 44
Gebruik ...................................................................................................................................................... 45
Systeemeffecten: local anesthetic systemic toxicity (LAST) ...................................................................... 45
Kankerpijn ......................................................................................................................................................... 46
Neuropathische pijn .......................................................................................................................................... 46
Algemene bemerkingen .................................................................................................................................... 47
Hoofdstuk 9: hypnotica – anxiolytica .................................................................................................................... 48
Inleiding............................................................................................................................................................. 48
Benzodiazepines ............................................................................................................................................... 48
Structuur ....................................................................................................................................................... 48
Werkingsmechanisme ................................................................................................................................... 48
Effecten ......................................................................................................................................................... 49
Psychotrope effecten ................................................................................................................................ 49
Motorische effecten .................................................................................................................................. 50
Tolerantie .................................................................................................................................................. 50
Afhankelijkheid en misbruik ...................................................................................................................... 51
Toxiciteit .................................................................................................................................................... 52
Andere ....................................................................................................................................................... 52
Farmacokinetiek ............................................................................................................................................ 52
Snelheid..................................................................................................................................................... 52
Duur .......................................................................................................................................................... 52
Interacties ................................................................................................................................................. 52
Indicaties ....................................................................................................................................................... 52
Slapeloosheid ............................................................................................................................................ 53
Angststoornis ............................................................................................................................................ 53
Pre-operatieve sedatie .............................................................................................................................. 53
Epilepsie .................................................................................................................................................... 53
Spierspasmen en spastische toestanden .................................................................................................. 53
6
, Delirium tremens ...................................................................................................................................... 53
Relatieve contra-indicaties............................................................................................................................ 54
Ademhalingsstoornis ................................................................................................................................. 54
Zwangerschap ........................................................................................................................................... 54
Andere ....................................................................................................................................................... 54
bijzonderheden ............................................................................................................................................. 54
Besluit............................................................................................................................................................ 54
Stoffen met analoge werking (z-drugs) ............................................................................................................. 54
Benzodiazepine-antagonist (flumazenil) ........................................................................................................... 54
Indicaties ....................................................................................................................................................... 55
β-blokkers ......................................................................................................................................................... 55
H1-receptor blokkers ......................................................................................................................................... 55
Antidepressiva................................................................................................................................................... 55
Fytotherapeutica ............................................................................................................................................... 55
Melatonine ........................................................................................................................................................ 55
Barbituraten ...................................................................................................................................................... 56
Eigenschappen .............................................................................................................................................. 56
Indicaties ....................................................................................................................................................... 56
7
,FARMACOLOGIE
DEEL 3
HOOFDSTUK 1: DEPRESSIE
Depressie = chronische terugkerende en potentieel levensbedreigende aandoening met een incidentie van 20%
wereldwijd
NEUROBIOLOGISCHE OORZAAK VAN DEPRESSIE
Ontdekking reserpine (antihypertensiva): depletie van mono-amino NT in centrale en perifere neuronen door
inhibitie van opname en opslag van NT in vesikels van zenuwuiteinden
➔ Verstoorde balans van noradrenerge of serotonerge transmissie in CZS ligt aan de basis van depressie
Werking antidepressiva: verhogen concentratie van mono-amino NT in synaptische spleet (SS)
- Remmen heropname NT (bv TCA)
- Remmen afbraak NT (bv monoamine-oxidase remmers)
➔ Verhogen noradrenerge of serotonerge transmissie (of beide)
Opm: niet-selectieve heropname remming treedt onmiddellijk op, terwijl maximale therapeutische werking pas
te zien is na enkele weken
ANTIDEPRESSIVA
INDELING EN STRUCTUUR
Selectieve heropnameremmers
- Selectieve serotonine reuptake inhibitors (SSRI): bv fluoxetine, fluvoxamine, paroxetine, citalopram,
sertraline
o Selectieve inhibitie serotonine reuptake transporter (SERT)
o
- Selectieve noradrenaline reuptake inhibitors: bv reboxetine, (atomoxetine) (behandeling ADHD,
narcolepsie)
o Selectieve inhibitie noradrenaline reuptake transporter (NET)
Niet-selectieve heropnameremmers
- Tricyclische antidepressiva (TCA): bv clomipramine, amitriptyline, imipramine, dosulepine, maprotiline
o Niet-selectieve inhibitie heropname NA en 5-HT
o Bijwerkingen geassocieerd met inhibitie van histaminerge, muscarinerge, adrenerge
receptoren
- Serotonine en noradrenaline reuptake inhibitors (SNRI, dual reuptake inhibitoren): bv venlafaxine,
duloxetine
- Noradrenaline en dopamine reuptake inhibitors (NET en DAT): bv bupropion (ook rookstop)
8
, Enzyme-inhibitoren
- Monoamine-oxidase inhibitoren (MAO-inhibitoren, reversibele MAO-A)
o MAO-A: voorkeur NA, 5-HT (niet-specifiek dopamine, tyramine), bv moclobemide, fenelzine
o MAO-B: voorkeur fenylethylamines (niet-specifiek dopamine, tyramine), bv selegiline
Directe werking op verschillende neuroreceptoren
- Bv mianserine, mirtazapine, trazodon, agomelatine
o Mirtazapine
▪ Antidepressief: antagonist PRE α2-receptoren, inhibitie POST serotonine en H1-
receptoren
▪ Verbetert slaap en eetlust
o Trazodon
▪ Minder antidepressiva, verbetert slaap
o Agomelatine
▪ Melatonerge agonist: stimulatie MT1 en MT2-receptoren (normaal endogeen
melatonine)
▪ 5-HT2C-antagonist: stimulatie 5-HT2C-receptoren (normaal endogeen serotonine)
- Betere tolerantie
- Toegenomen veiligheid bij overdosis
- Kleinere kans op interacties
➔ Beginnen met nieuwere producten en later met 1e generatie (TCA, MAO-inhibitoren)
Andere antidepressiva
- Vortioxetine
o Regulatie serotonine receptor activiteit, inhibitie SERT
o Regulatie dopamine, noradrenaline
- Esketamine
o Niet-selectief, niet-competitieve antagonist van N-methyl-D-aspartaat (NMDA) receptor
o Bij majeure depressie
o Combinatietherapie met SSRI of SNRI (na falen van 2 andere behandelingen)
o Bijwerkingen: abusus (misbruik), hypertensie, dissociatie
- Sint-Janskruid
o Bij milde tot matige depressie
o Potente pan-inductor van CYP2C9, CYP2C19, CYP3A4 en P-gp
o Bijwerkingen: doorbraakbloedingen, ongewenste zwangerschap (bij combinatie
anticonceptie), verminderde werkzaamheid VKA
WERKINGSMECHANISME
Werking door inhibitie van noradrenaline- of serotonine-reuptake transporter (NET, SERT)
- Uitz MAO-inhibitoren en direct werkend op neuroreceptoren
- Membraaneiwitten: transport van NA, serotonine, dopamine tegen concentratiegradiënt in
→ heropname uit SS (inhibitie door antidepressiva)
Blokkeren van NET of SERT is niet voldoende voor de antidepressieve werking → ook aanpassingen in
signaaltransductie van PRE en POST serotonine-receptoren
9
