23 Antipsychotic drugs Flashcards
23.01 FIRST-GENERATION ANTIPSYCHOTICS
Phenothiazines: chlorpromazine, fluphenazine, prochlorperazine - actions
antipsychotic
apathy and inertia
reduced aggression
antiemetic
23.01 FIRST-GENERATION ANTIPSYCHOTICS
Phenothiazines: chlorpromazine, fluphenazine, prochlorperazine - MOA
competitive antagonism of dopamine D2 receptors in the mesolimbic/mesocortical pathways
clinical benefits are delayed although receptor block is immediate, suggesting that more complex changes in neurotransmission occur
23.01 FIRST-GENERATION ANTIPSYCHOTICS
Phenothiazines: chlorpromazine, fluphenazine, prochlorperazine - abs/distrib/elim
given orally or by IM injection
half-life 16-32h
fluphenazine decanoate available as IM depot formulation
23.01 FIRST-GENERATION ANTIPSYCHOTICS
Phenothiazines: chlorpromazine, fluphenazine, prochlorperazine - clinical use
schizophrenia (less effective against negative symptoms) and other psychotic states
manic phase of bipolar disorder
Tourette’s syndrome
nausea and vomiting
aggression in children
persistent hiccups
23.01 FIRST-GENERATION ANTIPSYCHOTICS
Phenothiazines: chlorpromazine, fluphenazine, prochlorperazine - adverse effects
marked sedation
extrapyramidal symptoms (dystonias and parkinsonian symptoms) reduced by antimuscarinic action
endocrine effects (e.g. galactorrhoea, gynaecomastia, weight gain)
antimuscarinic effects (e.g. constipation, dry mouth)
hypotension (α-adrenoceptor antagonism)
rare, but serious, neuroleptic malignant syndrome
hypersensitivity reactions
agranulocytosis
hepatotoxicity
23.02 FIRST-GENERATION ANTIPSYCHOTICS
Butyrophenone: haloperidol - actions
antipsychotic
apathy
reduced aggression
antiemetic
23.02 FIRST-GENERATION ANTIPSYCHOTICS
Butyrophenone: haloperidol - MOA
competitive antagonism of dopamine D2 receptors in the mesolimbic/mesocortical pathways
clinical benefits are delayed although receptor block is immediate, suggesting that more complex changes in neurotransmission occur
higher potency compared to chlorpromazine
23.02 FIRST-GENERATION ANTIPSYCHOTICS
Butyrophenone: haloperidol - abs/distrib/elim
given orally or IM (also IM depot)
half-life 12-36h
23.02 FIRST-GENERATION ANTIPSYCHOTICS
Butyrophenone: haloperidol - clinical use
schizophrenia (less effective against negative symptoms) and other psychotic states
mania
Tourette’s syndrome
nausea and vomiting
aggressive behaviour
persistent hiccups
23.02 FIRST-GENERATION ANTIPSYCHOTICS
Butyrophenone: haloperidol - adverse effects
marked extrapyramidal symptoms
hyperprolactinaemia
little sedative, hypotensive or antimuscarinic actions neuroleptic malignant syndrome
23.02 FIRST-GENERATION ANTIPSYCHOTICS
Butyrophenone: haloperidol - special notes
contraindicated in patients with Parkinson’s disease
23.03 FIRST-GENERATION ANTIPSYCHOTICS
Thioxanthenes: flupentixol, zuclopentixol - actions
antipsychotic
antidepressant (tricyclic-like) activity
23.03 FIRST-GENERATION ANTIPSYCHOTICS
Thioxanthenes: flupentixol, zuclopentixol - MOA
competitive antagonism of dopamine D2 receptors in the mesolimbic/mesocortical pathways
clinical benefits are delayed although receptor block is immediate, suggesting that more complex changes in neurotransmission occur
23.03 FIRST-GENERATION ANTIPSYCHOTICS
Thioxanthenes: flupentixol, zuclopentixol - abs/distrib/elim
effective orally but most often given by IM depot
half-life 19-39h
23.03 FIRST-GENERATION ANTIPSYCHOTICS
Thioxanthenes: flupentixol, zuclopentixol - clinical use
schizophrenia and other psychotic states
bipolar disorder
depression
23.03 FIRST-GENERATION ANTIPSYCHOTICS
Thioxanthenes: flupentixol, zuclopentixol - adverse effects
extrapyramidal symptoms
hyperprolactinaemia
neuroleptic malignant syndrome
23.04 SECOND-GENERATION ANTIPSYCHOTICS
Clozapine, olanzapine - actions
antipsychotic
effective against positive and negative symptoms
23.04 SECOND-GENERATION ANTIPSYCHOTICS
Clozapine, olanzapine - MOA
MOA less well established than for typical agents
action on 5-HT2A receptors may be important
antagonist action at 5-HT2, muscarinic, H1 histamine receptors and α1 adrenoceptors
higher affinity for D4 than other dopamine receptors
23.04 SECOND-GENERATION ANTIPSYCHOTICS
Clozapine, olanzapine - abs/distrib/elim
orally active
half-life 12h
23.04 SECOND-GENERATION ANTIPSYCHOTICS
Clozapine, olanzapine - clinical use
schizophrenia
because of haematological toxicity, clozapine is used mainly in patients resistant to other drugs, for whom it is very effective
olanzapine is also used for manic episodes and bipolar disorder
23.04 SECOND-GENERATION ANTIPSYCHOTICS
Clozapine, olanzapine - adverse effects
little extrapyramidal symptoms (reduced D2 antagonism coupled with antimuscarinic action)
antimuscarinic actions (e.g. constipation)
agranulocytosis (not with olanzapine) - blood testing needed
sedation
epileptic seizures
weight gain (more than with other antipsychotics) hyperglycaemia
23.05 SECOND-GENERATION ANTIPSYCHOTICS
Risperidone - actions
antipsychotic
effective against positive and negative symptoms of schizophrenia
23.05 SECOND-GENERATION ANTIPSYCHOTICS
Risperidone - MOA
potent antagonist of D2 and 5-HT2A receptors and α1 adrenoceptors
as for other atypical agents, a combination of D2 and 5-HT2A antagonism may be important in modifying activity in the mesolimbic/mesocortical pathways
23.05 SECOND-GENERATION ANTIPSYCHOTICS
Risperidone - abs/distrib/elim
given orally or by IM depot
hepatic P450 metabolism
half-life 3-20h
active metabolite is longer acting
23.05 SECOND-GENERATION ANTIPSYCHOTICS
Risperidone - clinical use
schizophrenia and other psychotic states
manic phase of bipolar disorder
23.05 SECOND-GENERATION ANTIPSYCHOTICS
Risperidone - adverse effects
extrapyramidal symptoms (more than with other atypicals)
insomnia and sedation
anxiety
hyperprolactinaemia
weight gain
hypotension
23.06 SECOND-GENERATION ANTIPSYCHOTICS
Quetiapine - actions
antipsychotic
effective against positive and negative symptoms
23.06 SECOND-GENERATION ANTIPSYCHOTICS
Quetiapine - MOA
competitive antagonism of dopamine D2 and 5-HT2A receptors in the mesolimbic/mesocortical pathways
antagonism of H1 histamine receptors may underlie sedative action
23.06 SECOND-GENERATION ANTIPSYCHOTICS
Quetiapine - abs/distrib/elim
given orally
short (6h) half-life
23.06 SECOND-GENERATION ANTIPSYCHOTICS
Quetiapine - clinical use
schizophrenia and other psychotic states
bipolar disorder
23.06 SECOND-GENERATION ANTIPSYCHOTICS
Quetiapine - adverse effects
minor extrapyramidal symptoms
sedation
hyperprolactinaemia
weight gain
postural hypotension
constipation, dry mouth (antimuscarinic actions)
rarely, neuroleptic malignant syndrome
23.07 SECOND-GENERATION ANTIPSYCHOTICS
Aripiprazole - actions
antipsychotic
effective against positive and negative symptoms
23.07 SECOND-GENERATION ANTIPSYCHOTICS
Aripiprazole - MOA
modification of dopaminergic transmission in the mesolimbic/mesocortical pathways
aripiprazole binds strongly to dopamine D2 receptors but has partial agonist activity, which may explain its low incidence of extrapyramidal symptoms
5-HT2A antagonism is probably important
23.07 SECOND-GENERATION ANTIPSYCHOTICS
Aripiprazole - abs/distrib/elim
given orally
long (75h) half-life
23.07 SECOND-GENERATION ANTIPSYCHOTICS
Aripiprazole - clinical use
schizophrenia and other psychotic states
manic phase of bipolar disorder
23.07 SECOND-GENERATION ANTIPSYCHOTICS
Aripiprazole - adverse effects
fewer side effects than many other antipsychotics, e.g. minor extrapyramidal symptoms (some akathisia), less weight gain, less antimuscarinic, less prolactin secretion
some hypotension and nausea and vomiting
23.08 SECOND-GENERATION ANTIPSYCHOTICS
Amisulpride, sulpiride - actions
antipsychotic
effective against positive and negative symptoms of schizophrenia
23.08 SECOND-GENERATION ANTIPSYCHOTICS
Amisulpride, sulpiride - MOA
dopamine D2 and D3 receptor antagonists
preferential action on dopamine autoreceptors may explain the lower incidence of EPS and effectiveness against −ve symptoms
low affinity for 5-HT, muscarinic, histamine and α1 adrenergic receptors
23.08 SECOND-GENERATION ANTIPSYCHOTICS
Amisulpride, sulpiride - abs/distrib/elim
mostly excreted unchanged in kidney
half-life 12h
23.08 SECOND-GENERATION ANTIPSYCHOTICS
Amisulpride, sulpiride - clinical use
schizophrenia
23.08 SECOND-GENERATION ANTIPSYCHOTICS
Amisulpride, sulpiride - adverse effects
hyperprolactinaemia
insomnia
anxiety
weight gain
constipation and dry mouth
