schizo Flashcards
what is defining features in psychotic disorders
patients experience delusions or hallucinations but have lost insight into condition
how are psychotic disorders treated
all psychotic disorders are treated with neuroleptics (antipsychotics)
what are positive/ negative symptoms of schizo
positive (caused by excess excitatory neurotransmission): abnormal thoughts, perceptions, language and behaviour; including delusions, hallucinations and catatonic behaviour
negative (excess inhibitory neurotransmission): restrictions in range and intensity of emotional expression, communication, body language and lack of interest in activities that were once enjoyable
what are possible neuronal origins of scz
different theories:
excessive 5HT transmission in brain; all drugs which activate 5HT (2A/2C) receptors are hallucinogenic e.g LSD
excessive dopaminergic transmission in brain:
all neuroleptic drugs show some degree of D2 antagonism, however no good evidence for overactive DA function in schizo
amphetamine induced psychosis strongly resembles schizo, amphetamine causes increase in concentrations in dopamine, it is possible that dopamine simply mediates effects/ symptoms caused by other malfunctions
glutamate is also implicated:
NMDA receptor antagonists such as ketamine and phencyclidine produce symptoms very similar to schizo, phencyclidine is regarded as best research tool in animal models of schizo
what are neuronal targets of schizo treatment
it is generally assumed neuroleptics act primarily by antagonising the action of dopamine in its mesolimbic and mesocortical pathways, these are targets for drug action
neuroleptics also disrupt other dopaminergic pathways in brain
what are side effects of all neuroleptics
extrapyramidal side effects that emulate parkinsonism (pseudo-parkinsonism) which include release of prolactin
older/typical neuroleptics tendency to produce these side effects increases with antipsychotic potency and selectivity for D2 antagonism
however there are a few exceptions
what are examples of typical neuroleptics
most neuroleptics are typical neuroleptics
they are:
most phenothiazines e.g chlorpromazine
thioxanthines e.g flupenthixol
butyrophenones e.g haloperidol
what are advantages/disadvantages of typical neuroleptics
advantages: relieve positive symptoms, have sedative effect (may be disadvantage)
disadvantages:
ineffective against negative symptoms
extrapyramidal side effects such as dystonia and akathisia,
tardive dyskinesia (repetitive stereotyped movements which can endure after drug treatment has stopped)
hyperlactinaemia: leading to galactorrhea, and amenorrhea (reduced gonadal function resulting in impotence or absence of menstruation)
aplastic anaemia
what is pharmacological profile of typical neuroleptics
antagonists of D2 receptors, H1 receptors, muscarinic receptors and alpha adrenoceptors
specific binding pattern of drug to each receptor determines efficacy and side effects
binding to H1 receptors could explain sedative effects
antagonism of alpha 1 causes hypotension
muscarinic antagonism produces anti cholinergic effects but can also help relieve pseudo parkinsonism caused by dopamine antagonism
what are examples of atypical neuroleptics
dibenzazepine derivates e.g: clozapine
benzisoxazole derivatives e.g risperidone
what are advantages and disadvantages of atypical neuroleptics
advantages: relieve both positive and negative symptoms, can relieve psychosis resistant to typical neuroleptics,
much lower incidence of extrapyramidal side effects and tardive dyskinesia than typical neuroleptics
disadvantages:
dribbling
agranulocytosis (clozapine)
weight gain especially of systematic fat which leads to diabetes and CV disease
concern in fat increase is regarded by some as more problematic than extrapyramidal side effects associated with typical neuroleptics in terms of morbidity and patient compliance
prolongation of cardiac QT interval
what is pharmacological profile of atypical neuroleptics
clozapine:
clozapine shows relatively weak binding to D2 receptors, although it is still effective suggesting D2 antagonism may not be key factor
clozapine is 5HT 2a/2c receptor antagonist, could contribute to antipsychotic effect, also may account for increase in fat
weak partial agonist of 5HT1a receptors, leads to increase of dopamine from mesocortical neurones projecting to frontal cortex, could account for relief of negative symptoms
muscarinic and alpha 2 antagonism: these actions are thought to contribute to the lower incidence of extrapyramidal side effects
atypical neuroleptics only occupy 30% of D2 receptors (weak antagonism)
give and example of a 3rd gen neuroleptic and its effects on receptors
aripiprazole is a 3rd gen neuroleptic
D2 partial agonist (high affinity but low intrinsic activity) so may have physiological antagonistic effects
5HT1a partial agonist
5HT2a weak agonist
what are advantages and disadvantages of a 3rd gen neuroleptic
advantages:
few extrapyramidal side effects (no difference from placebo)
little weight gain and few CV abnormalities
safe in overdose
disadvantages:
hyperprolactinaemia
hypercholesterolaemia
akathisia
