Drugs for Psychosis and Mania Flashcards
What is psychosis?
a mental state in which there is a loss of contact with reality
What is mania?
madness or frenzy accompanied by an elevated or irritable mood, increased energy, reduced need to sleep, exaggerated self-importance, reckless behaviour and thought disturbances
What is schizophrenia?
a chronic disease with the onset in late adolescence/early adulthood and it is highly disabling to social and vocational functioning
What are the 5 domains of schizophrenia symptoms?
- positive symptoms
- negative symptoms
- aggressive symptoms
- cognitive symptoms
- anxiety/depression
What are positive symptoms of schizophrenia?
addition of abnormal behaviours interspersed between periods where negative symptoms dominate
Give examples of positive symptoms of schizophrenia
- delusions (often paranoid)
- hallucinations e.g. exhortatory voices
- thought disorder including feeling that thoughts are controlled by an outside agency
- abnormal behaviours e.g. stereotypical or aggressive behaviours
What are positive symptoms of schizophrenia generally the result of?
increased subcortical release of dopamine, which augments D2 receptor activation and a disturbed cortical pathway through the nucleus accumbens
Give examples of negative symptoms of schizophrenia
- withdrawal from social contacts
- flattening of emotional responses
What are negative symptoms of schizophrenia?
the subtraction of normal behaviours that become more dominant as the disease progresses
What are negative symptoms of schizophrenia generally the result of?
reduced D1 receptor activation in the prefrontal cortex and decreased activity of the nucleus caudatus
What is cognitive dysfunction?
the impairment of selective attention and working memory
Why are cognitive dysfunction symptoms important in schizophrenia?
they predict the level of social and vocational functioning, and hence treatment outcome, better than positive symptoms
What are environmental factors of schizophrenia?
- neurodevelopmental abnormalities
- maternal viral infections during pregnancy
- obstetric complications
What is the onset of schizophrenia in late adolescence consist with?
neurodevelopmental abnormality involving myelination of cortico-cortical pathways
What are the 3 proposed neurochemical theories of schizophrenia?
- dopamine theory
- 5-HT theory
- glutamate theory
What is the dopamine theory?
dysregulation of dopamine activity in the brain plays a central role in the development of symptoms
What is the 5-HT theory?
dysregulation of 5-HT system, particularly involving the 5-HT2A receptor, contributes to the development of symptoms
What is the glutamate theory?
dysregulation of the glutamate neurotransmitter system, particularly involving NMDA receptors, plays a central role in the development of symptoms
What are the 2 key typical antipsychotics?
chlorpromazine and haloperidol
What are the 4 key atypical antipsychotics?
amisulpride, clozapine, olanzapine, risperidone
What do typical antipsychotics do?
control positive symptoms and produce EPS by blocking D2 receptors
What do atypical antipsychotics do?
control positive and negative symptoms and produce less EPS
What EPS does blocking of D2 receptors cause?
- dry mouth, constipation, blurred vision via M1 receptors
- sedation, weight gain via H1 receptors
- postural hypotension, dizziness via alpha-adrenergic receptors
What is chlorpromazine derived from?
antihistamine drugs
What is the most widely used antipyschotic drug and why?
haloperidol since its single selective mechanisms reduce the side effects
What are motor EPS?
dystonias and tardive dyskinesia
What is the cause of motor EPS?
actions on the extrapyramidal motor pathways
What does the extrapyramidal motor pathway involve?
the basal ganglia, including the striatum and substantia nigra
What are the pyramidal motor pathways?
the output from the primary motor cortex via the pyramids of the medulla oblongata to the spinal cord
What is acute dystonia?
a tremor at rest due to D2 antagonism in the nigrostriatal pathway that occurs within the first few weeks of treatment and is reversible when the drug is stopped
What is tardive dyskinesia?
is involuntary movements of the face due to upregulation or super-sensitivity of dopamine receptors
What do many atypical antipsychotics have?
- greater affinity at 5-HT2 receptors
- greater affinity at D4 receptors
- mixed antagonism at α-adrenoceptors, H1 histamine receptors, muscarinic acetylcholine receptors, and 5-HT2 receptors
What is the core MOA of most atypical antipsychotics?
serotonin-dopamine antagonism
How do atypical antipsychotics reduce the incidence of tardive dyskinesia?
they dissociate more rapidly and so are more readily displaced by competition from endogenous dopamine
What are benefits of atypical antipsychotics?
- more effective against negative symptoms e.g. clozapine, olanzapine, risperidone
- ameliorate cognitive dysfunction better than typical antipsychotics e.g. clozapine, risperidone
- better at mood stabilization e.g. clozapine, olanzapine, risperidone
- antagonism at presynaptic 5-HT2 heteroreceptors on dopaminergic terminals may regulate dopamine levels in the PFC
What does combination of atypical antipyschotics with antidepressants do?
stabilise mood but also increase range of adverse effects
What are adverse effects of atypical antipsychotics?
- same EPS as typical antipsychotics
- clozapine-induced agranulocytosis
- hyperglaecemia
- diabetes
- increased prolactin secretion
