Antipsychotics Flashcards
what is psychosis
- a severe disturbance in brain function where normal perception of reality is disrupted
- associated with disorganized behaviour abd difficulties with social interactions
- may experience hallucinations, delusions, suspicion and paranoia
what is schizophrenia
- mind split from reality
- continuous or relapsing episodes pd psycholis (positive symptoms) + negative symptoms
positive symptoms of schizophrenia
- presence of something that shouldn’t be there
- includes hallucinations, paranoia, delusions
- often treatable with antpsychotic drugs
negative symptoms of schizophrenia
- absense of something that should be there
- includes apathy, social withdrawal, extreme inattentiveness
- not easily treatable
- show up later on in the disease
which drugs can induce psychosis
cocaine
amphetamine
PCP
LSD
stimulant induced psychosis (cocaine and amphetamine)
- their use increases dopamine transmission
- can lead to schizophrenia-like symptoms
- can cause hallucinations as a n adverse effect of L-dopa
- *supports the role of dopamine imbalance in psychosis
hallicinogen induced psychosis (PCP and LSD)
- PCP (NMDA antagonist) afefcts glutamate signalling
- LSD (5-HT2A agonist) affects serotonin signalling
- both linked with dopamine neurotransmission
the sopamine hypothesis of psychosis
- too musch dopamine can lead to psychosis
- drugs that increase dopamine could produce psychosis
- dopamine receptor density increases in those with schizophrenia
- antipsychotics block D2 receptors
what are the 3 main dopamine pathways in the brain
- Nigostriatal: associated with movement
- Mesocortical: associated with behaviour - +ve symptoms
- Mesolimbic: associated with behaviour - -ve symptoms
imbalances in dopamine pathways in the brain
- too much dopamine in the limbic system (mesolimbic) = positive symptoms
- too little dopamine in the cortex (mesocortical) = negative symptoms
properties of antipsychotic drugs
- decrease psychotic symptoms by decreasing dopamine synaptoc activity in the limbic pathway
- affinity of drug for D2 receptor determines its potency
problems with past antipsychotic drugs
- blocking D2 receptors in the cortex could enhance negative symptoms
how are newer drugs more effective at treating psychosis
- have higher affinity for 5-HT2A receptor than D2 receptor
- this allows DA transmission to be normalized in the limbic system and cortex
examples of antipsychotic (neuroleptic) drugs
Haloperidol (D2 > 5-HT2A)
Olanzapine (5HT2A > D2) - newer and more common
how is olanzapine comparable to haloperidol to treat schizophrenia
- olanzapine is superior in treating negative symptoms and also partially treats positive
- haloperidol treats positive symptoms but worsens negative symptoms
why are newer drugs (e.g. olanzipine) thought to be more effective to treat schizophrenia
- blocks 5HT-2A > D2 to prevent negative symptoms caused by dopamine hypofunction in the cortex
circuit of dopamine release in the limbic system
- seretonin binds to 5HT-2A receptor causing opioid release
- opioid binds mu receptor causing GABA release
- GABA binds GABAb on dopamine neuron and releases dopamine
- dopamine binds D2 receptor = reward
effects of olanzapine antagonism of 5HT-2A
- decrease DA in limbic system (good for positive)
- increase DA in cortex (ok for negative)
effects of 5HT-2A blockers in the cortex
- increase release of DA to alleviate negative symptoms of schizophrenia
what other neurotransmitter in the cortex can be released when 5HT-2A antagonists bind
glutamate
the glutamate hypothesis of schizophrenia
- PCP inhibits NMDA receptor (the glutamate receptor)
- increased PCP binding sites in these receptors in the cortex of those with schizophrenia
- lowered glutamic transmission is linked to negative symptoms
what 2 kinds of drugs are under investigation to treat schizophrenia
- drugs that increate NMDA receptor activation
- drugs that increase glycine levels or bind to glycine modulatory site of NMDA receptor
adverse effects in the CNS caused by antipsychotic drugs
- parkinson-like symptoms (D2 antagonism)
- hormonal/metabolic dysregulation (D2 antagonism in diencephalon)
- sedation (H1 and a1 antagonism)
adverse effects in the autonomic nervous system caused by antipsychotic drugs
- hypotension (a1 receptor blockade)
- atropine-like side effects (M receptor antagonisim)
