Antipsychotics Flashcards
What pathway is responsible for the positive symptoms of schizophrenia?
mesolimbic pathway
agitation, delusions, disorganised speech, disorganised thinking, hallucinations, insomnia
What pathway is responsible for the negative symptoms of schizophrenia?
mesocortical pathway
apathy, affective flattening, lack of motivation/pleasure (anhedonia), poverty of speech), social isolation
Discuss typical antipsychotics
Antagonists of D2 dopamine (R)
They have an equal or greater affinity for D2 receptor over 5HT-2
Higher risk of EPS
Discuss atypical antipsychotics
Antagonists, preferred treatment
Greater affinity for 5HT2 > D2 receptor
Some have greater affinity for D3 or D4 receptor
Less risk of EPS
Discuss some time dependent changes seen in neurotransmission with antipsychotics (early, intermediate, late)
There will be inc DA synth, release, metabolism = compensatory response
Eventual depol blockage –> inactivation of DA neuron –> reduce release of DA from mesolimbic (dec positive symptoms) and nigrostriatal pathway
Eventual inc in DA receptor number/sensitivity > delayed EPS
What is a permanent adaption seen with antipsychotics?
DA receptor upregulation and supersensitivity
–> delayed EPS (tardive dyskinesia)
List some typical antipsychotics
Chlorpromazine (one methyl group diff from promethazine)
Haloperidol (chem brace)
Droperidol
Fluphenthixol
Fluphenazine
Thiothixene
What are some receptors blocked by typical antipsychotics?
Block D2-R, a1-R, H1-R, 5HT2-R, M-R, D4-R
What will be the effects of an antipsychotic’s D2-R block?
EPS, Endocrine (growth hormone dec, prolactin inc)
Antiemetic = block of D2 receptor –> no signals to chemo-sensitive trigger zone due to block of D2-R –> reduced vomiting/nausea
What will be the effects of an antipsychotic’s a1-R block?
Alpha1-block = dec BP –> dizziness, hypotension, reflex tachycardia
What will be the effects of an antipsychotic’s H1-R block?
Sedation, drowsiness, inc appetite/weight
What will be the effects of an antipsychotic’s M-R block?
Dry mouth, urinary retention, dec HR, tachycardia, etc.
What will be the effects of an antipsychotic’s 5HT2R block?
Dec EPS, alleviate negative symptoms
Anxiety, insomnia
What will be the effects of an antipsychotic’s D4-R block?
Alleviate neg symptoms of schizophrenia, dec EPS
When is parkinsonism commonly seen in patients with antipsychotics?
5-30 days = tremors, rigidity, shuffling gait, postural abnormalities
Treat w/ antimusc (benzotropine, diphenhydramine = CAMS)
What movement disorders are commonly observed in people taking antipsychotics?
Akathisia
Parkinsonism
Dystonia
Dyskinesia
Tardive dyskinesia
What is dystonia?
neurological movement disorder causing contraction/spasming of muscles involuntarily
twisting, repetitive, patterned movement
What is akathisia?
Restlessness and agitation (seen as continuous movements)
What is dyskinesia?
Difficulty or distortion in performing voluntary movements
What is tardive dyskinesia?
late/tardy onset of dyskinesia, typically after drug treatment
Which typical antipsychotics cause the most EPS? (Why?)
Fluphenazine, Haloperidol
Strong D2 blockers
Which typical antipsychotics cause the most sedation? (Why?)
Chlorpromazine, thioridazine
H1 block
Which typical antipsychotics are the anticholinergic? (Why?)
Thioridazine
M-R block, very pro arrhythmic
Which typical antipsychotics cause the most orthostatic hypotension? (Why?)
Chlorpromazine, thioridazine
strong alpha1-block
What are the low potency antipsychotics?
Chlorpromazine, thioridazine
List the relevant atypical antipsychotics
Amisulpride/sulpride (D2 blocker)
Risperidone (paliperidone –> major active metabolite)
Clozapine, olanzapine, quetiapine, asenapine
arpiprazole
Ziprasidone
Which typical antipsychotics have an equal affinity for 5HT2 and D4?
Clozapine
What receptors are olanzapine and risperidone selective to?
5HT2 > D2
What is an important side effect of clozapine and chlorpromazine?
blood dyscrasias = neutropenia, severe constipation
Which antipsychotics have the most movement disturbances?
haloperidol
What is a common effect of typical antipsychotics?
Sedation, anticholinergic effect (esp clozapine and chlorpromazine)
How long are antipsychotics continued on for? Can you stop abruptly?
Continued for 12 months at least (aster acute psychotic symptoms)
Can consider change to low dose regimen/gradual withdrawal
All antipsychotics should be tapered slowly
