23: Antipsychotics Flashcards
Psychosis
abnormal condition of the mind
Antipsychotic drugs
those to treat schizophrenia (also for mania and acute behavioral disturbances
typical schizophrenia onset
20-30s
positive symptoms include
delusions hallucinations thought disorder abnormal disorganized disorders catatonia
negative symptoms include
withdrawal
flattening
anhedonia
reluctance to perform everyday tasks
cognitive symptoms
deficits in function- attention, memory
mesolimbic system is associated with + or - symptoms
+
2 pathologies of + symptoms
overactivation of D2 receptors in mesolimbic pathway
NMDA receptor hypofunction on GABAergic neurons =no inhibition on DA neuron with GABA receptor
pathology of - symptoms
decreased activity in D1 receptor pathways in mesocortical pathways. this is caused by NMDA receptor hypofunction on DA neurons
Cognitive impairment caused by
NMDA receptor hypofunction on cortical GABAergic interneurons = alter cortical processing
General mech of schizophrenia pharmacotherapy
antagonism of D2 DA receptors = relieve positive symptoms
therapeutic effects of medications require _____ D2 receptor occupancy
> 80%
are treatments better at + or - symptoms
+
_____% of patient are treatment resistant
30%
chlorpromazine is a
1st generation drug
clozapine is a
2nd generation drug
Similar selectivity for D2 nd D1 receptors
More extrapyramidal motor disturbances
Less effective against (-) symptoms
first generation
More selective for D2
Less extrapyramidal motor disturbances
More effective against negative symptoms
Can sometimes work for treatment resistant pts
second generation
motor disturbances are usually due to
block of D2 receptors in NS pathway
extrapyramidal side effects also include
Slow developing, often irreversible dyskinesia (face, tongue, limbs)
More prolactin secretion and galactorrhea (excessive milk production in both females and males)
Due to block of D2 in tuberohypophyseal pathway
Reduced pleasure - D2 block in ML pathway
May potentially worsen (-) symptoms due to block of D2 receptors in cortex
Antagonistic effects at other receptors
Antihistamine (h1) activity = sedation
mAchR inhibition
Alpha adrenoceptor blockade = orthostatic hypotension
what can cause leukopenia/ agranulocytosis
clozapine
what should you block when the D2 receptor is blocked and there is too much Ach release to prevent motor syndroms
mAchR
how to enhance DA release in the striatum to reduce motor side effects
inhibit mAchRs on DA nerve terminals