23: Antipsychotics

Question 1

Psychosis

Answer 1

abnormal condition of the mind

Question 2

Antipsychotic drugs

Answer 2

those to treat schizophrenia (also for mania and acute behavioral disturbances

Question 3

typical schizophrenia onset

Answer 3

20-30s

Question 4

positive symptoms include

Answer 4

delusions
hallucinations
thought disorder
abnormal disorganized disorders
catatonia

Question 5

negative symptoms include

Answer 5

withdrawal
flattening
anhedonia
reluctance to perform everyday tasks

Question 6

cognitive symptoms

Answer 6

deficits in function- attention, memory

Question 7

mesolimbic system is associated with + or - symptoms

Answer 7

+

Question 8

2 pathologies of + symptoms

Answer 8

overactivation of D2 receptors in mesolimbic pathway

NMDA receptor hypofunction on GABAergic neurons =no inhibition on DA neuron with GABA receptor

Question 9

pathology of - symptoms

Answer 9

decreased activity in D1 receptor pathways in mesocortical pathways. this is caused by NMDA receptor hypofunction on DA neurons

Question 10

Cognitive impairment caused by

Answer 10

NMDA receptor hypofunction on cortical GABAergic interneurons = alter cortical processing

Question 11

General mech of schizophrenia pharmacotherapy

Answer 11

antagonism of D2 DA receptors = relieve positive symptoms

Question 12

therapeutic effects of medications require _____ D2 receptor occupancy

Answer 12

> 80%

Question 13

are treatments better at + or - symptoms

Answer 13

+

Question 14

_____% of patient are treatment resistant

Answer 14

30%

Question 15

chlorpromazine is a

Answer 15

1st generation drug

Question 16

clozapine is a

Answer 16

2nd generation drug

Question 17

Similar selectivity for D2 nd D1 receptors
More extrapyramidal motor disturbances
Less effective against (-) symptoms

Answer 17

first generation

Question 18

More selective for D2
Less extrapyramidal motor disturbances
More effective against negative symptoms
Can sometimes work for treatment resistant pts

Answer 18

second generation

Question 19

motor disturbances are usually due to

Answer 19

block of D2 receptors in NS pathway

Question 20

extrapyramidal side effects also include

Answer 20

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

Question 21

Antagonistic effects at other receptors

Answer 21

Antihistamine (h1) activity = sedation
mAchR inhibition
Alpha adrenoceptor blockade = orthostatic hypotension

Question 22

what can cause leukopenia/ agranulocytosis

Answer 22

clozapine

Question 23

what should you block when the D2 receptor is blocked and there is too much Ach release to prevent motor syndroms

Answer 23

mAchR

Question 24

how to enhance DA release in the striatum to reduce motor side effects

Answer 24

inhibit mAchRs on DA nerve terminals

Question 25

5HT2A receptors in the CNS can be

Answer 25

inhibitory- Gi coupled

Question 26

what do 5HT2A receptors do in the nigrostriatal pathway

Answer 26

inhibit DA release from DA neurons

Question 27

blocking ___ in stiatum ____ dopamine release, _____ motor side effects associated with striatal D2 receptor inhibition

Answer 27

mAChR
increases
reducing

Question 28

in mesocortical circuits, a 5HT2A receptor antagonist may

Answer 28

improve negative symptoms by enhancing DA and glu release

Question 29

in mesolimbic pathway combined ___ and ____ receptor antagonist can counteract increased dopamine function

Answer 29

D2 an 5HT2A