Lecture 10: Antipsychotic drugs

Question 1

2 positive symptoms of schizophrenia

Answer 1

hallucinations
disorganized speech

Question 2

2 negative symptoms of schizophrenia

Answer 2

anhedonia
flattened affect - lack of emotion or expression of emotion

Question 3

3 cognitive symptoms of schizophrenia

Answer 3

decrease IQ
lack of attention
working memory impairments

Question 4

Chlorpromazine and haloperidol

Answer 4

D2 dopamine receptor antagonist
direct correlation between clinical potency and D2 receptor affinity

cause serious motor impairments due to D2R antagonism
cause anhedonia and sedation
have anti-emetic properties

Question 5

2 cause of schizophrenia

Answer 5

1. too much dopamine
2. GPCR signalling, Beta arrestin pathway inhibit

Question 6

Evidence that schizophrenia is caused by excess dopamine

Answer 6

amphetamine induce psychosis in patients as it pumps dopamine from the presynaptic terminal into the synpase
schizophrenia patients release more dopamine in basal ganglia when given amphetamine

Question 7

Evidence that schizophrenia is not only dependent on too much dopamine

Answer 7

amphetamine does not induce negative or cognitive symptoms
rather dysregulated than too much

Question 8

Extrapyramidal side effects (EPS)

Answer 8

immobility and muscle rigidity
can be overcome with the addition of muscarinic antagonist

Question 9

Tardive dyskinesia

Answer 9

occurs after long term treatment of antipsychotics
involuntary twitches of facial muscles
dopamine hypersensitivity

Question 10

Hyperprolactinemia by APS

Answer 10

antagonism of dopamine lead to less more secretion of prolactin
cause more producing of milk and suppression of GnRH
disruption of menstrual cycle and erectile dysfunction in male

Question 11

Clozapine, Risperidone, Olanzapine, Quetiapine, Ziprasidone, Aripiprazole

Answer 11

atypical APS
better tolerated
equal or greater affinity for 5HTw receptors than D2 receptor
antagonist at both
causes weight gain, increase cholesterol, diabetes

Question 12

One important adverse effect for clozapine

Answer 12

agranulocytosis

Question 13

Aripiprazole

Answer 13

partial agonist at the D2 receptor (instead of competitive antagonist)
In cortex and hippocampus, partial agonist with activate D2R
In striatum, partial agonist will decrease D2R transmission

Question 14

Aripiprazole MOA

Answer 14

In cortex not enough DA: partial agonist can bind more receptor to increase dopamine effect
In striatum too much DA: competes with DA so avoid full activation of dopamine as a full agonist (antagonizing effect)