Antipsychotic drugs

Question 1

What is schizophrenia

Answer 1

Combination of environmental and genetic factors.

It is a disease of hypoglutaminergic and/or hyperdopaminergic function altering input to the cortex.

Question 2

What are the positive symptoms of schizophrenia

Answer 2

Defusions (bizarre, persecutory
Hallucinations
Disorganized thought
Abnormal behaviours

Question 3

What are the negative symptoms of schizophrenia

Answer 3

Blunted emotions
Anhedonia – unable to experience pleasure form normal happy situations.
Poverty of speech
Attention impairment
Loss of motivation

Question 4

What are the mood symptoms of schizophrenia

Answer 4

Depression
Anxiety
Impulse control

Question 5

What are the cognition symptoms of schizophrenia

Answer 5

New learning
Memory
Executive function

Question 6

Give examples of first generation typical anti-psychotic drugs

Answer 6

Phenothiazines:

• ->Chlorpromazine
• ->Fluphenazine
• ->Thioridazine.

Butyrophenones:

• ->Haloperidol
• ->Pimozide

Question 7

What is the function of typical anti-psychotic drug

Answer 7

Primary D2-receptor antagonists but multiple sites of action:

Question 8

What are the mesolimbic actions of D2-receptor antagonism by typical anti-psychotic drugs

Answer 8

Reduces positive symptoms

no effect against negative symptoms

Question 9

What are the Mesocortical actions of D2-receptor antagonism by typical anti-psychotic drugs

Answer 9

Increases negative symptoms, cognitive deficits

Question 10

What are the Nigrostriatal actions of D2-receptor antagonism by typical anti-psychotic drugs

Answer 10

Induces motor side-effects (parkinsonian)

Question 11

What are the Tuberoinfundibular actions of D2-receptor antagonism by typical anti-psychotic drugs

Answer 11

Effects on hormone secretion (hyperprolactinaemia)

Question 12

What side effects does D2-receptor antagonism by typical anti-psychotic drugs have

Answer 12

good effect on positive symptoms:

• Defusions (bizarre, persecutory)
• Hallucinations
• Disorganized thought
• Abnormal behaviours

but major side effects

Question 13

Give examples of second generation atypical anti-psychotic drugs

Answer 13

Clozapine
Risperidone
Quetiapine
Zotepine
Aripriprazole

Question 14

What is the function of atypical anti-psychotic drugs

Answer 14

Serotonin (5-HT2) and dopamine (D2) antagonists

Question 15

Why are atypical anti-psychotic drugs beter than typical drugs

Answer 15

fast off theory

5HT-2A antagonism - rich expression in cortical and hippocampal regions

Question 16

What is the specific action of Aripriprazole

Answer 16

1. D2-receptor partial agonist

2. 5-HT2A antagonist

Question 17

What are the side effects of Aripriprazole

Answer 17

Extra pyramidal disturbances (blockade of DA2-receptors in nigrostriatal pathway)
Parkinsonian:
 	-Bradykinesia
 	-Rigidity
 	-Tremor

Question 18

What is the first and then second line treatment for atypical drugs

Answer 18

1st - Risperidone, Quetiapine, and Zotepine

2nd - Clozapine

Question 19

What is the risk associated with clozapine

Answer 19

Agranulocytosis

Question 20

Describe the dopamine theory

Answer 20

Disease of hyperdopaminergic dysfunction.

Evidence of increased dopamine in the amygdala, and increased receptor number in postmortem brain (but drug treated)

Question 21

Describe the 5HT theory

Answer 21

5-HT has important influences on DA pathways (particulary 5-HT2A receptors) – regulation
LSD causes schizophrenic symptoms → Hallucinations
Atypical antipsychotic drgus target serotonin and DA systems (rapid kinetics)

Question 22

describe the Glutamate theory

Answer 22

-Disease of hypoglutamatergic function
NMDA antagonists produce/enhance psychotic symptoms – PCP, Ketamine
-Mutation of neuroegulin -1, a gene involved with synaptic development and plasticity.
-Reduced glutamate and glutamate receptor densities found in schizophrenic patients
-Possible genes linked to schizophrenia are mainly effect glutaminergic transmission