Antipsychotics

Question 1

FGA

Originally developed as antihistamine

blocks D2 receptor –> effective for positive psychosis sx

increased 5HT worsens negative sx (less DA release)

blocks all D2 receptors –> Extra Pyramidal Side Effects

Answer 1

Chlorpromazine

Question 2

FGA

Parenteral form available, generic

Severe EPSE

Answer 2

Haloperidol

Question 3

FGA

slight ESPS, generic

no parenteral form

cardiotoxicity

Answer 3

Thioridazine

Question 4

SGA

depot form available

possible increased TD?

Answer 4

Fluphenazine

Question 5

SGA

approved in 1990

effective for both positive AND negative sx

Blocks D2 and 5HT receptors (still get DA in synapse)

No EPSE

1-2% get agranulocytosis (gotta watch WBC closely)

weight gain is side effect

Answer 5

Clozapine

Question 6

SGA

broad efficacy

little to no EPSE at low dose

EPSE and hypotension at high dose

“professor’s favorite”

Answer 6

Risperidone

Question 7

SGA

effective against negative and positive sx

side fx: weight gain, dose related lowering of seizure threshold

Answer 7

Olanzapine

Question 8

SGA

similar to Olanzapine but less weight gain

short 1/2 life (BID dosing)

Answer 8

Quetiapine

Question 9

SGA

less weight gain than clozapine

side fx: QTc prolongation

Answer 9

Ziprasidone

Question 10

SGA

low weight gain liability

long 1/2 life

novel mechanism potential

Answer 10

Aripiprazole

Question 11

Basis for dopamine hypothesis for Schizophrenia:

Answer 11

• Schizophrenic patients produce more dopamine than healthy brains
• increased DA is responsible for “positive” symptoms (ie. hallucinations, delusions, disorganized speech and behavior, catatonia)

Question 12

First generation antipsychotic mech of action?

Answer 12

blocks D2 receptors in limbic system

Question 13

Why do FGA increase negative symptoms of psychosis?

Answer 13

increased 5HT inhibits release of DA

Question 14

What are the four DA pathways in the brain?

Answer 14

1. Nigrostriatal: substantia nigra to basal ganglia nuclei
2. Mesolimbic: Ventral tegmentum to nucleus accumbens
3. Mesocortical: Ventral tegmentum to frontal and limbic cortex
4. Tuberoinfundibular: Hypothalamus to anterior pituitary

Question 15

DA pathway that mediates positive symptoms of Schizophrenia

site of positive sx mimicked by chronic use of DA increaseing drugs (cocaine, amphetamine)

Answer 15

Mesolimbic

Question 16

DA pathway that mediates negative sx of schizophrenia

decreasing DA here may produce or worsen these sx

helps explain why negative sx are unaffected or worsened by FGA that only bloch D2 receptors

Answer 16

Mesocortical

Question 17

DA pathway that results in Parkinsonian sx from D2 blocking FGAs

Answer 17

Nigrostriatal

Question 18

DA pathway that results in galactorrhea, amenorrhea, sexual dysfunction from increased DA which inhibits prolactin

Answer 18

Tuberoinfundibular