Lacher Antipsychotics

Question 1

What are the first generation antipsychotics?

Answer 1

Chlorpromazine/Haloperidol

Question 2

MOA of 1st generation antipsychotics?

Answer 2

Remember theyre Chlorpromazine/Haloperidol!!

Block D2 receptors in ALL 4 PATHWAYS (Mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular)

Question 3

What are the effects of 1st generation antipsychotics?

Answer 3

Chlorpromazine/Haloperidol
Only blocking D2 receptors

MESOLIMBIC - Decrease positive symptoms

MESOCORTICAL - INCREASE negative symptoms :( (we aren’t inhibiting 5HT and so 5HT will inhibit dopamine release and increase those negative symptoms)

NIGROSTRIATAL - Parkinsonism (we’re blocking any dopamine release by not inhibiting 5HT –> Parkinson like symptoms)

TUBEROINFUNDIBULAR - Galactorrhea, amenorrhea (we’re blocking dopamine release by not inhibiting 5HT –> increased prolactin)

Question 4

So… What should we do to 2nd generation antipsychotics to make them better?

Answer 4

Also inhibit 5HT!!! (still inhibit D2 too)

Question 5

What are my 2nd generation antipsychotics??

Answer 5

it’s Atypical for Old CLOSets to QUIETly RISPER from A to Z

O - Olanzapine
C - Clozapine!!!!!!!
Q - Quetiapine 
R - Risperidone 
A - Aripiprazole
Z - Ziprasidone

Question 6

What’s the 2nd generation antipsychotic that Lacher loves?

Answer 6

Clozapine

Question 7

MOA of 2nd generations

Answer 7

O - Olanzapine
C - Clozapine!!!!!!!
Q - Quetiapine 
R - Risperidone 
A - Aripiprazole
Z - Ziprasidone 

Block D2 and 5HT2a receptors –> no D2 activation (so allow for indirect pathway to work) and increased dopamine in the synapse (because we are inhibiting 5HT)

Question 8

Clozapine - tell me the good and the bad

Answer 8

Good - positive AND negative symptoms with no EPSE

Negative -
Weight gain, type II diabetes, increased LDL
AGRANULOCYTOSIS!!! (very low WBC count so watch that in your patients)

Question 9

What’s tardive dyskinesia?

Answer 9

Dopamine receptor DISUSE supersensitivity
More common with 1st generation antipsychotics (Chlorazapime/Haldol)

• You go off the antipsychotic so now the D2 receptors aren’t inhibited anymore
• Now… ANY dopamine that that D2 receptor gets it’s going to go full force with inactivation of the indirect pathway (so more movement)
• Leads to lip smacking and continuous oro-facial movements
• Might be irreversible :/