Anti-psychotic drugs

Question 1

What percentage of the schizophrenic population attempts suicide?

Answer 1

20-40%

Question 2

How does PCP (phencyclidine) work?

Answer 2

PCP blocks the NMDA glutamate receptor and causes psychosis in many individuals
- Sometimes this psychosis never subsides

Question 3

What are the typical antipsychotics (neuroleptics)?

Answer 3

D2 blockers (with extrapyramidal symptoms):

Chlorpromazine (Thorazine)
Perphenazine (Trilafon)
Haloperidol (Haldol)
Fluphenazine (Prolixin)

Question 4

What are the effects of typical antipsychotics?

Answer 4

Days: calm behavior, improve sleep, decrease confusion.
Days to weeks: decrease psychotic symptoms
Weeks to months: improve insight?

Question 5

In what ways are typical antipsychotics limited?

Answer 5

• Negative symptom improvement minimal
• Cognitive improvement usually minimal
• Disability may remain

Question 6

What typical antipsychotics are low potency?

Answer 6

Chlorpromazine (Thorazine)
Perphenazine (Trilafon) ———–mid range

*low potency => use more mg to have an effect

Question 7

What typical antipsychotics are high potency?

Answer 7

Haloperidol (Haldol)

Fluphenazine (Prolixin)

Question 8

What are the side effects of low potency typical antipsychotics?

Answer 8

• Dry mouth, blurred vision, constipation, urinary retention, hypotension, sedation, weight gain
• Less acute dystonia, NMS
• Parkinsonism, akathesia, tardive dyskinesia
• Prolactin elevation (dopamine blocks prolactin secretion)

Question 9

What are the side effects of high potency typical antipsychotics?

Answer 9

• More acute dystonia, NMS
• Parkinsonism, akathesia, tardive dyskinesia
• Prolactin elevation

Question 10

What are the neurological side effects of neuroleptics (i.e. typical antipsychotics)?

Answer 10

• Acute dystonia
• Parkinsonism
• Akathisia
• Tardive dyskinesia (25%)
• “Rabbit” syndrome

Question 11

What is neuroleptic malignant syndrome (due to neuraleptics)?

Answer 11

• Fever
• Rigidity
• Elevated CPK

Minor manifestations:

• tachycardia
• abnormal BP
• tachypnea
• altered consciousness
• diaphoresis

Question 12

What are the benefits of atypical/novel antipsychotic drugs?

Answer 12

• Less EPS
• Less prolactin elevation (except risperidone, paliperidone)
• Fewer relapses
• Fewer neurological side effects
• Useful in affective psychosis (also bipolar)
• Role in suicidal patients – clozapine data
• Role in comorbid substance use –clozapine data

Question 13

What are the major atypical/novel antipsychotic drugs?

Answer 13

• clozapine
• olanzapine
• aripiprazole

Others:

• risperidone
• quetiapine
• ziprasidone
• iloperidone
• asenapine
• lurasidone
• paliperidone

Question 14

What is the action of clozapine?

Answer 14

Clozapine is a weak DA D2 receptor antagonist

- Potent antagonism at 5HT2 and NE α2 receptors

Question 15

What are the benefits of Clozapine?

Answer 15

• Dramatically effective for positive and some negative symptoms.
• Minimal EPS effects.
• Minimal prolactin elevation
• Less relapse
• Can help with substance abuse remission

Question 16

What side effects are associated with clozapine?

Answer 16

• Agranulocytosis
• Seizures
• Myocarditis
• Weight gain, glucose and lipid dysregulation
• Tachycardia, hypotension
• Drooling
• Sedation
• Liver function changes

Question 17

What is the action of risperidone?

Answer 17

First post-clozapine atypical antipsychotic

• 5HT2/D2 ratio similar to clozapine
• alpha 2 receptor effects, strong D2 receptor blocker, some serotonin effects

*Fewer relapses than haloperidol

Question 18

What are the side effects of risperidone?

Answer 18

EPS (higher doses), prolactin elevation

Question 19

What is the action of olanzapine?

Answer 19

5HT/D2 receptor blockade similar to clozapine

Question 20

What are the improvements in olanzapine?

Answer 20

Low EPS, low prolactin elevation

Question 21

What are the side effects of olanzapine?

Answer 21

weight gain, glucose/lipid dysregulation, sedation

Question 22

What is the mechanism of action of quetiapine?

Answer 22

5HT/D2 ratio receptor blockade similar to clozapine

Question 23

What is quetiapine generally used for?

Answer 23

Quetiapine is a commonly used anti-psychotic for sedation

Question 24

What are the improvements in quetiapine?

Answer 24

Few serious side effects
Minimal EPS
Minimal prolactin elevation

Question 25

What is the mechanism of action of aripiprazole (abilify)?

Answer 25

Aripiprazole is a high-affinity D2 partial agonist

• Functional antagonist under conditions of dopamine hyperactivity =>control of positive symptoms
• Functional agonist in conditions of dopamine hypoactivity => control of negative symptoms, cognitive improvement, minimal motor effects

Question 26

How is aripiprazole safer than other antipsychotics?

Answer 26

Minimal EPS, no prolactin elevation, low weight gain.

Question 27

What side effects are associated with aripiprazole?

Answer 27

Early activation, insomnia

- partial agonism causes the drug to activate more than block (sometimes higher dosages are used initially)

Question 28

What is the best/most effective antipsychotic?

Answer 28

Clozapine (but not as widely used due to side effects)

Question 29

How do novel/atypical antipsychotics work?

Answer 29

Release of dopamine in prefrontal cortex

- alpha 2 effect on NorEpi => help to release dopamine in PFC

Question 30

What is clozapine’s effect on norepinephrine?

Answer 30

Clozapine treatment associated with dramatic increase in plasma norepinephrine
- α2 antagonists increase efficiency of firing patterns in DA neurons in mesocorticolimbic circuits

Question 31

What is the glutamatergic system?

Answer 31

NMDA receptors
KA receptors
AMPA receptors
Metabotropic receptors – mGluR (1 – 8)

Question 32

What are other uses of antipsychotic drugs?

Answer 32

• Bipolar disorder, psychotic depression
• Personality disorders
• Treatment resistant depression (as adjunctive treatment)