Antipsychotic Drugs

Question 1

What tract is the source of psychosis?

Answer 1

Mesolimbic Tract

Question 2

What is thought to be the cause of schizophrenia?

Answer 2

Too much DOPA activity

Question 3

What about the medications used to treat schizophrenia supported the dopamine hypothesis?

Answer 3

The greater the D2 antagonistic binding affinity of a drug, the less of that drug that was needed to reach a therapeutic dose in schizophrenia.

Question 4

What were the problems with the 1st generation treatments of schizophrenia?

Answer 4

They only treated the positive symptoms and a large proportion of patients did not respond to treatment.

Question 5

What was the first antipsychotic medication?

Answer 5

Chlorpromazine

Question 6

What is the main MOA of 1st generation antipsychotic drugs?

Answer 6

Blockage of D2 receptors in the mesolimbic tract

Question 7

What other receptors can chlorpramazine (low potency antipsychotic) bind to that leads to other SE?

Answer 7

• Muscarinic
• Adrenergic
• Histamine
• Non-mesolimbic dopamine (nigrostriatal, tuberoinfundibular)

Question 8

Chlorpromazine Ocular SE

Answer 8

Corneal deposits

Question 9

Thioridazine Ocular SE

Answer 9

Retinal deposits

Question 10

Chlorpramazine SE

Answer 10

DOPA - increased prolactin
M1 - blurred vision/urinary retention/dry mouth
α1 - orthostatic hypotension
H1 - sedation/weight gain

Question 11

What is the cholinergic activity of the low potency antipsychotics like chlorpramazine?

Answer 11

Anti-cholinergic

Question 12

What is the normal action of DOPA on ACh activity?

Answer 12

Inhibitory

Question 13

What are the high potency antipsychotics?

Answer 13

• Haloperidol

- Fluphenazine

Question 14

What other receptors can haloperidol (high potency antipsychotic) bind to that leads to other SE?

Answer 14

• Non-mesolimbic dopamine

Question 15

Haloperidol SE

Answer 15

• Parkinsonian-like effects
• Akathesia
• Tardive dyskinesia

Question 16

What patients are at greater risk for acute/tardive dyskinesia on haloperidol?

Answer 16

Young males

Question 17

What are the classic tardive dyskinesia movements?

Answer 17

Oro-facial movements of blinking and tongue movements

Question 18

What are the SE that occur due to action of antipsychotics on the tuberoinfundibular tract?

Answer 18

Increased prolactin leads to galactorrhea with interruption of menstruation and osteopenia.

Question 19

What are the most important 1st generation antipsychotics?

Answer 19

• Chlorpromazine
• Thiothixene
• Haloperidol

Question 20

What is the MOA of the 2nd generation antipsychotics?

Answer 20

5HT and DOPA dual antagonism blocking the dopamine and serotonin receptors

Question 21

How does serotonin antagonism reverse DOPA antagonism?

Answer 21

Serotonin normally acts on pre-synaptic DOPA neurons to inhibit the release of DOPA. Blockage of this receptor will cause the pouring out of DOPA from the presynaptic terminal.

Question 22

Risperidone SE

Answer 22

• Exrapyramidal effects
• Orthostatic hypotension
  NO M1 or H1 effects

Question 23

Ziprasidone SE

Answer 23

• Extrapyramidal effects
• Orthostatic hypotension
• Sedation

Question 24

Quetiapine SE

Answer 24

• Orthostatic hypotension
• Anticholinergic effects
• Sedation

Question 25

Olanzapine SE

Answer 25

- Extrapyramidal effects - Orthostatic hypotension - Anticholinergic effects - Sedation

Question 26

Clozapine SE

Answer 26

- Agranulocytosis - Myocarditis - Increased seizures - Orthostatic hypotension - Anticholinergic effects - Sedation

Question 27

What is a side effect that all of the 2nd generation antipsychotics have?

Answer 27

Metabolic syndrome - weight gain/glucose intolerance

Question 28

Aripiprazole MOA

Answer 28

Partial agonist of the D2 receptors that is unique because it will keep less than 80% of the D2 receptor blocked but also more than 65% by switching from agonist to antagonist

Question 29

What is a unique benefit of clozapine?

Answer 29

Decreases risk of suicide

Question 30

Neuroleptic Malignant Syndrome

Answer 30

DOPA systems goes haywire leading to fever, muscle rigidity and tremor and increased CPK

Question 31

What is the treatment for neuroleptic malignant syndrome?

Answer 31

Stop the DOPA blocker - use dantrolene as treatment but it's still controversial

Question 32

What is a rare SE of antipsychotics in the elderly with dementia?

Answer 32

Rare increase in sudden death

Question 33

Which of the 2nd generation antipsychotic has the longest half life?

Answer 33

Aripiprazole - around 3 days

Question 34

What 2nd generation antipsychotic can increase the QT interval?

Answer 34

Ziprasidone

Question 35

What is a unique SE of lurasidone?

Answer 35

Akathesia

Question 36

What is the metabolite of risperidone?

Answer 36

Palliperidone

Question 37

What is an advantage of haloperidol over chlorpromazine?

Answer 37

Haloperidol does not have any of the muscarinic, adrenergic or histamine related side effects.

Question 38

Hit and Run Concept

Answer 38

Atypical drug-induced blockade of DA2 receptors is looser and not as long-lasting as with typical drugs. The blockade is present long enough to have the antipsychotic therapeutic effect but not long enough to cause side effects.