Neuroleptic Drugs

Question 1

What drug classes are the 1st generation antipsychotics (3)? What is their mechanism?

Answer 1

• phenothiazine, thioxanthine, butyrophenone

- Catalepsy (trance, muscle rigidity, lack of voluntary movement) –> treat positive symptoms but not negative

Question 2

What are the side effects of chlorpromazine and the other drugs in its group?

Answer 2

NMS; Extrapyramidal (dystonia, akathisia, bradykinesia), tardive dyskinesia; sedation, hypotension, anticholinergic effects; sexual dysfunction, hyperprolactinemia [perphenazine and loxapine cause less sedation and EPS effects)

Question 3

What is Neuroleptic Malignant Syndrome? which 2 drugs have the highest risk?

Answer 3

• due to sudden reduction DA activity
• rare, life-threatening (10% mortality), fever from muscle rigidity, autonomic instability, cognitive changes, elevated serum CK, diaphoresis (usually happens with 1st dose or acute removal of DA agonist)
• haloperidol and chlorpromazine

Question 4

What 3 drugs are used to treat movement disorder in Huntington disease?

Answer 4

Chlorpromazine, Trifluoperazine & Haloperidol (low dose for severe)

Question 5

what is the preferred drug to treat hyperprolactemia?

Answer 5

bromocryptine (ergot derived D2 agonist)

Question 6

What are the 3 tricyclic 2nd generation anti-psychotic drugs? Mechanism and benefit over 1st generation? Which one can be used in pregnancy?

Answer 6

• Clozapine, Olanzapine, Quetiapine
• D2 receptor antagonist, 5HT2 receptor antagonist
• no catelpsy (i.e. no EPS, tardive dyskinesia), no NMS risk
• Clozapine can be used in pregnancy

Question 7

What is Clozapine’s therapeutic use and it’s side effects?

Answer 7

• Treatment-resistant psychoses (including schizophrenia); decreases risk of suicide; can be used in pregnancy
• Agranulocytosis; weight gain, type II DM, seizure risk, hyperlipidemia, GI hypomotility, myocarditis

Question 8

What are the therapeutic uses and side effects of Olanzapine and Quetiapine? Which one can be used to treat severe bipolar?

Answer 8

• Schizophrenia (effective against positive symptoms, modest effect on negative)
• Weight gain, hyperglycemia, postural hypotension, constipation, somnolence, dizziness (Olanzapine- posural hypotension, constipation, hyperprolactinemia, akathesia)
• Olanzapine can treat severe bipolar disease

Question 9

What are the 4 non-tricyclic Second-Generation Antipsychotics? Mechanism?

Answer 9

Risperidone, Ziprazidone, Paliperidone, Aripiprazole (Abilify)

• First 3 are all are D2 receptor antagonist, 5HT2 receptor antagonist (Pailperidone- active metabolite of risperidone after P450 metabolism)
• Aripiprazole- Partial D2 and D3 receptor agonist, partial 5HT1a agonist, 5HT2a antagonist

Question 10

What is the therapeutic use of Risperidone and the other drugs in its subclass? SIde effects?

Answer 10

• Schizophrenia (effective against positive symptoms, modest effect on negative)
• Weight gain, hyperglycemia, postural hypotension, constipation, insomnia, dizziness, hyperprolactinemia (Fewer metabolic complications compared to tricyclics)
• risperidone has risk of EPS at higher doses compared to Ziprazidone and Paliperidone

Question 11

What 3 drugs can be used to treat sever bipolar disease?

Answer 11

Aripirprazole (abilify), Risperidone, Olanzapine

Question 12

what is the therapeutic window percentage of D2 receptor occupancy?

Answer 12

65-80% (need >65% for therapeutic use but >80% occupancy produces EPS effects)

Question 13

Hyperactivity at which dopaminergic pathways produce the positive and negative symptoms of schizophrenia respectively?

Answer 13

Mesolimbic: + symptoms (psychosis)
Mesocortical: - symptoms (cognitive)

Question 14

What are the 8 ‘typical’ antipsychotic drugs?

Answer 14

Chlorpromazine, Fluphenazine, Trifluoperazine, Perphenazine, Thioridazine (phenothiazines)
Thiothixene (thioxanthine), Haloperidol (butyrophenone)