CNS IV: Antipyschotic drugs

Question 1

Give the three main symptoms (categories of symptoms) for schizophrenia

Answer 1

• Positive symptoms (hallucinations, delusions)
• Negative symptoms (withdrawal, inability to experience pleasure, motivation loss)

Cognitive symptoms (thought and speech disorganization)

Question 2

Define the psychoses associated with elevated dopaminergic transmission in the following pathways:

• Mesolimbic
• Mesocortical
• Nigrostriatal
• Tuberoinfundibular
• Chemoreceptor trigger zone

Answer 2

• Mesolimbic: positive symptoms
• Mesocortical: negative symptoms
• Nigrostriatal: Drug inhibition can cause Parkinsons like symptoms
• Tuberoinfundibular: Drug inhibition can lead to elevated serum prolactin
• Chemoreceptor trigger zone: Drug inhibition prevents vomiting

Question 3

What is chlorpromazine?

Answer 3

The first antipsychotic drug

• Anti-histamine being tested as adjunct to anesthesia
• Prevents hallucinations and delusions
• Blocks D2 receptors

Question 4

What are typical antipsychotic drugs? How do these relieve schizophrenia symptoms?

Answer 4

First generation/conventional

• Phenothiazines (eg. chlropromazine)
• Butyrophenones (eg. haloperidol)

These relieve positive symptoms of schizophrenia by antagonism of D2 receptors, which can have a side effect of causing Parkinsons like effects in striatum (extrapyramidal side effects)

Most effective on positive symptoms.

Question 5

What are atypical (second generation) antipsychotic drugs?

Name 4

Answer 5

Higher affinity for 5-HT2A than D2 receptors, these have reduced extrapyramidal (parkinsons like) side effects

But do have metabolic dysfunction (weight gain) and loss of white blood cells (clozapine) effects. Also more expensive.

• Clozapine
• Olanzepine
• Resperidone
• Quetiapine

Question 6

Describe the pharmacodynamics and pharmacokinetics of anti-psychotics.

Answer 6

Anti-psychotic
- Well absorbed orally, sequester in body tissues (long half life) and require metabolism for elimination.

• D2 receptor antagonism is the basis for antipsyhotic actions of older drugs and their efficacy as anti-emetics (prevent vomiting)

Question 7

Drugs that have a good binding affinity for D2 receptors, correlate well with the clinical dose that relieves psychosis.

What about D1 drugs?

Answer 7

No clear association between average clinical dose and D1 receptor binding affinity.

Question 8

What is the adverse long term effect of antipsychotics?

Answer 8

Tardive dyskinesia due to increased sensitivity of dopamine receptors.

Doesn’t go away for upwards of 6 months!!

Can be accompanied by:

• Constant chewing
• Facial grimaces
• Sharp body movements
• Protrusion and rolling of tongue

Question 9

Some antipsychotics (like clozapine, risperidone, olazapine and sertindole) inhibit α2 receptors. What is the consequence of this?

Answer 9

Hypotension