Psychotic Disorders

Question 1

What does the dopamine hypothesis suggest?

Answer 1

Psychosis is due to excess DA activity in the mesolimbic pathway. Theory is supported by iatrogenic psychosis caused by drugs that increase DA activity in the brain

Question 2

How does the mesolimbic pathway work?

Answer 2

Its the pathway responsible for rewards, motivation, emotions and positive schizo symptoms. D2 antagonism decreases positive symptoms.

Question 3

How does the mesocorticol pathway work?

Answer 3

It responds to cognition and executive functions, emotions and mood. Hypofunction of thus pathway leads to negative symptoms. Serotonin 2 antagonism leads to decrease in cognitive and negative symptoms

Question 4

How does the nigrostrital pathway work?

Answer 4

Its the pathway responsible for motor planning and appropriate movement. D2 antagonism cause EPSEs and Tardive Dyskinesia

Question 5

How does the tuberinfundibular pathway work?

Answer 5

Dopaminergic projections in hypothalamus. It inhibits prolactin release. D2 antagonism causes hyperprolactinemia.

Question 6

What is the serotonin hypothesis for schizophrenia?

Answer 6

Serotonin 2A receptors activation modulates release of DA, NA, glutamate. 2A antagonists provides an antipsychotic effect.

Question 7

What are some of the limitations of dop. Hypothesis?

Answer 7

Cognitive, Negative symptoms, Drug-Induced Psychosis, that is not dopamine related.

Question 8

What are some symptoms of schizophrenia?

Answer 8

Postive - psychosis, hallucinations, delusions
Negative - social withdrawal, anhedonia, lack of motivation
Cognitive - diorganised speech and thoughts.

Question 9

What are the catergories of antipsychotics?

Answer 9

1st generation - potent D2 antagonists
2nd generation - Serotonin 2 and D2 antagonists
3rd generation - Dopamine partial agonists.

Question 10

What are pharmacological effects of neurotransmitters to antipsychotics?

Answer 10

Dopamine - D2 antagonist
Serotonin - 5HT2A antagonist
Histamine - H1 antagonists
Cholinergic - M1-M4 antagonists
Noradrergic - alpha antagonists

Question 11

What is the relationship of D2 occupancy and EPSEs?

Answer 11

The higher the % of binding to dopamine receptors, the more likely the patient is likely to experience EPSEs. Hyperprolactinaemia is also seen in this way.

Question 12

What are side effects of 1st generation antipsychotics relating to neurotransmitters?

Answer 12

H1 - sedation, weight gain
Alpha1 - postural hypotension
M- anticholinergic SE

Question 13

List 4 examples of 1st generation agents

Answer 13

Chlorpromazine, Flupenthixol, Haloperidol, Pimozide, Sulpiride.

Question 14

What is the MOA of 2nd generation agents?

Answer 14

Block 5HT2A receptors, also 5HT2C, 1D and 5HT1 and also block dopamine 2 receptors to a lesser extent.

Question 15

What are 5 examples of 2nd generation agents?

Answer 15

Clozapine, Quetiapine, Risperidone, Ziprasidone, Olanzapine

Question 16

What is the MoA of 3rd generation agents?

Answer 16

They are partial D2 agonists, 5HT2a antagonists and partial 5HT1a agonist effects.

Question 17

Why was brexipiprazole brought to the market?

Answer 17

Aripiprazole is very effective but may cause agitation, anxiety and insomnia

Question 18

What are the pharmacokinetics of aripiprazole?

Answer 18

Time to peak plasma concentrations: 3-5 hours
Half-life 75 hours.
Highly plasma protein bound (99%)
Hepatically metabolized CYP3A4, CYP2D6

Question 19

What are the possible benefits of 5HT-1 agonism?

Answer 19

Anxiolytic, antidepressant, improves cognition.

Question 20

Which antipsychotics cause metabolic abnormalities?

Answer 20

Clozapine, Olanzapine cause weight gain, increase lipids, and increase in glucose.

Question 21

What are some cardiovascular effects?

Answer 21

Postural hypotension- chlorprozamine, clozapine and risperidone.
Soms agents (haloperidol and ziprasidone and quetiapine.)

Question 22

How is antipsychotic-induced EPSEs reduced?

Answer 22

Decrease dose of antipsychotic, recommend an anticholinergic agent (biperidin), amantidine, may add benzodiazepine.

Question 23

What is neuroleptic malignant syndrome?

Answer 23

More common with typical antipsychotics, symptoms include severe muscle rigidity, fever, leukocytosis, increased creatine kinase levels. Its due to excessive rapid blockade of D2 receptors.

Question 24

What is the treatment neuroleptic malignant syndrome?

Answer 24

Dopamine agonist, muscle relaxants, reduce fever, consider atypical agent.