Psychosis and schizophrenia

Question 1

Overactivity in mesolimbic pathway leads to positive symptoms. Describe positive symptoms ?

Answer 1

Hallucinations, delusions, disorganised speech/ thoughts

Question 2

under activity in mesocorticol pathway leads to negative symptoms. Describe negative symptoms ?

Answer 2

social withdrawal, poor hygiene, apathy, catatonia

Question 3

Antipsychotics are …. ?

Answer 3

dopamine repceptor 2 antagonist

Question 4

Antipsychotics are better at relieving positive or negative symptoms in schizophrenia ?

Answer 4

Help to relieve the positive symptoms of schizophrenia better

Question 5

Second or first generation antipsychotics are better at treating negative symptoms ?

Answer 5

Second generation are better

Question 6

Antipsychotics cause D2 antagonism in nigrostriatal pathway and therefore leads to what ?

Answer 6

extrapyramidal symptoms : Parkinsonism, tardive dyskinesia, akathisia, dystonia, dyskinesia

Question 7

Antipsychotics cause D2 antagonism in tuberofundibular pathway and therefore leads to what ?

Answer 7

hyperprolactinaemia: menstrual disturbances, galactorrhoea, breast enlargement, sexual dysfunction

Question 8

How does first generation antipsychotics work ?

Answer 8

block post synaptic dopamine D2 receptors in the brain

Question 9

first generation antipsychotics or second generation are associated with more entropyramidal symptoms and hyperprolactinaemia ?

Answer 9

first generation

Question 10

Name all first generation antipsychotics ?

Answer 10

PHENTOHIAZINES
-chlorpromazine ( contact sensitasion )
-levemopremazine
-promazine ( used as sedative OTC )
These three mentioned above are most sedative. 
-pericyazine ( least EPS )

-fluphenazine
-perphenazine
-prochlorperazine
-trifluoperazine
These four mentioned above have most EPS symptoms.

BUTYROPHENONES
- haloperidol ( qt interval prolongation ) - most EPS

THIOXANTHENES

• flupentixol ( alerting effect; don’t take in the evening)
• zuclopenthixol ( depot preparation used in agitated/agressive patients and more effective in preventing relapse)

Others:
pimozide ( qt interval prolongation ) sulpiride, loxapine ( bronchospasm )

Question 11

MOA of second generation antipsychotics ?

Answer 11

blocks post-synaptic dopamine D1-D4 receptors and act on wide range of other receptors

Question 12

Second generation have more EPS symptoms or more metabolic side effects ?

Answer 12

more metabolic side effects

Question 13

Name all second generation antipsychotics ?

Answer 13

• amisulpride ( most hyperprolactinaemia )
• aripiprazole ( does not cause hyperprolactinaemia )
• clozapine (agranulocytosis, myocarditis, and gastro- instetinal obstruction, most weight gain and diabetes
• lurasidone
• olanzapine ( most weight gain and diabetes )
• paliperidone
• quetiapine
• risperidone ( most hyperprolactinaemia )

Question 14

Which second generation antipsychotic is most effective ?

Answer 14

clozapine

Question 15

What is the licensing for clozapine ?

Answer 15

licensed for resistant schizophrenia. Clozapine can be prescribed when tried two or more antipsychotics for at least 6-8 weeks each.

Question 16

How long should clozapine be trialed for effectiveness ?

Answer 16

8-10 weeks. if no response, before augmenting with second antipsychotic measure clozapine plasma levels

Question 17

What action should be taken if clozapine doses have been missed ?

Answer 17

if missed more than 2 doses then refer to specialist for reinitiating

Question 18

Name the drugs the clozapine should not be given together due to increased risk of agranulocytosis ( blood dyscrasias) ?

Answer 18

aminosalicylates, immunosuppressants, methotrexate, cytotoxic drugs

Question 19

What are the side effects of clozapine?

Answer 19

-MYOCARDITIS AND CARDIOMYOPATHY: persistent tachycardia, especially in first 2 months. Stop permanently if myocarditis and cardiomyopathy occurs.
-GRANULOCYTOSIS AND NEUTROPENIA: clozapine monitoring, leucocyte and differential blood count. monitoring should be every week for 18 weeks , then every two weeks for a year, then monthly onwards.
-GASTROINTESTINAL OBSTRUCTION: intestinal peristalsis impaired = constipation, faecal impaction, paralytic ileus. Take caution with constipating medication e.g hyoscine used to treat hyper salivation with clozapine.
Patient counselling: report constipation before taking the next dose