Neuroleptics - SCZ

Question 1

What are the symptoms of SCZ? (3)

Answer 1

Need examples of all three for a SCZ diagnosis:
Positive symptoms (gain of function) - seeing/hearing things that aren’t there, paranoia, hallucinations
Negative symptoms - lack of drive, withdrawal from social situations, catatonia (rigid posture)
Cognitive impact - dementia-like effects, lack of short term memory

Question 2

What are the causes (NT involved) of SCZ?

Answer 2

XS 5-HT [evidence - drugs amphetemines which affect 5-HT (2A/C) receptors give the positive symptoms of SCZ]

XS DA transmission: D2-like agonists produce the positive symptoms

Glu: NMDA-R antagonists (ketamine, phencyclidine) produce symptoms indistinguishable from SCZ. Phencyclidine produces the negative symptoms of SCZ.

Question 3

Which dopaminergic pathways do neuroleptics affect?

Answer 3

Mesocortical (psychosis) and mesolimbic (reward); also nigrostriatal pathway (motor skills) - EPS

Baso affects all of them, inc median eminence (increased prolactin secretion)

Question 4

Typical neuroleptics?

Answer 4

1) Phenothiazines - chlorpromazine (alpha 1, mAChR, H1 antagonists - SIDE EFFECTS!), thioridazine
2) Thioxanthines - flupenthixol
3) Butyrophenones - haloperidol

Question 5

Pros and cons of typical neuroleptics

Answer 5

+ relieve the positive symptoms
+ sedative (also a con) - due to H1 antagonism

• don’t treat negative symptoms
• EPS
• tardive dyskinesia
• hyperprolactinaemia (galactorrhoea)
• aplastic anaemia
• autonomic effects (postural hypotension, dry mouth/mydriasis/blurred vision/constipation/urinary hesitancy)

Question 6

Atypical neuroleptics?

Answer 6

dibenzazepine-derivatives - clozapine, olanzepine, quetiapine
benzisoxazole-derivatives - risperidone

Question 7

Pros and cons of atypical neuroleptics?

Answer 7

+ relief of both negative and positive symptoms
+ fewer EPS
+ less tardive dyskinesia
+ can relieve psychosis resistant to typical drugs

• sialorrhoea (dribbling)
• hyperprolactinaemia, postural hypotension
• weight gain leading to DM, cardiovascular disease
• prolonged QT intervlal

Question 8

What (which R-type) causes an increase in visceral fat levels?

Answer 8

5-HT (2A/C) - potentially worse than EPS in terms of the cost of healthcare, morbidity, compliance?

Question 9

Why is haloperidol described as a ‘clean drug’?

Answer 9

It only really has an effect on D2 receptors (fairly selective); however there are lots of side effects, so not a good drug!!

Question 10

What is aripiprazole?

Answer 10

A 3rd generation antipsychotic. A D2 partial agonist, 5-HT(1a) partial agonist, 5-HT(2a) weak antagonist

Pros - few EPS, little weight gain
Cons - hyperprolactinaemia, hypercholesterolaemia, akathisia

Question 11

What’s the difference between clozapine, chlorpromazine and ___ ?

Answer 11

Clozapine is an atypical neuroleptic, chlorpromazine is a typical one. Compare pros and cons of both typical and atypical neuroleptics!