Antipsychotics

Question 1

What is the mechanism of action of antipsychotics?

Answer 1

• reduce levels of dopamine activity at D2
• targeting mesocortical and mesolimbic

Question 2

What are some indications for antipsychotics?

Answer 2

schizophrenia 3rd line when 2 others have failed
positive psychotic symptoms in depression, dementia, mania etc
violent, impulsive, psychomotor agitation

Question 3

Actions on what pathway causes the unwanted effects of antipsychotics?

Answer 3

nigrostriatal (movement) and tuberoinfundibulnar (HPA axis)

Question 4

As a whole what side effects do antipsychotics cause?

Answer 4

sedation
extra-pyramidal
weight gain
increase in prolactin

potential: acute dystonia, oculogyric crisis

Question 5

What are the two types of antipsychotics?

Answer 5

typical - older, causes more extra-pyramidal side effects! histaminic and muscarinic receptors

atypical - serotonergic activity

Question 6

What are some common typical antipsychotics?

Answer 6

haloperidol
flupenthixol
zuclopenthixol (accuphase)
chlorpromazine
sulpride

Question 7

What are some common atypicals?

Answer 7

clozapine
olanzapine
risperidone
quetiapine
aripiprazole - partial D2 agonist, fewer SE

Question 8

What are extra-pyramidal side effects?

Answer 8

bradykinesia
muscle stiffness
tremor
tardive dyskinesia - oropharynx
akathisia - urge to move

*typicals + dizzy and sexual dysfunction

Question 9

What side effects are atypicals more likely to cause?

Answer 9

weight gain
dyslipidaemia
diabetes

Question 10

What are the baseline investigations for antipsychotics starting?

Answer 10

FBC - BM suppression
lipids - increase in cholesterol
LFT - fatty liver
HbA1c - impaired glucose tolerance
weight -gain
ECG - QTC prolong
BP - metabolic syndrome
pulse - ^^

Question 11

How often are investigations done for monitoring of antipsychotics?

Answer 11

baseline
weekly weights
3 monthly all
yearly all

Question 12

What is neuroleptic malignant syndrome?

Answer 12

life threatening reaction to antipsychotics, or with dopaminergic drugs for Parkinson’s when suddenly stopped

dopamine blockade –> glutamate release –> damage to muscles and nerves

Question 13

What is seen in NMS?

Answer 13

pyrexia
muscle rigidity
sweating
confusion
fluctuating consciousness
autonomic instability - high HR etc

Question 14

What do the investigations show in NMS?

Answer 14

raised CK
leucocytosis?
deranged LFT

Question 15

What causes death in NMS?

Answer 15

rhabdomyolysis induced renal failure
seizures
VTE and PE due to immobilisation
shock
aspiration due to swallowing issues

Question 16

What treats NMS?

Answer 16

A&E
stop antipsychotic
benzo for acute disturbances
monitor vitals
IV fluids to prevent renal failure
dantrolene (muscle relax)

Question 17

Why would you consider anticholinergics to treat EPSEs?

Answer 17

if too much ACh in relation to dopamine you cannot increase dopamine activity –> reduce ACh by antagonising receptors

eg: Procyclidine (not for tar dive dyskinesia)

Question 18

What is an acute dystonia?

Answer 18

sustained, painful muscle spasm producing twisted and abnormal postures
–> stop antipsychotic, IM or IV anticholinergic like procyclidine

Question 19

What are some Clozapine specific side effects?

Answer 19

hypersalivation
agranulocytosis ( severe leukopenia like neutrophils)
GI hypo-mobility - bowel obstruction?
urinary incontinence

Question 20

What are some steps taken to avoid the clozapine side effects?

Answer 20

close FBC monitoring for agran - weekly for first 18 weeks, then fortnightly for a year then monthly
titrate up slowly over 2 weeks and monitor vital signs for autonomic dysreg.

Question 21

how would you treat agranulocytosis?

Answer 21

stop clozapine
stop any marrow suppressing drugs
avoid other antipsychotics, apiprazole if needed
haematology input
abx prophylaxis
lithium to increase WCC?
G-CSF