antipsychotics

Question 1

describe the main neurochemical theory leading to schizophrenia?

Answer 1

dopamine theory:

• amphetamine, a drug which increases dopamine, NA and 5-HT produces sx similar to acute schizophrenia
• it is the most important theory basis for pharmacotherapy that all antipsychotics are D2 antagonists
• affects mesocortical pathway and nigrostratial pathway (off-target effects)

Question 2

describe the 2 other theories relating to positive sx of schizo

Answer 2

5-HT: LSD which acts primarily as 5-HT agonist, produces sx similar to acute schizo
glutamate theory: drugs which block the NMDA receptor channel produce sx similar to acute schizo

Question 3

list the examples of typical antipsychotic drugs

Answer 3

chlorpromazine, haloperidol, trifluoperazine

Question 4

describe EPS

Answer 4

extrapyrimidal side effects

• acute dystonia: parkinsonism-like syndrome occurring within the first few weeks of tx (reversible)
• tardive dyskinesia and akathisia: involuntary movements & compulsion to act associated with restlessness, anxiety & agitation

Question 5

what are the general ADR of typical antipsychotics

Answer 5

• dry mouth, consti, blurred vision (only in chlorpromazine)
• postural HoTN, dizziness (only in chlorpromazine)
• sedation, weight gain

Question 6

what is the core characteristic of atypical antipsychotics?

Answer 6

serotonin-dopamine antagonism (SDA)

Question 7

list some examples of atypical antipsychotics

Answer 7

clozapine, amisulpride, olanzapine, risperidone, aripiprazole

Question 8

what is an ADR of clozapine which limits its use clinically?

Answer 8

clozapine-induced agranulocytosis

Question 9

what is the ADR unique to amisulpride?

Answer 9

effect on mammary glands and tissues:

• increase prolactin secretion due to block of dopamine receptors in anterior pituitary glands
• breast swelling, pain & lactation
• presents as gynecomastia in males

Question 10

what is the moa of aripiprazole

Answer 10

partial agonist which has antagonistic effects in the presence of an agonist

Question 11

what are the additional ADRs of atypicals

Answer 11

• new onset or exacerbation of diabetes (irreversible even when drug is stopped; does not occur in amisulpride)
• drug induced weight gain (unlikely in amisulpride)

Question 12

why do atypicals produce less EPS

Answer 12

• clozapine: potent 5-HT antagonism vs weak D2 antagonism; and high D4 vs D2 favours action in prefrontal cortex rather than striatum
• olanzapine: potent 5-HT vs weak D2
• amisulpride: high D3 vs D2 favours action on nucleus accumbens over striatum; high D2 vs D1 reduces impact of antagonism in striatum

Question 13

what are the additional benefits of atypicals?

Answer 13

clozapine, risperidone and olanzapine are more effective against negative sx & better at mood stabilisation
- clozapine & risperidone may ameliorate cognitive dysfunction