L4+5 - Antipsychotics

Question 1

What is the criteria for a biomarker to be called an endophenotype?

Answer 1

 The endophenotype is associated with illness in the population.
 The endophenotype is heritable.
 The endophenotype is primarily state-independent (manifests in an individual whether or not illness is active).
 Within families, endophenotype and illness co-segregate.
 Subsequently, an additional criterion that may be useful for identifying endophenotypes of diseases that display complex inheritance patterns was suggested:
 The endophenotype found in affected family members is found in nonaffected family members at a higher rate than in the general population.

Question 2

What is the CSTC for EF

Answer 2

It is the hypothesised loop for executive funcs

DLPFC > Striatum > Thalamus > DLPFC

Question 3

What is the CSTC loop for attention

Answer 3

Dorsal ACC > Bottom of Striatum > Thalamus > ACC

Question 4

Hypothetical loop for Emotions?

Answer 4

CSTC

Subgenual ACC > Nucleus Accumbens > Thalamus > Cortex

Question 5

CSTC Loop for impulsivity?

Answer 5

OFC > Bottom of caudate > Thalamus > OFC

Question 6

CSTC Loop for Motor activity?

Answer 6

PFC > Putamen (lateral striatum) > Thalamus > Cortex

Question 7

Some negative symptoms that can be observde?

Answer 7

• reduced speech
• poor grooming
• limited eye contact

Question 8

Some negative symptoms that can be identified with some questioning?

Answer 8

• reduced emotional responsiveness
• reduced interest
• reduced social drive

Question 9

What is the mechanism of action for typical antipsychotics?

Answer 9

D2 RECEPTOR ANTAGONISTS

• only effective at treating positive symptoms, though

Question 10

Side effects for typical antipsychotics?

Answer 10

parkinson-like symdrome

because youre blocking the DA in basal ganglia, too

Question 11

What are antipsychotics also called, traditionally?

Answer 11

MAJOR TRANQUILISERS

neuroleptics

Question 12

Tardive dyskinesia?

Answer 12

caused by long-term use of neuroleptics, a hypersensitivity syndrome

involuntary, repetitive movements.

e.g. buccolingual masticatory movements.

Question 13

Other than scz, what are antipsychotics used for

Answer 13

other acute psychoses:

• mania
• psychotic depression
• puerpral psychosis (post partum)

behavioural disturbance
- dementia - but caution is necessary

Question 14

What pathway causes positive symptoms?

Answer 14

overactivation of the mesolimbic pathway

Question 15

What pathway causes negative and cognitive symptoms

Answer 15

reduced activity of mesocortical pathway.

(mesocortical pathway to DLPFC) - cog sumps, negative and affective

mesocortical pathway to VMPFC - negative and affective symps

Question 16

side effects of antipsychotics?

Answer 16

Side effects due to low selectivity - affects other NT systems

Dopaminergic effects on the striatum (EPSE)
 Dystonia/oculogyric crisis
 Parkinsonism
 Akathisia
 Tardive dyskinesia and BLMs 

Anti-cholinergic
 Dry mouth
 Blurred vision
 Constipation
 Difficulty in passing urine

Anti-adrenergic (adrenaline)
 Drop in blood pressure on standing (postural hypertension)
 Sedation
 Failure of ejaculation (especially Thioridazine)
 Skin rashes, e.g., photosensitivity
 Weight gain

Question 17

Which drug is an alternative when there is treatment resistence to antipsychotic.

Answer 17

CLOZAPINE..

don’t usually start with it bc it has a lot of side effects

Question 18

What do new generation antipsychotics do now?

Answer 18

2ND GEN ATYPICAL ANTIPSYCHOTICS

• both D2 receptor and Serotonin 2A antagonists.

lower affinity to D2, less risk of parkinson like syndromes and tardive dyskinesia.

effective for positive and negative symptoms, but not cog dysfunc

Question 19

What are the three generations of drugs used to treat SCZ?

Answer 19

1st generation: neuroleptics or typical anti-psychotics

2nd generation: atypical anti-psychotics (SDAs)

3rd generation: Aripiprazole (Abilify)

Each generation differs in pharmacology
 Different neurotransmitter systems
 Different effects on symptoms
 Different side-effects

Question 20

Side effect of 2nd gen antipsychotic?

Answer 20

weight gain. because hypothalamus is being influenced.

Question 21

What are the three types of second + later gen antipsychotics?

Answer 21

pines, dones and pips!!!!

Question 22

What are the differences in the types of second gen + later antipsycholes

Answer 22

pines

• occupies 60-80% of D2
• 5-HT2a is more potent than their D2 binding

dones
- 5-h52a binding > D2 binding

pips

• 90% binding of d2
• d2 > 5-h5t2a

Question 23

Clozapine?

Answer 23

2nd gen antipsychotic

• unlikely to cause EPSE
• Dystonia and TD are rare
• sig improvement in negative and pos symptoms in treatment resistent patients

side effect - WEIGHT GAIN

Question 24

Apriprazole?

Answer 24

3rd gen antipsychotic

partial AGONIST at d2 receptor… PARTIALLY ACTIVATES D2

when dopamine is low, it acts like an agonist
but when dopamine is high, drug sits there only partially activating the receptor, so acting like an antagonist.

effective for both positive and negative symptoms.

no typical side effects

Question 25

name some pINES

Answer 25

quetiapine
olanzapine
clozapine

Question 26

what’s a pip?

Answer 26

aripiprazole

3RD GEN

Question 27

done?

Answer 27

risperidone

Question 28

Which 2 + gen antipsychotics have the most side effects

Answer 28

30% of cases get side effects of sedation, weight gain, hyperglycaema and anticholinergic effects with PINES

10% in DONES

2% in PIP