Antipsychotics

Question 1

what is the peak onset of schizophrenia?

Answer 1

Men 20-28 Yrs

Women 26-32 Yrs.

Question 2

what are the risk factors of schizophrenia?

Answer 2

• Genetic it appears that multiple genes are involved in creating a predisposition to developing the disorder SUSCEPTIBILITY GENES
• Environmental prenatal problems (maternal infection in 2nd or 3rd trimester can lead to developmental issues), obstetric complications, urban/city births, stressful life events and drug abuse

Question 3

what are positive symptoms?

Answer 3

something is added to a personality

• delusion
• hallucination
• disorganised speech

Question 4

what are negative symptoms?

Answer 4

depression like symptoms where it takes something away from a personality

• reduced emotions
• reduced motivations
• reduced interests
• reduced pleasure

Question 5

what are cognitive deficits?

Answer 5

different circuits in the brain are affected causing problems within the domains. Test the 8 domains of the brain to find the core set of symptoms

Question 6

what are moods symptoms?

Answer 6

depression
anxiety
hostility
aggression
suicide - this is a big issue and worry and needs to be assessed

Question 7

what part of the brain is involved with positive symptoms?

Answer 7

mesolimbic

Question 8

what part of the brain is involved with negative symptoms?

Answer 8

mesocortical and prefrontal cortex

Question 9

which part of the brain is involved in cognitive symptoms?

Answer 9

dorsolateral prefrontal cortex

Question 10

what part of the brain is involved with aggressive symptoms?

Answer 10

orbiofrontal cortex

Question 11

which part of the brain is part of the affective symptoms/

Answer 11

ventromedial prefrontal cortex

Question 12

what can you use to dry and diagnose psychosis/

Answer 12

Diagnostic and Statistical Manual of Mental Disorders

this is hard to use but they are best way at the moment. it asks lots of questions based on certain symptoms

Question 13

what is dopamine treatment?

Answer 13

• Increased dopamine in subcortical pathways causes the Psychotic Symptoms
• Agonists of dopamine neurotransmission induce psychotic symptoms
• Antipsychotics are antagonists at dopamine D2 receptors
• Antipscyhotics get into the brain and compete with the dopamine to block receptors.
  § D2 is inhibitory receptor – so when it is activated it inhibits the neurone

Question 14

why do we target dopamine?

Answer 14

§ When there is too much dopamine it is overexciting the D2 receptors and this is not what we want so we want to try and block some of these. Dopamine will compete with the antagonist.

Question 15

what is the glutamate theory?

Answer 15

§ NMDA receptor hypofunctional state induced by genetic and non-genetic factors instilled into the brain early in development triggers psychosis in adulthood
§ Clinical Observations (Phencyclidine)
§ People who take PCP and render their NMDA receptors hypofunctional not only experience positive symptoms such as delusions and hallucinations but also affective symptoms, such as blunted affect, negative symptoms, such as social withdrawal, and cognitive symptoms, such as executive dysfunction.
§ When you lose GABA neurons you have dysfunction

Question 16

what are the current typical treatments?

Answer 16

Haloperidol, Chlorpromazine
§ High affinity for dopamine D2 receptors
§ Effective against the +ve symptoms
§ Ineffective against the -ve symptoms

Question 17

what are the current atypical treatments?

Answer 17

Clozapine, Olanzapine, Resperidone
§ Higher affinity for serotonin (5-HT2) than dopamine D2 receptors
§ “Rich” pharmacology – dirty drug with bad side effects
§ Effective against the +ve symptoms
§ Improved efficacy against -ve symptoms ??

Question 18

would you use typical or atypical first?

Answer 18

typical
cause motor control impairments, due to their increased blockade of Dopamine D2 receptors Parkinsonal like symptoms. Also don’t treat the negative symptoms.
Atypicals can have less motor impairments but more significant side effects like weight gain, metabolic syndromes, agranulocytosis

Question 19

what are some of the reasons for side effects?

Answer 19

blocking D2 receptors increase production of prolactin

it can also lead to blockaeg of nigrostratial pathwa which leads to parkinsonal side effects

Question 20

what is the narrow therapeutic window?

Answer 20

you need to block around 65% if you get too much you will lead to Parkinsonal effects but you need enough to be abel to get effects of drug

Question 21

what is the mechanism of weight gain?

Answer 21

§	Theories include antagonism of
	- Histamine H1 receptors
	- Serotonin 5HT2c receptors
	- D2 receptors
§	Affecting hormonally controlled systems e.g. leptin

Question 22

how to manage the weight gain?

Answer 22

• Warn patients before starting high risk drgs
• Early hunger, snacking and early weight gain all predict long term weight gain
• Weight management
• Consider stopping or switching to a lower risk