Antipsychotics Flashcards
what is the peak onset of schizophrenia?
Men 20-28 Yrs
Women 26-32 Yrs.
what are the risk factors of schizophrenia?
- 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
what are positive symptoms?
something is added to a personality
- delusion
- hallucination
- disorganised speech
what are negative symptoms?
depression like symptoms where it takes something away from a personality
- reduced emotions
- reduced motivations
- reduced interests
- reduced pleasure
what are cognitive deficits?
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
what are moods symptoms?
depression anxiety hostility aggression suicide - this is a big issue and worry and needs to be assessed
what part of the brain is involved with positive symptoms?
mesolimbic
what part of the brain is involved with negative symptoms?
mesocortical and prefrontal cortex
which part of the brain is involved in cognitive symptoms?
dorsolateral prefrontal cortex
what part of the brain is involved with aggressive symptoms?
orbiofrontal cortex
which part of the brain is part of the affective symptoms/
ventromedial prefrontal cortex
what can you use to dry and diagnose psychosis/
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
what is dopamine treatment?
- 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
why do we target dopamine?
§ 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.
what is the glutamate theory?
§ 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
what are the current typical treatments?
Haloperidol, Chlorpromazine
§ High affinity for dopamine D2 receptors
§ Effective against the +ve symptoms
§ Ineffective against the -ve symptoms
what are the current atypical treatments?
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 ??
would you use typical or atypical first?
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
what are some of the reasons for side effects?
blocking D2 receptors increase production of prolactin
it can also lead to blockaeg of nigrostratial pathwa which leads to parkinsonal side effects
what is the narrow therapeutic window?
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
what is the mechanism of weight gain?
§ Theories include antagonism of - Histamine H1 receptors - Serotonin 5HT2c receptors - D2 receptors § Affecting hormonally controlled systems e.g. leptin
how to manage the weight gain?
- 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
