Antipsychotics Flashcards
Why are Psychosis and parkinsonism two sides of the same coin?
they stem from opposite issues with dopamine
treatment of psychois involves blocking DA receptors and has parkinsonism as a negative effect
Parkinsonisn treatment involves increasing DA levels and has psychosis as a negative effect
What is the dopamine hypothesis for schizophrenia?
psycosis is due to a hyperactive dopaminergic system, particularly with increased DA production and increased acvity at the D2 receptor subtype
What is the evidence supporting the dopamine hypothesis for schizophrenia?
- amphetamines work by causing the brain to produce more dopamine and have been shown to produce psychotic-like symptoms
- 1st gen anti-psychotics like haloperidol act by blocking dopamine receptors in the brain
What are the two weaknesses of the dopamine hypothesis for schizophrenia?
- amphatamines only mimic the POSITIVE symptoms of schizophrenia
- first generation antipsychotic drugs are only effective on the POSITIVE symptoms of the disease
What are the four DA pathways in the brain?
- mesolimbic
- mesocortical
- nigrostriatal
- tuberoinfundibular
Where does the mesolimbic pathway go to?
What symptoms of schizophrenia doe sit mediate?
it runs form the tegmentum (VTA) to the nucleus accumbens in the limbic system
it’s the proposed area of the brain that mediates the positive symptoms of schizophrenia
If you block the D2 DA receptors in this area you have a decrease in the positive symptoms
Where does the mesocortical pathway go? What symptoms of schizophrenia does it mediate?
it runs form the tegmentum to the frontal and limbic cortices
proposed to mediate the negative (and maybe cognitive) symptoms of schizophrenia
Oddly enough, decreaseing DA levels or activity in the mesocortical pathway may _______ negative symptoms of schizophrenia.
What is this likely due to?
it actually produces or worsens the negative symptoms!!
It’s probably due to an increase in 5HT, which inhibits DA release here
this explains why negative symptoms are unaffected or worsened by antipsychotics that only block DA receptors
Why are 2nd generation antipsychotics more beneficial in treating negative symptoms?
they block both DA and 5HT receptors, not just DA receptors
Where does the nigrostriatal pathway run?
What is the effect on this area form the first generation antipsychotics?
it runs form the substantia nigra to the basal nuclei - they regulate posture and voluntary movement
the first gens block DA receptors in the stratum, so you get a parkinsonism like syndrome. SGAs are less likely to produce these
Where does the tuberoinfundibular pathway run? How is this affected by FGAs?
it runs from the hypothalamus to the anterior pituitary, where DA inhibits prolacting secretion
With FGAs, female patients can experience galactorrhea, amenorrhea and sexual dysfunction
FGAs block what receptors? What symptoms are they good for?
they all block D2 receptors in the limbic system
most effective against positive symptoms
(may also affect muscarinic, adrenergic, and histaminergic receptors too)
What receptors are blocked by the second gen antipsychotics?
DA and 5HT
Why is affecting both DA and 5HT receptors better than just DA?
presynaptic 5HT receptors regulate DA release
- activating them blocks the release of DA
- Inhiting them increases the release of DA
Why do the SGAs have fewer extrapyramidal symptoms than the FGAs?
they block 5HT receptors in the stratum, so you get increased DA release in the nigrostratal pathway, counteracting the DA receptor blockade and avoiding the parkinsonism symptoms
