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cell bodies in the substantia nigra project to the striatum which release DA which inhibits GABA ergic neurons
parkinsons dz has a loss of DA neurons leading to excessive ACh activity
functions include regulation of affect, reinforcement. related to psychotic disorders and addiction
drugs that increase DA function lead to psychosis
DA blockers decrease cognitive function
converted by DA by aromatic amino acid decarboxylase (AAAD) and given with carbidopa (irreversible peripheral inhibitor of AAAD)
side effects include dyskinesia, "on-off" effects, psychosis, hypotension, vomiting
COMT converts L-dopa to 3-O-methyldopa, a partial agonist at dopamine receptors
inhibit COMT and enhance levodopa uptake and efficacy
decrease ACh function
benztropine, trihexyphenidyl, and diphenhydramine; which decrease tremor and rigidity
side effects: atropine-like (antidote physostigmine)
antiviral which blocks muscarinic receptors and increase DA release
side effects: atropine-like and livedo reitcularis (dilated vessels with edema and rash)
uses of antipsychotics
schizophrenia, bipolar, tourette syndrome and huntington dz (for dyskinesia), drug or radiation emesis (antiemetic)
side effects from DA blockade
acute EPS - pseudoparkinsonism, dystonia (torticollis), akathisia (hyperkinetic movements)
management: antimuscarinic drugs (benztropine or diphenhydramine)
chronic EPS - tardive dyskinesia (TD) [irrversible upregulation of receptors] management - discontinue/ switch to atypical
dysphoria (leads to decreased compliance); endocrine dysfn - temperature regulation problems (NMS), treated with dantrolene and bromocriptine); increased PRL, increased eating behaviours
also get muscarinic blockade and alpha blockade (quinine like effects)
haloperidol - most EPS, most likely to cause NMS and TD
thioridazine (thio-allergies) - high antimuscarinic effects and sedation therefore less EPS but can cause torsades
clozapine (prototype) - blocks D2c (mesolimbic) and 5HT2 receptors (decrease negative symptoms); no TD; agranulocytosis (weekly blood test); increased salivation ("wetpillow" syndrome) -> due to increased to serotonin
seizures (3C's due to m block effect)
olanzapine, risperidone - blocks 5HT2 receptors
ariprazole - blocks 5HT2 receptors and partial agonist of DT2
also quetiapine and ziprasidone
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