pharm - parkinson, psychosis and dopaminergic pathways

15 terms by rmathew1 

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nigrostriatal tract

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

mesolimbic-mesocortical tracts

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

tuberoinfundibular

relelated to PRL release

CTZ

activated DA receptors increase emesis
DA blockers are antiemetic

dopamine receptors

d1 = Gs
d2 = GI
D2A nigrostriatal, D2C mesolimbic (clozapine

levodopa

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

tolcapone/entacapone

COMT converts L-dopa to 3-O-methyldopa, a partial agonist at dopamine receptors

inhibit COMT and enhance levodopa uptake and efficacy

selegiline

MAOb-selective inhibitor (no tyr interactions)
side effects: metabolized to amphetamine

bromocriptine (pramipexole and ropinirole)

DA receptor agonist - for hyperPRL and acromegaly

decrease ACh function

benztropine, trihexyphenidyl, and diphenhydramine; which decrease tremor and rigidity

side effects: atropine-like (antidote physostigmine)

amantadine

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

dyskinesias (EPS)
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)

typical antipsychotics

haloperidol - most EPS, most likely to cause NMS and TD
chlopromazine
thioridazine (thio-allergies) - high antimuscarinic effects and sedation therefore less EPS but can cause torsades

atypical antipsychotics

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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