Drugs Used in Parkinson Disease and Psychosis Flashcards
Describe where the Nigrostriatal tract starts and ends. Also described what is released from it that may be related to management of Parkinsons.
Cell bodies in substantial nigra project to striatum and release DA which is inhibitory on GABA ergic neurons
In Parkinson disease loss of DA leads to excessive ACH activity
Describe projection of mesolimbic mesocortical tract.
cell bodies in midbrain project to cerebrocortical and limbic structures
Compare DA receptor antagonists to DA agonists as it relates to Parkinsons.
DA receptor antagonists > pseudo-Parkinsonism (reversible)
DA agonists may cause dyskinesia
Mesolimbic regulation is associated with what conditions?
DA increase in these pathways is associated with psychotic disorders and addiction
DA antagonists at mesolimbic pathway may lead to what condition?
dec. in cognitive function
Describe the Tuberoinfundibular pathway.
cell bodies in hypothalamus project to anterior pituitary and release DA > dec. prolactin
Compare DA agonists and antagonists and their effects on prolactin on the body as well as implications? (DA agonist use and DA antagonist effects)
DA agonists are used in hyperprolactinemic states
DA antagonists may cause endocrine dysfunction (gynecomastia and amenorrhea/galactorrhea
What are the effects on GnRH, FSH, and LH when there is increased prolactin?
dec. GnRH > dec FSH and LH > amenorrhea
How does activation of DA receptors trigger emesis?
they are found in CTZ (chemoreceptor trigger zone) or AP area postrema when it is triggered vomiting may occur
D2 receptors are coupled to what G protein?
Gi
Which D2 receptor is for nigrostriatal pathway?
D2A
Which D2 receptor is for mesolimbic pathway
D2C
What is the pharmacologic strategy for treating Parkinsons
restore normal dopamine and decrease ACh activity
Levodopa is a prodrug converted to dopamine by what enzyme?
AAAD aromatic amino acid decarboxylse or dopa decarboxylase
What drug is levodopa given that increases activity in CNS?
carbidopa
What are the S/E of Levodopa
dyskinesias, “on-off” effects, psychosis, hypotension, vomiting
What enzyme converts L-dopa to 3-O-methyldopa a partial agonist at dopamine receptors?
COMT catechol- O- methyltransferase
What drugs inhibit COMT to enhance levodopa uptake and efficacy?
tolcapone and entacapone
Tolcapone is toxic to what organ in the body?
hepatotoxic (liver)
Selegeline indication?
initial treatment and adjunct to levodopa
S/E of Selegiline?
dyskinesias, psychosis, insomnia
Selegiline is metabolized to what?
amphetamine
What are some dopamine receptor agonists used for hyperprolactinemia and acromegaly?
bromocriptine
How is Amantadine used in the treatment of Parkinsons? MOA? What type of drug is it?
blocks muscarinic receptors and inc. dopamine release
antiviral
What is the dopamine hypotheses?
states symptoms arise because of excessive dopaminergic activity in the mesolimbic system
MOA to take in treating schizophrenia?
blockade of DA receptors
blockade of 5HT2 receptors
What are uses for antipsychotic drugs?
Treatment of:
schizophrenia and schizoaffective states
BPD
Tourette syndrome and Huntington disease
Drug or radiation emesis
S/E from antipsychotic drugs?
dyskinesias. *extrapyraidal symptoms” EPS
- dysphoria
- endocrine dysfunction
increased prolactin
NMS (neuroleptic malignant syndrome)
Temperature reg problems
Eating disorders (weight gain - tachycardia and decreased seizure threshold from (muscarinic blockade)
- hypotension from alpha blockade
Acute EPS and management?
psedoparkinsonism, dystonia, akathisia (management: antimuscarinic drugs)
What is Chronic EPS and management?
dyskinesia (management: discontinuation switch to atypical antipsychotics
How would you treat NMS?
Dantrolene and bromocriptine
Bromocriptine MOA?
D2 agonist
What are 2 D2 agonist that are ergot alkaloid derivatives that can be used for initial treatment of Parkinsons?
Pramipexole and Ropinrole
Suffix to remember the typical antispsychotics
“zines”
basically haloperidol and the zines
Name some typical antipsychoitcs
chlorpromazine
thioridazine
fluphenazine
haloperidol
What is the suffix association for atypical antipsychotics?
“idones”
“ apines”
Important S/E to remember for thioridazine?
cardiotoxicity (torsades “quinidine like”)
retinal deposits
Name the atypical antipsychotics.
clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole
Which antipsychotic is most commonly linked to NMS?
haloperidol
Clozapine MOA?
blocks D2c and 5HT2 receptors
MOA olanzapine.
blocks 5HT2 receptors and DA receptors
MOA of risperidone.
blocks 5HT2 receptors and D2 antagonist
MOA Aripiprazole
Partial agonist of D2 receptor and blocks 5HT2 receptor
S/E clozapine
agranulocytosis,
weight gain
increased salivation (wet pillow syndrome)
seizures
Olanzapine benefit in treating schizo?
improves negative symptoms
Risperidone benefit in treating schizophrenia?
improve negative symptoms
S/E of use of risperidone?
increases prolactin
