Drugs Used in Parkinson Disease and Psychosis

Question 1

Describe where the Nigrostriatal tract starts and ends. Also described what is released from it that may be related to management of Parkinsons.

Answer 1

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

Question 2

Describe projection of mesolimbic mesocortical tract.

Answer 2

cell bodies in midbrain project to cerebrocortical and limbic structures

Question 3

Compare DA receptor antagonists to DA agonists as it relates to Parkinsons.

Answer 3

DA receptor antagonists > pseudo-Parkinsonism (reversible)
DA agonists may cause dyskinesia

Question 4

Mesolimbic regulation is associated with what conditions?

Answer 4

DA increase in these pathways is associated with psychotic disorders and addiction

Question 5

DA antagonists at mesolimbic pathway may lead to what condition?

Answer 5

dec. in cognitive function

Question 6

Describe the Tuberoinfundibular pathway.

Answer 6

cell bodies in hypothalamus project to anterior pituitary and release DA > dec. prolactin

Question 7

Compare DA agonists and antagonists and their effects on prolactin on the body as well as implications? (DA agonist use and DA antagonist effects)

Answer 7

DA agonists are used in hyperprolactinemic states

DA antagonists may cause endocrine dysfunction (gynecomastia and amenorrhea/galactorrhea

Question 8

What are the effects on GnRH, FSH, and LH when there is increased prolactin?

Answer 8

dec. GnRH > dec FSH and LH > amenorrhea

Question 9

How does activation of DA receptors trigger emesis?

Answer 9

they are found in CTZ (chemoreceptor trigger zone) or AP area postrema when it is triggered vomiting may occur

Question 10

D2 receptors are coupled to what G protein?

Answer 10

Gi

Question 11

Which D2 receptor is for nigrostriatal pathway?

Answer 11

D2A

Question 12

Which D2 receptor is for mesolimbic pathway

Answer 12

D2C

Question 13

What is the pharmacologic strategy for treating Parkinsons

Answer 13

restore normal dopamine and decrease ACh activity

Question 14

Levodopa is a prodrug converted to dopamine by what enzyme?

Answer 14

AAAD aromatic amino acid decarboxylse or dopa decarboxylase

Question 15

What drug is levodopa given that increases activity in CNS?

Answer 15

carbidopa

Question 16

What are the S/E of Levodopa

Answer 16

dyskinesias, “on-off” effects, psychosis, hypotension, vomiting

Question 17

What enzyme converts L-dopa to 3-O-methyldopa a partial agonist at dopamine receptors?

Answer 17

COMT catechol- O- methyltransferase

Question 18

What drugs inhibit COMT to enhance levodopa uptake and efficacy?

Answer 18

tolcapone and entacapone

Question 19

Tolcapone is toxic to what organ in the body?

Answer 19

hepatotoxic (liver)

Question 20

Selegeline indication?

Answer 20

initial treatment and adjunct to levodopa

Question 21

S/E of Selegiline?

Answer 21

dyskinesias, psychosis, insomnia

Question 22

Selegiline is metabolized to what?

Answer 22

amphetamine

Question 23

What are some dopamine receptor agonists used for hyperprolactinemia and acromegaly?

Answer 23

bromocriptine

Question 24

How is Amantadine used in the treatment of Parkinsons? MOA? What type of drug is it?

Answer 24

blocks muscarinic receptors and inc. dopamine release

antiviral

Question 25

What is the dopamine hypotheses?

Answer 25

states symptoms arise because of excessive dopaminergic activity in the mesolimbic system

Question 26

MOA to take in treating schizophrenia?

Answer 26

blockade of DA receptors blockade of 5HT2 receptors

Question 27

What are uses for antipsychotic drugs?

Answer 27

Treatment of: schizophrenia and schizoaffective states BPD Tourette syndrome and Huntington disease Drug or radiation emesis

Question 28

S/E from antipsychotic drugs?

Answer 28

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

Question 29

Acute EPS and management?

Answer 29

psedoparkinsonism, dystonia, akathisia (management: antimuscarinic drugs)

Question 30

What is Chronic EPS and management?

Answer 30

dyskinesia (management: discontinuation switch to atypical antipsychotics

Question 31

How would you treat NMS?

Answer 31

Dantrolene and bromocriptine

Question 32

Bromocriptine MOA?

Answer 32

D2 agonist

Question 33

What are 2 D2 agonist that are ergot alkaloid derivatives that can be used for initial treatment of Parkinsons?

Answer 33

Pramipexole and Ropinrole

Question 34

Suffix to remember the typical antispsychotics

Answer 34

"zines" basically haloperidol and the zines

Question 35

Name some typical antipsychoitcs

Answer 35

chlorpromazine thioridazine fluphenazine haloperidol

Question 36

What is the suffix association for atypical antipsychotics?

Answer 36

"idones" " apines"

Question 37

Important S/E to remember for thioridazine?

Answer 37

cardiotoxicity (torsades "quinidine like") retinal deposits

Question 38

Name the atypical antipsychotics.

Answer 38

clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole

Question 39

Which antipsychotic is most commonly linked to NMS?

Answer 39

haloperidol

Question 40

Clozapine MOA?

Answer 40

blocks D2c and 5HT2 receptors

Question 41

MOA olanzapine.

Answer 41

blocks 5HT2 receptors and DA receptors

Question 42

MOA of risperidone.

Answer 42

blocks 5HT2 receptors and D2 antagonist

Question 43

MOA Aripiprazole

Answer 43

Partial agonist of D2 receptor and blocks 5HT2 receptor

Question 44

S/E clozapine

Answer 44

agranulocytosis, weight gain increased salivation (wet pillow syndrome) seizures

Question 45

Olanzapine benefit in treating schizo?

Answer 45

improves negative symptoms

Question 46

Risperidone benefit in treating schizophrenia?

Answer 46

improve negative symptoms

Question 47

S/E of use of risperidone?

Answer 47

increases prolactin