Drugs for movement disorders

Question 1

Levodopa and Combinations

- drug list

Answer 1

Levodopa
Carbidopa
Carbidopa/levodopa (Sinemet, Sinemet CR)
Carbidopa/levodopa/entacapone (Stalevo)

Question 2

Dopamine agonist drug list

Answer 2

Bromocriptine
Pramipexole
Ropinirole

Question 3

Monoamine Oxidase Inhibitors (MAOIs)

- drug list

Answer 3

Rasagiline

Question 4

Catechol-O-Methyltransferase (COMT) Inhibitors

drug list

Answer 4

Entacapone

Question 5

Antimuscarinic Agents

drug list

Answer 5

Benztropine

Question 6

A loss of neurons in which region is most likely associated with Parkinson’s?

Corpus striatum
Medial segment of the globus pallidus
Substantia nigra
Subthalamic nucleus
Ventral anterior and ventral lateral thalamic nuclei

Answer 6

Substantia nigra
- dopaminergic neurons

Disinhibition of GABAergic neurons (dopamine no longer inhibiting them)

–> inhibition of the subthalamic nucleus (indirect pathway)

and

–> disinhibition of direct pathway (ACH)

Question 7

Levodopa is prescribed (for the parkinson’s patient). Which agent is also prescribed to greatly improve the efficacy of levodopa, reduce the adverse effects of levodopa, and improve the patient’s motor symptoms?

Bromocriptine
Carbidopa
Pramipexole
Selegiline
Tolcapone

Answer 7

Carbidopa - inhibiting peripheral conversion of l-dopa to dopamine (takes away toxicity- nausea, vomiting, CV)

Bromocriptine- dopamine agonist (ergot derivitive)
Carbidopa- dopamine decarboxylase inhibitor
Pramipexole- non-ergot dopamine agonist
Selegiline- MOA B inhibitor
Tolcapone- catechol-o-methyltransferase inhibitor

Question 8

Levodopa PK

Answer 8

Rapidly absorbed
Peak conc. 1-2 hours
Only 1-3% of dose reaches brain unaltered
Combination with carbidopa ↓ peripheral metabolism, ↑ plasma levels, ↑ t1/2, ↑ availability to brain, ↓ daily dose

Question 9

The parkinson’s patient is successfully treated with levodopa/carbidopa for the next three years. He is now 75 y/o, at this time, he presents for regular follow-up.

Which of the following symptoms is he most likely to present with?

Anorexia, nausea, vomiting
Impotence
Lightheadedness, dizziness, and occasionally syncope
Multiple episodes of immobility per day
Psychotic episodes

Answer 9

Multiple episodes of immobility per day

Question 10

Changes in Motor Response (with parkinson’s therapy)

Answer 10

“Wearing off” – rigidity and akinesia return rapidly at end of dosing interval
“On-off phenomenon” – off periods of akinesia followed by improved mobility but often with marked dyskinesia

Question 11

At this appointment, an agent that targets catechol-O-methyltransferase is prescribed to treat his presenting symptoms of frequent episodes of immobility.
Which drug is prescribed?

Amantadine
Apomorphine
Bromocriptine
Rasagiline
Tolcapone

Answer 11

TOLCAPONE

Amantidine- antiviral (and has some anti parkinson’s effects)

apomorphine- non-ergot dopamine agonist

bromocriptine- ergot dopamine agonist

rasagiline- monoamine oxidase B inhibitor

Question 12

Two weeks after initiating tolcapone, liver function tests indicate hepatic damage.
Which injectable drug could be substituted for tolcapone that will also address his immobility symptoms?

Amantadine
Apomorphine
Bromocriptine
Rasagiline
Trihexyphenidyl

Answer 12

apomorpine (given sub q as rescue therapy)

Question 13

A 68 y/o female presents with recent diagnosis of Parkinson’s disease and is administered appropriate, first-line therapy. Shortly after beginning therapy, she begins to vomit.
This adverse effect is most likely associated with activation of which receptor?

Cannabinoid (CB1)
Dopamine (D2)
Muscarinic acetylcholine (M1)
Nicotinic acetylcholine (NN)
Serotonin (5HT3)

Answer 13

Dopamine (D2)

Question 14

Chemoreceptor Trigger Zone

Answer 14

Located in brainstem but outside blood-brain barrier
CTZ monitors for toxic substances and relays info to emesis center to trigger nausea and vomiting

D2 receptor,
NK receptor

Question 15

A 57 y/o male, recently retired from the local Fire Department, presents with tremors in this right hand which have progressively worsened in the past 6 months.
He is having backaches and difficulty walking which is preventing him from enjoying his favorite hobby, golf.
Which of the following is the best treatment for this man?

Alprazolam
Apomorphine
Benztropine
Entacapone
Ropinirole

Answer 15

Ropinirole, a dopamine agonist

not Benztropine, an antimuscarinic, because already having trouble walking

Question 16

What is Appropriate Therapy for Parkinson’s?

Answer 16

Levodopa
Most effective symptomatic treatment
First choice if symptoms become troublesome

Dopamine agonists
Monotherapy in early PD or combination in more advanced disease
Ineffective in those with no response to levodopa
May delay need to initiate levodopa

Levodopa vs. dopamine agonist?
Dopamine agonist benefits:
Fewer motor fluctuations
They do not require enzymatic activation
Potentially no toxic metabolites
Do not compete for active transport across BBB

Question 17

Appropriate Therapy Cont

Answer 17

Patients under 65 years old:
Dopamine agonist

Patients ≥ 65 years old
Levodopa

MAO B Inhibitors:
Reasonable in early PD; modest benefit as monotherapy

Anticholinergic drugs:
Useful if under 70 years old, with tremor without significant bradykinesia or gait disturbance

Amantadine:
Relatively weak; may be useful in young patients with early/mild PD

Question 18

A patient who has been treated for Parkinson’s disease for about a year presents with purplish, mottled changes to her skin.
What drug is the most likely cause of this cutaneous response?

Amantadine
Bromocriptine
Levodopa (alone)
Levodopa + carbidopa
Pramipexole

Answer 18

Amantadine –> livedo reticularis

Question 19

A 67 y/o male with a history of Parkinson’s Disease is receiving the following medications:
Carbidopa/levodopa PO four times daily
Trihexyphenidyl PO three times daily
His wife reports that the patient is often confused and experiences constipation; he is also having difficulty speaking because of dry mouth.
Which of the following changes should be made to his medication regimen to resolve these symptoms?

Decrease carbidopa/levodopa dose
Decrease trihexyphenidyl dose
Increase carbidopa/levodopa dose
Increase trihexyphenidyl dose

Answer 19

Decrease trihexyphenidyl dose

Question 20

Trihexyphenidyl is prescribed as an adjunct to other drugs. What is the most likely purpose or action of this drug as part of the overall drug treatment plan?

A. To counteract sedation that is likely to be caused by the other medications
B. To help further correct the dopamine-ACh imbalance that accounts for parkinsonian signs and symptoms

To manage cutaneous allergic responses that are so common with typical antiparkinson drugs
To prevent the development of manic/hypomanic responses to other antiparkinson drugs
To reverse tardive dyskinesias if the parkinsonism was induced by an antipsychotic drug

Answer 20

To help further correct the dopamine-ACh imbalance that accounts for parkinsonian signs and symptoms

Question 21

A 45 y/o female presents to her PCP with complaints of daytime fatigue and difficulty sleeping. She can’t sleep because she has “jumpy legs”.
She describes the sensation as tingling but not painful and the symptoms worsen in the evening and bedtime.
She has to get up and walk around to relieve the symptoms.

Initial thoughts?

Answer 21

Restless legs

• night time
• paresthesias
• has to get up and walk around

Question 22

Which of the following is not an appropriate pharmacologic treatment for restless legs?

Clonazepam
Haloperidol
Levodopa
Oxycodone
Pramipexole

Answer 22

Answer: haloperidol

clonazepam- GABA agonist
haloperidol- antipsychotic, dopamine receptor antagonist
levodopa- dopamine precursor
oxycodone- opioid
pramipexole- dopamine agonist

Question 23

what movement disorder may be treated with dopamine receptor blockade?

Answer 23

Huntington’s