Drugs for movement disorders Flashcards
Levodopa and Combinations
- drug list
Levodopa
Carbidopa
Carbidopa/levodopa (Sinemet, Sinemet CR)
Carbidopa/levodopa/entacapone (Stalevo)
Dopamine agonist drug list
Bromocriptine
Pramipexole
Ropinirole
Monoamine Oxidase Inhibitors (MAOIs)
- drug list
Rasagiline
Catechol-O-Methyltransferase (COMT) Inhibitors
drug list
Entacapone
Antimuscarinic Agents
drug list
Benztropine
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
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)
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
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
Levodopa PK
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
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
Multiple episodes of immobility per day
Changes in Motor Response (with parkinson’s therapy)
“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
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
TOLCAPONE
Amantidine- antiviral (and has some anti parkinson’s effects)
apomorphine- non-ergot dopamine agonist
bromocriptine- ergot dopamine agonist
rasagiline- monoamine oxidase B inhibitor
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
apomorpine (given sub q as rescue therapy)
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)
Dopamine (D2)
Chemoreceptor Trigger Zone
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
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
Ropinirole, a dopamine agonist
not Benztropine, an antimuscarinic, because already having trouble walking
What is Appropriate Therapy for Parkinson’s?
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
Appropriate Therapy Cont
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
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
Amantadine –> livedo reticularis
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
Decrease trihexyphenidyl dose
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
To help further correct the dopamine-ACh imbalance that accounts for parkinsonian signs and symptoms
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?
Restless legs
- night time
- paresthesias
- has to get up and walk around
Which of the following is not an appropriate pharmacologic treatment for restless legs?
Clonazepam Haloperidol Levodopa Oxycodone Pramipexole
Answer: haloperidol
clonazepam- GABA agonist haloperidol- antipsychotic, dopamine receptor antagonist levodopa- dopamine precursor oxycodone- opioid pramipexole- dopamine agonist
what movement disorder may be treated with dopamine receptor blockade?
Huntington’s
