NEMS 4.03 Pharmacology of Movement Disorders Flashcards
What is Levodopa used to treat? Describe typical patient reactions
Parkinson Disease (about 1/3 pt. respond well and tolerate well, 1/3 don’t respond, 1/3 have bad reactions.
What is the site and MOA for Levodopa?
A. Site of Action: Brain, pars compacta of substantia nigra
B. MOA: Exogenous Dopamine makes up for degeneration of Pars compacta (in substantia nigra).
Describe the Administration, Metabolism, and Distribution of Levodopa
A. ADME:
- Administration: Oral.
- Metabolism: Periphery Crosses ΒBB and is converted to Dopamine in the brain via DOPA decarboxylase. Some can erroneously be converted in the periphery Want to give Carbidopa to block DOPA decarboxylase in periphery and decrease the amount that is metabolized in the GI tract.
- Distribution: only 1-3% of Levodopa alone actually gets to the brain. Levodopa with Carbidopa or Sinemet (peripheral decarboxylase inhibitor/combination) increases 10% in the brain.
Describe side effects and cautions for Levodopa
A. Side Effects:
- GI
- CVS (arrhythmias and hypotension)
- Dyskinesia’s, fluctuations in response (On-Off not related to dose timing, End of dose akinesia),
- Behavioral changes,
- Diminished response over time (on scale of years, diminished function of pars compacta vs. tolerance potential, also worsening side effects).
- Cautions:
a. Above side effects: Peptic ulcers, Psychotic disorders, Recent MI.
b. Drug interactions: MAO inhibitors (anti-depressants/anti-anxiety drugs) risk for hypertensive crisis. MAO-B inhibitors can be used in conjunction safely.
c. Possible decreased impulse control.
What is Ropinirole used to treat?
Parkinson’s
What is Pramipexole (Mirapex) used to treat?
Parkinson’s
What is the site and MOA for Ropinorole/Pramipexole?
A. Site of Action: Substantia Nigra
B. MOA: D2 and D3 agonists (high concentration in susbtantia nigra)
Describe the administration, Side Effects/Cautions for Ropinirole/Pramipexole
A. ADME:
1. A: Oral
B. Side Effects: similar but less severe compared to Levadopa
1. GI
2. CVS (arrhythmias and hypotension)
3. Dyskinesia’s, fluctuations in response (On-Off not related to dose timing, End of dose akinesia),
4. Behavioral changes,
5. Diminished response over time (on scale of years, diminished function of pars compacta vs. tolerance potential, also worsening side effects).
6. Cautions
a. Above side effects: Peptic ulcers, Psychotic disorders, Recent MI.
b. Drug interactions: MAO inhibitors (anti-depressants/anti-anxiety drugs) risk for hypertensive crisis. MAO-B inhibitors can be used in conjunction safely.
c. Possible decreased impulse control.
What is Selegiline (Emsam) used to treat? With what drug is it commonly combined?
A. Indication: Parkinson’s. Alone or with Levodopa.
Describe the site and MOA for Selegiline (Emsam).
When is it most effective?
A. Site of Action: Pars compacta of substantia nigra
B. MOA: MAO-B Selective Inhibitor
Minor side effects at lower doses. Seems to produce beneficial effects in early PD.
Describe the side effects of Selegiline
A. Side Effects: Unclear if effective in the long term, watch for drug-drug interactions (certain antidepressants/anti-anxiety: Tricyclics and SSRI’s) Serotonin Syndrome. Otherwise similar side effects to Levodopa (dyskinesias, psychosis, CVS/GI, etc).
What is Serotonin Syndrome and what drug is it associated with?
Selegiline.
1. Serotonin Syndrome: Autonomic dysfunction (hyperthermia) + Neuromuscular dysfunction + altered mental status.
What is Entacapone (Comtan) used to treat? With what drugs it is commonly combined?
A. Indication: Use with Levodopa or Sinemet to enhance levodopa’s effects. (Stalevo combines Levodopa, Cabidopa, and Comtan)
Describe the site and MOA for Entacapone (Comtan)
A. Site of Action: Peripheral tissues.
B. MOA: Prevents metabolism of Levodopa into inactive form in peripheral tissues allows more to reach brain.
Describe the Pros and Cons of Entacapone (Comtan) use Especially regarding its role with Levodopa
A. ADME: Allows lower levodopa dose to be used, may reduce the flucutations in levodopa response.
B. Side Effects: Possible initial increase in Levodopa side effects as more can be converted to Dopamine in periphery.
What is Benztropine (Cogentin) used to treat? Is it used in combination or alone?
A. Indication: Tx of Parkinson’s in combination with other drugs.
Describe the MOA for Benzotropine?
A. MOA: basal ganglia muscarinic Ach receptor blockers
Describe the Side effects of Benztropine (Cogentin)
A. Side Effects:
- Fairly non selective
- Not as effective as other drugs when used alone. (don’t help with Bradykinesias)
- Do not have effect on all aspects of PD.
- Both CNS (mood changes) and Peripheral sx. (same anti-cholinergics as before: dry mouth, tachycardia, constipation, urinary retention, etc).
- Caution: Elderly over age 65 don’t tolerate well)
What are the disease and specific indications for use of Amantadine (Symmetrel)?
A. Indication: decrease rigidity, tremor, bradykinesia of PD
Describe the MOA and time of use for Amantadine
A. MOA: antiviral with PD effects, possibly via dopamine function.
B. ADME: Only useful in short term.
Describe the side effects of Amantadine. In what condition is it contraindicated?
A. Side Effects: milder side effects than some PD drugs. Orthostatic hypotension, CNS/mood disturbance.
1. Seizure history contraindicated. Caution related to side effects or heart failure.
What is Tetrabenzaine used to treat?
Huntington’s
Describe the site and MOA of Tetrabenzaine
A. Site of Action: Substantia nigra pre-synaptic terminal.
MOA: vesicular membrane-associated transporter (VMAT) inhibitor). Typically allows Dopamine to go into the vesicle (decreasing how much Dopamine can be release
Describe side effects of Tetrabenzaine
A. Side Effects: Hypotension, Depression, Sedation, Diarrhea.