* Parkinson's Pharm Flashcards
What is the neurochemistry of PD?
Synthesis of DA:
- L-tyrosine -> L-dopa (med. by tyrosine hydroxylase) -> Dopamine (med. by DOPA carboxylase)
Breakdown of DA:
- Dopamine -> Homovanillic acid (med. by COMT & MAO)
D1 and D2 receptors
- G-protein couple receptors (GPCR)
~ 1 for excitatory 1 for inhibitory
What are the main strategies for treating PD?
1) Increase dopamine synthesis
- by Inc L-dopa (DA precursor)
2) Inhibit DA breakdown
- by COMT inhibitors
- by MAO-B inhibitors
3) Treat symptoms
- by Anticholinergics
What are the neuroprotective therapies for PD?
1) SELEGILINE
- Monoamine Oxidase (MAO-B) enzyme inhibitors
2) COENZYME Q-10
- Antioxidant
Both reduces the rate of progression of PD
How do MAO-B inhibitors work?
- Inhibits monoamine oxidase B -> inhibits breakdown of DA
- Can be taken by itself
What are the early symptomatic therapies for PD and when are they used?
When symptoms interfere with daily activities
1) SELEGILINE
2) AMANTADINE
- Antiviral agent
- Relieves symptoms
3) BENZHEXOL / ARTANE
- Anticholinergic
- Treats tremors, dry mouth, urinary retention, hallucinations
What are the side effects of Amantadine?
- Ankle swelling
- Skin rashes
- Hallucinations
How do anticholinergics help to treat the symptoms of PD?
- Controls tremors and stiffness
- Treats sialorrhea
What are the side effects of anticholinergics?
- Dry mouth
- Sedation
- Constipation, urinary retention
- Delirium, confusion, hallucinations
What are the main symptomatic therapies of PD and when are they used?
When symptoms become more significant and require dopamine replacement
1) MADOPAR / SINEMET
- Most potent
- Contains LEVODOPA + dopa-carboxylase inhibitor (CARBIDOPA)
- Converted to dopamine in the brain
2) BROMOCRIPTINE, PRAMIPEXOLE / SIFROL, ROPINOROLE / REQUIP, PERGOLIDE
- Dopamine agonists
- Acts like dopamine in the brain (but not better than levodopa)
Why does Levodopa need to be mixed with peripheral decarboxylase inhibitors?
- Enzyme inhibitor helps to reduce side effects of N/V and get more levodopa into brain
- Prevent conversion of dopamine in peripheries
~ Prevents tremors
In younger PD patients, do you start treatment with levodopa or dopamine agonists?
Dopamine agonists first
What are the side effects of Levodopa and the dopamine-agonist drugs?
- N/V
~ Domperidone (anti-emetic) used to counter - Giddiness on standing
- Hallucinations
- Postural hypotension
- If >5 years on Levodopa:
~ Wearing-off effect
~ Levodopa-related dyskinesias
~ Motor fluctuations
DA agonists:
- Pedal edema
- Fibrosis
- Intense sleepiness (somnolence) with ROPINIROLE
- Arrhythmia
- Restrictive valvular heart disease with PERGOLIDE
What is the “wearing-off effect”?
Duration of drug effectiveness shortens
How do you counter the wearing-off effect of Levodopa?
To counter:
- Take levodopa on an empty stomach
- Adjust dose/take it more frequently
~ Note: Failure to respond to large doses likely means px does not have idiopathic PD
- Take extended-release drug formulation and additional anti-Parkinson medication
- Take with AMANTADINE
~ Reduce severity of dyskinesias - Take ENTACAPONE or STALEVO
~ Catecholamine-O-methyltransferase (COMT) inhibitors
~ Prolongs duration of action of levodopa
How do COMT inhibitors work?
- ENTACAPONE, TOLCAPONE, STALEVO
- Blocks enzyme that inactivates levodopa -> more Levodopa to enter brain
- Increases duration of efficacy of levodopa
