Parkinson's Drugs

Question 1

Overview of the pharmaceutical management of EARLY PD symptoms (2)

Answer 1

1. Start with a Monoamine Oxidase B inhibitor (Rasagiline or Selegiline)–helps keep dopamine around longer!

Alternatively, start with cabidopa/levodopa (+Sinemet)–precursor to dopamine

2. Proceed to either Amantadine (may increase dopamine release) or a dopamine agonist (ropinirole, pramipexole

Question 2

2 drug choices for tremor predominate PD

Answer 2

1. Dopamine synthesizer / antiepileptic agent (Zonisamide)

2, Anti-cholinergic (Trihexyphenidyl)

Question 3

For treatment of tremor-predominate PD, what should you tell your pt of side effects he should expect to see? What reccommendations should you give?

Answer 3

Zonisamide (antiepileptic agent): can cause kidney stones (nephrolithiasis), so important to stay well hydrated

Trihexyphenidyl (anticholinergic): can cause fatigue, confusion, hallucinations, dry mouth, dry eyes. Usually limit dose titration. Do not use in patients with cog impairment.

Question 4

When do motor fluctuations occur? What are 3 pharmacologic strategies?

Answer 4

• Occur when dopaminergic meds remain effective but for much shorter periods of time
  
  • increase dosing frequency
  • block dopamine breakdown with MAOB inhibitors (Selegiline, Rasagiline) and COMT inhibitors (entacapone, tolcapone)
  • new long acting formuations (Rytary, Duodopa)

Question 5

What are the 7 different types of dopaminergic agents?

Answer 5

1. Dopamine precursor (levodopa)
2. Decarboxylase inhibitors (carbidopa, benserazide)
3. MAO B inhibitors (selegiline, rasagiline, lazabemide)
4. COMT inhibitrs (entacapone, tolcapone)
5. Dopamine agonists (pramipexole, ropinrole, apomorphine, lisuride, rotigotine, carbergoline, bromocriptine, pergolide)
6. Dopamine releaser (amantadine)
7. Dopamine synthesizer (Donisamide)

Question 6

Levodopa is the strongest anti-parkinsonian effect of available drugs. What is its unique characteristics?

Answer 6

Crosses the BBB where it is taken up by dopaminergic neurons and converted to dopamien by aromatic amino acid decarboxylase. (given with a peripheral decarboxylase inhibitor)

Question 7

Pt taking drugs for parkinsons complains of drowsiness, nausea, orthostatic hypotension, confusion and hallucinations, and dyskinesias. Which drug is he most likely taking?

Answer 7

Levodopa

Question 8

Pharmacokinetics of Levodops (onset of action, lenght of benefit)

Answer 8

• onset of action: 30 min
• length of benefit not dependent on serum half-life
• length of benefit decreases as the disease progresses
• motor fluctuations in late stages of PD

Question 9

Sinemet is the long acting form of levodopa that breaks down more slowly. Why is it considered unreliable? What is it useful for?

Answer 9

Absorption is often incomplete, has different breakdown rates, dependent on digestion. Useful before bedtime in pts who wake up with symptoms in the middle of the night.

Question 10

How do dopamine agonists compare to levodopa?

Answer 10

the anti-arkinsonian effect is not as strong as with levodop, but it does allow levodop sparing strategy.

Question 11

pt on drugs for parkinsons complains of compulsive behaviors recently, confusion, hallucinations, drowsiness/sleep attacks, some nausea, and leg edema an dorthostatic hypotension. What is the probable drug causing these side effects?

Answer 11

Dopamine agonist (pramipexole, ropinrole, apomorphine, lisuride, rotigotine, cabergoline, bromocriptine, pergolide)

Question 12

What does COMT inhibitors require to be effective? When is it particularly used? What additional side effect does it cause?

Answer 12

Not effective without levodopa. Added when patients being to notice wearing off between doses of carbidopa/levodopa. Can increase severity of levodopa’s side effects (hallucinations, orthostasis)

Question 13

Difference between selegiline and rasagiline, both MAO B inhibitors

Answer 13

Selegiline has amphetamines among its breakdown products, while rasagiline does not. Rasagiline has greater clinical efficacy than selegeline.

Question 14

Amantadine has a mild anti-parkinsonian effect and has severeal MOAs. what are the 3 important ones?

Answer 14

1. Activates release of dopamine from nerver terminals (dopamine releaser…“a real man would let her go”)
2. anti-muscarinic
3. NMDA antagonist

Question 15

4 uses of Amantadine

Answer 15

1. Helps with tremor and rigidity in early disease
2. Helps treat dyskinesias in later stages of disease (L-dop induced)
3. Can be helpful for patients experiencing constant fatigue
4. patients with atypical parkinsonism