1. Plethora of PD Meds Marian L. Dale, MD Assistant Professor, Neurology
Medical University of South Carolina

2. Thank you!
For welcoming me to Charleston and introducing me to your active support group
A little about me
Oregonlive.com
12 years in NBA, including Portland Trail Blazers – dx at age of 36 in 2008
Exercises programs for young diagonosed

3. Disclosures No financial interest Provider practice preferences vary
Colors may vary
The “right” med for PD patients is an individual decision: pro/con discussion between patient and physician
Plenty of non-medication ways to treat PD: exercise!!!

4. Plan of Attack 1. The “big two” symptomatic meds
2. Possibly neuroprotective meds
3. Add-ons for wearing off with levodopa
4. Treatment for dyskinesia
5. Meds for tremor & dystonia
6. Other forms of levodopa and rescue meds
7. Other symptomatic treatments

5. Overview 1: The “Big 2” For Symptoms
Levodopa: carbidopa-levodopa (sinemet)
Dopamine agonists: mirapex (pramipexole) & requip (ropinirole)
For symptomatic therapy

6. What’s The Difference In How They Work?
Carbidopa-levodopa replaces the missing dopamine in the brain
Dopamine agonists attach to the dopamine receptors in the brain and mimic dopamine
Made in substantia nigra and VTA ventral tegmental area> up to striatum (caudate, putamen) to frontal cortex, nucleus accumbens, hippocampus

7. Pros & Cons of Levodopa “tried and true” efficacy for bradykinesia
inexpensive
less waiting time to build up to required dose
dyskinesia (“wiggles”) over time
timing: better to separate from high protein meals
Amino acid, big mac attack

8. Pros and Cons of Dopamine Agonists
less risk of dyskinesia (though still possible, especially when adding to levodopa)
generic, but insurance may still prefer one over the other
obsessive-compulsive behaviors, impulsivity
ankle swelling
“sleep attacks”
requires patience with titration
may not treat bradykinesia adequately
Apomorphine injectable rescue DA

9. Side Effects of Both Levodopa and Dopamine Agonists?
nausea
lightheadedness
Hallucinations
more about these later….

10. How We Generally Put It All Together
Prefer to start dopamine agonist (DA) on a younger patient (because they have more years ahead of them to develop dyskinesia), assuming no risk factors for OCD/impulsivity
Prefer to bypass DA for an older patient, especially if bradykinesia is significant
Older have more issues tolerating the dopamine agonists

11. More About Levodopa: “What’s the Carbidopa About?”
carbidopa-levodopa 25/100 = sinemet= “without emesis”
Top 3 levodopa questions, blocks dopa decarboxylase DDC enzyme
slideshare.net

12. “Does Levodopa Stop Working Over Time?”
Due to natural progression of PD, patients require more levodopa over time…
>more dyskinesia and complications
But even advanced PD patients have more symptoms if levodopa is missed
Not good literature on negative feedback mechanisms; “will my body stop making levodopa if I take it in pill form?”
My advice is to take it when bradykinesia is limiting exercise efforts
Short answer: no

13. “What’s A High Dose Of Sinemet?”
25/100 or 25/250 : add up all the second parts
Starting dose generally 25/100, 1 tab 3x daily= 300 mg daily
High dose ~1500 mg levodopa total daily
Needed and tolerated amount varies from person to person
May have nausea when starting, watch for lightheadedness and hallucinations when increasing
About 30 minutes before or 1.5 hours after a high protein meal

14. Plan Of Attack 1. The “big two” symptomatic meds
2. Possibly neuroprotective meds
3. Add-ons for wearing off with levodopa
4. Treatment for dyskinesia
5. Meds for tremor & dystonia
6. Other forms of levodopa and rescue meds
7. Other symptomatic treatments

15. Overview 2: Possibly Neuroprotective Meds- MAO-B Inhibitors
Azilect (rasagiline) and selegiline
Work on the back end to prevent dopamine breakdown
May slow down PD progression
Some patients also notice a mild symptomatic benefit
Some ask why would I take a medication if I can’t tell that it is improving my symptoms?
Thought to work in striatal glia (support cells) bc absent from nigrostriatal nerve terminals

16. Rasagiline vs Selegiline and Why Do We Say “May Slow Down Progression
rasagiline (azilect)
selegiline
once daily dosing
study data stronger for neuroprotection, but cautious interpretation*
2x daily dosing (am and midday)
usually cheaper
TEMPO delayed start, one group got it right away, one group had it delayed, progressed more slowly in immediate group; ADAGIO 1 mg group did better (UPDRS wise) than 2 mg group also a delayed start study
(both may cause dry mouth, nausea, but generally well tolerated)
*TEMPO study & ADAGIO study

17. What About Red Wine or Antidepressants With MAO-B Inhibitors?

18. Plan Of Attack 1. The “big two” symptomatic meds
2. Possibly neuroprotective meds
3. Add-ons for wearing off with levodopa
4. Treatment for dyskinesia
5. Meds for tremor & dystonia
6. Other forms of levodopa and rescue meds
7. Other symptomatic treatments

19. Overview 3: Add-ons For Levodopa Wearing Off
COMT-inhibitors: entacapone
(COMTAN)
100 or 200mg tabs
with every IR levodopa
administration
side effects: discolored
urine, levodopa-like:
nausea, dry mouth,
dyskinesia
Bridging medication
also may need to make levodopa more frequently throughout the day

20. Plan Of Attack 1. The “big two” symptomatic meds
2. Possibly neuroprotective meds
3. Add-ons for wearing off with levodopa
4. Treatment for dyskinesia
5. Meds for tremor & dystonia
6. Other forms of levodopa and rescue meds
7. Other symptomatic treatments

21. Overview 4: Treatment Of Dyskinesia (Wiggles)
amantadine
1, 2 or less commonly 3x a day medication
usually 100mg 2x daily
rare side effect: livedo reticularis
also some symptomatic benefit
in older patients: confusion, can
also be activating: restlessness,
difficulty sleeping> can take
morning and midday
Mechanism of action: works on multiple receptors

22. Plan Of Attack 1. The “big two” symptomatic meds
2. Possibly neuroprotective meds
3. Add-ons for wearing off with levodopa
4. Treatment for dyskinesia
5. Meds for tremor & dystonia
6. Other forms of levodopa and rescue meds
7. Other symptomatic treatments

23. Overview 5: Meds For Tremor And Dystonia
anticholinergics: artane (trihexiphenidyl), parsitan (ethopropazine)
these work on a different neurotransmitter chemical (acetylcholine, not dopamine)
caution: may worsen walking,
balance and thinking in the
long run
Only helps tremor and dystonia (though levodopa timed right also helps dystonia)

24. Plan Of Attack 1. The “big two” symptomatic meds
2. Possibly neuroprotective meds
3. Add-ons for wearing off with levodopa
4. Treatment for dyskinesia
5. Meds for tremor & dystonia
6. Other forms of levodopa and rescue meds
7. Other symptomatic treatments

25. Overview 6: Other Forms of Levodopa
carbidopa-levodopa ER/SA/long acting: I prefer to use at night; “erratic release”
parcopa: orally disintegrating tab; discoloration of saliva
stalevo: carbidopa-levodopa + entacapone (Stalevo 100= 25 carbidopa levodopa entacapone)
“Football pills”
On tongue- ODT- orally disintegrating tablet
Should not crush stalevo or long acting SA carbidopa-levodopa

26. Overview 6: Other Forms of Levodopa
Duopa Jan 2015: pump
to small intestine
Rytary Jan 2015: short and long-acting
carbidopa-levodopa together,
95/145/195/245mg levodopa
CVT-301: inhaled levodopa: in
phase 3 studies (Hinson PI)
FDA approval dates
Rytary is a lot of capsules /dose but supposedly less doses; can be difficult to adjust to; shouldn’t be crushed
Duodopa in Europe since 2004
Phase 3: effectiveness, side effects- etc placebo controlled – if passes, released: past IV is post marketing surveillance

27. Overview 6: Rescue Meds-an Injectable Dopamine Agonist
apomorphine
designed as a rescue injection for off periods
same side effects of dopamine agonists in general
test doses must be given with nurse supervision, primarily to monitor blood pressure changes
Subcutaneous injection, needs to be titrated up, initial test dose 2 mg, monitor BP and often anti-nausea medication when starting

28. Plan Of Attack 1. The “big two” symptomatic meds
2. Possibly neuroprotective meds
3. Add-ons for wearing off with levodopa
4. Treatment for dyskinesia
5. Meds for tremor & dystonia
6. Other forms of levodopa and rescue meds
7. Other symptomatic treatments
Won’t spend as long on these since I think Dr. Cooper went over PD non-motor symptoms last month

29. Overview 7: Hallucinations
donepezil/Aricept (Alzheimer’s medication conserves acetylcholine): for low heart rate
seroquel: EKG first
clozapine: atypical antipsychotic,
WBC frequently
new: pimavanserin “Nuplazid”: EKG
Anecdotally dyskinesias with pimavanserin and in someone with duopa pump actually WORSE hallucinations (%5) confusion (6%), nausea 7%, leg swelling 7%
QTc prolongation/interval/cardiac meds
Enroll in program/weekly at first
Check EKG with nuplazid not required but I would still check risk for QTc prolongation : mech action, inverse agonist and antagonist for 5HT2A (specific type of serotonin receptor), supposedly doesn’t work on/have affinity for dopamine receptors

30. Overview 7: Low BP (Orthostatic Hypotension)
For lightheadedness, especially when
getting up
fludrocortisone (florinef): watch for low potassium, avoid in heart failure
midodrine: sleep with head of bed at 45◦, avoid at bedtime
newer: droxidopa (similar, but works on norepinephrine system specifically)
also increase salt in diet, compression stockings, calf pumping exercises, get up more deliberately
Florinef not good for heart failure conditions, promotes resorption of sodium
Midodrine alpha agonist, risk supine hypertension, avoid if kidney disease
Droxidopa (Northera) works more on epinephrine system

31. Overview 7: Nausea With Levodopa
can take it with bread/carbohydrates (avoid simultaneous protein)
take extra carbidopa with each dose (Lodosyn)
some try zofran initially
domperidone from Canada (more dopamine specific)
avoid phenergan, reglan (metaclopromide)!!!
May make PD symptoms worse

32. And On That Note…