PARKINSONS TREATMENTS

Supplements
- Vitamin E - not shown to have any benefit in a large trial
- Coenzyme Q10 - not shown to have any benefit in large trial
- Exercise - actually works

MAO-B inhibitors
- Selegiline - helps with some motor symptoms
- Rasagaline - may slightly slow progression of disease (ADAGIO trial)
- Rasagaline might be a little more effective than selegiline but its way more $$$
- This class of drugs is relatively ineffective but relatively benign; good to start with
- The whole wine-and-cheese tyramine thing is a bit oversold, you can probably eat tyramine containing food as long as you don't go overboard

Anticholinergics 
- Triheyxyphenyldil  (Artane): most effective for tremor. Causes urinary retention and all the other anticholinergic things. Causes significant confusion/cognitive fog -- which may be a dealbreaking side effect for people in school/taking classes, with jobs that take a lot of thinking, or in old people who are already pretty confused.

Dopamine Agonists 
- Ropinirole (Requip)
- Pramipexole (Mirapex)
- Come in TID or extended release formulations (reallllly $$$)
- Rotigatine - patch - q24h
- Generally first-line in people under 65 - as they can delay the onset of dyskinesias. In people over 70, these drugs are both more likely to cause side effects (like confusion), and you're less worried about the progression of the disease over time.
- Side effects - Fatigue/somnolence, sleep attacks (seriously, people fall asleep at the wheel and get into accidents), nausea/vomiting, confusion, leg edema, postural hypotension, hallucinations

Sinemet 
- Levodopa is the most effective drug we have in the management of symptoms - and most people will end up on it eventually
- Carbidopa is a DOPA decarboxylase inhibitor
- Levodopa crosses the BBB and is converted to dopamine in the blood - dopamine itself doesn't cross BBB. Carbidopa prevents conversion of levodopa to dopamine in periphery. Carbidopa also doesn't cross BBB.
- The old school "controlled release" sinemet (sinemet CR) was crappy - depended on acid degradation in the stomach, and on gastric transit and motility, so the blood levels fluctuated like crazy and were really unreliable. Sometimes now we use it at night, where it gives nighttime symptom relief or AM effects.
- There's a new extended release sinemet called Rytany that depends on differential sized beads and is much more reliable in terms of drug levels. Unfortunately its really, realllllly, realllllllllly expensive, and you have to take a lot of pills (ie like 3-4 pills TID or QID - the median is 3.6 times a day)
- However regular sinemet some people have to dose q2 hours, or q3 hours, which is just agonizing, and going from q2 to q5 or q6 dosing can be life-altering in a good way

COMT inhibitors 
- Entacapone
- Tolcapone - more potent because better CNS penetration, but more reported cases of severe liver failure-possibly a fluke in early trials as the reported incidence is dropping with time; have to get monthly LFTs for the first 6 months
- In the late game, they decrease off time when given with sinemet
- Only given in combination with levidopa, not given alone-- they don't have much effect on their own. Also they result in disease with worse dyskinesias if given early, alone or in combo with sinemet.

Apomorphine
- Injection, subQ, need to premedicate with antiemetic, lasts 30-60 min, can bridge - i.e. take your sinemet and the injection and by the time injection wears off, pills have taken effect.

Duodopa 
- gel delivered into the intestines, 89% rate of pump complications/malfunction/failure

DBS 
- Usually can reduce the dose of meds, but still need meds


Treating Side Effects

Dyskinesias
- treatment: amantadine is very good for this. Doesn't affect PD itself.
- can decrease dose of sinemet

Freezing
- Can increase sinemet

Halluciinations 
- stop Dopa agonist, MAOs, anticholinergics, amantadine
- decrease sinemet
- add seroquel
- add cholinesterase inhibitor

To be avoided in PD: anti dopamine drugs
- Neuroleptics - haldol, etc
- Antiemetics - promethazine, metoclopramide, etc