treatment options for parkinson’s disease · pdf filetreatment options for...
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TREATMENT OPTIONS FOR PARKINSON’S
DISEASEKarin M. Durant, Pharm.D.
Florida Hospital East Orlando
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Goals of Therapy
Symptom management Tremor, rigidity, bradykinesia, gait
disturbances (freezing)
Halting or slowing the disease progression Neuroprotection
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Current Therapies Available
Levodopa/Carbidopa Sinemet®, Atamet®
COMT Inhibitors Entacapone (Comtan®), Tolcapone (Tasmar®)
Combination products: Levodopa/Carbidopa/Entacapone (Stalevo®)
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Current Therapies Available Anticholinergics
Benztropine (Cogentin®), Trihexyphenidyl(Artane®), Biperiden (Akineton®), Amantadine(Symmetrel®)
Dopamine Agonists Bromocriptine (Parlodel®), Pramiprexole
(Mirapex®), Ropinirole (Requip®), Apomorphine (Apokyn®)
MAO-Inhibitors Selegiline (Eldepryl®), Rasagiline (Azilect®)
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Why is Levodopa always given in combination with
Carbidopa (Sinemet®)?Levodopa is broken down by enzymes before it
reaches the brain. Carbidopa inhibits this enzymeactivity allowing levodopa to reach the brain
where it is metabolized to dopamine. This allowsa lower dose of levodopa to be used which helpslimit side effects such as nausea and vomiting.
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Levodopa/Carbidopa Levodopa is converted to dopamine Reduces extrapyramidal movements, rigidity,
tremor and gait disturbances Available as immediate release, extended
release and dissolvable oral formulations Doses and frequencies vary widely among
patients and may vary over time Do not take within 2 weeks of Selegiline or if
history of narrow angle glaucoma
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Levodopa/Carbidopa Avoid sudden withdrawal Side effects: nausea, vomiting, loss of appetite,
dyskinesia, confusion, orthostatic hypotension (feeling faint upon standing)
Proteins can interfere with levodopa absorption Take 30-60 minutes before a meal For nausea, take with crackers or other low
protein foods
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COMT Inhibitors Entacapone (Comtan®), Tolcapone (Tasmar®) Selective inhibitor of COMT, which is the major
metabolizing enzyme of levodopa No effect on Parkinson’s symptoms without
levodopa – used in combination with levodopa Multiple drug interactions Side effects: nausea, diarrhea, hallucinations,
confusion, dyskinesia, orthostatic hypotension Tasmar® has been associated with a risk of
acute fulminant (sudden and severe) liver failure Avoid sudden withdrawal
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Stalevo®
Combination product containing levodopa, carbidopa, and entacapone
March 2010 FDA Safety Announcement Patients taking Stalevo may be at increased
risk of developing prostrate cancer August 2010 FDA Safety Announcement
Patients taking Stalevo may be at increased risk of cardiovascular events such as heart attack and stroke
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Anticholinergics Benztropine (Cogentin®), Trihexyphenidyl
(Artane®), Biperiden (Akineton®), Amantadine (Symmetrel®)
Cogentin® is available as an injection Reduces extrapyramidal movements, rigidity,
tremor and gait disturbances Side effects: dry mouth, urinary retention,
sedation, constipation, blurred vision, confusion, increased intraocular pressure, impaired heat regulation, peripheral edema (amantadine)
Avoid sudden withdrawal
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Dopamine Agonists Bromocriptine (Parlodel®), Pramiprexole
(Mirapex®), Ropinirole (Requip®), Apomorphine(Apokyn®)
Exact mechanism in Parkinson’s disease is unknown
Reduces extrapyramidal movements, rigidity, tremor and gait disturbances
Apomorphine is given by subcutaneous injection Rotate injection sites
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Dopamine Agonists Watch for drug interactions Side effects: Nausea, constipation, drowsiness,
confusion, dizziness, insomnia, dyskinesias, orthostatic hypotension, hallucinations
Take oral products with food to minimize stomach upset
Use Apomorphine with caution in patients with cardiovascular disease
Avoid sudden withdrawal
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MAO Inhibitors Selegiline (Eldepryl®), Rasagiline (Azilect®) Selective inhibitor of monoamine oxidase, type B
Blocks the breakdown of dopamine May also increase dopamine activity Effective when used by itself or in combination
with Levodopa Reduces extrapyramidal movements, rigidity,
tremor and gait disturbances Improves mood
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MAO Inhibitors Major drug interactions, including
antidepressants, Ma Huang, Kava, St John’s Wort and Ginseng
Side effects: nausea, vomiting, indigestion, constipation, dry mouth, weight loss, headache, orthostatic hypotension, hallucinations
Use caution with tyramine containing foods such as wine, aged cheese, and liver
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Vitamins/Herbs/Supplements Coenzyme Q10 Vitamins C and E (antioxidants) Ginko biloba Ginger
The FDA does not regulate herbs and supplements
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Protective Treatments Recent research is now focusing on
neuroprotective effects of the medications Goal is to halt or slow the disease
progression Initiating treatment in early disease (before
symptoms require treatment) has been studied
Levodopa, Rasagiline, Coenzyme Q10, Simvastatin
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Role of Rasagiline Has demonstrated some neuroprotective
properties Results of recent studies:
Improved Unified Parkinson’s Disease Rating Scale (UPRDS) scores over a 6.5 year period in patients who started therapy early vs. late
Early treatment with rasagiline 1mg daily showed benefits that may be consistent with a disease modifying effect. This same effect was not seen with a dose of 2mg daily.
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Role of Coenzyme Q10
Nutraceutical product that has been used in angina, congestive heart failure, and cardiac surgery
Potent antioxidant Improves mitochondrial function
(increases cell energy) Side effects: nausea, lack of appetite,
diarrhea
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Role of Coenzyme Q10 Results of recent studies:
Adding Coenzyme Q10 in midstageParkinson’s disease does not improve symptoms or UPDRS scores
Combination of Coenzyme Q10 and Creatinemay produce additive protective effects against dopamine depletion, reduce lesions, and improve motor performance in a mouse model
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Role of Coenzyme Q10 QE3 Study
National Institute for Neurological Disease and Stroke (NINDS)
Designed to examine high dose Coenzyme Q10 in slowing the progression of Parkinson’s or providing neuroprotection
Study halted in early June 2011 Investigators determined that there was no
neuroprotective or symptomatic benefit
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The Role of Simvastatin
Simvastatin (Zocor®) is an antihyperlipidemic Other medications in this class include:
Pravastatin (Pravachol®), Atorvastatin(Lipitor®), Lovastatin (Mevacor®), Rosuvastatin (Crestor®)
Reviewed for reduction in the incidence of dementia as well as prevention of disease progression
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The Role of Simvastatin
Results of recent studies: May reduce dementia
Also shown with atorvastatin to a lesser extent Lovastatin does not appear to reduce
Prevents some neurotoxic damage in rat models
May provide cell protection and improve motor function in mice models Pravastatin also protected cells but to a lesser
extent
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Important Points About Medications
Each person is unique! Different symptoms are present Different medications, doses, and frequency may be
needed Always take your medication on time
Do not double doses Store your medications in a cool, dry place Do not crush or chew extended release products Always check with your physician and pharmacist Check the $4 drug lists (currently only
benztropine and trihexiphenidyl)
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Contact Information
Karin M. Durant, Pharm.D.Director of Pharmacy
Florida Hospital East OrlandoPhone: 407-303-6707
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Questions?