Medications For Parkinson’s Disease

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Medications forParkinson’s DiseaseGail A. Kang, M.D.San Francisco VA Medical CenterParkinson’s Disease Research Education Clinical CenterNovember 15, 2007History of Parkinson’s Disease First described in 1817 byJames Parkinson, Englishphysician Disease named in hishonor 50 years later1

Parkinson’s Disease Average age of onset: 60 years Approximately 1 million individuals in United States Second most common neurodegenerative disease Slightly higher rate of PD in men Rural living, agricultural work and exposure to wellwater associated with higher incidence Minority of cases have strong family historyWhat happens to the brain inParkinson’s Disease?2

Abnormal Communicationof Motor Pathway in PDBasalGangliaSubstantiaNigraPrimary Clinical Features ofParkinson’s DiseaseA neurological disorder characterized by: Slowness of movement Tremor Rigidity Postural instability3

What types of treatment are therefor Parkinson’s Disease? Symptomatic Pharmacological Motor Non-motor Surgical Neuroprotective RestorativeMedications toTreat Motor Symptoms Dopaminergic Medications Sinemet Dopamine agonists (pramipexole, ropinirole,apomorphine, rotigotine) MAO-B Inhibitors selegiline, rasagiline COMT Inhibitors entacapone, tolcapone4

Sinemet (Carbidopa/Levodopa) Levodopa was discovered in early 1960’s Remains most effective pharmacologicaltreatment for Parkinson’s Disease Metabolizes to dopamine in the brain as wellas in the rest of the bodySinemet has two components:carbidopa and levodopaSinemet 25/100Sinemet 25/250Sinemet SA 50/2005

Carbidopa helps in minimizing sideeffects of Levodopa Carbidopa helps minimize stomach upset andlightheadedness Need at least 75 mg carbidopa for every 300 mglevodopa Additional supplementation is availableTiming of when Sinemet is taken Protein can interfere with the absorption oflevodopa to the brain take Sinemet 45 minutes before or aftermeals If have stomach upset, can take with nonprotein containing food Directions for administration frompharmacy may be incorrect6

What symptoms typicallyimprove with Sinemet? Slowness of movement Tremor Rigidity /-Balance and FreezingWhat symptoms do not typicallyimprove with Sinemet? Memoryproblems Depression Urinary problems Low blood pressure7

Potential Side Effects of Sinemet Nausea/vomitingLightheadedness/decrease in blood Methods to CounteractPotential Side Effects of Sinemet Nausea/Vomiting Carbidopa Non-protein containing food Anti-nausea medications Fatigue Minimize naps during day Exercise Provigil Selegiline8

Methods to CounteractDecrease in Blood Pressure Decrease/discontinue medications which maybe contributing (blood pressure medications,diuretics, selegiline, dopamine agonist)Increase salt/fluids in dietEat small mealsRaise head of bedSupport hose to prevent pooling of blood inlegsMethods to TreatPsychosis Reduce or eliminate any non-essential medicationswhich may be contributing to confusion Reduce Parkinson’s disease medications ifpossible from motoric standpoint 1st discontinue selegiline, Artane, amantadine 2nd lower dopaminergic medications Anti-psychotic medications Quetiapine (Seroquel) Clozapine (Clozaril): need for weekly blooddraw; 1% patients develop drop in white bloodcell count9

Dyskinesia VideoDyskinesias and Sinemet Dyskinesias typically begin three to five years aftertreatment initiation More common in patients with younger onset ofdisease Non-pulsatile delivery may decrease or delay risk ofdyskinesias10

Treatment of Dyskinesias Decrease Sinemet dosage amount Consider addition of dopamine agonist Consider addition of amantadine If severe dyskinesias, consider deep brainstimulation surgeryDopamine Agonists Examples: Pramipexole(Mirapex) Ropinirole (Requip) Apomorphine infusion (Apokyn) Rotigotine patch11

How is a dopamine agonist differentfrom Sinemet? 1997-2007 GlaxoSmithKlineAdvantages of Dopamine Agonists Can be effective at treating all of motor symptoms ofParkinson’s disease, especially tremor Can delay need for Sinemet Can decrease “off time” when used in combinationwith Sinemet Delay in development of dyskinesias when used asmonotherapy early in disease Provides possible neuroprotection Good choice for initial treatment in many patients,especially young-onset12

Potential Side Effectsof Dopamine Agonists Nausea/vomitingLightheadedness/Decrease in Blood PressureConfusion/HallucinationsFatigueSleep AttacksImpulse Control BehaviorsSleep Attacks13

Impulse Control BehaviorsApomorphine(Apokyn) Fast-acting“rescue” treatmentSelf-injected underthe skinPremedicationwith anti-nauseamedication14

Rotigotine Patch (Neupro) Advantages: only requires once a dayadministration absorption not influenced by food continuous drug delivery Disadvantages: skin area irritation less effective than oral dopamineagonists dosages used in some studies werehigher than FDA approved doseMAO-B Inhibitors:Rasagiline 5x more potent that selegiline No methamphetamine metabolite Mild benefit in motor symptoms In patients not taking any other PD medications(TEMPO study, 2002) Decreases “off” time by almost two hours inpatients already taking Sinemet (PRESTO study)15

MAO-B Inhibitors:Rasagiline May provide some degree of neuroprotection metabolite may aid in cell death prevention patients on rasagiline for one year had less severemotor problems in comparison to individuals onrasagiline for only six months (Delayed-StartTEMPO study, 2004)Well-tolerated; most common side effects includeweight loss, nausea/vomitingFinal Tips for Managementof PD Medications Pill timer Symptoms in relation to timing of medications Recognize each patient’s medication regimen istailored for him/her Ongoing communication with health care providerregarding benefits/side effects16

San Francisco VA Medical Center Parkinson’s Disease Research Education Clinical Center November 15, 2007 History of Parkinson’s Disease First described in 1817 by James Parkinson, En