medication management and strategies for wearing off ... • side effects
TRANSCRIPT
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
“When the levodopa honeymoon is over”
Eric J Pappert, MDParkinson’s Disease & Movement Disorders Center
Neurology Associates
“When the levodopa honeymoon is over”
Eric J Pappert, MDParkinson’s Disease & Movement Disorders Center
Neurology Associates
Medication Management& Strategies
Medication Management& Strategies
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Medication Options in Parkinson’sMedication Options in Parkinson’s• Carbidopa/Levodopa• Dopamine agonists• COMT-inhibitors• MAO-B Inhibitors• Antiviral agents (amantadine)• Anticholinergic medications
• Carbidopa/Levodopa• Dopamine agonists• COMT-inhibitors• MAO-B Inhibitors• Antiviral agents (amantadine)• Anticholinergic medications
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Carbidopa/LevodopaCarbidopa/LevodopaTreats symptoms of: • Stiffness / rigidity• Tremor• Slowness of movement• Walking problems
– Carbidopa reduces nausea and vomitingExamples: Sinemet®, Sinemet CR®, Rytary®, Duopa™, Parcopa®
Treats symptoms of: • Stiffness / rigidity• Tremor• Slowness of movement• Walking problems
– Carbidopa reduces nausea and vomitingExamples: Sinemet®, Sinemet CR®, Rytary®, Duopa™, Parcopa®
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Carbidopa/LevodopaCarbidopa/LevodopaAdvantages: • Most effective agent in treating symptoms• Robust response • Long history of use• Relatively rapid absorption• Well tolerated in many people
Advantages: • Most effective agent in treating symptoms• Robust response • Long history of use• Relatively rapid absorption• Well tolerated in many people
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Carbidopa/LevodopaCarbidopa/LevodopaLimitations:• Short half-life
– Pulsatile stimulation of dopamine receptors• Does not treat all features of PD
– Freezing, postural instability, autonomic dysfunction, speech abnormalities, dementia
– Eventual diminished response
Limitations:• Short half-life
– Pulsatile stimulation of dopamine receptors• Does not treat all features of PD
– Freezing, postural instability, autonomic dysfunction, speech abnormalities, dementia
– Eventual diminished response
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Carbidopa/LevodopaCarbidopa/LevodopaLimitations:• Reduced conversion as disease progresses
– Does not stop disease progression• Emergence of complications
– Motor fluctuations, dyskinesias (involuntary movements caused by medication)
Limitations:• Reduced conversion as disease progresses
– Does not stop disease progression• Emergence of complications
– Motor fluctuations, dyskinesias (involuntary movements caused by medication)
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Predictable: Wearing “Off” – Return of Parkinsonian signs or symptoms– Cramping / spasm – “Off Dystonia”– “Sensory / Behavioral / Autonomic Off”
§ Pain, restlessness§ Depression, anxiety, panic attacks§ Sweating, bloating, trouble breathing
Predictable: Wearing “Off” – Return of Parkinsonian signs or symptoms– Cramping / spasm – “Off Dystonia”– “Sensory / Behavioral / Autonomic Off”
§ Pain, restlessness§ Depression, anxiety, panic attacks§ Sweating, bloating, trouble breathing
Motor FluctuationsMotor Fluctuations
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Response to Levodopa and Disease Progression – “On/Off”Response to Levodopa and Disease Progression – “On/Off”
EarlyEarly Moderate Moderate AdvancedAdvanced
Clinical Effect
0 2 4 6Time (h)
Olanow CW, Agid Y. Available at: http://www.medscape.com/viewprogram/1847
• Very short duration of motor “ON” response
• “ON” time consistently associated with dyskinesias
• Very short duration of motor “ON” response
• “ON” time consistently associated with dyskinesias
• Shorter duration of motor “ON” response
• Increased incidence of dyskinesias
• Shorter duration of motor “ON” response
• Increased incidence of dyskinesias
• Long duration ofmotor response
• Low incidence of dyskinesias
• Long duration ofmotor response
• Low incidence of dyskinesias
Clinical Effect
0 2 4 6
Clinical Effect
0 2 4 6
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Motor FluctuationsMotor FluctuationsUnpredictable:
– Delayed “On” periods, dose failures – Sudden “Off” periods– “Super Offs”– Weak response at end of day
Unpredictable: – Delayed “On” periods, dose failures – Sudden “Off” periods– “Super Offs”– Weak response at end of day
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Strategies for Wearing OffStrategies for Wearing Off• Smaller doses of Levodopa less frequently• Low protein diet• Take Levodopa 90 mins
before meals• Consider change in medications:
– Long-acting Levodopa (Sinemet CR®)– Dopamine agonists or MAO-B inhibitors– Continuous dopamine infusion (Duopa®)
• Smaller doses of Levodopa less frequently• Low protein diet• Take Levodopa 90 mins
before meals• Consider change in medications:
– Long-acting Levodopa (Sinemet CR®)– Dopamine agonists or MAO-B inhibitors– Continuous dopamine infusion (Duopa®)
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
The Classics: Therapies for Motor Fluctuations
Entacapone/ComtanTolcopone/Tasmar
TrihexyphenidylBenztropine
MAO-B InhibitorsRasagiline/AzilectSelegiline/Eldepryl
Levodopa/Carbidopa
Ropinirole/RequipPramipexole/MirapexRotigotine/NeuproApomorphine/Apokyninjection
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Dopamine AgonistsDopamine AgonistsAdvantages:• Mimic the effect of dopamine• Longer-lasting effect than Levodopa• Effective single therapy (early Parkinson’s)• Reduced Levodopa-related motor complicationsExamples: Parlodel®, Requip®, Mirapex®, Neupro®, Apokyn®
Advantages:• Mimic the effect of dopamine• Longer-lasting effect than Levodopa• Effective single therapy (early Parkinson’s)• Reduced Levodopa-related motor complicationsExamples: Parlodel®, Requip®, Mirapex®, Neupro®, Apokyn®
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Dopamine AgonistsDopamine AgonistsDisadvantages:• Side effects• Does not completely prevent Levodopa-related motor
complications• Additional dopaminergic therapy needed as disease
progresses• Does not treat all features of PD (freezing, postural
instability, autonomic dysfunction, dementia)
Disadvantages:• Side effects• Does not completely prevent Levodopa-related motor
complications• Additional dopaminergic therapy needed as disease
progresses• Does not treat all features of PD (freezing, postural
instability, autonomic dysfunction, dementia)
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
COMT InhibitorsCOMT InhibitorsAdvantages• Extends duration of Levodopa effect
– By inhibiting enzyme COMT• Addition to Caribdopa/Levodopa for individuals
experiencing “wearing off” effect– No role as single therapy – used only in combination
with LevodopaExamples: Coman®, Tasmar®, Stalevo®
Advantages• Extends duration of Levodopa effect
– By inhibiting enzyme COMT• Addition to Caribdopa/Levodopa for individuals
experiencing “wearing off” effect– No role as single therapy – used only in combination
with LevodopaExamples: Coman®, Tasmar®, Stalevo®
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
• Light-headedness• Dry mouth• Confusion• Nightmares• Dyskinesias• Drowsiness
• Light-headedness• Dry mouth• Confusion• Nightmares• Dyskinesias• Drowsiness
Common Side Effects of MedicationsCommon Side Effects of Medications
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
• Impulse control disorders
• Sleep attacks
• Leg swelling
• Impulse control disorders
• Sleep attacks
• Leg swelling
Less Common Side Effects of MedicationsLess Common Side Effects of Medications
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Via ElectrodesVia Electrodes
Connected by a Subcutaneous Wire
Connected by a Subcutaneous Wire
Implantable Pulse Generator: Many Current ConfigurationsImplantable Pulse Generator: Many Current Configurations
Deep Brain Stimulation:Chronic (high-frequency) Electrical StimulationDeep Brain Stimulation:Chronic (high-frequency) Electrical Stimulation
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
/carbidopa
Levodopa/carbidopa IR & CR(RytaryTM)
Levodopa/carbidopa infusion(Duopa®)
The Newcomers: Therapies for Motor Fluctuations
The Newcomers: Therapies for Motor Fluctuations
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Opicapone
#1 Inhaled Apomorphine#2 Apomorphine infusion#3 Sublingual Apomorphine
MAO-B InhibitorsSafinamide
/carbidopa#1 Orafuse™ levodopa/carbidopa#2 Inhaled levodopa/carbidopa#3 Melevodopa- Liquid LD/CD#4 Levodopa/carbidopa infusion
Amantadine ER
The Future: Therapies for Motor Fluctuations
The Future: Therapies for Motor Fluctuations
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Adenosine A2A Inhibitors: TozadentGlutamate Antagonists: MavoglurantSerotonergic Agonists: Eltoprazine
Adenosine A2A Inhibitors: TozadentGlutamate Antagonists: MavoglurantSerotonergic Agonists: Eltoprazine
The Future:Treatments for DyskinesiasThe Future:Treatments for Dyskinesias
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Medication Action ItemsOr “Tenets To Live By”
Medication Action ItemsOr “Tenets To Live By”
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Tenet #1Tenet #1You must properly grieve the loss of part of your health and accept this as part of you
1. Denial2. Anger3. Bargaining4. Depression5. Acceptance
You must properly grieve the loss of part of your health and accept this as part of you
1. Denial2. Anger3. Bargaining4. Depression5. Acceptance
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
You must accept your portion of responsibilityfor your well-being
– General health & diet– Avoiding harm & vanity: using walker– Exercise your body & mind:
• Physical / speech / occupationaltherapies
• Home exercise program / POPS
You must accept your portion of responsibilityfor your well-being
– General health & diet– Avoiding harm & vanity: using walker– Exercise your body & mind:
• Physical / speech / occupationaltherapies
• Home exercise program / POPS
Tenet #2Tenet #2
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Be an effective communicator with MD & team– When do you wake up / sleep / eat meals?– List of your medications & times of day– What has changed & when does it occur?– What can’t you do that you must do or want to do?– Non-motor complaints:
• Memory / anxiety / sadness
Be an effective communicator with MD & team– When do you wake up / sleep / eat meals?– List of your medications & times of day– What has changed & when does it occur?– What can’t you do that you must do or want to do?– Non-motor complaints:
• Memory / anxiety / sadness
Tenet #3Tenet #3
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Tenet #4Tenet #4Focus on the positive:
– All that remains good– Have a purpose– Don’t allow PD to be who you are
Focus on the positive:– All that remains good– Have a purpose– Don’t allow PD to be who you are
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Questions:Questions:“Can you tell us if there are any new medication treatments
in the pipeline for Parkinson’s?”
“What is dystonia?Is it a disease, or just a symptom?”
“Is there anything I can do to slow downthe progression of the disease?”
“Can you tell us if there are any new medication treatmentsin the pipeline for Parkinson’s?”
“What is dystonia?Is it a disease, or just a symptom?”
“Is there anything I can do to slow downthe progression of the disease?”
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Questions:Questions:“I’ve been told that exercise is important.
How truly important is exercise to a personwith Parkinson’s?”
“Is it true that taking Levodopa earlier in PD decreases the medication’s long term usefulness?
Does this apply to higher doses also?”
“I’ve been told that exercise is important. How truly important is exercise to a person
with Parkinson’s?”
“Is it true that taking Levodopa earlier in PD decreases the medication’s long term usefulness?
Does this apply to higher doses also?”
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Questions:Questions:
“I can’t move at all sometimes. What is the cause, and what should I do about it?
“Do all people with Parkinson’s eventually have dementia? How severe will my cognitive problems become?
“I can’t move at all sometimes. What is the cause, and what should I do about it?
“Do all people with Parkinson’s eventually have dementia? How severe will my cognitive problems become?
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Questions:Questions:
Additional questions…Additional questions…
©2015 Davis Phinney Foundation
The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org
Thank You…Thank You…
Eric J. Pappert, MDParkinson’s Disease & Movement Disorders Center,
Neurology AssociatesSan Antonio, TX
Eric J. Pappert, MDParkinson’s Disease & Movement Disorders Center,
Neurology AssociatesSan Antonio, TX