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Parkinson’s Disease Foundation  

PD ExpertBriefing: Maximizing PD Medications: How to Get the Most Out of Your

Treatment Plan

Led By: Connie Marras, M.D., Ph.D., Associate Professor of Neurology, University of Toronto, Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson’s Disease, Toronto

Western Hospital, Canada

  To hear the session live on: Tuesday, April 28, 2015 at 1:00 PM ET.

DIAL: 1 (888) 272-8710 and enter the passcode 6323567#.

  View the session live on the computer by visiting:

http://event.netbriefings.com/event/pdeb/Live/medications2/ If you have any questions, please contact: Valerie Holt at vholt@pdf.org or call (212) 923-4700

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Introduction

James Beck, Ph.D. Vice President, Scientific Affairs Parkinson’s Disease Foundation

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Maximizing Medications: How to Get the Most Out of Your Treatment Plan

Connie Marras M.D., Ph.D. Associate Professor, University of Toronto

Morton and Gloria Shulman Movement Disorders Centre Edmond J Safra Program in Parkinson’s disease

Toronto Western Hospital

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Objectives

•  Review the classes of medication for Parkinson’s disease.

•  Learn about what effects (good and bad) can be expected from PD medications.

•  Understand ways to maximize the effectiveness of PD medications and minimize side effects.

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Classes of Medication for Motor Symptoms in PD

•  Levodopa •  Dopamine agonists •  Monoamine oxidase B (MAO-B) inhibitors •  Catechol-O-Methyl Transferase (COMT)

inhibitors •  Anticholinergics

Dopaminergic medications

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Classes of Medication for Motor Symptoms of PD

•  Levodopa –  Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide

(Prolopa), intestinal gel (Duodopa, Duopa)

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Classes of Medication for Motor Symptoms of PD

•  Levodopa –  Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide

(Prolopa), intestinal gel (Duodopa, Duopa) •  Dopamine agonists

–  Pramipexole, ropinirole, rotigotine (patch), cabergoline, apomorphine, others

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Classes of Medication for Motor Symptoms of PD

•  Levodopa –  Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide

(Prolopa), intestinal gel (Duodopa, Duopa) •  Dopamine agonists

–  Pramipexole, ropinirole, rotigotine (patch), cabergoline, apomorphine, others

•  Monoamine oxidase B (MAO-B) inhibitors –  Selegiline, rasagiline

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Classes of Medication for Motor Symptoms of PD

•  Levodopa –  Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide

(Prolopa), intestinal gel (Duodopa, Duopa) •  Dopamine agonists

–  Pramipexole, ropinirole, rotigotine (patch), cabergoline, apomorphine, others

•  Monoamine oxidase B (MAO-B) inhibitors –  Selegiline, rasagiline

•  Catechol-O-Methyl Transferase (COMT) inhibitors –  Entacapone, tolcapone

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Classes of Medication for Motor Symptoms of PD

•  Levodopa –  Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide

(Prolopa), intestinal gel (Duodopa, Duopa) •  Dopamine agonists

–  Pramipexole, ropinirole, rotigotine (patch), cabergoline, apomorphine, others

•  Monoamine oxidase B (MAO-B) inhibitors –  Selegiline, rasagiline

•  Catechol-O-Methyl Transferase (COMT) inhibitors –  Entacapone, tolcapone

•  Anticholinergics –  Trihexyphenidyl, cogentin, ethopropazine, others

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Classes of Medication for Non-Motor Symptoms in PD

•  Antidepressants •  Bladder antispasmodics for urinary

urgency •  Cholinesterase inhibitors for cognitive

impairment •  Remedies for constipation •  …

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How Do They Work?

•  Dopaminergic medications

– Levodopa Dopamine

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How Do They Work?

levodopa levodopa

dopamine

dopamine

COMT Inhibitor

COMT inhibitors (entacapone, tolcapone)

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How Do They Work?

•  Dopaminergic medications

– Levodopa Dopamine – COMT inhibitor: action of levodopa

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How Do They Work?

•  Dopaminergic medications

– Levodopa Dopamine – COMT inhibitor: action of levodopa

– Dopamine agonist •  Mimics dopamine at dopamine receptors

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How Do They Work?

•  Rasagiline, selegiline – Reduce breakdown of dopamine

•  Anticholinergics – Reduce activity of acetylcholine

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How Are They Used?

•  Levodopa – Cornerstone of treatment – Usually initial medication in patients >60 – Often initial medication in younger patients – Most effective medication for Parkinson’s

disease – Often least side effects

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How Are They Used?

•  Dopamine agonists (ropinirole, pramipexole, cabergoline…)

•  MAO-B inhibitors (selegiline, rasagiline)

– Longer acting than levodopa – May be used alone as initial treatment in

younger patients – Often used in combination with levodopa to

smooth out wearing off

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How Are They Used?

•  COMT inhibitors (entacapone, tolcapone) – Used in conjunction with levodopa – Increases duration of action of levodopa – Used to reduce end of dose wearing off

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How Are They Used?

•  Anticholinergics (trihexyphenidyl, others) – Used to treat tremor preferentially

•  Amantadine – Used primarily to reduce dyskinesias

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What Benefits to Expect from Your Medications

1.  Better speed of movement 2.  Better dexterity 3.  Less stiffness 4.  Less tremor (most but not all patients) 5.  Also possible:

•  Clearer thinking •  Less pain •  Better balance (esp. early on)

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Problems Encountered with Medications

•  Nausea (levodopa, dopamine agonists)

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Problems Encountered with Medications

•  Nausea (levodopa, dopamine agonists) •  Sleepiness (levodopa, dopamine agonists)

23  

Problems Encountered with Medications

•  Nausea (levodopa, dopamine agonists) •  Sleepiness (levodopa, dopamine agonists) •  Hallucinations/Confusion (particularly older

patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists)

24  

Problems Encountered with Medications

•  Nausea (levodopa, dopamine agonists) •  Sleepiness (levodopa, dopamine agonists) •  Hallucinations/Confusion (particularly older

patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists)

•  Lightheadedness (levodopa, dopamine agonists, amantadine)

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Problems Encountered with Medications

•  Nausea (levodopa, dopamine agonists) •  Sleepiness (levodopa, dopamine agonists) •  Hallucinations/Confusion (particularly older

patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists)

•  Lightheadedness (levodopa, dopamine agonists, amantadine)

•  Constipation (levodopa, anticholinergics)

26  

Problems Encountered with Medications

•  Nausea (levodopa, dopamine agonists) •  Sleepiness (levodopa, dopamine agonists) •  Hallucinations/Confusion (particularly older

patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists)

•  Lightheadedness (levodopa, dopamine agonists, amantadine)

•  Constipation (levodopa, anticholinergics) •  Dyskinesias (levodopa, dopamine agonists)

27  

Wearing off and Dyskinesias

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Maximizing Benefits

•  Dose •  Timing •  Food •  Constipation •  Stomach emptying •  Mood

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Maximizing Benefits

Dose •  Wide range, particularly with levodopa •  Increase dose gradually until sufficient benefit •  Reduce when adverse effects appear •  Do not stop suddenly!

Years D

ose 30  

Maximizing Benefits

•  Timing (levodopa, dopamine agonists) – Early on rarely matters – Later can be very important

Hours

Levodopa

dose dose dose

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Maximizing Benefits

Hours

Levodopa

dose dose dose

Dyskinesia

Wearing off (tremor, slowness)

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Patient Diary

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End of Dose Wearing Off •  Reduce interval between doses •  Levocarb CR (controlled release) •  Add dopamine agonist •  Add COMT inhibitor •  Add selegiline •  Liquid Sinemet •  Advanced therapies (levodopa/carbidopa

intestinal gel, deep brain stimulation)

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Food •  Protein competes with levodopa for transport

from gut to blood and into brain •  Can result in sudden OFF periods or delayed ON •  Avoiding protein 30 minutes before and one

hour after medication may improve effect –  Meat, fish, eggs, dairy

•  Medication on empty stomach may be even better

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Constipation

•  Is a symptom of Parkinson’s disease •  Can be made worse by PD medications •  Reduces absorption of medication •  Tips:

– Drink plenty of water – Exercise – Take daily laxative for prevention if necessary

36  

Slow Stomach Emptying

•  Delayed emptying of the stomach is a symptom of Parkinson’s disease

•  Delays onset of action of levodopa •  Causes bloating, reflux •  Tips:

– Domperidone (not available in US)

37  

Mood

•  Depression and anxiety are common symptoms of PD

•  Depression and anxiety commonly precede motor symptoms

•  Mood has a profound effect on efficacy of medication

38  

Minimizing Adverse Effects

•  Nausea – Take medication with food (non-protein if

necessary) •  E.g. bread, crackers, apple sauce, other fruit

– Domperidone, other antinauseant medications

39  

Minimizing Adverse Effects

•  Lightheadedness on standing –  Drink plenty of water –  Take extra salt –  Compression stockings –  Elevate head of bed –  Reduce dose of levodopa, dopamine agonist,

amantadine –  Domperidone, extra carbidopa –  Medications to raise blood pressure: midodrine,

fludrocortisone

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41  

42  

43  

Dyskinesias

Levodopa

Hours

1. Peak Dose Dyskinesias At best effect of levodopa/dopamine agonist

44  

Dyskinesias

Levodopa

Hours

1.  Peak Dose Dyskinesias At best effect of levodopa/dopamine agonist

Reduce peak action of medication

45  

Peak Dose Dyskinesias: Treatment

•  Reduce dose of medication (number of tablets with each dose)

•  Amantadine •  Advanced therapies (duodopa, deep brain

stimulation)

46  

Dyskinesias

Levodopa

Hours

2. Diphasic dyskinesias With wearing off and start of effect

47  

Dyskinesias

Levodopa

Hours

2. Diphasic dyskinesias With wearing off and start of effect

Reduce wearing off 48  

Diphasic Dyskinesias (Dyskinesias with Wearing Off): Treatment

•  Reduce wearing off: •  Take medication more frequently •  Lengthen duration of action of levodopa

–  Sinemet CR –  COMT inhibitor

•  Adjunctive medication for wearing off (MAO-B inhibitor, dopamine agonist)

•  Advance therapies (levodopa/carbidopa intestinal gel, deep brain stimulation)

49  

Hallucinations/Confusion •  Reduce medications •  Remove

1.  Anticholinergics 2.  Amantadine 3.  COMT inhibitor 4.  MAO-B inhibitor

•  Reduce levodopa •  Antipsychotic medications (quetiapine,

clozapine)

50  

Sleepiness

•  Reduce dose of medication •  Minimize dopamine agonist •  Medications to promote wakefulness (e.g.

modafinil)

51  

Impulse Control Disorders

•  Compulsive – Gambling – Shopping – Eating – Hypersexuality

•  Associated with dopamine agonists, levodopa

52  

Impulse Control Disorders: Management

Early detection: have partner, family look out for concerning behaviours Prevent loss: prevent access to cash if necessary Treatment: Reduce/discontinue dopamine agonist

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Key tips •  Don’t delay treatment at the expense of quality of life •  Treatment of depression and anxiety are critical to good

effect of medication •  Timing of benefits and adverse effects in relation to dose

are often key to optimizing benefit •  PD does not change suddenly! Look for other causes:

–  Constipation –  Infection (urine, lungs) –  Other medical illness

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Thank You!

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“Just like the Tin Man in the Wizard of Oz, I need my oil can to live with Parkinson's disease. The pillbox depicted in my digital photograph is much like that oil can; it keeps me moving day by day.”

“Day by Day” by Wendell Lowe, PDF Creativity Artist

Questions and Discussion

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Resources from PDF

Parkinson’s  HelpLine    • Available  at  (800)  457-­‐6676  or  info@pdf.org  • Monday  through  Friday  • 9:00  AM  –  5:00  PM  ET  

Fact  Sheets  • Understanding  Parkinson’s  MedicaLons  

PD  Resource  List  • 750  resources  in  the  Parkinson’s  community  

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Upcoming PD ExpertBriefings

Challenges of Advanced PD and Tips for Better Living Tuesday, June 23, 1:00 PM - 2:00 PM ET Peter Fletcher, M.B.Ch.B., M.Sc., Consultant Physician, Department of Old Age Medicine, Gloucestershire Hospitals NHS Foundation Trust, United Kingdom

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