PARKINSONS DISEASE - PowerPoint PPT Presentation

1 / 25
About This Presentation
Title:

PARKINSONS DISEASE

Description:

Bradykinesia/Akinesia. Postural imbalance. Simian posture. Propulsion/retropulsion ... Sleep benefit lost; early morning akinesia (foot dystonia) ... – PowerPoint PPT presentation

Number of Views:317
Avg rating:3.0/5.0
Slides: 26
Provided by: marc2201
Category:

less

Transcript and Presenter's Notes

Title: PARKINSONS DISEASE


1
PARKINSONS DISEASE
  • Marc Lapointe, BS, PharmD, BCPS, BCNSPAssociate
    ProfessorCollege of Pharmacy, Pharmacy and
    Clinical ServicesCollege of Medicine,
    Neurological Sciences

2
Objectives
  • GOAL After attending this session the student
    should be able to assess a patient with
    Parkinsons disease and develop a rational
    therapeutic plan to manage and monitor this
    patient.
  • LEARNING OBJECTIVES
  • List the clinical characteristics of Parkinsons
    disease.
  • Identify the medications used to treat
    Parkinsons disease, their mechanism of action,
    effectiveness and adverse effects.
  • Recommend dosing of the medications used to treat
    Parkinsons disease.
  • Be able to educate patients/families regarding
    Parkinsons disease.
  • Use problem solving skills and knowledge of
    Parkinsons disease to resolve patient cases.

3
Facts
  • Incidence
  • 100 to 200 cases per 100,000 people.
  • 500,000 to 1 million people affected in the U.S
  • 20 new cases out of 100,000 in the population are
    diagnosed with Parkinsons each year.
  • Pharmacoeconomics of Parkinsons disease
  • 26 billion annually in direct and indirect costs
  • Medication costs average 5000 per person per year

4
Classification
  • Primary Idiopathic Parkinsons Disease
  • Secondary
  • Infectious
  • Atherosclerotic
  • Drug Induced
  • Toxins
  • Structural CNS Disorders
  • Metabolic disorders

5
Clinical Characteristics
  • Tremor
  • Rigidity
  • Bradykinesia/Akinesia
  • Postural imbalance
  • Simian posture
  • Propulsion/retropulsion
  • Short shuffling steps/festinating gait

6
Epidemiology
  • Occurs equally in males and females.
  • Age of onset 50 to 80 years.
  • 1 of persons age of 65 years or older
  • 6.8 of persons older than 80 years old

7
Pathophysiology
  • Degeneration of dopamine neurons
  • Disruption of normal dopamine levels
  • Neurotransmitter imbalances
  • Acetylcholine
  • Norepinephrine
  • Serotonin
  • GABA
  • Lewy bodies
  • Free radical formation

8
Assessment
  • Hoehn and Yahr of Parkinsonism
  • Stage 1 Unilateral involvement
  • Stage 2 Bilateral involvement no postural
    abnormalities
  • Stage 3 Bilateral involvement mild postural
    imbalance
  • Stage 4 Bilateral involvement postural
    instability
  • Stage 5 Fully developed disease restriction to
    bed or chair

9
Non-Drug Therapies
  • Diet
  • Exercise
  • Coping skills
  • Compliance
  • Management of side effects
  • Communication
  • Surgical Transplantation
  • Deep brain stimulation
  • Pallidotomy, Thalamotomy

10
History
  • 1967 Levodopa-Carbidopa
  • Benztropine
  • Biperiden
  • Ethopropazine
  • Procyclidine
  • Trihexyphenidyl
  • Diphenhydramine
  • Orphenadrine
  • Amantadine
  • Pergolide
  • 1997 Pramipexole
  • 1997 Ropinirole
  • Selegiline
  • Tolcapone
  • Entacapone
  • Rasagiline

11
Indications for Anti-Parkinsonian Agents
  • Treatment of Mild to Moderate Symptoms
  • Anticholinergic Agents
  • Amantadine
  • Dopamine Agonists
  • Selegiline
  • Treatment of Moderate to Severe Symptoms
  • Levodopa-Carbidopa
  • Cathechol-O-Methyl Transferase Inhibitors (COMT)
  • Dopamine Agonists
  • Selegiline

12
Dopamine
13
Mechanism of Action
  • Anticholinergics decrease cholinergic function
  • Effective for tremor and dystonia
  • Amantadine enhances the production and release
    of dopamine and inhibits uptake.
  • Effective for mild bradykinesia and rigidity
  • Tachyphylaxis
  • Levodopa-Carbidopa replaces dopamine via
    conversion by dopa decarboxylase within
    presynaptic neurons

14
Mechanism of Action
  • Dopamine Agonists
  • stimulate dopamine receptors directly, bypassing
    the presynaptic neurons.
  • Effective for tremor, bradykinesia, rigidity
  • Selegiline
  • Irreversibly inhibits oxidative deamination of
    dopamine by monoamine oxidase type B, increasing
    dopamine concentrations
  • Cathechol-O-Methyl Transferase Inhibitors (COMT)
  • maximizes the brain entry of levodopa by
    decreasing its peripheral metabolism and
    extending the time levodopa is present in the
    circulation

15
Choosing an Agent
  • Anticholinergic mild to moderate symptoms only
    (Stage 1, Stage 2)
  • Amantidine mild to moderate symptoms only (Stage
    1, Stage 2)
  • Dopamine agonists mild to moderate (Stage 2 to
    Stage 3)
  • Selegiline mild to moderate, moderate to severe
    in conjunction with levodopa (Stage 2 Stage V)
  • Levodopa-Carbidopa moderate to severe (Stage 3
    5)
  • COMT inhibitors moderate to severe and only in
    conjunction with Levodopa-Carbidopa (Stage 3 5)

16
(No Transcript)
17
Predictors of Clinical Response
  • Accurate diagnosis
  • Accurate medication for the correct stage of
    illness
  • Compliance with medications
  • Length of illness

18
Anti-Parkinsonian Drug Efficacy
  • Antiparkinsonian agents are 20 to 25 effective
    for the treatment of mild to moderate
    Parkinsons disease
  • Amantadine is 50 effective in the treatment of
    mild to moderate Parkinsons disease.
  • Levodopa/Carbidopa is 50 to 85 effective for the
    treatment of moderate to severe Parkinsons
    disease.
  • Dopamine agonists are 75 effective in moderate
    Parkinsons disease
  • Selegiline is 50 to 70 effective in the
    treatment of moderate Parkinsons
  • COMT Inhibitors are 85 effective in the
    treatment of moderate to severe Parkinsons.

19
Monitoring Drug Therapy
  • Wearing off phenomenon
  • If wearing off persists but is less than 60
    minutes, increase the dose of levodopa-carbidopa.
  • If wearing off persists but is more than 60
    minutes, increase the frequency of the dose.
  • On-Off phenomenon
  • Add dopamine agonists selegiline tolcapone
    infusions of L-dopa or dopamine agonists
    consider a drug holiday.
  • Decline of the response to individual doses of
    levodopa-carbidopa
  • Patient not aware of the effects of an individual
    dose
  • Mid-afternoon loss of benefit requires an
    additional dose
  • Sleep benefit lost early morning akinesia (foot
    dystonia)
  • Regular wearing off every 4 hours, levodopa
    response gradually shortens more
  • Frequent wearing off with abrupt on-off
    reactions requires dosing at intervals of two
    hours or less, response to each dose is
    unpredictable.
  • Freezing
  • Increase carbidopa/L-dopa dose, dopamine
    agonists gait modifications (tapping, rhythmic
    commands, stepping over objects, rocking)

20
Treatment Resistance
  • Individualization of doses
  • Move to sustained release formula of
    levodopa/carbidopa when wearing off becomes
    prevalent.
  • With disease progression, amantadine,
    anticholinergics, and selegiline lose their
    effectiveness, use a brief trial off therapy to
    re-evaluate therapy
  • Add a COMT inhibitor to extend the duration of
    action of carbidopa/levodopa

21
Clinical Pearls
  • Levodopa and Bioavailability
  • Amantadine and Tachyphylaxis
  • Dose of levodopa and Dyskinesia
  • Intra- and intersubject variability with
    anticholinergic
  • Immediate-release / Sustained-release Levodopa
  • Bioavailability
  • Onset
  • Conversion
  • Levodopa vs Dopamine agonists
  • Motor vs Neuropsychiatry
  • Relative efficacy
  • Fluctuations
  • 25 reduction of levodopa

22
Case / Discussion
  • A.B., a 53 year old surgical nurse complains to
    you about stiffness in her hands and asks you if
    you think the stiffness might be due to her
    arthritis. On observation you note that she has
    a tremor in her left hand. What questions might
    you ask A.B.?
  • You refer A.B. to a physician and the diagnosis
    is Parkinsons disease. The physician asks you
    for the starting dose for levodopa.
  • What do you think about the choice of medication?
  • Would you recommend levodopa? If you why, if no,
    what would you choose?
  • What would you monitor in AB?
  • What is a typical starting dose for Sinemet?
    Explain how you would titrate it to a maintenance
    dose.

23
Case / Discussion
  • B.C., a 76 year old male with a 15 year history
    of Parkinsons disease complains that she is
    having an increasing number of off episodes.
  • What is an off episode? Differentiate it from
    a wearing off episode.
  • What pharmacologic suggestions could be made to
    improve B.C.s function?
  • What non-pharmacologic suggestions could be made
    to improve BCs function?
  • In speaking with BC, you realize he has been
    doubling some of his Sinemet CR doses and
    occasionally he chews them because he has
    difficulty swallowing. Explain how you will
    educate BC?
  • If you were going to add something to BCs
    regimen explain what you would choose, and how
    you would dose it.

24
Case / Discussion
  • KM is an 81 year old female with a history of
    Parkinsons disease. Her son tells you that KM
    has been talking to people who are not there, and
    has been waking up in the middle of the night
    with nightmares. Her physician recently attempted
    to decrease the dose of her Sinemet, but KM did
    not tolerate the decrease in dose. On your
    profile you find the current medications.
  • Verapamil CR 240 mg
  • Amantadine 200 mg/day
  • Levodopa/Carbidopa 25/250 one tablet tid
  • Trihexiphenidyl 2 mg tid
  • Glucotrol 5 mg qd
  • What questions would you ark KM and her son?
  • What changes would you recommend in her therapy?
  • If you found out that she was also experiencing
    constipation and falls, what would you recommend?

25
Case / Discussion
  • MP, a 59 year old male, asks you about recent
    onset of stiffness and cogwheel rigidity. You
    examine the patients profile.
  • Indomethacin 50 mg tid
  • Captopril 12.5 mg/day
  • Famotidine 40 mg/day
  • Paroxetine 20 mg/day
  • Haldol 5 mg bid
  • What do you think is happening to MP?
  • What would you recommend to MPs physician?
Write a Comment
User Comments (0)
About PowerShow.com