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Pharmacology and

Parkinson’s Disease:

What Every Therapist

Should Know

KIRK SEALE, PHARM D, MS

KSEALE@UFL.EDU

Disclosure

I have no actual or potentially relevant

financial relationship to disclose and no

conflict of interest in relation to this

program.

Objectives

Discuss the prevalence, the risk factors, and the diagnosis of Parkinson’s disease

Discuss the Clinical presentation of PD

Review common medications used to

treat PD

Examine medication strategies

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"The most humbling experience in my life has been

the time that I spent with families and with patients

suffering from Parkinson's..... time after time ...

we have uncovered simple issues and secrets that

have changed people's lives".

Michael S. Okum, MD University of Florida Center for Movement disorders

5,000

B.C.Mucuna Pruriens

"VELVET BEAN“

5,000 B.C.Mucuna Pruriens

"VELVET BEAN“

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http://visibleearth.nasa.gov/view_cat.php?scheme=COLLECTION

Risk Factors:

Advancing age

>60 y/o

Family history

first degree relative

Male’s White, Black, Hispanics

EnvironmentWillis AW, et al. Geographic and Ethnic Variation in Parkinson Disease: A Population-Based Study of US Medicare Beneficiaries,

Neuroepidemiology. 2010 April; 34(3): 143–151. Published online 2010 January 15

Diagnosis of Parkinson’s disease

No single method to make positive diagnosis

Relies heavily on

Risk factors

Medical / Medication history

Physical Exam

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DIAGNOSIS OF PARKINSON’S DISEASE

Progressive Supranuclear Palsy (PSP)

Multiple System Atropy (MSA)

Dementia with Lewy bodies (DLB)

Corticobasal Degeneration (CBD)

Multiple System Atropy (MSA)

Vascular Parkinsonism

DRUG INDUCED PARKINSONISM(pseudoparkinsonism)

Shin,HW, Chung SJ, Drug induced parkinsonism, J Clin Neurol. 2012 March; 8(1): 15–21.

Antipsychotics (Typical and Atypical)

METOCLOPRAMIDE (Reglan, Others)

Stimulants

SOME CALIUM CHANEL BLOCKERS

Nausea medications

Antiepileptic drugs

Reserpine- limited use

EXAMPLES:

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SYMPTOMS OF

PARKINSON’S DISEASE

MOTOR SYMPTOMS NON-MOTOR

SYMPTOMS

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NON-MOTOR SYMPTOMS (C. A. P. S.)

Cognitive Disorders

Autonomic Dysfunction

Psychiatric Symptoms

Sleep Disorders

SYMPTOMS OF

PARKINSON’S DISEASE

MOTOR SYMPTOMS NON-MOTOR SYMPTOMS

_________________________

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_C_______________________

_A_______________________

_P_______________________

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_S______________________

T.R.A.P.

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SYMPTOMS OF

PARKINSON’S DISEASE

MOTOR SYMPTOMS NON-MOTOR SYMPTOMS

_T________________________

_R________________________

_A________________________

_________________________

_P________________________

_C_______________________

_A_______________________

_P_______________________

_________________________

_S______________________

1) TREMOR

2) RIGIDITY

3) AKINESIA or

BRADYKINESIA

4) POSTURAL INSTABILITY

http://www.pharmacytimes.com/publications/issue/2010/March2010/FeatureParkinsons0310 Wick, Janette Y. Treating Parkinson's disease: The Pharmacist Role, Pharmacy Times, March 19, 2010.

MOTOR SYMPTOMS:

Begins:

Unilaterally

Localized

Non-purposeful movement

TREMOR

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Mr. B. described a “shaking” of his index

finger, however upon further Examination

you see a definite “pill rolling” of the index

finger and thumb.

PILL ROLLING TREMOR

COURTESY OF

http://www.youtube.com/watch?v=ZY1uEmgvp0U

RIGIDITY

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AKINESIA or BRADYKINESIA

A= Without, KINETIC = Movement

BRADY= Slow, KINETIC= Movement

Slowed movement and reaction times

Reflect repetitive movements

Irregular pattern with repetition

Appears to be related to the degree of

dopamine deficiency

Postural Instability

Impaired balance

Stiff muscles

Shuffling gait

Slowed reflexes

Occurs late in disease

Balance + gait training

PARKINSON’S DISEASE GAIT DEMONSTRATIONCourtsy of Yasser Metwally Professor of neurology

http://www.youtube.com/watch?v=j86omOwx0Hk&NR=1&feature=endscreen

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http://schoolworkhelper.net/parkinson%E2%80%99s-disease-symptoms-inheritance/

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5 STAGES OF PARKINSON’S

STAGE ONE

STAGE TWO

STAGE THREE

STAGE FOUR

STAGE FIVE

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“MEDICATIONS ARE PROBABLY THE SINGLE MOST IMPORTANT HEALTH

CARE TECHNOLOGY IN PREVENTING

ILLNESS, DISABILITY AND DEATH IN

THE GERIATRIC POPULATION.”

Avorn J. Medication use and the elderly: current status and opportunities Health Affairs, 14, no. 1, (1995)

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Balance:

Acetylcholine

Dopamine

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Video Courtesy of Dr. Prodigious

http://www.youtube.com/watch?v=jyBakRkzswU

MEDICATION

THERAPY

Mr. B. is in good health and takes no medications.

Upon PE you notice there is a slight tremor of the head,

a stooped posture and he ambulates with slow

shuffling steps. He appears very unsteady.

His wife later confides in you that

He has been very forgetful lately and does not sleep well

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SYMPTOMS OF

PARKINSON’S DISEASE

MOTOR SYMPTOMS NON-MOTOR SYMPTOMS

_T____tremor______________

_R____rigidity?_____________

_A____bradykinesia_________

_________________________

_P____postural instability____

_C___________?___________

_A___________?___________

_P___________?___________

_________________________

_S___________?___________

MEDICATION TREATMENT

LEVODOPA (L-DOPA) Most commonly used

Most potent, most effective for PD

Usually combined with Carbidopa

(Sinemet).

Immediate release and Sustained release

Provides best symptomatic effects

Increases dopamine in the brain

CARbidopa

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Levodopa /Carbidopa (Sinemet) Side Effects

Nausea/ Vomiting

Drowsiness

Postural hypotension

Hallucinations / Very vivid dreams

Compulsive behavior

Anxiety, Nervousness, Agitation

Dyskinesias- usually with long-term use

Levodopa / Carbidopa

High protein diet interferes

with absorption

L-Dopa should be taken with: A) Carbidopa B) in the evening after

supperC) With a Big MacD) None of the above

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You are giving PT to Mr. B. currently taking L-Dopa/

Carbidopa for 5 years. He complains that his

medications seem to be less effective. The PD

symptoms reappear hours before the next scheduled dose

of his medications. This is referred to as?

A. FreezingB. Medication Non-Compliance

C. On-Off PhenomenonD. None of the above

ON-OFF PHASE VIDEO COURTESY OF

Professor Kurt Illig, University of Saint Thomas, St. Paul, MN

http://www.youtube.com/watch?v=sf1N0Zf5IqA

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On-Off Fluctuations

On period / Off period

Mornings or prior to next dose

High protein meals?

Timing is everything

Levodopa / Carbidopa

Immediate release – take 1 Hr after meals

Sustained release – with meals

ON-OFF treatment options:

Timing of medication

Diet

Release formulation

sustained vs immediate release

Other medications

Medication TreatmentDopamine Agonist

Can be used early in treatment

Generally used as add-on therapy to Levodopa/Carbidopa

Drugs most commonly used:

Primipexole (Mirapex)

Ropinirole (Requip, Requip XL)

Bromocriptine (Parlodel)

Apomorphone (Apokyn)- injection form only

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SIDE EFFECTS Dopamine Agonist

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You are giving PT to a patient that has had PD for 7 years. You notice he is unable to move for short

periods of time. Even with encouragement he states “My feet feel like they are glued to the floor.” This PD phenomenon is referred to as:

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Freezing Of Gait

Disabling

May worsen as

disease progresses

Tend to occur

End of dosing interval

Can be unpredictable

Freezing of Gait Treatments:

Timing of medications

Dose increase

Dosing interval

Addition of other medications

MAO-B INHIBITORS

Eldepril (Selegiline)

Azilect (Rasagiline)

Help increase Dopamine in the brain

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Selegiline (Eldepril)

Eldepril (Selegiline)

May produce a wake enhancing effect

May lead to

Nervousness

Agitation

confusion

INSOMNIA

Take medication in AM.

SIDE EFFECTS MAO-B Inhibitors:

Insomnia – esp. with seleigline

Lightheadedness (postural hypotension)

Agitation

Vivid dreams

Hallucinations

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Freezing: Other Treatment Options:

Rhythmic auditory cues

Visual stimuli

Carrying out each sequence consciously

Use of correct walking aids

Use of correct footwear

Mr. B has been taking L-Dopa for more than 7 years plus

a dopamine agonist for his PD and Rasagiline for freezing episodes. During PT you notice abnormal involuntary movements of

his neck and arms. These abnormal involuntary movements are referred to as:

Video dyskinesia

Neal Hermanowicz, MDDepartment of NeurologyUniversity of California, Irvine

http://www.dailymotion.com/video/xgfy5m_parkinson-s-symptoms-what-is-dyskinesia_lifestyle#.UW7h2Mpu5_c

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NO EFFECT- off phase

DRU

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TRATIO

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TIME

DYKSINESIA OPTIONS:

TIMING??

Change in medication

Change in dosing

Other medications

Other treatments

Amantadine

Place in therapy:

Side effects Orthostatic hypotension

Edema of extremities

Confusion

Hallucinations

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COMT INHIBITORS

PREVENTING THE

PERIPHERAL BREAKDOWN

OF LEVODOPA

NEVER USED ALONE

DYSKINESIA, HYPERKINESIA

AND HALLUCINATIONS CAN

OCCUR

Anticholinergics:

Cogentin (Benztropine)

Artane (Trihexyphenidyl)

Limited use in the elderly

Side effects:

On the Horizon

Levodopa / Carbidopa ER Capsule (Rytary®)

•Pending FDA approval

• Novel formulation and dosage

• Immediate and ER components

• Longer duration of action

36.25/145 mg, 61.25/245 mg, 97.50/390 mg

• Early to Advanced PD

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Deep Brain Stimulation

Requiring additional symptomatic control

Patients responsive to Levodopa / Carbidopa but still with motor

symptoms despite best medical therapy

Deep Brain Stimulation

Symptomatic for motor symptoms

Does not replace medications

Reduces fluctuations and dykinesias

“May” improve gait/posture Does not slow progression of PD

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BALANCE

“My point is, life is about balance.

The good and the bad.

The highs and the lows.

The pina and the colada.”