Parkinson’s Disease
Dr. Andrew Schmelz,
PharmD
anschmel@purdue.edu
Post-Doctoral Teaching Fellow
Dept of Pharmacy Practice
Purdue University
March 4, 2009
Objectives
Describe physiologic changes in patients
with Parkinson’s Disease
 List symptoms with which Parkinson’s
patients typically present
 List and define extrapyramidal symptoms
 For each drug class, state one example
drug, mechanism of action, common dose,
and associated side effects

Background
Parkinson’s disease: a
degenerative disease
of the brain that
impairs motor skills,
speech, and other
functions
 Especially prevalent in
elderly white males
 Characterized by
specific changes in
motor function

Pathophysiology

Substantia nigra
– Region in brain that plays a role in movement
– Parkinson’s is characterized by loss of
neuronal cells in this region
Pathophysiology (cont.)

Neurons depleted in the substantia nigra
result in imbalance of dopamine and
acetylcholine
– Reduced dopamine activity
– Normal acetylcholine activity
Dopamine
Acetylcholine
Acetylcholine
Dopamine
Symptoms
Tremor (and pill rolling)
 Bradykinesia
 Rigid muscles (cogwheel rigidity)
 Impaired posture/balance
 Loss of autonomic movement
 Speech changes
 Dementia

YouTube Video

http://www.youtube.com/watch?v=S5EE8
EVv600&feature=related
Extrapyramidal (EPS) Symptoms
EPS symptoms usually occur secondary to
medication
 Dyskinesias (Movement disorders)

– Irregular body movements
– Tongue movements, lip smacking
– Finger movements, arm/leg movements

Akathisia (Restlessness)
– Extreme form of internal/external restlessness
– Can be exhausting and debilitating
EPS Symptoms (cont.)

Dystonia (Muscle tension disorders)
– Very strong, painful muscle contractions
– Unusual twisting of parts of the body

“Tardive” Disorders
– Indicates long-term observation of EPS
symptoms
– Can be of any classification listed above
– Often indicate permanence
YouTube Videos

Dyskinesias
– http://www.youtube.com/watch?v=FUr8ltXh1
Pc&feature=related

Akithisias
– http://www.youtube.com/watch?v=pSXzuCNlI
6Q

Dystonias
– http://www.youtube.com/watch?v=nG1XrmEa
sVk&feature=related
Pharmacotherapy

Approaches of therapy
– Slow loss of dopamine in brain
– Improve symptoms by other means
– Prevent/delay non-muscular complications
– Prevent/delay institutionalization

Choice of medications used early in
therapy will have a STRONG impact on
long-term course of the disease
Levodopa/Carbidopa
Example: Sinemet® (levodopa/carbidopa)
 MOA:

– L-Dopa - converted to DA in brain
– Carbidopa – inc effectiveness and reduces SEs
Dose: 25mg/100mg carbi/levo TID
 SE: EPS symptoms, orthostatic
hypotension, “wearing off”, N/V
 Most effective, used as late as
possible

“Wearing-Off” Phenomenon

Loss of effectiveness of levodopa before
next dose
– Increased with duration of therapy
– Indicates need for dosage increase
– Limits duration of therapy
Dopamine Agonists
Example: Mirapex® (pramipexole)
 MOA: Dopamine receptor agonist
 Dose: 0.125mg – 1.5mg TID
 SEs: orthostatic hypotension, impulsive
behavior, hallucinations, EPS (especially
when taken with levodopa)
 Often used as initial treatment
 Can be used concurrently with
levodopa

COMT Inhibitors
Example: Comtan® (entacapone)
 MOA: inhibit COMT, responsible for
breakdown of L-Dopa in periphery
 Dose: 200mg with each
levodopa/carbidopa dose
 SEs: increase in EPS symptoms, N/V, dry
mouth
 Used in combination with
levodopa/carbidopa

MAO-B Inhibitors
Example: Deprenyl® (selegiline)
 MOA: inhibit MAO-B, responsible for
breakdown of DA in brain
 Dose: 5mg BID
 SEs: dizziness, N/V, EPS symptoms
 Use with low-tyramine diet
may be required
 Potential for drug interactions

Anti-cholinergic Drugs
Example: Cogentin® (benztropine)
 MOA: inhibit ACh; restore balance to DAACh relationship
 Dose: 0.5-6mg daily
 SEs: anti-ACh effects (see prev lecture!)
 Can impair cognitive function which limits
use

Amantadine
Example: Symmetrel® (amantadine)
 MOA: enhance dopamine release, antiACh properties, NMDA antagonist
 Dose: 100-400mg/day (daily to BID)
 SEs: dizziness, anxiety, N/V/D, anti-ACh
effects
 Most commonly used later in
therapy as adjunct

PT Considerations

Coordinate therapy session with peak
effects of drugs
– After breakfast dose of levodopa

Need to monitor BP while receiving
antiparkinsons meds
– Concern for orthostatic hypotension

PT can reduce need for Parkinson’s drugs
Features of PT Program

Regular exercise
– Walking (1+ miles/day), swimming, golf, etc
Stretching and strengthening
 Exaggerated or patterned movements
 Mobility aids, orthotics
 Training in transfer techniques
 Training in techniques to improve posture
and walking

Questions?
Alzheimer’s Disease
Objectives
Describe physiologic changes in patients
with Alzheimer’s Disease
 For each drug class, state one example
drug, mechanism of action, common dose,
and associated side effects

Background

Alzheimer’s Disease is an age-related,
non-reversible brain disorder
– Characterized by memory loss and confusion
– Gradually leads to personality and behavioral
changes

Most common cause of dementia in
patients age 65 and older
Pathophysiology
Etiology of Alzheimer’s disease is unknown
 Disease is characterized by:

– Amyloid plaques
– Neurofibrillary tangles
– Loss of connection of neurons responsible for
memory and learning
Pharmacotherapy
Currently, no FDA-approved treatment for
slowing progression of disease
 Pharmacotherapy aimed at treating
symptoms and improving cognitive
function

Cholinesterase Inhibitors
Example: Aricept® (donepazil)
 MOA: Increase ACh, increasing cholinergic
function
 Dose: 5 – 10mg daily at bedtime
 SEs: SLUD, N/V, bradycardia, hypotension,
GI bleeding (rare)

Cholinesterase Inhibitors (cont.)

Other examples:
– Exelon® (rivastigmine)
– Reminyl® (galantamine)
Appear to help patients for months to a
few years
 Indicated for mild to moderate Alzheimer’s
symptoms

NMDA Antagonist
Example: Namenda® (memantine)
 MOA: inhibit NMDA receptor, which plays
a role in transmission of excitatory
neurotransmission
 Dose: 5mg daily to 10mg BID
 SEs: Drowsiness/dizziness

PT Considerations

Cognitive impairment will have negative
effect on ability to follow instruction
Questions?