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Drugs For Parkinson's Disease
History of Parkinson's Disease

First characterized in 1817 by James
Parkinson : An Essay On The
Shaking Palsy

Dr. Parkinson characterized the
disease:
 rigidity
 tremor
 mask face
 stooped body posture
 festinating gait
Epidemiology

The Real Cause Is Under
Investigation

Loss of dopamine production and
release in the basal ganglia

Presence of persistent cholinergic
output in the basal ganglia in the
absence of dopaminergic
influences

Environmental Toxins - Possible
Causes?
 Manganese Workers In Chile
 Tetrahydroisoquinoline (TIQ) - A
Toxic Chemical Also Causes
Parkinsonism

N-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) - A
Toxic Chemical Causing
Parkinsonism - Is Refractory To
Treatment
Parkinsonian Drugs



Anticholinergic Agents
Dopaminergic Agents
Dopamine-Like Agents
Anticholinergic Drugs






Trihexyphenidyl HCl (Artane)
Benztropine Mesylate (Cogentin)
Biperiden HCl (Akineton)
Procyclidine HCl (Kemadrin)
Ethopropazine HCl (Parsidol)
Diphenhydramine HCl (Benadryl)


Mainline Medications Until The
Early 1960's
Now Are Used In A Supportive Role
 Useful In Patients With Minimal
Symptoms
Useful In Patients Who Cannot
Tolerate Levodopa
 Useful In Patients In Whom
Levodopa Does Not Appear
Effective

Mechanism Of Action


Mainly Controls Salivation and
Drooling
Anticholinergics Blunt Excitatory
Effects Of Acetylcholine
 Anticholinergics Competitively
Block The Adrenergic Receptors
Thus Reduce The Effects Of
Acetylcholine
Adverse Side Effects Of
Anticholinergics




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Tachycardia
Photosensitivity Of The Skin
Constipation
Urinary Retention
Psychiatric Disturbances





Dry Mouth (Xerostomia)
Blurred Vision
Pupillary Dilatation (Mydriasis)
Hallucinations
Confusion
Dopaminergic Drugs

True Dopamine Medications
Levodopa (Larodopa, Levodopa)
 Carbidopa-Levodopa (Sinemet)

The Problem With Levodopa

When Levadopa is taken orally,
it is changed in the gut into
dopamine by an enzyme called
dopa decarboxylase.

Herein lies the problem …..
Dopamine cannot cross the
blood-brain barrier. So, it is
useless to the Parkinson’s patient
if it never gets into the brain !!


So….. the key is to keep levadopa
as levadopa until it reaches the
blood-brain barrier.
How do we keep levadopa from
being converted to dopamine ?

You have to combine levadopa
with a dopa decarboxylase
inhibitor to insure that levadopa
gets to and can cross over the
blood-brain barrier.


Carbidopa is the name of the dopa
decarboxylase inhibitor that is
combined with levadopa which
enables levadopa to get to and
cross over the blood-brain barrier
This medication combination is
called Sinemet


At the blood-brain barrier,
carbidopa is cleaved from
levadopa.
Levadopa than easily crosses
over the blood-brain barrier into
the brain.

In the brain, levadopa is
converted to dopamine where it
exerts its inhibitory effects and
calms the tremors, and other
symptoms of Parkinson’s Disease
Medical Uses
Treat The Symptomatology
To Improve Fine Motor Control
 To Improve Gross Motor Control
& Balance During Ambulation

To Decrease Tremor, Rigidity,
Bradykinesia
 Improve Speech
 Improve Handwriting
 Improve Swallowing
 Normalization Of Respiratory
Movement

Adverse Side Effects

Levodopa
 Tachycardia - Dopamine has beta1 effects on the cardiovascular
system
 Postural Hypotension - Is lessened
when Levodopa is taken with
Carbidopa (Sinemet)



Tics
Spasms
Ballistic Movements


Behavioral Changes
 Depression, Manic Behavior,
Anxiety Attacks, Confusion,
Hallucinatory Behaviors
May Require A Drug Holiday
Dopamine-Like Drugs

Amantadine HCl (Symmetrel)
Amantadine
Mechanism Of Action
This Medication Is An Antiviral
Medication
 Its Mechanism Of Action Is
Unknown
 Believed to facilitate release of
dopamine from storage sites in the
basal ganglia

Adverse Side Effects
Orthostatic Hypotension
 Nightmares
 Confusion
 Depression
 Hallucinatory Behavior

Dopamine-Like Drugs


Bromocriptine Mesylate (Parlodel)
Pergolide Mesylate (Permax)

These Medications Are Ergot
Alkaloids & Belong To The Same
Family As LSD

These Medications Are Used To
Decrease The Untoward Side
Effects Seen In Patients Using
Levodopa - i.e. Involuntary
Movements
Ergolines : Adverse Side Effects





Nausea
Vomiting
Postural Hypotension
Visual and Auditory Hallucinations
Livedo Reticularis - Purple
Discoloration Of The Skin
Dopamine-Like Drugs

Selegiline HCl (Eldepryl)
Selegiline
Mechanism Of Action

This Medication Is A Monoamine
Oxidase (MAO) Inhibitor
 It inhibits MAO, the enzyme which
destroys dopamine
 Selegiline prolongs the biological
half-life of dopamine

This Medication Is More Effective
When Given To New Parkinson's
Patients

Selegiline allows the patient to:
 Take a lower dose of Levodopa
 Lengthens out the dosing intervals
 Side effects are insignificant
Selegiline : Adverse Reactions
 Nausea
& Vomiting
 Orthostatic Hypotension ***
 Fainting & Dizziness ***
 Hallucinations ***
 Loss Of Balance & Syncope ***
 Depression
Dopamine-Like Drugs
 Pramipexole
(Mirapex)
 Ropinrole (Requip)
Mechanism Of Action
 Mechanism
is not exactly clear
Stimulates the dopamine receptors
of the Corpus Striatum
Adverse Side Effects
 Drowsiness
 Orthostatic
Hypotension
 Hallucinations
 Dizziness
 Syncope
Clinical Considerations

Schedule The Rehab Session One Hour
After The Morning Dose
 The patients will be rested from the
night's sleep
 The drug will be at its peak
effectiveness
 Maintain
Joint Range Of Motion
During A Drug Holiday



Maintain As Much Cardiovascular
Fitness As Possible During The Drug
Holiday
Monitor The Patient's Blood
Pressure - Orthostatic Hypotension
Be Aware Of The Patient's Balance
& Gross Motor Control - Protect
Against Falling