Jieun Park

Chem-5398

Outline
Overview
Diagnosis
Treatment

Physical Therapy
Drug Therapy
Surgery

New Research

Overview
Second most common human
neurodegenerative disorder.
Prevalence of 1 out 272 in U.S.
Increases to 4 to 5% for ages 85 and over.

Degeneration of dopaminergic neurons in

the substantia nigra.
Dopamine
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Overview contd

Symptoms caused by insufficient dopamine.

3 main symptoms:
Tremors
Rigidity
Slowed motion (Bradykinesia)

Other symptoms include:

Dementia, sleep disturbances, depression, etc.
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Overview contd
Common cause of chronic progressive
parkinsonism.
Exact causes still yet unknown.

Gene mutation

Toxins
Trauma

Diagnosis
No definitive tests for PD. PET scans
can aid to determine levels of dopamine.
Difficult to diagnose, many symptoms
shared with other disorders.
Medical history and neurological tests
are conducted to diagnose.

Usually, if two of the cardinal symptoms are

present.

Treatment Parkinsons
Disease
No cure for PD.
Treatment can be divided into two stages.

Early and Later stages

Early stage
Onset of symptoms, treated with physical therapy and

medications (Levodopa, dopamine agonists, etc)

Later stage
Usually after having received 5+ years of levodopa

treatment.
Wearing-off and On/Off effect develops, other
medication in conjunction levodopa is commenced.
MAO-B and COMT inhibitors.
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Treatment Physical
Therapy

Regular exercise
Recommended throughout the life of disorder.
Helps maintain and improve mobility and strength.
Physical exercise aids in rigidity relief, muscle

strength and flexibility, balance, etc.

Caution is advised to avoid sudden movements or
strenuous activities fall could result in serious
injury.

Treatment Drug Therapy

Levodopa (L-DOPA)
Preferred medication to control major symptoms.
Usually administered at the early onset of disorder.
Drug is well tolerated and side affects are limited.

Levodopa

Dopamine
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Drug Therapy L-DOPA

L-DOPA is converted to Dopamine by

enzyme DOPA decarboxylase (DDC).

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Drug Therapy L-DOPA

Used with Carbidopa, which blocks the early

conversion of L-DOPA into dopamine.

Carbidopa

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Drug Therapy L-DOPA

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Drug Therapy L-DOPA

Side effects include

Psychiatric symptoms; linked to depression
Nausea and vomiting

Prolonged use can cause wearing-off effect.

Leads to other motor complications, such as

dyskinesia.

Still the preferred treatment for symptoms.

Drug brand name: Sinemet

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Drug Therapy L-DOPA

L-DOPA can cross blood-brain barrier, when
dopamine cannot. This led to the idea of
using L-DOPA as treatment for PD.
First used in the 1960s, with daily increase
dosage program.
L-DOPA used in combination with Carbidopa
in 1967.

Increases potency of L-DOPA up to 4-fold.

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Treatment Drug Therapy

Dopamine Agonists
Acts directly on the dopamine receptors.
Initially was used with L-DOPA.
Today, sometimes prescribed before L-

DOPA, to delay wearing-off effect and

other motor complications brought on by
prolonged use of L-DOPA.

Pramipexole

Dopamine
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Drug Therapy - DOPA agonists

Triggers dopamine receptors in place of

depleted dopamine neurotransmitters.

http://www.youtube.com/watch?v=dTdW8q9hukw&feature=related

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Drug Therapy DOPA

agonists

Adverse side effects

Nausea, dizziness, hallucinations
Sleep attacks, hypotension
Permax (pergolide) pulled after direct link

to fibrosis of cardiac valves that can lead to

death. Unavailable in U.S. since 2007.

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Treatment Drug Therapy

Monoamine Oxidase B (MAOB) Inhibitors

Delays or reduces breakdown of dopamine by

MAO-B.
Used as monotherapy or in conjunction with
L-DOPA, it can reduce the dosage of L-DOPA by
15%.

Selegeline

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Drug therapy MAO-B

Inhibitors
MAO-B is an enzyme that metabolizes
dopamine.
From the breakdown of dopamine,
hydrogen peroxide is produced, which the
oxidative stress can damage
dopaminergic neurons in the substantia
nigra. (Possibly neuroprotective)
MAO-B inhibitor delays or reduces the
metabolism of dopamine.

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Drug therapy MAO-B

Inhibitors
Side effects of L-DOPA may be
enhanced by selegeline.
Nausea and dizziness.

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Treatment Drug Therapy

Catechol O-Methyl Transferase (COMT)

Inhibitors
Inactivates and degrades neurotransmitters,

such as dopamine.
Mainly used in combination with L-DOPA, it
increases the half-life of L-DOPA.
Delays wearing-off effect of L-DOPA and
other motor complications such as dyskinesia
Tolcapone(Tasmar )

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Drug therapy COMT

Inhibitors
COMT catalyses methylation of L-DOPA.
Addition of COMT inhibitor along with LDOPA and carbidopa prolongs the half-life
of L-DOPA and increases the amount in
the CNS.

This increases on time for L-DOPA.

Tasmar are hepatotoxic.

Diarrhea and sleep disturbances

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Treatment Drug Therapy

Amantadine
Antiviral agent.
Known to aid in reducing dyskinesia.

Anticholinergics
Improve tremors and stiffness
Cause impairment and constipation

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Treatment - Surgery
Before commerciality of levodopa, surgical
treatment were preferred.
Early surgeries were successful with
tremors, but failed to relieve other symptoms.
Means of last resort due to high risk of
potential complications.
Recent advances in neurosurgical
procedures allow for better treatment.

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Surgery

Deep Brain Stimulation

Brain pacemaker, sends electrical impulses to

brain to stimulate the subthalamic nucleus.

Improves motor functions and reduce motor
complications.
Complications include: brain
hemorrhage, seizures, death.

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New Researches

Nicotine
Intake of nicotine has shown to slow the

degeneration of neurons.
Acts similar to levodopa.

Melatonin
Serotonin derivative that helps insomnia.
Also shown to cause a reduction in

production of neurodegenerative radicals.

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Assigned Reading
Jankovic, Joseph; Aguilar, L. Giselle. Current
approaches to the treatment of Parkinson's
disease. Neuropsychiatric Disease and
Treatment (2008), 4(4), 743-757.

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Homework Problems
Which medicinal treatment is generally
started for younger patients with mild
symptoms in early-stage treatment?
2. Levodopa is used with which drug and why?
3. Describe wearing-off and on-off effect.
1.

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References
Davie, C. A. A review of Parkinsons disease, British
Medical Bulletin, 86 (2008): 109-127
Munchau, A., Bhatia, K P. Pharmacological treatment
of Parkinsons disease, Postgrad Med J, 76
(2000): 602-610
Rao, Shobha A., Hoffman, Laura A., Shakil, Amer.
Parkinsons Disease: Diagnosis and Treatment.,
American Family Physician, 74 (2006): 2046-2054
Singh, N., Pillay, V., Choonara, Y. E. Advances in the
treatment of Parkinsons disease, Progress in
Neurobiology, 81 (2007): 29-44

Images from Wikipedia, Google

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