Parkinson’s Disease

Dr.M.Ashfaq Burney 1
 Historical Perspective
Dr. James Parkinson (1755-1824)
 1817
“involuntary tremulous motion”
“pass from a walking to a running pace”
“shaking palsy”

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 Epidemiology
Average incidence is 20 per 100,000 in
North America.
1 Million affected in the United States.
50,000 new cases per year.
Cost estimated to exceed $5.6 Billion
annually.
More than 10 million people worldwide are
living with PD
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 Epidemiology (Cont.)
Average age of onset 62.5
Men and women affected equally
Genetic Link
African-Americans and Asians less likely
than Caucasians to develop Parkinson’s
Caffeine and smoking shows some
protective effects

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 Case Example

Mr.JJ is a 66 y/o Caucasian man who underwent

surgical management for spinal stenosis and was
admitted for rehabilitation. JJ has a past history of
Parkinson’s, hypertension, coronary artery disease,
GERD, and depression. Upon admission appropriate
measures were taken for pain management and
aforementioned medical conditions. JJ’s surgical
management and rehabilitation was complicated by
advanced Parkinson’s. During his stay advances were
made in his strength, endurance, and ADL’s (Activity of
daily livings). JJ was discharged and would receive
assistive care from his wife. Overall, the care for JJ was
appropriate and followed standard of care practices.

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 Medication Profile of Mr.JJ

Carbidopa/Levodopa (Sinemet) 25/100/po-6times daily-(Parkinson's)

Lansoprazole (Prevacid) 30mg/po-ACBR-(GERD)
Baclofen (Lioresal) 10mg/po-qhs-(Parkinson's Dystonia)
Quinine sulfate (Quinidine) 260mg/po-qhs-(Muscle Cramps)
Quetiapine (Seroquel) 25mg/po-qhs-(Hallucinations)
Ropinirole (Requip) 1mg/po-1mg 5Xdaily & 2mg q 6 am-(Parkinson's)
Docusate Sodium (Colace) 100mg/po-bid-(Constipation)
Metoprolol (Lopressor) 50mg/po-qd-(Hypertension)
Calcium Carbonate (Tums) 500mg/po-1000mgbid-(Calcium supplement)
Oxaprozin (Daypro) 600mg/po-qd-(Osteoarthritis)
Propoxyphen/APAP (Darvocet N-100) 100mg/650mg/po-1q4hprn-(Pain
Management)
Bethanechol (Urecholine) 10mg/po-20mg prn-(Urinary Retention)
Docusate Sod-Casanthranol (Pericolace) 100mg/30mg/po-qdprn-
(Constipation)
Bisacodyl Supp (Dulcolax) 10mg/pr-qd prn-(Constipation)

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 Pathogenesis
Four Theories
 Oxidative damage
Impaired protection
 Environmental toxins
MPTP-Methyl-phenyl tetra hydro-pyridine
 Genetic predisposition
Mutations in the gene for the protein alpha-
synuclein located on chromosome 4
 Accelerated aging

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 Pathophysiology
Imbalance of dopamine and acetylcholine
Loss of 80 to 90% of dopaminergic
production in the substantia nigra
Lewy Bodies

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 Diagnostic Features
Four Cardinal Signs
 T remor
 R igidity
 A kinesia and bradykinesia
 P ostural instability

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 Characteristic Problems
Micrographia-small handwriting
Hypomimia-decreased facial animation
Hypophonia-soft speech
Dysarthria-unclear
pronunciation
Dyspnea-labored breathing
Festination-Shuffling gait

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 Diagnosis
Bradykinesia must be present with at least two of the following:
limb muscle rigidity, resting tremor (abolished with movement), or
postural instability.
Need to eliminate secondary causes;
 Post-encephalitic
 Drug-Induced
 Toxic
 Stroke
 Trauma
 Neoplasm
 Other neurodegenerative conditions
Wilson’s disease
Alzheimer’s
Lewy Body dementia   Kayser-Fleischer ring
Diagnosis is mainly made on medical history and neurological examination.
There is no lab test that will clearly identify the disease, but brain scans are
sometimes used to rule out disorders that could give rise to similar symptoms.
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 Hoehn and Yahr Staging of Severity of
Parkinson’s Disease
Stage Description

0 No clinical signs evident

I Unilateral involvement

II Bilateral involvement but no postural abnormalities

III Bilateral involvement with mild postural imbalance on

examination or history of poor balance or falls; patient leads
independent life
IV Bilateral involvement with postural instability; patient requires
substantial help
V Severe, fully developed disease; patient restricted to bed or
wheelchair
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Schwab & England Activities of Daily Living Scale

100% Completely independent. Able to do all chores without slowness,

difficulty or impairment. Essentially normal. Unaware of any difficulty
80% Completely independent in most chores. Takes twice as long.
Conscious of difficulty and slowness
60% Some dependency. Can do most chores, but exceeding slowly
and with much effort. Error; sometimes impossible
40% Very dependent. Can assist with all chores, but few alone

20% Nothing alone. Can be slight help with some chores.

0% Cannot swallow, bladder and bowel not functioning, Bed-ridden.

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 Pharmacotherapy

Levodopa (Amino acid , Administered orally combination

with carbidopa)

Dopamine agonists
COMT inhibitors 
Amantadine (Antiviral drug, Increases dopamine)
Anticholinergics (Anti-muscarinic , Effect Acetylcholine
the neurotransmitter)

Selegiline (Selective MAO inhibitor orally given)

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 Levodopa
L-Dopa (Larodopa by Roche)
Introduced in the late 1960s
“Gold Standard”
Crosses the blood-brain barrier
Adverse effects such as nausea, vomiting,
postural hypotension, involuntary
movements, restlessness, and cardiac
arrhythmias
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 Levodopa
Today L-dopa/carbidopa (Sinemet) used almost
exclusively
Initial dose of 25/100mg ½ QD for 7 days, increase by ½
tab daily for 7 days until up to 1 tablet TID. Extended
release dose as 25/100mg QD and titrated up to TID over
a months time. Maximum dose of L-dopa is 800mg/day.
Adverse effects minimized with carbidopa
“End-of-dose wearing-off effect”
“On-off effect”

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 Dopamine Agonists
“Synthetic Dopamine”

Bromocriptine Mesylate (Parlodel)

Pergolide Mesylate (Permax)
Pramipexol (Mirapex)
Ropinirole HCL (Requip)

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 Dopamine Agonists
Monotherapy or combination
Are particularly useful for:
 Prolonging the effective treatment period in patients with
deteriorating response.
 Delaying the onset of L-dopa therapy, particularly in younger
patients.
 Treating patients who cannot tolerate high doses of L-dopa.
Associated with more side effects than L-dopa
Potential adverse effects include somnolence,
dyskinesia, nausea, vomiting, orthostatic hypotension,
nightmares, hallucinations, confusion, dizziness

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 Ergot Agonist Dosing

Bromocriptine (Parlodel)
 Initial 1.25mg QD-BID
 Titrate 1.25mg to 2.5mg/d, every week
 Average dose <30mg/day. Some patients may require up to
120mg/day

Pergolide (Permax)
 13 times more potent than bromocriptine
 Initial 0.05mg/d for 2 days, increasing by 0.1 to 0.15mg/d, every
3 days over a 12 days period
 May increase by 0.25mg every 3 days until symptoms are
eliminated or adverse effects occur
 Mean dose 3mg/d

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 Nonergot Agonist Dosing
Pramipexole (Mirapex)

 Monotherapy or Adjunct
 Initial dose of 0.125 mg TID and increased every 5 to 7 days as
tolerated up to 3 to 4.5mg/d
 Higher doses are not more effective than 1.5mg/d and are
associated with more side effects
 Mean 27% reduction of L-Dopa
 Decrease dose with renal function impairment
 Drugs that are secreted by the cationic transport system may
decrease the clearance of pramipexole by 20%. These include:
cimetidine, ranitidine, diltiazem, verapamil, triamterene, quinidine
and quinine.

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 Nonergot Agonist Dosing
Ropinirole (Requip)

 Monotherpy or Adjunct
 Initial dose of 0.25mg TID and increased by 0.25mg TID on a
weekly basis. After the fourth week doses may be increased by
1.5mg/d up to 9mg/d. Further adjustment may be obtained by
3mg/d increases up to 24mg/day
 Mean 19% reduction of L-dopa
 Drugs that inhibit or induce CYP1A2 will affect the clearance of
ropinirole. Inhibitors such as cimetidine, omeprazole, ciprofloxacin,
enoxacin, norfloxacin, clarithromycin, erythromycin, troleandomycin,
ritonavir, diltiazem, mexiletine and fluvoxamine. Inducers such as
carbamazepine, phenobarbital, phenytoin, and rifampicin.
 If therapy is stopped, discontinue over seven days

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 COMT Inhibitors
Entacapone (Comtan)
Tolcapone (Tasmar)

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 COMT Inhibitor Dosing
Entacapone (Comtan)
 Adjunct therapy
 Initial dose of 200mg with each dose of
levodopa up to 8 times daily
 Decrease of L-dopa may be necessary
 Exacerbation of L-dopa side effects, diarrhea,
urine discoloration, abdominal pain

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 COMT Inhibitor Dosing
Tolcapone (Tasmar)
 Adjunct therapy
 Initial 100mg TID up to 200mg TID
 More potent and longer acting than
entacapone
 Decrease L-dopa by 25 to 50%
 Exacerbation of L-dopa side effects: diarrhea,
urine discoloration, liver toxicity.
 Monitor LFTs every 2 weeks for 1 year, every
4 weeks for 6 months, then every 8 weeks
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 Amantadine
Amantadine HCL (Symmetrel)
 Inhibits dopamine recapture
 Blocks acetylcholine and glutamate receptors
 Dose 100mg BID to TID
 Caution in renal failure patients
 Currently used to reduce choreic movements
 Narrow therapeutic range
 Unpleasant side effects such as nausea, dizziness,
confusion, hallucinations, nightmares, dry mouth
peripheral edema, and livedo reticularis

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 Anticholinergics
Trihexyphenidyl HCL (Artane)
Benztropine Mesylate (Cogentin)
 Monotherapy or adjunct
 Pre-dopaminergic therapy
 Long touted as most effective for reducing
tremor
 Use Limited by side effects especially in the
elderly.

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 Anticholinergics
Trihexyphenidyl HCL (Artane)
 Initial dose of 1mg and increase by 2 mg every 3 to 5 days until
6 to 10 mg/day. Usually given TID with meals or QID with meals
and at bedtime.
 Possible adverse effects include dry mouth, blurred vision,
somnolence, hallucinations, memory impairment, confusion,
urinary retention, cardiac arrythmia and constipation.

Benztropine Mesylate (Cogentin)

 Initial dose of 0.5 to 1 mg at bedtime. Increase by 0.5mg every 5
to 6 days up to a total daily dosage of 6mg.
 Possible adverse effects include dry mouth, blurred vision,
somnolence, hallucinations, memory impairment, confusion,
urinary retention, cardiac arrythmia and constipation.

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 Selegiline
Selegiline HCL (Eldepryl)

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 Selegiline
Selegiline HCL (Eldepryl)

 Mono therapy or adjunct

 MOA-inhibits monoamine oxidase-B (MAO-B)
 Inhibition of MAO-A does not occur
 Dosage of 5 mg BID with breakfast and lunch
 When used as mono therapy delays the need of
L-dopa by an average of nine months.
 Possible adverse effects include nausea, dizziness,
abdominal pain, confusion, and exacerbation of L-dopa
side effects
 Controversial theory of decreased rate of neuronal
death due to a reduction of free radicals.

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 Surgical Options
Pallidotomy and Pallidal Stimulation
Thalamotomy and Thalamic Stimulation
 Introduced in 1950
 Pallidotomy improves tremor, rigidity, and
bradykinesia
 Thalamotomy relieves tremor, rigidity, but not
bradykinesia
 Neurosurgical treatment came to an end with the
introduction of L-dopa in late 1960s
 Resurgence of neurosurgical intervention with the
failure of pharmacological treatments after 10 to 15
years of disease progression
 Two methods: Ablation and deep brain stimulation
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 Grafting
Suprarenal to brain transplantation
Fetal tissue transplantation
Cell culture transplantation

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 Under Investigations
Implantable pumps
Implantable capsules containing
dopamine-producing cells
New medications to target one of the five
individual brain receptors for dopamine
Continued genetic research

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 References
Cosgrove, G. Rees, Eskandar, Emad N., Shinobu, Leslie A. “Surgical Treatment of
Parkinson Disease.” JAMA December 26, 2001;286:3056-3059.
Dipiro, Joseph T., ed. Pharmacotherapy Fourth Edition. Stamford, Connecticut:
Appleton & Lange, 1999.
“Early Parkinson’s Disease: Dopamine Agonists Have Increasingly Important Role in
Symptom Management.” Drug Ther Perspect 2001;17(17):5-9.
Faulkner, Thomas P. “Parkinson’s Disease.” 7 December 1999.
http://www.onu.edu/user/FS/tfaulkner/parkinso.html 23 May 2002.
Hermanowiez, Neal. “Management of Parkinson’s Disease.” Postgraduate Medicine
2001;110(6):15-28
Korczyn, Amos D. “Hallucinations in Parkinson’s Disease.” Lancet
2001;358(9287):1031-1032.
Lindvall, Olle. “Stem Cell Transplantation.” Lancet 2001;358(Supplement);s47.
Nicholl, David. “Parkinson’s Disease.” 22 April, 1998.
http://medweb.bham.ac.uk/http/depts/clin_neuro/teaching/tutorials/parkinsons/parkinsons
1... 27 May, 2002.
Ninds. “Parkinson’s Disease-Hope Through Research.”
http://accessible.ninds.nih.gov/health_and_medical /pubs/parkinson_disease_htr.htm
Referenced on 5/27/02.
Stephenson, Joan. “Exposure to Home Pesticides Linked to Parkinson Disease.” JAMA
June 21, 2000;283(23):3055-3058.

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THANK YOU

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