Hi, This is Syed Masood Ahmed Quadri, Pharm.D this presentation has varied range of details like, history of disease, signs and symptoms, prevalence, facts, risk factors, manifestations, diagnosis, pathology, treatment, and other interesting slides hope you enjoy the read

1. PARKINSON’S DISEASE
BY
SYED MASOOD AHMED QUADRI
Doctor of Pharmacy
MESCO College of Pharmacy

2. PARKINSON’S DISEASE BACKGROUND
 Best described as
“shaking palsy” by james
parkinson in 1817.
 “Involuntary tremulous
motion, with lessened
muscular power, in parts
not in action and even
when supported; with a
propensity to bend the
trunk forwards, and to
pass from a walking to a
running pace: the senses
and intellects being
uninjured.”

4. NEURODEGENERATIVE DISEASES
PREVALENCE IN US
# per 100,000
Alzheimer’s disease 4,000,000 1,450
Parkinson’s disease 1,000,000 360
Frontotemporal dementia 40,000 14
Pick’s disease 5,000 2
Progressive supranuclear palsy 15,000 5
Amyotrophic lateral sclerosis 20,000 7
Huntington’s disease 30,000 11
Prion disease 400 <1

5. FAST FACTS ABOUT PD
 Annual incidence: 60,000 new cases/yr.
 Increase with age (3% population >65 years old).
 Slightly more common in men.
 Mean age at onset: 60 years old.
 85% of patients are over 65 years old.

6. RISK OF PARKINSON’S DISEASE
Increased risk
 Age,
 High body mass index,
 Male gender,
 Family history,
 Depression,
 Environment factors :
 Rural living,
 Well-water drinking,
 Welding,
 Head injury.
Decreased risk
 Caffeine intake,
 Smoking cigarettes,
 Anti-oxidants in diet.

7. MOTOR SYMPTOMS
 Tremor at rest,
 Rigidity,
 Akinesia/bradykinesia,
 Postural instability,
 Decreased arm swing when walking,
 Micrographia,
 Hypophonia,
 Masked face,
 Slow, shuffling gait,
 Stooped posture.

8. MANIFESTATIONS OF PD
Additional features:-
 Cognitive, mood, and behavioral dysfunction,
 Olfactory disturbance,
 Sleep disturbance,
 Constipation,
 Seborrheic dermatitis,
 Pain,
 Autonomic disturbances.

9. DIAGNOSING PD
 United Kingdom Brain Bank Criteria.
 Stage I Hoehn and Yahr (H&Y)- unilateral.
 Stage II H&Y – bilateral.
 Stage III H&Y – bilateral with loss of balance/falls.
 Stage IV H&Y – all above and significant disability.
 Stage V H&Y- bedbound.

10. CLINICAL DIFFERENTIATING OF PARKINSONIAN
DISORDERS
PD MSA PSP CBD
Symmetry of deficits + +++ +++ --
Axial rigidity ++ ++ +++ ++
Limb dystonia + + + +++
Postural instability ++ ++ +++ +
Vertical gaze restriction
+ ++ +++ ++
Frontal behavior + + +++ ++
Dysautonomia + ++ -- --
L-dopa response early +++ + + --
L-dopa response late ++ + -- --
Asym cortical atrophy
on MRI
-- -- -- ++

11. PARKINSON’S DISEASE PATHOLOGY
Lewy body

12. CNS MOTOR ORGANIZATION
 Pyramidal system
 Weakness.
 Extrapyramidal system
 Modulator of pyramidal
system.
 Symptoms :
 Involuntary movement
 Slow, interrupted
movement
 Low posture/tone

13. NEUROPATHOLOGY OF PD
 Key Points:
 Parkinson’s disease is characterized by progressive
degeneration of dopaminergic neurons. Most prominent is the
profound loss of dopaminergic neurons in the substantia nigra
(SN) of the midbrain, observed as a loss of pigmented
streaks. Imaging can also identify loss of dopamine terminals
in the striatum.
 A hallmark feature of pd is lewy bodies, dense protein
aggregates revealed by postmortem analysis. Lewy bodies
are principally composed of the α-synuclein protein and are
found in the SN, as well as other regions of the brain.

14. DOPAMINE DEFICIENCY IN PD
PET SCAN

15. TREATMENT BASED ON REPLACING
DOPAMINE
Presymptomatic phase
Onset
Sleep
Olfactory*
Mood
Autonomic system
Diagnosis
Early nonmotor symptoms Specific symptoms
Motor
Dopaminergic neuron loss in PD
%Remaining
DopaminergicNeurons
Time (years)
Nonmotor
*Olfactory dysfunction may predate clinical PD by at least 4 years.

16. BRAAK STAGING OF PD

17. ALPHA-SYNUCLEIN PATHOLOGY IN THE
SUBSTANTIA NIGRA AND NEOCORTEX
Cerebral cortex Substantia nigra

18. ALPHA-SYNUCLEIN

19. TOXIC ALPHA-SYNUCLEIN
 Chaperones prevent
toxic alpha-synuclein
from forming
 Develop antibodies that
keep alpha-synuclein
from forming aggregates
 Find small molecules
that can prevent
misfolding

20. MECHANISMS OF
NEURODEGENERATION
Oxidative stress
MPTP
Pesticides
Herbicides
Bacterial toxins
ENVIRONMENTAL FACTORS GENETIC FACTORS
Mitochondria
Complex I
ROS
PARK1 (α-synuclein)
PARK2 (Parkin)
PARK5 (UCH-L1)
PARK6 (PINK1)
PARK7 (DJ-1)
PARK8 (LRRK2, dardarin)
Other genes
NIGRAL CELL DEATH
Toxic injury
Apoptosis
Inflammation
Excitotoxicity
a-Synuclein
Related proteins?
Altered protein
conformation
Ubiquitin system
Proteasome dysfunction?
Protein aggregates
(Lewy bodies:
good or bad?)

21. SITES OF ACTION OF PD DRUGS
Periphery Brain
Dopamine receptors
DA
L-DOPA
3-OMD
DA
Dopamine
agonists
COMT
inhibitors
Carbidopa
MAO-B
inhibitors
DA
3-MT
DA
DA
AADC
DA
COMT
inhibitor*
L-DOPA
DADA
Blood-brain barrier Neuron
*Only tolcapone inhibits
COMT in brain.
L-DOPA => levodopa
3-OMD => 3-O-methyldopa
DA => dopamine
AADC => aromatic acid decarboxylase
DOPAC => dihydroxyphenylacetic acid
3-MT => 3-methoxytyramine

22. PD: TREATMENT
 Amantadine
 Anticholinergics
 Carbidopa/levodopa (SINEMET)
 Immediate release (IR), controlled release (CR),
combined with entacapone (COMTAN)
 Stalevo
 Dopamine agonists
 Pramipexole (MIRAPEX)
 Immediate, CR release
 Ropinirole (REQUIP)
 Immediate release, CR release
 MAO-B inhibitors
 Rasagiline (AZILECT)
 Selegiline (ELDEPRYL, ZELAPAR)

23. PURPOSE’S AND CONSEQUENCE’S OF
AVAILABLE
FDA-APPROVED MONOTHERAPY
AGENT PURPOSE CONSEQUENCE’s
MAO B
Inhibitors
Effective
Once-daily dosing
Profile similar to that of placebo
Potential drug
interactions
Carbidopa/
Levodopa
Highly effective
Rapid onset of action
Motor fluctuations and
dyskinesia are common
with long-term use
Dopamine
agonists
Effective
Delays start of L-dopa
Low risk of motor complications
Neuropsychiatric AEs
Somnolence warning
Agonist-specific AEs
Amantadine Beneficial for tremor
Antiparkinsonian effects
Cognitive AEs
Anticholinergic AEs
Withdrawal effects

24. LEVODOPA:
THE CORNERSTONE OF PD THERAPY
 Levodopa provides substantial antiparkinsonian
symptom control, and significantly improves
patient quality of life
 Levodopa is the most efficacious antiparkinsonian
medication in moderate and advanced disease
 Levodopa provides relatively rapid symptomatic
benefits
 Levodopa is generally well tolerated with few
initial side effects
 Levodopa continues to provide antiparkinsonian
benefits through the course of the illness
 All PD patients eventually require levodopa
therapy

25. AS THE DISEASE PROGRESSES,
THE THERAPEUTIC WINDOW NARROWS
Symptoms and side effects occur as the levodopa therapeutic window diminishes*
Smooth, extended response Diminished duration Shorter, unpredictable response
Absent or infrequent dyskinesia Increased incidence “On” time with increased dyskinesia
of dyskinesia
Plasma Levodopa Concentrations

26. KEY POINTS: EARLY BUT NO
IMPAIRMENT
 Early patients- no functional impairment
 Easiest treatment category
 Adagio, tempo (rasagiline) and elldopa trial
indicate earlier treatment may be better
 Consider rasagiline (azilect), selegiline
(eldepryl,zelapar)
 Refer for potential neuroprotective trials
 Coenzyme Q10, selegiline, rasagiline, creatine

27. KEY POINTS: EARLY WITH IMPAIRMENT
 Early patient-functional impairment
 Bothersome tremor, stiffness, slowness, decrease in
dexterity interfering with ADLs or job
 AAN guidelines 2002
 MAO B inhibitors provide some benefit
 Dopamine agonists
 Levodopa
 If the patient is chronologically or physiologically young
(<70) try a dopamine agonist as the first robust
treatment
 If older, or cognitively impaired, use levodopa first

28. KEY POINTS: MIDDLE STAGE PATIENTS
 Starting to have wearing off of drug benefit prior to next
dose
 Goal is to enhance dopamine system in the brain, since
these medications have different mechanisms of
action=Polypharmacy is expected!
 Layer on medications and adjust to best benefit

29. KEY POINTS: LATER MID-STAGE
PATIENT
 Experiencing fluctuation in motor control to
include significant wearing off with poor mobility
and dyskinesias
 Have patients keep diaries of motor control
 Add additional medications
 Consider smaller, more frequent doses of medications
to minimize “off” time and dyskinesia
 Onset or worsening of many non-levodopa
responsive symptoms, such as falling, worsening
cognition, dysphagia, autonomic dysfunction

30. KEY POINTS: ADVANCED PARKINSON’S
DISEASE
 Treatment is made difficult by the worsening of motor
complications, cognitive, psychiatric and autonomic
disturbances
 Medications may need to be streamlined (reduced or
eliminated) because of confusion or psychosis

31. REFERENCE
 http://www.ssu.ac.ir/fileadmin/templates/fa/daneshkadaha/
daneshkadah_pezeshki/goroha/farmacology/Upload_DP_far
macology/tarhdars/amoozesh/parkinson.pptx
 http://www.healthsciences.okstate.edu/college/clinical/crh/r
ural_clinic/docs/Parkinson_Disease_Update.ppt
 http://faculty.smu.edu/jbuynak/Parkinson'sDisease2010.ppt
 http://www.parkinsons.va.gov/Consortium/Presentations/A
udio_Conference/Lai.ppt
 http://www.parkinsonsnsw.org.au/assets/attachments/docu
ments/presentation_kit.ppt
 http://gptraining.dundee.ac.uk/docs/Educators%20Page/Par
kinson's%20Disease.ppt
 http://www.npidaho.org/documents/dr-seeberger-
parkinsons-disease-2010-09-10.ppt
 K.D.Tripathi 6th édition chapter 31 page no. 412 - 422

32. THAN
K