Parkinson's disease is a progressive neurological disorder caused by the loss of dopamine-producing neurons in the substantia nigra region of the brain. This leads to dopamine deficiency and symptoms like tremors, rigidity, slow movement, and impaired balance and coordination. It commonly occurs in older adults and has no known cure. Treatment aims to manage symptoms by enhancing dopamine or reducing acetylcholine activity in the brain using medications.

1. Parkinson's Disease
D.Pharm Second Year
Presented By Miss Sudipta Roy
Associate Professor
East Point College of Pharmacy Bangalore

2. Parkinson's Disease
• It is a chronic progressive neurological disease that
is associated with loss of dopaminargic neurons in
substantia nigra of brains which is characterized by
tremor of resting muscles, rigidity, slowness of
movement , impaired balance.
• or
• It is chronic , progressive ,motor disorder due to
degeneration of dopaminargic neurons in the
substantia nigra pars cmpacta (SN-PC) results in
dopamine deficiency characterized by rigidity ,
tremor of testing muscles, bradykinesia and
postural instability.

3. • It occurs in 2% elederly population . This disease
develops when cells are destroyed in certain parts
of the brain stem, particularly the crescent-shaped
cell mass known as the substantia nigra.

4. Substantia Nigra
• The substani nigra (SN) is a basal ganglia structure
located in the midbrain that plays important role in
reward and movement. Substantia nigra is Latin for
'Black Substance", reflecting the fact that parts of
the subtantia nigra appear darker than neighboring
areas due to high levels of neuromelanin in
dopaminargic neurons.

5. • It actually consists of two parts with very different
connections and functions : the pars compacta and
the pars reticulate.
• 1. Th pars compacta serve mailny as an output to
the basal ganglia circuit, supplying the striatum
with dopamine.
• 2. The pars reticulate serves mainly as an input,
conveying signals from the basal ganglia to
numerous other brain structures.

6. Neurotransmitters Imbalance.
• It was described by James Parkinson in 1817 ,
therefore named after him. It is usually occurred
above 65 years of age.
• Parkinson Disease results an imbalance between
dopaminargic (inhibitory neuron) and cholinergic
(excitatory neuron ) system in the brain.
(cholinergic over activity).

7. Etiology .
• The cause of Parkinson's disease is unknown , but
several factors appear to play a role ,
• including :
• 1. Genese : Research has shown certain specific genetic
mutations to be associated with Parkinson's Disease.
But these occur in rare cases with many family
members affected by Parkinson's Disease.
• 2. Environmental triggers : Exposure to certain toxins or
environmental factors may increase the risk of later
Parkinson's Disease , but the risk is relatively small.
• 3. Destruction of Dopaminargic neurons in Substantia
Nigra of Brain.

8. Abnormal Protein Deposition in
Brain Cells.
• Lewy Bodies :
• Clumps of specific substances within brain cells are
microscopic markers of Parkinson's Disease. These are
called Lewy Bodies, and researcher beleive these Lewy
bodies hold an important clue to the cause of Parkinson's
Disease.
• b. Alpha-synuclein : Although many subdtances are found
within lewy bodies , scientists beleive an important one is
a natural and widespread protein called alpha-synuclein
(a-synuclein). It's found in all lewy bodies in a clumped
form that cells can't break down.This is currently an
important focus among Parkinson's disease researchers.
• c.Drugs : Generally dopaminargic antagonist therapy may
elicit the development of PD.

9. Pathophysiology.
• Basal ganglia normally contains balance of
dopamine and actylcholine.The balance between
both neurotransmitters is necessary to regulate ,
muscle tone and voluntary movement. Inhibition of
dopaminargic activity leads to excessive cholinergic
activity. In parkinson's disease , there is
degeneration of dopaminargic neurons in the
substantia nigra that results dopamine deficiency.

10. Clinical Manifestations.
• Parkinson's disease signs and symptoms can be
diiferent for everyone. Early signs may be mild and
go unnoticed . Parkinson's signs and symptoms may
include :
• Tremor : A tremor or shaking usually begins in a
limb, often your hand or fingers. You may rub your
thumb and forefinger back and forth, known as a
pill-rolling tremor. Your hand may trempble when
it's at rest.

11. Slowed movement (bradykinesia)
• Over time , Parkinson's Disease may slow your
movement , making simple tasks difficult and time-
consuming . Your steps may become shorter when
you walk. It may be difficult to get out of a chai. You
may drag your feet as you try to walk.
• Rigid Muscles : Muscle stiffness may occur in any
part of the body . The stiff muscles can be painful
and limit your range of motion.
• Impaired posture and imbalance :
• Your posture may become stopped, or you may
have balance problems as a result of Parkinson's
disease.

12. Loss of automatic movements.
• You may have a decreased ability to perform
unconscious movements, including blinking ,
smiling or swinging your arms when you walk.
• Speech changes : You may speak softly , quickly ,
slur or hesitate before talking . Your speech may be
more of a monotone rather than have the usual
inflections.

13. Writing Changes.
• It may become had to write and your writing may
appear small.
• Excessive salivation.
• Seborrhea (excessive discharge of sebum from the
sebaceous glands ).
• Mood chages.

14. Stages of Parkinson's Disease.
• On the basis of symptoms , PD is classified into five
stages. These stages are -
• Stage 1 - Develop mild symptoms but patient is
able to go about day-to day life.
• Stage 2- Symptoms such as tremors and stiffness
begin to worsen , patient may develop poor
posture or have trouble walking.
• Step 3- Movement begins to slow down and loos of
balance.
• Step 4 - Symptoms are severe and cause significant
issues with day-to-day life , patient is unable to live

15. • Waliking or standing may be impossible at this point, people at
this stage are confined to wheelchair or bed.
• Diagnosis :
• No specific test exists to diagnose Parkinson's disease.
Newrologist can diagnose Parkinson's disease based on :
• Medical History
• Review of signs and symptoms
• Blood test : To rule other conditions that may be causing
symptoms.
• Physical Examination :
• Nerological Exaination : Doctor may suggest a specific single-
Photon Emission Computerized GTomography (SPECT) scan called
a dopamine transporter scan (DaTscan). It can help support the
suspicion that you have Parkinson's Disease, it is your symptoms
and neurologic examination that ultimately determine the correct
diagnosis.

16. • Imaging Tests : Such as MRI , ultrasound or the
brain, and PET sans also may be used to help rule
out other disorders.
• Treatment :
• Antiparkinsonian drugs can only help to reduce the
symptoms and improve the quality of life. Two
categories in the treatment are :
• 1. To enhance dopamine activity.
• 2. To depress cholnergic overactivity.

17. • 1. Drugs affecting brain dopaminargic system :
• a. Dopamine precursors - Levopdopa
• b. Peripheral decarboxylase inhibitors - Carbidopa ,
Benserazide.
• c. Dopaminergic agonists - Bromocriptine , Ropinirole ,
Pramipexole.
• MAO- B inhibitors - Selegiline
• COMT inhibitors - Entacapone , Tolcapone
• Dopamine facilitator- Amantadine
• 2. Drugs affecting brain cholinergic system :
• a. Central anticholinergics - Trihexyphenidyl (Benzhexol) ,
Procyclidine , Biperiden
• b. Antihistainics - Orphenadrine , Promethazine