Parkinson's Disease and Alzheimer Disease

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PARKINSONS
DISEASE
Sandip S Chaudhari
Shree Dhanvantary Pharmacy College

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Essay on the Shaking Palsy
“…the senses and intellects being uninjured.”
James Parkinson, 1817
Parkinsonism Disease:-

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Parkinsonism Disease:-
Definition:-
It is neurodegenerative disorder characterized by the
progressive loss of the Dopaminergic neurons in the
substantia nigra pars compacta which innervates the dorsal
striatum.

4. • Rigidity:
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5. • Tremors and Akinesia
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Famous Faces of Parkinson
Michael J. Fox Muhammad Ali Katharine Hepburn
Pope John Paul II
Johnny Cash
Mao Tse Tung

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Pathophysiology
• Parkinson disease is
caused by the death of
the nerve cells in the
substantia nigra, which
produce the
neurotransmitter
dopamine.

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• Without dopamine, the brain is unable to
transmit messages between nerve cells,
resulting in a decrease in muscle function.
• When 80% of dopamine producing cells are
damaged, the symptoms of Parkinson disease
start to appear.

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1) Oxidative Stress:-
Neurons depends on oxidative metabolism for
survival in which shows production of reactive
compound such as H2O2and oxiradicals is may
lead to cell death.(KDTripathi, 2003)
2) Apoptosis:-
It is a process of programmed cell death.
It often associated with excitotoxicity.

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3) Genetics:-
4) Enviromental Triggers:-
• Infectious agent
• Environmental Toxins
• Acquired brain injury

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Clinical Presentation:-
1) Bradykinesia (akinesia) :-
This is a lack or difficulty in initiating voluntary
muscle movement & in advanced stages is
characterized by ‘frozen” muscle.
2) Muscular rigidity :-
This is usually of the plastic type i.e. it gives way
in series of jerks.

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3) Resting tremor :-
Repetitive muscle activity usually worse when the
patient at rest. (Barar,2006)
4) An impairment of postural balance leading to
disturbances of gait and falling.(Wardas,2003)
5) Parkinsonian patients also display depressed mood and
cognitive deficit. (Milan et.al.2001)

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Secondary characteristics :-
- Impaired speech
- muscle weakness
- autonomic hyperactivity
eg. Salivation

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Diagnosis
• The patient has BRADYKINESIA, Plus One or More
Following:-
Classic Rest Tremor
Muscular Rigidity
Postural Instability, without other explanation.
• CT-Computed Tomography
• MRI-Magnetic Resonance Imaging

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Treatment
• Non-Pharmacological Treatment:-
• Physical Therapy to delay disability
• Emotional Support to lessen feelings of
helplessness and inadequacy in the patient

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Pharmacological Treatment:-
1) Drug affecting brain dopaminergic system
a] DA precursor :-
Levodopa:-100mg,250mg,500mg.
b] Peripheral decarboxylase inhibitor:-
Carbidopa
Dose-10mg,25mg
c] Dopaminergic agonist :-
Bromocryptine,
Pergolide, Piribedil,
Ropinirole

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d] MAO- B inhibitor :-
Selegiline
e] COMT inhibitor :-
Entacapone,
Tolcapone
f] DA facilitator:-
Amantadine

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Levodopa
• The standard when it comes to treating
Parkinson’s Disease.
• Dopamine, which is the true problem with PD, can
not fit through the Blood Brain Barrier. Doctors
prescribe levodopa because it can squeeze through
the barrier. Once in the brain, L-Dopa is changed
in dopamine.
• The most effective treatment on the market. It
helps to reduce tremors, stiffness, slowness, and
balance problems.
• COBINATION THERAPY:-Levodopa/Cabidopa-
250mg/10mg

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COMT Inhibitors
• COMT inhibitors allow a larger amount of
levodopa to cross the Blood Brain Barrier,
allowing a more constant supply of dopamine.
• COMT inhibitors can be used to treat levodopa
related motor complications
• Entacapone-
Tolcapone-

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Anti-Cholinergic Agents
• These Agents block nerve impulses that help
control the muscles in the arms, legs and body.
• Anti-Cholinergic Agents also reduce the amount
of acetylcholine (which helps control muscle
movement) in the brain.
• Anti-Cholinergic Agents are fairly effective in
reducing only a few symptoms.
• Procyclidine-2.5mg (T.D.S.),
Biperiden-5mg (T.D.S.)
Benzatropine-2mg (T.D.S.)

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Surgical Options
• Surgical procedures are now available for
specific patients who no longer respond to
drug treatments.
• Pallidotomy
– Is a neurosurgical procedure that can reduce many of the
symptoms of Parkinson Disease
– Not a cure
– It can permanently eliminate dyskinesias
– Reduces tremor, rigidity, bradykinesia and shuffling gait.

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• Parkinson's Disease may be affected
following System-
1. Mental Functions
2. Sensory Functions
3. Voice & Speech
4. Skin & Related Functions

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Mental Functions
• Depression
• Persons with Parkinson disease may be up to
eight times as likely to develop Alzheimer's
disease
• Problems relating to confusion, dementia,
anxiety, stress, tension, impaired thinking,
memory, language, and problem solving skills
often appear in the later stages of Parkinson
progression.
• Sleep disturbances (insomnia, fragmented
sleep)
• Bradyphrenia – slowness of thought

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Work
• Limitations in mobility, voice/speech,
cognitive functioning will affect job
performance.

27. ALZHEIMER’S DISEASE
Dr. H. M. Patel

28. Dr Alois Alzheimer
1864 - 1915
German
neuropathologist &
psychiatrist.
In a 1906 lecture he
first described the
disease which now
carries his name.

29. Auguste D.
-First seen by Dr Alzheimer
in 1901 when she was in her
early 50s
-Memory impairment
-Hallucinations
-Executive dysfunction

30. Alzheimer’s disease is an
progressive nervous disorder
that slowly impairs memory
and cognition function.
What is AD?
Slide 4

31. Inside the
Human Brain
Slide 8

32. Neurons
• The brain has billions of
neurons, each with an axon
and many dendrites.
• To stay healthy, neurons
must communicate with
each other, carry out
metabolism, and repair
themselves.
• AD disrupts all three of
these essential jobs.
Inside the
Human Brain
Slide 14

33. Plaques and Tangles: The Hallmarks of AD
The brains of people with AD have an abundance of two
abnormal structures:
An actual AD plaque An actual AD tangle
• beta-amyloid plaques, which are dense deposits of protein
and cellular material that accumulate outside and around
nerve cells
• neurofibrillary tangles, which are twisted fibers that build up
inside the nerve cell
AD and the Brain
Slide 16

34. Beta-amyloid Plaques
Amyloid precursor protein (APP) is the
precursor to amyloid plaque.
1. APP sticks through the neuron
membrane.
2. Enzymes cut the APP into fragments
of protein, including beta-amyloid.
3. Beta-amyloid fragments come
together in clumps to form plaques.
1.
2.
3.
AD and the Brain
In AD, many of these clumps form,
disrupting the work of neurons. This
affects the hippocampus and other areas
of the cerebral cortex.
Slide 17

35. Neurofibrillary
Tangles
Neurons have an internal support structure partly made up of
microtubules. A protein called tau helps stabilize microtubules. In AD,
tau changes, causing microtubules to collapse, and tau proteins clump
together to form neurofibrillary tangles.
AD and the Brain

36. Slide 19

37. Deficiency of Acetylcholine is also responsible for generating
confused state in AD
Acetylcholine Hypothesis
Slide 19

38. •MEMORY LOSS IS THE FIRST SIGN
OF AD.
•COMMUNICATION DIFFICULTIES
FINDING THE RIGHT WORDS
USING PROPER GRAMMER
PRONOUNCING WORDS
• DISINTEREST IN GROOMING
• OVERREACTION TO STRESS

39. Mild to Moderate AD
• AD spreads through the brain. The
cerebral cortex begins to shrink as
more and more neurons stop
working and die.
• Mild AD signs can include memory
loss, confusion, trouble handling
money, poor judgment, mood
changes, and increased anxiety.
AD and the Brain
Slide 21

40. • CONTINUED MEMORY LAPSES
• FORGETFULLNESS ABOUT
PERSONAL HISTORY
• INABILITY TO RECOGNIZE
FRIENDS AND FAMILY
• PERSONALITY CHANGES
CONFUSION
ANXIETY
SUSPICIONS
SADNESS/DEPRESSION
HOSTILITY

41. Severe AD
• In severe AD, extreme
shrinkage occurs in the
brain. Patients are
completely dependent
on others for care.
AD and the Brain
Slide 22

42. • LOSES ABILITY TO SPEAK
• BECOMES INCONTINENT
• INABILITY TO SWALLOW
• MAY BECOME
UNRESPONSIVE ( COMA )
• ENDS IN DEATH

43. A Normal Brain and an AD Affected One

44. Amyloid Plaques and Neurofibrillary Tangles in
Alzheimer’s Disease and Normal Aging
Alzheimer’s NormalNormal
TanglesTangles
PlaquesPlaques
Courtesy of Harry Vinters, MD.Courtesy of Harry Vinters, MD.

45. Treatment of Alzheimer’s Disease
• Anti-Cholinestrase
• Nootropic Agents (Cognition Enhancer)
• Vasoactive Cerebral Protector
• Glutamate Antagonist
• Beta Amyloid Synthesis Inhibitors
• Tau Fibrillation Inhibitor