PHARMACOLOGIC

MANAGEMENT OF PARKINSON
DISEASE
Dr. Mehwish Waseem

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PARKINSONISM:
It is a chronic, progressive neurological
syndrome due to lesion in basal ganglia
resulting in

 Resting tremors.
 Rigidity.
 Bradykinesia
 Postural instabilities

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PARKINSON DISEASE

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 InParkinson disease
 there is a slow, progressive degeneration of certain dopamine
secreting neurons in the basal ganglia.

 Parkinsondisease usually begins in the fifth or sixth decade,

and symptoms progressively worsen over a period of 10 to 20
years.

 In addition to the symptoms of bradykinesia and rigidity, a

patient with advanced Parkinson disease maintains a flexed
posture and speaks in a low, soft voice (microphonia).

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 The basal ganglia are groups of nuclei located in the
brain that are involved in the coordination and
regulation of motor function.
 One such nucleus, the substantia nigra, contains the cell
bodies of neurons that project to other areas such as the
putamen and caudate nucleus (known collectively as the
“corpus striatum”). The neurotransmitter used in this
nigrostriatal pathway is dopamine.

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The primary neural abnormality in Parkinson disease is that
dopamine-producing cells in the substantia nigra begin to
degenerate, resulting in the eventual loss of dopaminergic
input into the corpus striatum. it also appears that the lack of
dopamine results in an activity increase in basal ganglia
cholinergic pathways.

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PATHOPHYSIOLOGY:
 Since dopamine is an inhibitory neurotransmitter which is released
in nigrostriatal pathway to perform its functions.

 Due to etiological factors progressive dopaminergic cells

degeneration inside substantia nigra takes place.

 Due to absence of dopaminergic inhibitory response cholinergic

excitatory response superceeds and causes adverse effects.

 Lewy bodies formation: These are neuronal eosinophillic

inclusions formed due to degeneration in substantia nigra that
cause decreased dopamine production.

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Basal ganglia
 base of forebrain……connected with cortex and thalamus

 Caudate
 Putamen
 Globus pallidum composed of globus pallidus externa (GPe) or
globus pallidus interna (GPi)
 Subtantia nigra ....pars compacta (SNc) & substantia nigra pars
reticulata (SNr)

 Sub thalamic

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Normal function
Basal ganglia involves in
Control of motor activities in association with
cerebral cortex
Control autonomic associative movements0-
armswing
Check abnormal involuntary movements
Cognitive function
Control group movement for emotional
expressions
integrating sensory information
Have an inhibitory control over spinal reflexes
Have an inhibitory control over muscle tone

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DISCOVERY:
Parkinson disease was first discovered by
JAMES PARKINSON in 1817. He
named it PARALYSIS AGITANS means
shaking palsy.

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OCCURANCE:
AGE: > 60 yrs.
SEX: Male: Female ( 1:1).
INCIDENCE: 1-2 per 1000
• The second most common neurodegenerative disorder after
Alzheimer´s disease (AD).

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 Etiology
Age - the most important risk factor
Positive family history
Male gender
 Genetic factors…formation of oxygen free radical.
 environmental toxins (e.g.,herbicides, insecticides,
fungicides) accelerate the neuronal destruction in
people with Parkinson disease…MPTP toxicity
 {1-methyl-4phenyl-1236tetrahydropyridine(neurotoxin)}.
 Trauma, infectious diseases, CVA, alzhimer’s,
antipsychotic drugs…
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 CLINICAL FEATURES:
Primary
Secondary
1. Resting tremors 1.Psychological problems
2. Bradikinesia 2.Personality problems
3. Rigidity 3.Autonomic disturbances
4. Postural abnormalities 4.Sensory problems
5. Masked face 5.Sleep disturbances
6. Abnormal gait 6.Speech problems
7.Micrographia
8.Cough

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Management
Pharmacological

Physical Therapy

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 THERAPEUTIC AGENTS
1. LEVODOPA
• Resolves dopamine deficiency by being converted
to dopamine after crossing blood-brain barrier.
• immediate precursor to dopamine…
dihydroxyphenylalanine (L-isomer of dopa)…
crosses the blood-brain barrier quite readily.
• dopa decarboxylase covert levodopa into
dopamine.

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 Cont…
PHARMACOKINETICS: Given orally in combination
with carbidopa(peripheral decarboxylase inhibitor)…
SINEMET…or benserizide…MADOPAR
PROBLEMS AND ADVERSE EFFECTS
• GIT
• CVS
• Postural hypotension
• DYSKINESIA
• BEHAVIORAL CHNGES
• DEMINISHED RESPONSE TO LEVODOPA
• FLUCTION IN RESPONSE
• DRUG HOLIDAY
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 DOPAMINE AGONIST
BROMOCRIPTINE
PERGOLIDE
PREMIPEXOLE
ROPINIROLE

Mild to moderate parkinsonism

To cover the fluctuating effects of L-Dopa
Neuroprotective effects…normalize endogenous dopamine
activity
Side effects…nausea, vomiting, post.hypotension, confusion,
hallucination.
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 ANTICHOLENERGIC DRUGS
BENZTROPINE
BEPERDIN
DIPHENHYDRAMINE

Block Ach. Receptors in basal ganglia.

mood change, confusion, hallucinations,drowsiness,

and cardiac irregularity.In addition,blurred vision,
dryness of the mouth, nausea/vomiting,
constipation, and urinary retention are fairly
common. 21
 AMANTADINE

antiviral drug…discovered by chance.

blocking the Nmethyl-D-aspartate (NMDA)

receptor in the brain, thereby inhibiting the effects
of excitatory amino acids such as glutamate.
orthostatic hypotension, CNS disturbance(e.g.,
depression, confusion, hallucinations), and patches
of skin discoloration on the lower extremities

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Selegiline
MAO –b inhibitor….breakdown of dopamine.
can be used alone in the early stages of Parkinson
disease to Prolong the effect of endogenous
dopamine produced within the basal ganglia.

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 Catechol-O-Methyltransferase
Inhibitors
Convert levodopa to 3-O-methyldopa
preventing levodopa conversion in peripheral
tissues, more levodopa is available to reach the
brain and exert beneficial effects.

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THANK YOU

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