Download What is Parkinson`s Disease?

Parkinson s disease
Niazy Burhan aldin
What is Parkinson’s Disease?
Parkinson's disease (PD) is a movement disorder that is
chronic and progressive, meaning that symptoms
continue and worsen over time. Nearly one million
people in the US are living with Parkinson's disease. The
cause is unknown, and although there is presently no
cure, there are treatment options such as medication
and surgery to manage its symptoms
Epidemiology
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2nd common neurodegenerative disease,
. After Alzheimer s disease
PD affect 1% of the population over 65
years of age ,rising to 2% over the age of
80
Although it my be less common in china
and west Africa. Most epidemiological
studies have indicated a small male- to –
female predominance .
Aetiology
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Parkinson's disease occurs when a group of cells in an
area of the brain called the substantia nigra begin to
malfunction and die. These cells in the substantia nigra
produce a chemical called dopamine. Dopamine is a
neurotransmitter, or chemical messenger, that sends
information to the parts of the brain that control
movement and coordination.
When a person has Parkinson's disease, their
dopamine-producing cells begin to die and the
amount of dopamine produced in the brain decreases.
Messages from the brain telling the body how and when
to move are therefore delivered more slowly, leaving a
person incapable of initiating and controlling movements
in a normal way.
Aetiology
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Both genetic and environmental factor
have been implicated as a cause of
parkinson s disease
The discovery of a mutation in the gene
coding for a synaptic protein called alphasynuclein provided tremendous impetus to
research .
Environmental – chronic systemic
exposure to the pesticide rotenone can
reproduce the clinical and pathological
features of parkinson s
pathophysiology
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Neuronal loss in pigmented
brainstem nuclei, together with the
presence of esinophilic inclusion
bodies, called Lewy bodies;in
surviving cell .loss of 80% of nigral
neurons before symptoms appear
Host of other nuclei and
neurotransmitter systems are
involved. For example, cholinergic
neurons. Swallowing difficulty
(dysphagia) and sleep disturbance
(REM disterbance)
Pathophysiology
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The loss of noradrenergic and serotogenic
neurones wthin the locus coeroleus and
raphe nucleus , respectively , may provide
a pathophysiological basis for depression
which is common in PD.
Drug induced parkinsonism
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(DIP) is potentially reversible upon
cessation of the offending agent.
Chlorpromazine
Fluphenazine as neuroleptic drugs
Prochlorperazine and cinnarzine
The pathogenesis of drug-induced
parkinsonism due to dopamine receptor
blocked.
Non – neuroleptic drugs associated with
drug induced parkinsonism see table 32.3
Investigations
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Clinically Should be based
Copper studies and DNA testing to exclude
wilsons disease and Huntingtons disease
respectively .
Brian imaging by computed tomography
(CT) or magnetic resonance image (MRI)
to exclude hydrocephalus ,
cerebrovascular disease or basal ganglia
abnormalties .
SPECT test imaging to identify loss of
nigrostriatal dopaminergic terminals in
Clinical features
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Bradykinesia is general in parkinsonism
Rest tremor, extra pyramidal rigidity (so called
lead pipe –and/or cog- wheel) rhythmic
movement it some times described as pill-rolling
in nature from movement of thumb across the
fingers.
Postural instability is a late feature of parkinson
s disease and loss of arm swing in walking .
There is reduced blink frequency and facial
expression .
60% of people with PD may have a dominant
postural tremor .
Clinical features
Clinical features
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Postural instability is a late feature of PD
There is reduced blink frequency and facial
expression with reduced volume (hypophonic) .
Autonomic dysfunction may occur in parkinson
disease ,urogenitial difficulties ,with erectile
dysfunction in males and urinary urgency in both
sexes.
Depression affects approximately 40% of
patients .
Occurrence of dementia related to the age in PK
Treatment (General approach )
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All currently available drugs for PD are
symptomatic .
A number of factors including age ,
severity and type of disease ( tremordominant versus bradykinesia-dominant )
The limitation of levodopa treatment
(levodopa syndrome)
Treatment
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Drug treatment
1-Levodopa preparations
A/Immediate- release Levodopa remain the most
effective oral symptomatic treatment for PD . It is
administered with the peripheral dopa-decarboxylase
inhibitors carbidopa or benserazide, 50 mg per day
increasing every 3-4 days take with food to minimize
nausea
B/Controlled –release Levodopaving both
sinemet and madopar simplifying drug regimens ,
relieve fluctuation.
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Duodopa a highly soluble form of levodopa is
administered directly into small bowel .
Co-careldopa intestinal gel
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. An intestinal gel preparation
of levodopa and carbidopa (Duodopa®) is
available that is administered directly into
the small bowel (specifically, the jejunum)
via a percutaneous route, using a portable
electronic pump. Through continuous
delivery in this way, motor fluctuations
may be significantly reduced. Although
effective, this treatment modality requires
Co-careldopa intestinal gel
Treatment
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2- Dopamine agonists – Bromocriptine
Cabergoline ,Ropinirol pramipexole and pergoide
3-Catechol-O- methyl transferase inhibitors
(COMT) Entacapone Tolcapone(Hepatotoxic)
4-Monoamine oxidase inhibitors type B inhibitors
propargylamines Selegiline and rasagiline
5- Amantadine blocking dopamine reuptake An
anticholinergic effect.
6- Anti cholinergic drugs (trihexyphenidyl &
orphenadrine modret effect in reducing tremor
2- Dopamine agonists
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Dopamine agonists differ in their affinity for a number of
receptors, including the dopamine receptor family. It is not
known whether these differences are clinically significant, but
experience to date would suggest not. Cabergoline is an ergot
dopamine agonist with a much longer plasma half-life of 63–
68 h than other agents in this class. This means that oncedaily dosing is possible. Ropinirole and pramipexole are nonergot derivatives that originally had to be administered three
times daily. Slow release preparations of ropinirole
(XL) and pramipexole (PR) are now available for once-daily
dosing. A transdermally administered non-ergot dopamine
agonist, rotigotine, is also available as a 24-h adhesive
patch.
Dopamin Agonist
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Dopamine agonists have also been
associated with impulse control disorders
(ICDs). These disorders include
pathological gambling, hypersexuality and
excessive shopping. The onset may relate
to dopamine D2/3 receptor stimulation in
predisposed individuals.
Catechol-O-methyl transferase
inhibitors
3-Catechol-O-methyl transferase
inhibitors
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Inhibitors of the enzyme catechol-O-methyl transferase
(COMT) represent a novel addition to the range of
therapies available for Parkinson's disease (Schrag,
2005). Use of the first agent in this class, tolcapone, was
originally suspended in Europe because of fears over
hepatotoxicity, although the drug became available again
in 2005, accompanied by strictprescribing and
monitoring guidelines. Entacapone is also available and
studies have not shown derangement of liver
function with this drug
Monoamine oxidase type B
inhibitors
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The propargylamines selegiline andrasagiline are
inhibitors of monoamine oxidase type B. Inhibition
of this enzyme slows the breakdown of dopamine in
the striatum. These agents effectively have a
‘levodopa-sparing’ effect and may delay the onset
of, or reduce existing, motor complications. Both
drugs may also have an antiapoptotic effect
(apoptosis is a form of programmed cell death
thought to be important in several
neurodegenerative conditions, including
Parkinson's disease).
buccal selegiline.
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A single daily dose of 5 or 10 mg of
selegiline is prescribed.
Higher doses are associated with only
minimal additional inhibition of monoamine
oxidase. Selegiline may also be
administered as a lyophilised freeze-dried
buccal preparation.The dose of rasagiline
is 1 mg daily.Both selegiline and rasagiline
may be used as de novo or adjunctive
treatments in Parkinson's disease,
although trial data for the latter indication
are strongest for rasagiline and buccal
Amantadine
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Amantadine was introduced as an anti-Parkinsonian
treatment in the late 1960s. It has a number of possible
modes of action, including facilitation of presynaptic
dopamine release, blocking dopamine reuptake, an
anticholinergic effect, and also as a N-methyl- -aspartate
(NMDA) receptor antagonist. Initially employed in the early
stages of treatment, where its effects are mild and relatively
short-lived, interest has focused more recently upon the use
of amantadine as an antidyskinetic
agent in advanced disease Daily doses of 100–300 mg
amantadine may be used
d
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Amantadine
Treatment
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Tricyclic antidepressant have
anticholinergic properties, alow dose of
TCAs e.g amitriptyline 10 -25mg at night
improving sleep and improving
performance early in the morning .
Apomorphine the most potent dopamine
agonist used SC injection alternatives
route is transdermal and transnasal route.
Treatment
Surgical treatment
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Deep brain stimulation has the advantage
of being reversible but is costly.
Surgery may also play role in
neurorestorative treatment such
approaches include stem cell and fetal cell
transplantation.and also
xenotransplantation
Patient care
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See table 32.5 lists some common
therapeutic problem page 470 .
Diary cards when they begin to experience
problems with either bradykinesia or
dyskinesia .
Careful changes in timing of drug therapy
or meals may intially be sufficient to
reduce variation in performance
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The treatment of the patient with severe
disease remains one of the greatest
challenges in the management of
Parkinson's disease. On–off fluctuations
may be refractory to oral dopaminergic
therapies. Sudden freezing episodes
compound failing postural stability
Autonomic problems
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Disorder of gut motility – constipation or
difficulty with swallowing , disturbances of
micturition , nocturia and postural
hypotension . See page 471
Solving these problems recommended .
Psychosis and dementia
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When cognitive impairment is problematic,
the use of conventional antipsychotic
medication is inappropriate because such
drugs can precipitate a catastrophic
worsening of Parkinsonism. Behavioural
disturbances require discussion with carers
and, if possible, with the patient him- or
herself an atypical antipsychotic drug may
be considered. In practice, the choice
narrows down to quetiapine or clozapine,
since risperidone and olanzepine are