If levodopa is administered alone, the drug is largely decarboxylated by enzymes in the peripheral sites so that little unchanged drug reaches the cerebral circulation. In addition, dopamine release into the circulation by peripheral conversion of levodopa produces undesirable effects,
Parkinson disease with Pharmacotherapy
Parkinson disease with
By Sara Sami
Supervisor: Oruc Allahverdiyev
We can define PD as a slowly progressive of
neurodegenerative disorder of the production
neurotransmitter dopamine and with no identifiable
While Dopamine is a chemical messenger that transmits
signals between two regions of the brain.
Any deficiency in the dopamine in the striatum will
leaves the person unable to control movements and will
then initial symptoms of Parkinson’s.
Striatum – Caudate
Through the spinal
Degeneration of neurones
in the substantia nigra pars
Results in deficiency of
Dopamine in Striatum -
Parkinson's disease has been known to mankind
since ancient times. It is referred to in the ancient
Indian medical system of Ayurveda under the name
Kampavata (where “kampa” means tremor in
In Western medicine it was described by the
physician Galen as "shaking palsy" in AD 175.
Ancient Chinese sources also provide descriptions
that suggest Parkinson's disease.
James Parkinson: Whom was named Parkinson’s disease after him. In 1817
He detailed medical essay called “An Essay on the Shaking Palsy”
Jean Martin Charcot: A French neurologist which found two types
of clinical spectrum – the tremor stage and the rigidity stage
William Gowers: In his “Manual of Diseases of the Nervous System,”
described his personal experience with 80 patients in the 1880s. He
correctly identified the men were more prone to the disease and also
detailed the joint deformities typical of the disease.
In the 1960s chemical differences in the brains of
Parkinson's patients were identified.
The researchers found that there were low levels of
dopamine and degeneration of nerve cells in part of
the brain called the substantia nigra This made
effective treatment of Parkinson’s disease with
◦ In the 1960s, Levodopa was first administered to treat the symptoms PD 
◦ Using of Belladonna alkaloids in treatment of the disease which active
anticholinergic drugs was wildly used however the production of Hyoscyamine
as anticholinergic agent had better results .
◦ Dopamine was synthesized first in 1910 by G. Barger and J. Ewens. P. Holtz and
discovered the enzyme, dopa decarboxylase that documented broken down
levodopa to dopamine through its action.
◦ In1961 levodopa injected intravenously for the first time to PD 
Parkinson’s disease is the second most common neurodegenerative
disease after Alzheimer’s disease. The prevalence rate of PD varies between 15 and
657/100.000 among different populations worldwide.
Turkey: in a small area in the
eastern part Baskale with a
population of 26.991
inhabitants in 2011
prevalence of PD in Turkey
was 202/100.000 that is
slightly lower than those of
European countries, which
may be caused by ethnical
environmental factors 
•It’s has been reported that 4% elderly
over 60 years of the population over
80 with PD however young onset
begin between the ages of 20 and 50 is
•It’s less prevalent in African and Asian
•More common in men than women
•Coffee and tea drinking,cigarette
smoking anti-inflammatory drug
,high serum uric acid, physical
activities  issued to lower the
risk of PD however vitamin D
deficiency index for higher risk of PD
It has been reported to
vary from 15 (per
100,000 population) in
China to 657 in
the number of new cases
per year of PD is
between 8 and 18 per
The exact cause is unknown, however seems to relate to a combination of impaired
degradation of proteins intracellular or protein accumulation or oxidative stress or
mitochondrial damage or inflammatory cascades or and apoptosis. 
from : pesticide
injuries, and living in
the country or
places. And the
drinking of un well
water exposure to
Gentitc : occurs in
patients under age 50
. Mutations in the
parkin, LRRK2, and
are commonly found in
with familial early PD
αsynuclein) in fetal
transplante into the
brain of parkinsonian
patients some years
provided some support
for suggestions that
may represent a prion
Ageing : affects over 1% of the
population over the age of
60while in individuals over the
age of 85 this prevalence
reaches 5%, 
Lysosomes :The most important functions of the lysosome is to store
iron in a place in the cell where it is not accessible to participate in
toxic oxidative stress-producing reactions," Mutation in a lysosomal
gene results in the toxic release of iron into the cell, that resulting in
neuronal cell death.
The solution :
By tying up excess iron with a metal chelator that protect mice from
the ravaging effects of the well-known Parkinson's. It pulls iron from
the cells indiscriminately and iron is needed throughout the body for
many biological functions,“ 
Although There is no “one way” to diagnose Parkinson’s disease there
must be two of the four main symptoms present over a period of time for a
neurologist to consider a PD diagnosis, however new studies have found
that the oxygen consumption in the mitochondria, which leads to a build
up of toxic byproducts that cause damage to brain cells and cause of the
Australia’s La Trobe University a blood test was developed of abnormal
metabolism of blood cells in people with Parkinson. they said “We were
able to show the mitochondria were perfectly normal but, were working
four times as hard, which also leads to increased production of poisonous
byproducts to occur.” 
The test involves inserting a needle into the
submandibular gland under the jaw and withdrawing
the needle to obtain the core of gland tissue within.
The researchers looked for a protein in the cells from
patients who have early Parkinson's disease and
compared this to subjects without the disease.
Lewy bodies : A proteins fold into the wrong shape and stick
together with other proteins, eventually forming thin filament-like
structures called amyloid fibrils. These amyloid deposits of
aggregated α-synuclein, also known as Lewy bodies, are the
hallmark of Parkinson’s disease.
Genetic factors ,ageing or trauma in the head, has produce extra
soluble protein that interacted with alpha-synuclein protein to
produce toxic effects of Lewy bodies.
The researchers used different forms of α-synuclein and added to
alpha-synuclein fibrils of the neurons, they interacted and no toxic
effects were present.
Drugs affecting brain cholinergic system
◦Central anticholinergics: Trihexyphenidyl,
Procyclidine, Biperiden that are not used in
◦Antihistaminics: Orphenadrine, Promethazine,
dopamine produced is responsible for the therapeutic effectiveness of the
drug in PD; after release, it is either transported back into dopaminergic
terminals by the presynaptic uptake mechanism or metabolized by the
actions of MAO and catechol-O-methyltransferase (COMT) .
Dopamine itself does not cross the blood-brain
barrier and therefore has no CNS effects. However,
levodopa, as an amino acid, is transported into the
brain by amino acid transport systems, where It is
converted to dopamine by the enzyme L-aromatic
amino acid decarboxylase.
levodopa can pass freely through the brain barrier reaching
the CNS, however it administered with COMT inhibitor such
as carbidopa that do not penetrate into the CNS The most
commonly prescribed form of carbidopa/levodopa is the
25/100.  and its limited by the development of
Nasal mucosal grafting is a technique regularly used in the ENT field to
reconstruct the barrier around the brain after surgery to the skull base.
ENT surgeons commonly use endoscopic approaches to remove brain
tumors through the nose by making a window through the blood-brain
barrier and access the brain. Once they have finished the treatment,
they use adjacent nasal lining to rebuild the hole in a permanent and
safe way. The safety and efficacy of these methods have been well
established through long-term clinical outcomes studies in the field,
with the nasal lining protecting the brain from infection just as the
blood brain barrier has done.
1) Gastrointestinal effect: nausea and vomiting
2) Cardiovascular Effects: tachycardia , hypotention
3)Mental effects : Depression, anxiety.
3) Dyskinesias as chorea and tremor
4) Miscellaneous: acute glaucoma, blood dyscrasias,
Four orally administered dopamine-receptor agonists are
available for treatment of PD 
1) Ergot derivatives: as Bromocriptine or Pergolide old
drugs are not wildly used these days.
2) Non ergot derivatives as Ropinirole, pramipexole
Ergot or ergot fungi refers to a group of
fungi of the genus Claviceps. The most
prominent member of this group is
Pramipexole: agonist of D3,monotherapy for mild to advance PD,
starting with the dose of 0.125mg , 0.5 and 1.5 mg 3 times s day
for a week then doubled after the next week.
Ropinirole: agonst for D2, monotherapy smoothing the response
to levodopa in patients with more advanced disease and response
fluctuations. Starting with 0.25 mg three times daily and
gradually increase reaching 1.5mg.
Rotigotine: available in skin patches
Monoamine oxidase (B) metabolizes dopamine.
Mechanism of action:
• Selective inhibitor of monoamine oxidase B (retards the
breakdown of dopamine). Given alone, it has a weak action. It
is therefore used as adjunctive therapy for patients with a
declining response to levodopa of the stander dose 5mg.
• May cause insomnia when taken later during the day.
• It should not be taken by patients receiving tricyclic
antidepressants, or serotonin reuptake inhibitors because of
the risk of acute toxic interactions.
Meperidine: one of it’s contaminated manufacture product is
MPP+ that selectively taken up by cells in the substantia nigra to
inhibits mitochondrial complex oxidative phosphorylation that
cause cell death and dopamine depletion and parkinsonism accrue.
Exposuring to toxin environmental that is similarly selective in
MPP+ target, may lead to cell death by the same pathway However,
no such toxin has been identified yet.
Pretreatment with a monoamine oxidase B inhibitor such as
selegiline/ Arsagilin prevents the conversion of MPTP to MPP+ and
thus protects against the occurrence of parkinsonism.
• Mechanism of action:
1. Inhibit catechol O methyl transferase (COMT) which is
responsible for the conversion of dopa into 3 – O methyl
dopa. Elevated levels of methyldopa decreases the response
to levodopa, because methyldopa competes with levodopa
for an active carrier mechanism that governs its transport
across the blood-brain barrier.
• These agents may be helpful in patients receiving levodopa
to reduce dose and decrease fluctuations in response
• Side effects are similar to levodopa
Amantadine, an antiviral agent. Its mode of action in parkinsonism is unclear but
it may potentiate dopaminergic function by influencing the synthesis, release, or
reuptake of dopamine
• Amantadine is less potent than levodopa and its effects disappear after only a few
weeks of treatment
1. Central nervous system effects
2. Peripheral edema
4. Heart failure
5. postural hypotension
6. urinary retention
• Amantadine should be used with caution in patients with a history of seizures or
Antimuscarinic drugs may improve the
tremor and rigidity of parkinsonism but have
little effect on bradykinesia.
1) Central nervous system
2) Atropine – like actions: dryness of the mouth, blurring of vision.
withdrawal should be gradual in order to prevent acute
exacerbation of parkinsonism.
1. Prostatic hyperplasia,
2. Obstructive gastrointestinal disease (eg, paralytic ileus)
3. Angle-closure glaucoma.
None of the above drugs alter the basic
pathology of PD – the disease continues to
progress. Drugs only provide symptomatic
relief and give most patients an additional 3-
10 years of happier and productive life.
A neurosurgical procedure: Is a neurostimulator delivers
electrical signals to specific areas of the brain to help regulate
abnormal signals, Stimulation of the subthalamic nucleus or
globus pallidus by an implanted electrode and stimulator has
yielded good results for the management of the clinical
fluctuations occurring in advanced
However it’s benefit occurred in
younger (less than 60 years old)
Rivastigmine: It’s already know that Rivastigmine
works to treat dementia by preventing the breakdown
of acetylcholine, however our study shows for the first
time that it can also improve regularity of walking,
speed, and balance. This is a real breakthrough in
reducing the risk of falls for people with
Howevre other thinking agents like of Memantine or
Donepezil or placebo drug use in Alzheimer may be
useful in nonmotor manifestation of PD.
GM1 Ganglioside: Is normally made by nerve cells in the brain, but the
substance is made at much lower levels in patients with Parkinson's.
It was extract from cow brains to improve earlier symptoms and
progression of PD However new reseacher suggested instead of putting
more GM1 into the brain, why not try to get the brain to make more of
it. They he found an enzyme called sialidase was capable of converting
other naturally occurring ganglioside molecules in the brain into GM1
Reserpine and the related drug Tetrabenazine deplete
Haloperidol, Metoclopramide, and the Phenothiazines
block dopamine receptors and meperidine all those
induce PD usually within 3 months after introduction
Life is easier with the right
Thank you for your
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2- Figure :2 book katzung book bag 484
3- Figure : 3 book katzung book bag 485
4- Vedio : 4 https://www.youtube.com/watch?v=jyBakRkzswU
5 - http://www.parkinsons.org/parkinsons-history.html
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24- 39 katzung book bag484
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26- 41 katzung book bag486
27- 42 katzung book bag488
28- 43katzung book bag490
29- 44katzung book bag488
30- Figure http://www.biotechnologyforums.com/thread-6958.html
31 – figure https://www.youtube.com/watch?v=E8AJylo4-To
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National Academy of Sciences, 2016 DOI:10.1073/pnas.1516546113
39 - https://www.youtube.com/watch?v=j86omOwx0Hk
40- Figure https://www.studyblue.com/notes/note/n/parkinson-s-disease-/deck/7642706?blurry=e&ads=true
41 – figure http://tmedweb.tulane.edu/pharmwiki/doku.php/pd_pathways_targets
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43- Hacer Durmus • Mehmet A. Gokalp • Hasmet A. Hanagasi from Prevalence of Parkinson’s disease in Baskale, Turkey: a population based