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What treatments are available for parkinsons disease

Parkinson’s disease is a neurodegenerative disorder. The disorder is cause by gradual loss of cells in a small part of substantia nigra which is in the brain. The reduction of these cells will directly cause the number of dopamine to decrease. Lack of dopamine will cause the symptoms like shaking of hands, stiffness and slow down of movement. While other symptoms that appear include loss of facial expression, reduction in speech volume and clarity, difficulty in swallowing, change in the size of handwriting, dry skin, constipation, urinary difficulties and depression. As Parkinson’s disease is a progressive disorder, the patient’s symptoms will continue to worsen over time. [1]. According to the Parkinson Study Group (PSG), there are approximately 1 million people in the United States are having Parkinson’s disease. The disease most often affect the older person mostly those who over the age of 55. PD appears to be affected more in men rather than in women. The World Health Organization (WHO) point out that by 2040 the PD will surpass the cancer and become the second most common cause of death. [2] There’s no cure for the Parkinson’s disease at the moment. Currently, there are treatments that can help the patient to relieve from the symptoms. What is the exact treatment for the Parkinson’s patient?

http://rst.gsfc.nasa.gov/Intro/pettrans.gif Figure 1: The MRI scan brain for the PD patient. [3]

Pharmacological Treatments

Sinemet

Sinemet is the combination of levodopa and carbidopa. Levodopa is a metabolic precursor of dopamine while carbidopa is an inhibitor of the aromatic amino acid decarboxylase enzyme which means that carbidopa helps to reach the brain. Levodopa decarboxylases when it reaches the brain. As for carbidopa, the drug which does not crosses the haematoencephalic barrier only limited to extra cerebral decarboxylation of the levodopa and therefore providing the great amount of levodopa to the brain. [4] By the aid of the carbidopa, it proves that there will no needs of large quantities of levodopa at frequent interval. After many years have been testing, levodopa is still considered the best treatment for the Parkinson’s patient. But, the levodopa will only work in the best when it is taken with or combine with another drug like carbidopa.

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Figure 2 Changes on Total Scores on the Unified Parkinson's disease Rating Scale (UPDRS) in 361 Patients Receiving Different Levodopa Regimens.

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After baseline evaluations, patients were randomly assigned to receive one of three levodopa–carbidopa regimens or placebo for a comparison of clinical outcomes during a 40-week period. The points on the curves indicate mean changes from baseline on total scores on the UPDRS, which measures motor function and activities of daily living, with lower scores indicating improvement. Patients show a dose-related improvement in parkinsonian signs and symptoms. Data are from the Parkinson Study Group. [5]

Dopamine agonists

Dopamine agonists are the chemicals which have the similar structure with the dopamine in the brain. This kind of drug is very useful to the Parkinson’s patient especially to the patients which have developed “motor complications” in the Sinemet therapy. [2] Besides that, dopamine can also treat non-motor symptoms of Parkinson’s Disease which are the depression. Dopamine agonists act directly on the dopaminergic systems. The D2 receptors of nigrastriatal pathway are mainly responsible for the motor symptoms for the PD.[6] The D3 receptors of the mesolimbic pathway, including the amygdala, may be involved in mood and behaviour, so preferential stimulation of the D3 receptors relative to other receptor types may help explain the antidepressive and antianhedonic properties of some dopamine agonists. [6] The clinically available dopamine agonists fall into two groups: 1) the ergot-derived agonists (pergolide, bromocriptine, lisuride) and 2) the nonergot derived drugs (apomorphine, pramipexole, ropinirole). [7] More information about the dopamine agonists is this kind of drug contain oral drug. The oral drug includes bromocriptine, pramipexole and ropinirole. This kind of oral dopamine agonists can be taken as the monotherapy and not same like the levodopa must combine with other type of drug. The dopamine agonists are useful in all stages of treatment especially in the later stages when the brain responses to the levodopa is decreases and the dyskinesias and the on-off effects is happened. [8]

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Dyskinesias

Wearing-off

Insufficient motor control

Untreated

Increase frequency

of levodopa

administrations

Consider

liquid/effervescent

formulations

Consider

association with a

COMT inhibitor

(entacapone or

tolcapone)

Consider rasagiline

Adjust levodopa

dose

Consider

liquid/effervescent

formulations to

shorten time-to-on

Consider duodenal

levodopa infusion

Increase individual

levodopa doses

Consider levodopa

triple combination

with entacapone

Consider rasagiline

Levodopa may be

Started

Try not to exceed

300−500 mg/day

Figure3.Proposed algorithm of levodopa-based strategies in patients with Parkinson’s disease at different disease stages. COMT= catechol-O-methyltransferase. [9]

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Some Commonly Used Oral Antiparkinsonian Drugs

Drug

Starting Dose

Average Daily Dose

Usual Dose Range

SINEMET

25/100, 10/100, or 25/250 mg (immediate-release or dissolvable)

25/100 mg tid

25/100 mg tid to 25/100 mg 6 times/day

tid to 25/250 mg 8 times/day

Carbidopa/levodopa

SINEMET

25/100 or 50/200 mg (controlled-release)

25/100 mg bid

50/200 mg tid to qid

75/300–600/2400 mg (total daily), in divided doses

Dopamine agonists

Bromocriptine

1.25 mg bid

10–40 mg once/day

1.25–40 mg once/day

Pramipexole

0.125 mg tid

0.5–1 mg tid

1.5 mg tid

Ropinirole

0.25 mg tid

3–4 mg tid

0.25–8 mg tid

Figure 4: Drug treatment of Parkinson’s disease [8] .

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Benefits and risks

Through the consumptions of the drug like the sinemet, this drug can bring negative effects to the Parkinson’s patient. The patient will suffer from the drowsiness, dizziness and lightheadache. The situation will continue to worsen if the patient continue to take the medicine together with the alcohol.[10] There have been a study that Parkinson’s patient who have taken this kind of drug have a higher risk to suffer from the melanoma than the general populations. [11] There also has been reported that the patient might develop compulsive gambling. The cases that the compulsive gambling also has been reported that those who use levodopa as the monotherapy. [11]

The benefits that the patient can gain from the Sinemet are that the drug eliminates the side effects for those patients who undergo the levodopa-treatment as the treatment can cause nausea, anorexia and vomiting. [10] The Sinemet do help the patient to relieve the parkinson symptoms.

Social and Economic Implications

There are many challenges have to be solve if one of our family members are a parkinson’s patient. According to the survey, the direct and the indirect cost for the care of parkinson’s patient especially the drug treatment has cost about US $1100 million worldwide. [2] This will definitely burden other family members.

The parkinson’s patient face the problem when they mix around with other people. As parkinson’s patient experience a variety of speech difficulties and it does affect their communication skills when they mix along with people. This definitely brings bad implications to their social life. Research has shown that many people with Parkinson's disease do not see a speech and language therapist even though they have speech difficulties (Oxtoby, 1982). [14] From the books “Saving Milly” which I see , the main character in the novel named Milley Martinez who discovered that she is suffering from the Parkinson’s and how the PD bring uncomfortable and troublesome in her life.

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Alternative Solutions

Deep Brain Stimulations (DBS)

DBS is a procedure which includes implanting an electrode into the brain, which is connected to the pulse generator which is externally generated. [12] This surgery is carried out when the conditions of the motor fluctuations and the dyskinesias are happened frequently. The DBS not only decrease the need of the drug such as the levodopa, it also decreases the implications on the motor fluctuations and dyskinesias. [12] According to a study, DBS has successfully improved the parkinsonism and decreased the dyskinesias at least 50% and this improvement can last long for at least 4—5 years. [12]

An MRI scan.

Figure 5: Luis Carlos Torres/iStockphoto

MRI scans are used to help the surgeon accurately locate structures within the patient's brain. [22]

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http://aerzteblatt.lnsdata.de/bilder/2010/03/img144189.gif

Figure 6: Target areas for deep brain stimulation [23]

Stem cells

Another alternatives treatment for the Parkinson’s disease is the stem cell treatment. The stem cell treatment has grown more popular among the patients. The increase of the knowledge in the field of the stem cell, especially the pluripotent stem cell has greatly improved the life of the Parkinson’s patient

The pluripotent stem cell first must be derieved from the embryos or through reprogramming the somatic cell. The pluripotent stem cell has higher potency compare to the adult stem cell and can easily differentiate into another cell types. In PD, most motor features results from the selective loss of the pigmented neurons of the substantia nigra pars compacta which will provide the doparmigenic innervations to the medium spiny neuron of the starium. [13] By knowing the appropriate locations of the dopamine producing areas, the therapy can be carried out. By now, the embryonic stem cell is the most reliable source as it can easily differentiate into the dopaminergic neurons. From the figure below, the stem cells from feotus and the adult are not suitable. The technology still: (i) does not produce cells fully identical to pluripotent ESC, and (ii) relies on transgenic expression of pluripotency factors in genetically modified cells. [13]

Figure 5 Various sources for stem cells for PD’s cell therapy. Pluripotent Stem Cells can be generated either from embryonic material (Embryonic Stem Cells) or from somatic cells reprogrammation (induced Pluripotent Stem Cells). Another source of stem cells (adult or fetal neural progenitors) are considered to be non-pluripotent but also emerged for their putative capacity to be differentiated towards dopaminergic neurons. (Parkinson patient, drawing by SirW.R. Gowers, 1886.) [13]

Evaluations

From the websites, http://www.parkinsonstudygroup.org/What%20is%20Parkinson%20Disease.html, I found that the data and information provided is the latest as it only up loaded on 14 Jun 2010. The information and the data provided from the Parkinson Study Group. The data is based on the research carried all around the world. (1728 words)

As from the websites, http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=6&hid=8&sid=c9163907-aee9-4ce7-98d0-a7a867675268%40sessionmgr13 the information about the drug Sinemet is believelable as the information comes from Merck Frosst Canada Ltd. The company already carried out the experiment on animals to identify the side effects of using the Sinemet.

From the movie “Saving Milly” which directed by Dan Curtis at the year 2005 prove that the storyline is not a fake one. The whole story is based on the real life journey of political journalist named Mort Kondracke. [22] The movie how Mort take care of his lovely wife, Milly when she was diagnosed of having parkinson in the year 1987.

Besides that, the websites, www.elsevier.com/locate/parkreldis shows that the result is unbiased as the research is done on a large sample and has provided the exact percentage on how many Parkinson patient suffer from motor fluactuations and the need to carried out the surgery.

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