Medical Treatment and Therapy of Parkinson's Disease

       How to treat patient with Parkinson's Disease? To know the answer, lets read the explain. Parkinson's disease is a degenerative disease, which develops progressively, and the cause is unknown, therefore its management strategies are
1) symptomatic therapy, to maintain the independence of the patient,

2) neuroprotection and

3) neurorestoration,
both to inhibit the progression of Parkinson's disease. These strategies are aimed at maintaining the life quality of patient.

Pharmacologic Therapy

a. Dopamine replacement drugs (Levodopa, carbidopa)

          Levodopa is the main treatment for Parkinson's disease. Levodopa is converted in the brain into dopamine. L-dopa is converted into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (DOPA decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic neurons, the remainder is metabolized in any place, resulting in extensive side effects. Since the feedback mechanism, there would be inhibition of endogenous formation of L-Dopa. Carbidopa and benserazide are dopa decarboxylase inhibitor, helps prevent the metabolism of L-dopa before it reaches the dopaminergic neurons.

      Levodopa reduces tremors, muscle rigidity and improve movement. Patients with mild Parkinson's disease will back to do activities normally. The drug is administered with carbidopa to enhance its effectiveness and reduce side effects. Many physicians delay treatment with levodopa symptomatic until it is needed. If the patient's symptoms are mild and do not interfere, with levodopa therapy should not be done. It is given that the effectiveness of levodopa associated with duration using this drug. Levodopa crosses the blood-brain-barrier and enter the central nervous system and changes ensimatik into dopamine. Inhibit the activity of dopamine neurons in the basal ganglia.

The side effects of levodopa can be:
1) Nausea, vomiting, abdominal distress
2) Postural hypotension

3) Once in a while we will get cardiac arrhythmias, particularly in patients who are elderly. This effect is caused by beta-adrenergic effects of dopamine on the cardiac conduction system. It can be treated with medications such as beta-blocker propranolol.

4) dyskinesia most frequently found involving limbs, neck or face. Dyskinesia often occur in patients who respond well to levodopa therapy. Some patients show symptoms on-off which is very annoying because people do not know when a sudden movement to a standstill, freeze, hard. So the movement momentarily interrupted.

5) laboratory abnormalities. Granulositopenia, abnormal liver function and increased blood urea is a rare complication of levodopa therapy.

       The side effects of levodopa in use for many years is that dyskinesia uncontrolled motor movements in the limbs and body. Response of patients who take levodopa also becoming increasingly diminished. In order to eliminate the side effects of levodopa, the schedule is set and improved dose delivery, as well as giving additional drugs that have different mechanisms work like dopamine agonists, COMT inhibitors or MAO-B inhibitor.

b. Dopamine Agonists
       Dopamine agonists such as Bromocriptine (Parlodel), Pergolid (Permax), Pramipexol (Mirapex), Ropinirol, cabergoline, apomorphine and lisurid considered quite effective for treating the symptoms of Parkinson's. This drug works by stimulating dopamine receptors, but it also causes a progressive decrease in dopamine receptors which in turn will cause an increase in symptoms of Parkinson's.
      These drugs may be useful for treating patients who have experienced attacks fluctuations and dyskinesia as a result of high doses of levodopa. Apomorphine can be injected subcutaneously. Low doses are given every day can reduce the fluctuations of motor symptoms. The side effects of this drug are hallucinations, psychosis, eritromelalgia, leg edema, nausea and vomiting.

c. Anticholinergics
         This drug inhibits the cholinergic system in the basal ganglia and inhibits the action of the brain neurotransmitter called acetylcholine. These drugs can help correct the balance between dopamine and acetylcholine, which can reduce the symptoms of tremor. There are two anticholinergic preparations are widely used for Parkinson's disease, namely thrihexyphenidyl (Artane) and benztropin (congentin). Other preparations are also included in this group are biperidon (akineton), orphenadrine (disipal) and procyclidine (Camadrine).
         Drug side effects are dry mouth and blurred vision. These drugs should not be given to patients with Parkinson's disease over 70 years of age, as it can cause loss of memory.

d. Monoamine oxidase inhibitors (MAO inhibitors)
       Selegiline (Eldepryl), Rasagaline (Azilect). MAO inhibitors allegedly useful in Parkinson's disease because dopamine neurotransmission can be improved by preventing destruction. Selegiline may also slow the worsening of Parkinson's syndrome, thus levodopa therapy may be deferred for some time. Useful for controlling the symptoms of Parkinson's disease is to smooth the movement. Selegilin and rasagilin menginhibisi reduce symptoms with a monoamine oxidase B (MAO-B), thus inhibiting the dopamine released by dopaminergic neurons. Metabolites containing L-amphetamine and L-methamphetamine. Usually used in combination with levodopa-carbidopa combination. In addition it also serves as a mild antidepressant. The side effects are insomnia, decreased blood pressure and arrhythmias.

e. Amantadine
       Serve as a substitute for dopamine, but it works in other parts of the brain. The drug is first discovered as an antiviral drug, then known to relieve symptoms of Parkinson's disease are tremor decreased symptoms, bradikinesia, and fatigue in early Parkinson's disease and motor fluctuations can eliminate (the phenomenon of on-off) and dyskinesia in patients with advanced Parkinson. Can be used alone or in combination with levodopa or dopamine agonists. The side effects can lead to drowsiness.

f. Inhibitors of catechol 0-methyl transferase / COMT
       Entacapone (Comtan), tolcapone (Tasmar). The drug is still relatively new, serves to inhibit the degradation of dopamine by the enzyme COMT and improve the transfer of levodopa to the brain. Began to be used as a combination of levodopa when levodopa decreased effectiveness. Supplied with each dose of levodopa. These drugs improve the on-off phenomenon, improve the ability of activities of daily living.
The side effects of this drug in the form of impaired liver function, so it needs to be examined in serial liver function tests. This medication also causes changes in urine color is red-orange.

g. Neuro protection
        Neuroprotective therapy can protect neurons from cell death induced disease progression. Which is being developed as a neuroprotective agent is apoptotic drugs (CEP 1347 and CTCT346), lazaroids, bioenergetics, antiglutamatergic agents, and dopamine receptors. The frequently used in the clinic is a monoamine oxidase inhibitors (selegiline and rasagiline), dopamine agonists, and complek I mitochondrial fortifier coenzyme Q10.


Surgical Treatment
Aiming to improve or restore it atologis processes underlying (neuro restoration).
a. Therapeutic ablation of lesions in the brain
        Including the category is thalamotomy and pallidotomy
Indications:
 - Severe motor fluctuations that continuously
- Dyskinesia that can not be resolved with medical treatment
Do destruction in central lesions in the brain by using cautery. The effect of this operation is permanent for life and is not safe for ablation in both places.

b. Deep Brain Stimulation (DBS)
       Such electrodes placed at several centers in the brain lesions associated with booster tool mounted on the chest under the skin such as a pacemaker. In this procedure there is no destruction of lesions in the brain, so it is relatively safe. The benefit is to improve the time off from levodopa and controlling dyskinesia.

c. Transplant
         Experiments transplantation in patients with Parkinson's disease begins 1982 by Lindvall and colleagues, adrenale medullary tissue (autologous adrenal) that produce dopamine. Tissue transplants (graft) had ever used, among other mesencephalon ventral embryonic tissues using tissue premordial steam or progenitor cells, non-neural cells (usually fibroblasts or astrosytes), testis-derived Sertoli epithelial cells and carotid body glomus cells. To prevent tissue rejection reactions given immunosupressant drug cyclosporin A, which inhibits the proliferation of T cells so that the lifetime of the graft becoming longer. A successful transplant may reduce the symptoms of Parkinson's disease for 4 years and then the effect is decreased 4-6 years after transplantation. This surgical technique is often hit various barriers such as lack of donor, either technical difficulties or licensing procedures.

Non-pharmacologic
a. Education
        Patients and families are given an understanding of the disease, such as the importance of taking medicine regularly and avoid falling. Creates a feeling of sympathy and empathy from family members so that the physical and psychic support them to the maximum.

b. Rehabilitation therapy
        Medical rehabilitation goal is to improve the quality of life of patients and inhibit the increased severity of disease symptoms, as well as address the following issues: Abnormality of movement, posture trend wrong, autonomic symptoms, self-care Disorder (Activity of Daily Living - ADL), and psychological changes. Patients with Parkinson's workout includes exercises needed physiotherapy, occupational therapy, and psychotherapy.
       Physiotherapy exercises include: exercises bracelet shoulder with a cane, trunk extension exercise, exercise frenkle to run to set foot on the signs on the floor, isometric exercises for the quadriceps femoris and hip extensor muscles in order to make it easier to climb stairs and rise from a chair. Exercise occupation which requires the patient ADL assessment, environmental assessment residence or employment. In practice the implementation of various strategies used are:
- Cognitive strategy: to draw attention / concentration, speak clearly and quickly, being able to use the signs of verbal or visual, and only doing a cognitive or motor task.
- Motion Strategy : as if would turn corners while walking using a rather wide, the distance should be somewhat wide legs if you want to pick up something on the floor.
- Balance Strategic : perform ADLs by sitting or standing with your legs wide open and with the arm holding on to the wall. Avoid escalators or revolving doors. While walking in a crowded place or uneven floors have full concentration do not talk or look around.
       A psychologist is required to assess cognitive function, personality, mental status of patients and their families. The results are used to perform cognitive rehabilitation therapy and psychotherapy interventions.

RELATED ARTICLES

•    Parkinson Disease
•    Clinical Manifestations of Parkinson's Disease
•    Pathophysiology of Parkinson's Disease
•    Diagnosis of Parkinson's Disease



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1. Picture: http://news.christianacare.org/2010/09/thinking-big-improves-function-for-some-parkinson%E2%80%99s-patients