Parkinson's disease medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Medical Therapy
Parkinson's disease is a chronic disorder that requires broad-based management including patient and family education, support group services, general wellness maintenance, exercise, and nutrition. At present, there is no cure for PD, but medications or surgery can provide relief from the symptoms.
Levodopa
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Stalevo for treatment of Parkinson's disease
The most widely used form of treatment is L-dopa in various forms. L-dopa is transformed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by its former name dopa-decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic neurons. The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so eventually becomes counterproductive.
Carbidopa and benserazide are dopa decarboxylase inhibitors. They help to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons and are generally given as combination preparations of carbidopa/levodopa (co-careldopa) (e.g. Sinemet, Parcopa) and benserazide/levodopa (co-beneldopa) (e.g. Madopar). There are also controlled release versions of Sinemet and Madopar that spread out the effect of the L-dopa. Duodopa is a combination of levodopa and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly absorbed.
Tolcapone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa. However, due to its possible side effects such as liver failure, it's limited in its availability.
A similar drug, entacapone, has similar efficacy and has not been shown to cause significant alterations of liver function. A recent follow-up study by Cilia and colleagues[1] looked at the clinical effects of long-term administration of entacapone, on motor performance and pharmacological compensation, in advanced PD patients with motor fluctuations: 47 patients with advanced PD and motor fluctuations were followed for six years from the first prescription of entacapone and showed a stabilization of motor conditions, reflecting entacapone can maintain adequate inhibition of COMT over time.[1] Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa, and has been under some investigation[2]
Dopamine agonists
The dopamine-agonists bromocriptine, pergolide, pramipexole, ropinirole , cabergoline, apomorphine, and lisuride, are moderately effective. These have their own side effects including those listed above in addition to somnolence, hallucinations and /or insomnia. Several forms of dopamine agonism have been linked with a markedly increased risk of problem gambling. Dopamine agonists initially act by stimulating some of the dopamine receptors. However, they cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms.
Dopamine agonists can be useful for patients experiencing on-off fluctuations and dyskinesias as a result of high doses of L-dopa. Apomorphine can be administered via subcutaneous injection using a small pump which is carried by the patient. A low dose is automatically administered throughout the day, reducing the fluctuations of motor symptoms by providing a steady dose of dopaminergic stimulation. After an initial "apomorphine challenge" in hospital to test its effectiveness and brief patient and caregiver, the primary caregiver (often a spouse or partner) takes over maintenance of the pump. The injection site must be changed daily and rotated around the body to avoid the formation of nodules. Apomorphine is also available in a more acute dose as an autoinjector pen for emergency doses such as after a fall or first thing in the morning.
MAO-B inhibitors
Selegiline and rasagiline reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. Metabolites of selegiline include L-amphetamine and L-methamphetamine (not to be confused with the more notorious and potent dextrorotary isomers). This might result in side effects such as insomnia. Use of L-dopa in conjunction with selegiline has increased mortality rates that have not been effectively explained. Another side effect of the combination can be stomatitis. One report raised concern about increased mortality when MAO-B inhibitors were combined with L-dopa;[3] however subsequent studies have not confirmed this finding.[4] Unlike other non selective monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis.
Speech therapies
The most widely practiced treatment for the speech disorders associated with Parkinson's disease is Lee Silverman Voice Treatment (LSVT). LSVT focuses on increasing vocal loudness.[5]
A study found that an electronic device providing frequency-shifted auditory feedback (FAF) improved the clarity of Parkinson's patients' speech.[6]
Physical exercise
Regular physical exercise and/or therapy, including in forms such as yoga, tai chi, and dance can be beneficial to the patient for maintaining and improving mobility, flexibility, balance and a range of motion. Physicians and physical therapists often recommend basic exercises, such as bringing the toes up with every step, carrying a bag with weight to decrease the bend having on one side, and practicing chewing hard and move the food around the mouth.[7]
Parkinson's disease is considered an absolute contraindication to the use of the following medications:
References
- ↑ 1.0 1.1
R. Cilia; et al. (2006). "Long-term Efficacy of Entacapone in Patients with Parkinson's Disease and Motor Fluctuations - A Six-Year Clinical Follow-Up Study". line feed character in
|title=at position 50 (help) - ↑ Katzenschlager R, Evans A, Manson A; et al. (2004). "Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study". J. Neurol. Neurosurg. Psychiatr. 75 (12): 1672–7. doi:10.1136/jnnp.2003.028761. PMID 15548480.
- ↑ Thorogood M, Armstrong B, Nichols T, Hollowell J (1998). "Mortality in people taking selegiline: observational study". BMJ. 317 (7153): 252–4. PMID 9677215.
- ↑ Marras C, McDermott M, Rochon P, Tanner C, Naglie G, Rudolph A, Lang A (2005). "Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort". Neurology. 64 (1): 87–93. PMID 15642909.
- ↑ "What is LSVT?" http://www.lsvt.org/main_site.htm
- ↑ Lowit, A., Brendel, B. "The response of patients with Parkinson's Disease to DAF and FSF," Stammering Research April 2004.
- ↑ Garg, R and Lakhan, S. Parkinson's Disease - Pharmaceutical and Physical Therapies. GNIF Brain Blogger. August, 2006.