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Thursday, June 20, 2013
In the treatment of Parkinson's disease (PD), there is often debate regarding the best treatment strategy. The fact is that because PD affects every patient differently, the best treatment often depends on the patient. Therefore, therapy is significantly individualized with various factors taken into consideration.
Common factors include:
The most important goal in developing a treatment strategy for PD is to maintain a patient's independence and quality of life, while minimizing potential complications of treatment.
There have been numerous medications developed for the treatment of motor symptoms of PD, such as rigidity, slowness, and tremor. However, patients with PD may not understand the purpose of each medication. With the various pills and doses prescribed, patients may begin to feel overwhelmed and confused. Therefore, it is best to learn a few basic properties of each medication. This can help in understanding to what extent each medication is useful.
PD medications can be classified based on the way they act in the body. This can help the patient understand the uses of the agent and recognize any potential side effects associated with each class.
The treatment of PD is currently largely focused on increasing brain dopamine activity. The ideal treatment would attempt to mimic the body's natural levels by replacing dopamine at a steady dose throughout the day. Unfortunately, the body breaks down the dopamine replacement, which creates a challenging environment. Therefore, a steady delivery of dopamine is almost impossible.
The most effective agent available to for alleviating motor symptoms of PD is the dopamine precursor levodopa. Levodopa is taken orally and absorbed in the intestine. Eventually, it is delivered by the blood stream to the brain. In the brain, the levodopa is taken up and converted into dopamine. Only levodopa (not dopamine) can cross into the brain.
Levodopa has a very short half life - the time required for half the amount of drug to be eliminated from the body. This means the levodopa does not stay in the body very long, which causes problems in advanced PD. As the disease progresses, the mechanisms for storing dopamine in brain cells become more impaired. This results in the body needing higher and more frequent doses of the levodopa for treatment.
It is believed that by creating frequent peaks and troughs of brain dopamine levels throughout the day over a number of years, motor complications are induced. Motor complications consist of dyskinesias (excessive movements) and fluctuating responses to levodopa. These complications can often be as debilitating as the symptoms of PD.
When taken alone, most of the levodopa is converted into dopamine prior to reaching the brain. However, the brain cannot uptake the dopamine, only the levodopa. Therefore, the absorption of the levodopa not only causes gastrointestinal side effects, but also results in only 1-5% of the ingested levodopa to be available for the brain.
To improve brain levels, levodopa is given in combination with carbidopa. Carbidopa is a medication that decreases the conversion of levodopa into dopamine outside of the brain. The result of using this combination allows for 5-10% of the ingested levodopa to be available for the brain. Though this is a small percentage, it is enough to provide symptom relief. The combination therapy of carbidopa/levodopa enables the patient to use lower therapeutic doses of levodopa, and it decreases the potential side effects of high doses of levodopa.
Common potential side effects that might be experienced with carbidopa/levodopa include:
Serious potential side effects from the levodopa component also include:
Carbidopa/Levodopa is available in a few forms:
Each of these has unique benefits and indications. Both the standard and controlled release forms of Sinemet® are equally effective in treating the PD symptoms. The Sinemet CR® can be beneficial for patients that are experiencing end of dose wearing off. It can also help those finding themselves with decreased mobility during the night or upon awakening in the morning. The response often depends on the patient's gastrointenstinal absorption. Sometimes, there may be no differences in the products except for price. Parcopa® has the benefit of dissolving in the mouth and is used especially when a patient is having difficulty swallowing.
These medications act on dopamine receptors ("switches") and bypass the degenerating nerve cell. Agonists are indicated for initial treatment for PD or as adjunctive therapy to levodopa.
Side effects that are more commonly reported include:
Other adverse reactions that are reported include obsessive-compulsive behaviors (like compulsive gambling) and sudden sleep attacks.
These medications need to be started at a very low dose and gradually increased to a therapeutic dose over the course of weeks. Thus, the response to treatment with these medications is not as sudden as with levodopa therapy. However, these medications are found to prolong the onset of motor complications when started before levodopa therapy. This has been shown especially in younger patients that are more prone to motor complications. In addition, these medications are often adequate when used alone for initial treatment of mild PD. Dopamine agonists are best tolerated by younger patients. Increasing age increases potential side effects.
Dopamine Agonist agents include:
MAO-B inhibitors block one of the enzymes responsible for breaking down dopamine, thus extending dopamine activity in the brain. These can be used as initial treatment of PD or as an adjunctive medication to levodopa, depending on the agent.
Potential side effects of these medications include:
There are some medications, such as meperidine (Demerol), that are absolutely contraindicated with this class of medication.
MAO inhibitors available include:
Standard selegiline is dosed twice a day (morning and noon). Zelapar and rasagiline are dosed once a day. Rasagiline is a newer medication that is more selective, more potent, and has less action outside the brain (thus decreased peripheral side effects). Zelapar® dissolves rapidly on the tongue and is absorbed into the blood stream bypassing the gut. This allows for the dose of Zelapar® to be lower and lessens peripheral side effects.
COMT inhibitors increase the duration of levodopa therapy by blocking its breakdown in the bloodstream, allowing for more to be available to the brain. These medications are helpful for people experiencing increasing PD symptoms prior to their next dose of levodopa.
Side effects that are more commonly reported with these medications include:
COMT inhibitors are available in the following forms:
Tolcapone is more potent than entacapone and requires close monitoring of liver function. Entacapone needs to be taken with every dose of levodopa to be effective. Stalevo® is one formulation that combines carbidopa/levodopa with entacapone into one pill. The maximum dose of entacapone per dose is 200 mg.
These medications are useful in early PD and as adjunctive therapy. They are most commonly prescribed to help parkinsonian tremors. The biggest concern with these medications is that they can lead to confusion and agitation, especially in elderly individuals. Therefore, they must be used with extreme care in this population or any individual with history of cognitive issues.
Potential side effects that are commonly reported include:
Anticholinergic formulations commonly used in PD include:
One form of NMDA receptor antagonist, Amantadine, is useful for both monotherapy of new onset PD and as adjunctive treatment for people on other Parkinson's medications. It was originally used as an antiviral agent, but subsequently found to benefit people with parkinsonism.
This medication can be helpful with:
Possible side effects that may be experienced include:
The formulation used is:
This medication works via numerous mechanisms and is not really well understood. Typical dosing starts at 100 mg twice a day, and may be increased. It is not recommended to take this medication past 5 pm, since it could be stimulating in some patients.
Another treatment used is an injectable medication classified as a dopamine agonist. It is very effective for acute treatment of hypomobility. This is useful when patients with PD experience sudden end of dose "wearing off" or unpredictable "off" periods. This injection is usually prescribed to be taken with an anti-nausea medication.
Potential side effects include:
The most common available form of this medication is:
This medication is initially titrated and is started in the physician's office.
The vast amount of medications and treatments for Parkinson's disease can be very overwhelming. However, the classification of medications into groups based on how they act in the body can help patients understand why they are taking each drug, and how it is helping to alleviate their symptoms. Because there is no one treatment that works best for everyone, patients should consult their physician to determine what medication would be most helpful for them.
This article is a NetWellness exclusive.
Last Reviewed: Dec 11, 2006
Punit Agrawal, DO
Assistant Professor of Neurology
College of Medicine
The Ohio State University