Medical Health Encyclopedia

L-dopa is usually taken lifelong. Over time, however, it has significant adverse effects (notably, motor fluctuations and the wearing-off effect).

To reduce these complications, physicians typically add other agents to maintain as consistent a level of dopamine as possible. Such drugs include the following:

• Dopamine agonists. These agents activate certain receptors that bind to dopamine. A number of dopamine agonists. Newer drugs include pramipexole and ropinirole. Older agents, including pergolide, lisuride, and bromocriptine contain ergot alkaloids. They are effective for improving symptoms in the early stages of the disease. They also may delay the need for L-dopa and delay its use. They are useful for improving both early wearing off and on-off motor fluctuations.
• Catechol-o-methyl transferase (COMT) inhibitors. COMT inhibitors prolong the activity of dopamine availability. Entacapone is the standard COMT inhibitor and is somewhat effective in the early stages of the disease. It is also useful for the wearing-off effect and motor fluctuations if dyskinesia (uncontrolled movement) is not a factor. A combination of entacapone, levodopa, and carbodopa is now available (Stalevo) as a single pill, simplifying the drug regimen for some patients.
• Amantadine. This is the only drug at this point that can improve dyskinesia (uncontrolled movement). It may also be beneficial for patients with atypical PD (early problems in thinking and poor response to levodopa), who tend to be non-Caucasians.

Some experts strongly recommend starting out with low doses of several drugs rather than high doses of a single one.

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Most of the drug studies have been small and there have been few comparative studies. It is therefore difficult, even for physicians to know which agents are better than others. There are many options, however, and there is no one optimal approach for all patients. None have proved yet to actually protect nerve cells and therefore slow down disease progression itself.

Treating Advanced Disease

Eventually, symptoms such as stooped posture, freezing, and speech difficulties may not respond to drug treatment. (Total unresponsiveness is unlikely, however, even after 20 years of treatment.) The following approaches may be tried:

• Simply increasing the dose of levodopa or its frequency raises an unacceptable risk of the distressing side effects. Some physicians have tried hospitalizing patients, totally withdrawing the levodopa, and then readministering it. Benefits were seen for only a few months, however, and there were some dangerous risks to the process of withdrawal, including pneumonia and blood clots in the lungs.

An embolus is a blockage of an artery in the lungs by fat, air, tumor tissue, or blood clot.

• Surgical treatments, including pallidotomy, neurostimulation, and transplantation may help some patients.
• Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.