Drugs Helping People with Parkinson's Disease : Part 2

by Food and Drug Administration (FDA)

(Page 2 of 3)

Researchers found that when carbidopa was added to levodopa, it blocked the enzyme responsible for the breakdown of levodopa in the body, and allowed more levodopa to get to the brain. Carbidopa makes it possible to use about 75 percent less levodopa, thereby reducing nausea and vomiting. This combination of levodopa and carbidopa is marketed as Sinemet.

Another problem with levodopa medications is that some patients develop complications with long-term use. This has made some doctors reluctant to prescribe them until symptoms interfere with the quality of life. (Recent studies have shown that it may make no difference to the eventual outcome when levodopa drugs are started, because no anti-parkinsonian agent can slow the natural progression of the underlying disease.) After about four or five years, sometimes sooner, the patient begins to respond less satisfactorily to levodopa. Dyskinesias, or involuntary movements (such as lip smacking or tongue thrusting), may develop. Reducing the dose helps reduce the dyskinesias, but results in a worsening of Parkinson symptoms.

Some Parkinson disease patients may have "on-off" effects, which means that their movements fluctuate from normal to abnormal in a random fashion, or as a "wearing off," when symptoms return as the blood level of levodopa decreases. The controlled-release form of Sinemet, Sinemet CR, which was approved for use by FDA in 1991, was formulated to help keep blood levels of levodopa more constant throughout the day, possibly preventing these fluctuations.

Modernizing Old Therapies

Anticholinergic drugs have been used to treat Parkinson's disease for almost a century. (Those old botanical preparations had anticholinergic properties.) Used along with levodopa, modern anticholinergic drugs are useful in reducing tremor. As decreased amounts of dopamine are produced in the brain, an imbalance with the neurotransmitter acetylcholine occurs, making symptoms worse. Anticholinergics work by partially blocking the action of acetylcholine. Examples of anticholinergic medications used to treat Parkinson's disease are Artane (trihexyphenidyl), Akineton (biperiden), Kemadrin (procyclidine), Pagitane (cycrimine), and Cogentin (benztropine).

Although used primarily in treating asthma and allergies, antihistamines are also effective against tremor because of their anticholinergic properties. Most frequently used antihistamines for this purpose are Benadryl (diphenhydramine) and Phenoxene (chlorphenoxamine).

Like antihistamines, Symmetrel (amantadine), an antiviral drug, was serendipitously discovered to benefit patients with Parkinson's disease. Prescribed for a woman to prevent flu, Symmetrel relieved some of her Parkinson symptoms and made her generally feel better. It is helpful both in the early and late stages. In addition to its anticholinergic properties, Symmetrel promotes the release of dopamine in the brain.

Other drugs, called dopamine agonists (activators), bypass the degenerating nerve cells in the substantia nigra and directly stimulate the striatal dopamine receptors. Though dopamine receptors are selective about which chemical messengers they'll receive, they can respond to synthetic compounds that aren't dopamine, but act like dopamine in the brain. Dopamine agonists can be used alone, but are more effective when used with Sinemet. They are usually added to the treatment when the patient is encountering too many side effects, such as dyskinesias, with Sinemet. Dopamine agonists available in the United States are Parlodel (bromocriptine) and Permax (pergolide). They don't necessarily have the same effects in all patients, so if one drug loses its efficacy or causes too many side effects, the physician may prescribe the other drug.

MAO-B inhibitors block the MAO-B enzyme in the brain that helps break down and metabolize dopamine. When the enzyme's action is slowed down, more dopamine may be available to relieve symptoms and improve motor performance, allowing Parkinson patients to move about more freely. Eldepryl (deprenyl) is the only MAO-B inhibitor to be approved for use in treating Parkinson's disease in this country. It is useful for patients with advanced disease who are having problems with Sinemet. In a large clinical trial in 1989, Eldepryl showed a possible neuroprotective effect by prolonging the time before the patient needed levodopa treatment.

Many Parkinson's disease patients suffer from profound depression, as well as insomnia. Doctors may prescribe tricyclic antidepressants (such as Elavil, Endep and Tofranil) that have both anticholinergic and sedative properties. Medications that relieve symptoms of depression, such as Prozac and Desyrel, are also used.

Many doctors say that levodopa preparations will probably continue to be the most useful drugs in treating Parkinson's disease for a long time. Researchers are studying newer drugs that will enhance levodopa's effectiveness by slowing down the rate at which the body breaks it down. They have also found that medications approved for other uses (such as Clozaril) can reduce side effects. Other substances (such as Eldepryl and vitamins C and E) are under study to see if they can reduce the rate of disease progression.

It's unlikely that results will be available soon enough to benefit Walter, who now lives in a nursing home in the small Midwestern town where he grew up and served on the police force. In general, he is doing fairly well, but no sooner is his medication adjusted to get rid of one troublesome side effect than a different one appears in its place. The usual infirmities of old age have added to his problems.

Krohnfeldt's symptoms are under control, except that her hand still trembles and she is suffering from dyskinesia — her right foot sometimes moves spastically back and forth and she is unable to stop it. But Krohnfeldt retains her good spirits. "I've always said it's my cross to bear. If I can stick with it, I'll hang in there. It's better than a lot of other diseases I wouldn't care to have. I started an exercise program about six weeks ago and it's doing me a world of good. I play golf occasionally and work out for two hours a day three times a week, and I feel just great. I get a lot of support from my family. My kids are behind me and that helps."

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