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• Tolcapone (Tasmar)

COMT inhibitors prolong the effect of levodopa by blocking the enzyme known as catechol-O-methyltransferase (COMT) that breaks down dopamine in the liver and other organs. As a result, many of the adverse effects of levodopa which result because of sudden drops or fluctuations in the levels of levodopa are reduced. This reduces the "off" duration which is seen in motor complications of levodopa. COMT inhibitors also decrease the "wearing off" effect.

Tolcapone

Tolcapone (Tasmar) is a very potent drug which easily crosses the blood/brain barrier and is used as an adjunct to levodopa. Because it increases the half-life of levodopa, the patient can reduce levodopa intake by 25-30%.

The major side effect of tolcapone is liver toxicity leading to liver failure. Because of this, tolcapone is given only to Parkinson's disease patients who are not responding to other medications. Once a patient begins taking tolcapone, they require very close monitoring of liver function. The Food and Drug Administration suggests that patients be monitored every two weeks for the first year; then every four weeks for the following 6 months; and every eight weeks, thereafter. The FDA also suggests that if a patient does not exhibit substantial improvement within the first 3 weeks of taking the first dose, the drug should be withdrawn.

Other adverse effects of tolcapone may include:

• Dyskinesia
• Nausea
• Sleep disorder
• Muscle cramps

Entacapone

Entacapone (Comtan) is similar in composition to tolcapone but does not cross the blood/brain barrier. It is used as an adjunct to levodopa and is effective in reducing the "wearing-off" effect. Because of the lower risk of complications involved with this drug, it is the COMT inhibitor usually prescribed.

The main adverse effects associated with entacapone include:

• Urine discoloration
• Nausea
• Dyskinesia

Anticholinergic Agents

• Trihexyphenidyl (Artane)
• Benztropine (Cogentin)

Anticholinergic agents do not act directly on dopamine as do the other drugs previously mentioned. Rather, they decrease the effect of acetylcholine which counteracts the benefits of dopamine in the brain. They are most effective for the control of tremor. Even so, they are only moderately beneficial.

Anticholinergics were the drug of choice for Parkinson's disease before the discovery of levodopa. Since only about half the people who take anticholinergics respond, and even then only for a brief time, they are not used often. Also, since tremors are often not such a disabling aspect of Parkinson's symptoms there is less need to add this medication to control them.

Side-Effects of Anticholinergic Agents

Adverse reactions to anticholinergic drugs include:

• Dry mouth
• Nausea
• Urine retention
• Constipation
• Memory loss
• Confusion
• Hallucinations

Because of the side effects, anticholinergics are rarely prescribed people over 70 years of age or for any patient already experiencing mental impairment. In some circumstances, doctors find that older people who cannot tolerate anticholinergics may tolerate antihistamines (e.g., Benedryl) and antidepressants (e.g., Elavil) that have similar effects on Parkinson's symptoms. In general, anticholinergic drugs are not widely used in treatment of Parkinson's disease because of their minimal efficacy and the side effects associated with them.

Antiviral Drugs