Drug Therapy in Parkinson’s Disease

Parkinson’s disease is a degenerative disease of the brain where there is decreased production of the chemical transmitter known as dopamine. The classical symptoms of Parkinson’s disease are tremor, rigidity, bradykinesia (slowing of movement) and loss of postural reflexes. Drugs are the mainstay of treatment in Parkinson’s disease and while there is no definite cure, drug therapy is used to help control the symptoms.

Types of Parkinson’s Drugs

Levodopa

Various drugs have been used for the treatment of Parkinson’s disease but the most effective treatment so far is a combination of levodopa and a peripheral acting dopa-decarboxylase inhibitor. Levodopa is a natural substance in our body which is converted to dopamine in the brain. However, if taken orally, about 90% of it is converted to dopamine outside the brain and only a small proportion of it reaches the brain. This causes side effects like nausea and vomiting, which can be offset by combining levodopa with peripheral decarboxylase inhibitors like carbidopa. Levodopa is especially effective in improving bradykinesia and rigidity of Parkinson’s disease, and tremor to a lesser extent, but initial treatment with levodopa should be delayed because of the long term side effects such as involuntary movements, depression, hallucinations and delusions. With long term use, the effect of levodopa shows some fluctuation in response, known as the ‘on-off phenomenon’ where there is unpredictable action of the drug. This can be treated by variations in dose.

Dopamine Receptor Agonists

These drugs are not as effective as levodopa in the treatment of Parkinson’s disease but their action lasts longer and they help considerably during the on-off effect of levodopa. Side effects such as dose fluctuations or dyskinesia (involuntary movements) are rare, although once dyskinesia develops, dopamine agonists tend to make them worse. Other side effects are nausea, vomiting, confusion and hallucinations. Pramipexole and ropinirole are administered as oral preparations while rotigotine can be used in patch form. Pergolide and bromocriptine are not used because of causing problems in heart valves. Apomorphine injection maybe used to give rapid short term relief.

Monoamine Oxidase B (MAO-B) Inhibitors

Drugs like selegiline and rasagiline are mildly effective. There may be drug reaction with other medications, especially narcotics and antidepressants.

Catechol-Omethyl Transferase (COMT) Inhibitors

COMT inhibitors like entacapone can be used with levodopa by helping to reduce its dose and thus reduce the instance of motor fluctuations caused by levodopa.

Anticholinergics

Anticholinergics like benzhexol are effective in controlling tremor and rigidity but not bradykinesia, hence they may be used in the early stage of the disease. The side effects are confusion and hallucinations, especially in the older age group, in whom these drugs are best avoided. The other side effects are blurred vision, dryness of mouth, constipation and retention of urine.

Amantadine

Amantadine can be used in early stage of Parkinson’s disease before starting with stronger drugs, and in the later stage along with carbidopa-levodopa preparations to offset side effects such as involuntary movements. The side effects of this drug are confusion, seizures, ankle edema.

These drugs are currently used in Parkinson’s disease but ongoing drug research to isolate compounds to reduce the severity of Parkinson’s symptoms offers hope for more effective drugs in the future.

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