The majority of medications developed specifically to treat Parkinson’s disease target common motor symptoms. Many of these treatments are designed to increase the level of the dopamine, a neurotransmitter (chemical messenger) that transfers signals between nerve cells. Dopamine is involved in regulating signals for movement, which is reduced in the brains of Parkinson’s disease patients.
Levodopa is the most common first-line treatment prescribed to Parkinson’s disease patients and is generally prescribed for all stages of the disease. Levodopa is used to manage Parkinson’s symptoms such as tremors, stiffness, and slowness of movement. It is absorbed in the intestine and is transported to the brain, where it is converted to dopamine.
There are several adverse effects associated with levodopa treatment. Initial common side effects are nausea and vomiting, but also can include drowsiness, low blood pressure, and hallucinations. Extended use of levodopa can result in the patient experiencing dyskinesia (involuntary movements) and motor fluctuations (where the patient experiences “off-time” periods, as the drug wears off and symptoms re-emerge).
Levodopa is almost always given in combination with carbidopa and is available in different forms. Examples include:
- Sinemet, an immediate-release carbidopa-levodopa preparation available in pill form. This is generally the first line of levodopa treatment.
- Controlled release preparations, such as Rytary, which allow for an immediate release dose of carbidopa-levodopa with extended release over time. This results in a higher daily dosage of levodopa, but fewer pills needed throughout the day.
- Duopa, a carbidopa-levodopa gel formulation that is administered through a surgically implanted tube in the intestine, providing a continuous 16-hour release of levodopa, directly at the site of absorption. This aims to significantly reduce the “off-time” periods and the incidence of dyskinesia.
Carbidopa acts to enhance the effect of levodopa treatment, by preventing the conversion of levodopa to dopamine before it enters the brain. It also can reduce levodopa-induced nausea and vomiting, and additional carbidopa (Lodosyn) can be prescribed to combat this.
Dopamine agonists act as a substitute for dopamine in the brain and, once in the body, require no further modifications to mimic the action of dopamine. Dopamine agonists may cause less dyskinesia and motor fluctuations compared to levodopa. However, they can increase side effects such as hallucinations, drowsiness, leg swelling, and sudden onset of sleep. Because of this, patients normally are started on a low dose that is increased slowly.
Dopamine agonists can be in immediate-release form, in pill forms, such as Mirapex (pramipexole) or Requip (ropinirole), or extended-release forms, such as the skin patch Neupro (rotigotine) or the injected Apokyn (apomorphine).
Monoamine oxidase-B (MAO-B) inhibitors
MAO-B inhibitors increase the length of time dopamine is active in the brain by preventing it from being broken down. This treatment can be prescribed alone or in combination with other treatments. Using MAO-B inhibitors, some patients may be able to delay taking levodopa in the early stages of the disease before symptoms become more severe.
Catechol-O-methyltransferase (COMT) inhibitors
COMT inhibitors enhance the effectiveness of levodopa treatment, by preventing it from being broken down before it reaches the brain. This prolongs the effect of levodopa treatment, and delays the “off-time” period. COMT inhibitors often are used initially in lieu of increasing the levodopa dose.
The most common COMT inhibitor is Comtan (entacapone). However, Tasmar (tolcapone) occasionally is prescribed if Comtan is ineffective. The use of Tasmar is sometimes associated with liver failure, so patients who are taking Tasmar must have regular blood tests to monitor liver functions.
Entacapone also is available as a combination drug, Stalevo, containing levodopa, carbidopa, and entacapone.
Anticholinergics do not affect the dopamine levels. Instead, they act to regulate brain chemistry that is disrupted by lower-than-normal levels of dopamine. They block the action of a different neurotransmitter, acetylcholine, to restore the balance compared to dopamine. This treatment may help control tremors and dystonia. However, they usually are prescribed only when dopaminergic medications are ineffective. Anticholinergics include Artane (trihexyphenidl) and Cogentin (benztropine).
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