Dopamine agonists provide symptomatic benefit when taken with levodopa, or as taken alone (monotherapy) in early stages of Parkinson's disease. There is interest as to whether their early and sustained use can forestall long-term levodopa-associated complications. Monotherapy with dopamine agonists is generally as effective as levodopa/PDI when a patient first requires symptomatic therapy. After one to three years of disease progression, monotherapy with a dopamine agonist often becomes inadequate and levodopa therapy must be added. In moderate and advanced disease, patients with motor fluctuations on levodopa may benefit from the addition of a dopamine agonist to smooth motor fluctuations and improve symptom control.
Examples of Dopamine Agonists
Side effects of Dopamine Agonists
Dopamine agonists can cause nausea, vomiting, and orthostatic hypotension by stimulating peripheral dopamine receptors. They may also cause central dopaminergic side effects such as nightmares, hallucinations, or psychiatric symptoms. Cognitive side effects are dose related but nausea and orthostatic hypotension can occur even with small initial doses. Other possible side effects include leg edema and constipation.
How Do You Take It
Dopamine agonists can be taken with or without food. Patients with nausea should take their medication after a meal. For patients on combination therapy with levodopa, the dopamine agonist is usually scheduled to be taken when levodopa is administered as a matter of convenience.Advantages of Using Dopamine Agonists There are two main concerns regarding possible harm from chronic levodopa therapy:
Unlike levodopa, dopamine agonists directly stimulate post-synaptic dopamine receptors. They do not undergo oxidative metabolism and there is no concern that they might accelerate the disease process. In fact, animals fed a diet including pergolide were found to experience less age-related loss of dopamine neurons. Bromocriptine, pergolide, ropinirole, pramipexole, and cabergoline all have significantly longer half-lives than levodopa and do not expose receptors to rapidly fluctuating levels of stimulation. Animal studies have demonstrated that dopamine agonists are associated with a lower incidence of dyskinesia than levodopa. Several investigators have examined the possibility that dopamine agonists, alone or in combination with levodopa, could delay motor fluctuations and dyskinesia. A series of retrospective studies found fewer motor complications in patients treated with agonists rather than levodopa. Initial treatment with a dopamine agonist followed by the addition of levodopa, when necessary, is associated with a lower prevalence of dyskinesia.
The main limitation of dopamine agonist rnonotherapy is that symptoms are adequately controlled for a period of only one to three years. One study found that after three years of bromocriptine monotherapy only 28%, and after 5 years only 7%, of patients were still adequately maintained on monotherapy alone. After a few years, most patients require levodopa to sustain good benefit.
In moderate and advanced disease, dopamine agonists provide benefit for patients with motor fluctuations on levodopa therapy. When an agonist is added, off time is reduced, motor function is improved and levodopa doses may be reduced. Only rarely can a patient with fluctuations and dyskinesia be adequately managed with dopamine agonists alone.
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