Response fluctuation

The goals of treatment are to maintain patient independence, activities of daily living (ADL), and quality of life (QOL) by alleviating the patient s symptoms, minimizing the development of response fluctuations, and limiting medication-related adverse effects. 

As the disease progresses, most patients develop response fluctuations. Treatment is based on optimizing the pharmacokinetic and pharmacodynamic properties of Parkinson s disease medications. 

Response fluctuations occur with disease progression as the patient s dopamine reserves are depleted in the brain and as a complication of PD treatment. Motor fluctuations include delayed peak response, early wearing off, random unpredictable on-off, and freezing. Dyskinesias include chorea, dystonia, and diphasic dyskinesia. Wearing off can be visualized by imagining the therapeutic window of dopamine narrowing over time. The therapeutic window is defined as the minimum effective concentration of dopamine required to control PD symptoms (on without dyskinesia) and the maximum concentration before experiencing side effects from too much dopamine (on with dyskinesia). Early in the disease, a dose of... 

There is no evidence that one agonist is superior to another individual patients, however, may respond to one but not another of these agents. Apomorphine is a potent dopamine agonist but is discussed separately in a later section in this chapter because it is used primarily as a rescue drug for patients with disabling response fluctuations to levodopa. 

Pramipexole is not an ergot derivative, but it has preferential affinity for the D3 family of receptors. It is effective as monotherapy for mild parkinsonism and is also helpful in patients with advanced disease, permitting the dose of levodopa to be reduced and smoothing out response fluctuations. Pramipexole may ameliorate affective symptoms. A possible neuroprotective effect has been suggested by its ability to scavenge hydrogen peroxide and enhance neurotrophic activity in mesencephalic dopaminergic cell cultures. 

Another nonergoline derivative, ropinirole (now available in a generic preparation) is a relatively pure D2 receptor agonist that is effective as monotherapy in patients with mild disease and as a means of smoothing the response to levodopa in patients with more advanced disease and response fluctuations. It is introduced at 0.25 mg three times daily, and the... 

In patients with severe parkinsonism and long-term complications of levodopa therapy such as the on-off phenomenon, a trial of treatment with a COMT inhibitor or rasagiline may be helpful. Regulation of dietary protein intake may also improve response fluctuations. Deep brain stimulation is often helpful in patients who fail to respond adequately to these measures. Treating patients who are young or have mild parkinsonism with rasagiline may delay disease progression and merits consideration. 

Djaldetti R, Melamed, E. Management of response fluctuations practical guidelines. Neurology. 1998 51 (suppl 2) S36-S40. 

Dopamine agonists have an important role as first-line therapy for Parkinson s disease, and their use is associated with a lower incidence of the response fluctuations and dyskinesias occurring with... 

An interesting case report has drawn attention to the fact that severe response fluctuations can occur soon after the start of treatment in patients with severe disease (17). 

L-Dopa response fluctuations may be explained primarily by its pharmacokinetic and pharmacodynamic properties. 

Most carbidopaA-dopa-treated patients eventually wil velop response fluctuations. 

Selegiline, catechol-O-methyl-transferase (COMT) inhibitors, and control led-release carbidopaA-dopa decrease response fluctuations through pharmacokinetic mechanisms. 

Dopamine agonists are i-dopa-sparing and decrease response fluctuations but are more likely to cause psychiatric symptoms such as hallucinations. 

Van Laar T. Levodopa-induced response fluctuations in patients with Parkinson s disease Strategies for management. CNS Drugs 2003 17 475-489. 

D) Response fluctuations ( on-ofF phenomena) are common in patients treated with levodopa... 

Cedarbaum JM, Silvestri M, Clark M, Harts A, Kutt H. L-Deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson s disease. Clin Neuropharmacol (1990) 13, 29-35. 

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