Pramipexole extended release: new options for continuous dopaminergic stimulation in Parkinson’s disease

The most important approach to dopaminergic stimulation in Parkinson’s disease is the use of dopamine agonists. Compared with levodopa agents, dopamine agonists are characterized by a lower risk of drug-induced dyskinesia and motor fluctuations, no need for brain metabolism and the neuroprotective potential established in the experiment. One of the most effective drugs in this group is pramipexole — a synthetic benzothiazole derivative (tetrahydrobenzothiazole). Pramipexole is a potent D2-receptor agonist with maximal affinity for the D3-receptor subtype. Stimulation of D2-receptors of the basal ganglia provides the effect of the drug on motor manifestations of the disease, while stimulation of D3-receptors of the limbic system reduces non-motor manifestations, including a positive effect on neuropsychological status and reduced severity of depressive syndrome in patients with Parkinson’s disease. The effectiveness of pramipexole has been proven by numerous studies both in the early stages of Parkinson’s disease — as monotherapy and in the advanced stages — in combination with levodopa agents. With the development of the disease, the scheme of its treatment became more complex due to an increase in the number of drugs taken and the frequency of their administration. This inevitably creates a problem of insufficient adherence of patients to treatment. In this regard, a new dosage form of pramipexole has been developed — long-acting pramipexole, which ensures its extended release and allows a single dose during the day. This not only makes the treatment of the patient more convenient, but also improves the adherence of patients to treatment, increases the long-term effectiveness of therapy. In addition, with the slow release of pramipexole during the day, its concentration in the blood is more stable, which can provide better tolerance and effective control of symptoms of the disease throughout the day (both during the day and at night).

Biphasic (Subtherapeutic) Levodopa-induced Respiratory Dysfunction in Parkinson Disease

ABSTRACTObjectiveTo evaluated three cases illustrating a rarely recognized phenotype of Parkinson disease (PD), namely biphasic levodopa-induced respiratory dysfunction manifesting as dyspnea.MethodsTo appreciate the nature of the fluctuations of respiratory function in response to levodopa, we measured changes in respiratory muscle control before and after the best therapeutic response to levodopa in three PD patients with fluctuating dyspnea.ResultsEpisodes of breathlessness were accompanied by shallow tachypnea and reduced respiratory muscle control, as measured by maximal expiratory pressure (MEP), peak cough flow (PCF), and Forced Expiratory Volume in 1 second (FEV1).ConclusionsThe spectrum of respiratory dysfunction in PD includes a biphasic reduced respiratory muscle control accompanying periods when the effect of levodopa is subtherapeutic. This biphasic levodopa-related complication represents a rarely recognized non-motor phenomenon in PD. Management requires increasing the levodopa dose, shortening the interdose interval, or implementing a program of continuous dopaminergic stimulation.

When Less Is More

The natural history of PD produces a predominance of nonmotor complications in the later years that can often be more disabling than the motor complications due to their impact on quality of life. Quality of life is less impaired by motor symptoms than it is by cognitive impairment, hallucinations, autonomic involvement, and sleep disruption. Carer burden can be significant, and a shift of emphasis toward maximizing quality of life for patient and carer over the achievement of continuous dopaminergic stimulation is required. Recognition of the carer burden is an important facet of the palliative neurology consultation, which should target resources to limit carer burnout in recognition of their critical role.