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December 5, 2019
Istradefylline: an Adenosine A2A Receptor Antagonist to Treat Off Episodes in Parkinson Disease: Istradefylline (Nourianz) is the first adenosine A2A receptor antagonist approved in the U.S. to treat off episodes in Parkinson disease. Adenosine A2A receptors are located in GABAergic (γ-aminobutyric acid) neurons within the indirect pathway of the basal ganglia system. Blocking of A2A receptors (ie, inhibition of the indirect pathway) can result in prolongation of dopaminergic action. In randomized, placebo-controlled trials, istradefylline resulted in statistically significant reductions in daily off time. The most common adverse reaction to istradefylline is dyskinesia followed by dizziness, nausea, hallucinations, and insomnia. The recommended dosage is 20 mg orally once daily with or without food. The dosage may be increased to a maximum of 40 mg once daily.
Upon completion of the chapter, the reader will be able to:
Describe the pathophysiology of Parkinson disease (PD) related to neurotransmitter involvement and targets for drug therapy.
Recognize the cardinal motor symptoms of PD and determine a patient’s clinical status and disease progression based on the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS UPDRS).
For a patient initiating therapy for PD, recommend appropriate drug therapy and construct patient-specific treatment goals.
Recognize and recommend appropriate treatment for nonmotor symptoms.
Formulate a plan to minimize patient “off-time” and maximize “on-time” including timing, dosage, and frequency of medications.
Recognize and treat various motor complications in PD.
Construct appropriate patient counseling regarding medications and lifestyle modifications for PD.
Develop a monitoring plan to assess effectiveness and adverse effects of treatment.
Parkinson disease (PD) is a slow, progressive neurodegenerative disease of the extrapyramidal motor system. Dopamine neurons in the substantia nigra are primarily affected, and degeneration of these neurons causes a disruption in smooth motor control. Cardinal features of PD include tremor at rest, rigidity, akinesia/bradykinesia, and postural instability. There is no cure, and treatment aims at controlling symptoms and maintaining quality of life (QOL) or functioning.
EPIDEMIOLOGY AND ETIOLOGY
PD affects approximately 1 million Americans, and a lifetime risk of developing the disease is 1.5%. Median age of the onset is 60 years, but about 10% of people with PD are younger than 45 years. The average time span from diagnosis to death is about 15 years. Approximately 15% of patients with PD have a first-degree relative with the disease.1,2
The etiology of neuron degeneration in PD remains unknown, but aging is a primary risk factor. Thus, as the fraction of the population that is elderly continues to increase, this disease may see a subsequent increase in prevalence. Cell death may be caused by oxidative stress, mitochondrial dysfunction, increased excitotoxic amino acids and inflammatory cytokines, immune ...