CHAPTER 10: Pharmacological Management of Parkinson Disease

INTRODUCTION

Parkinson disease is a movement disorder characterized by resting tremor, bradykinesia, rigidity, and postural instability.^1,2 In Parkinson disease, there is a slow, progressive degeneration of certain dopamine-secreting neurons in the basal ganglia.^1,3 Several theories have been proposed to explain this spontaneous neuronal degeneration, including the possibility that the disease may be caused by a combination of genetic and environmental factors (see “Etiology of Parkinson Disease: Genetic and Environmental Factors").^4–6 However, the precise initiating factor in Parkinson disease is still unknown.

The clinical syndrome of parkinsonism (i.e., rigidity, bradykinesia) may be caused by other factors such as trauma, infectious agents, antipsychotic drugs, cerebrovascular disease, and various forms of cortical degeneration, including Alzheimer disease.^7–10 However, the most frequent cause of parkinsonism is the spontaneous slow, selective neuronal degeneration characteristic of Parkinson disease itself.¹ Also, the drug management of parkinsonism caused by these other factors closely resembles the management of Parkinson disease.¹ Consequently, this chapter will address the idiopathic onset and pharmacological treatment of Parkinson disease.

Parkinson disease usually begins in the fifth or sixth decade, and symptoms progressively worsen over a period of 10 to 20 years. It is estimated that more than 1 percent of the U.S. population older than 65 years is afflicted with Parkinson disease, making it one of the most prevalent neurological disorders affecting elderly individuals.¹ In addition to the symptoms of bradykinesia and rigidity, a patient with advanced Parkinson disease maintains a flexed posture and speaks in a low, soft voice (microphonia). If left untreated, the motor problems associated with this illness eventually lead to total incapacitation. Parkinson disease is also associated with a wide variety of nonmotor symptoms such as depression, cognitive impairment, memory loss, sleep disorders, impulsiveness, fatigue, and chronic pain.

Fortunately, the pharmacological management of Parkinson disease has evolved to where the symptoms associated with this disorder can be greatly diminished in many patients. The use of levodopa (L-dopa) alone or in combination with other drugs can improve motor function and general mobility well into the advanced stages of this disease. Drugs used in treating Parkinson disease do not cure this condition, and motor function often tends to slowly deteriorate regardless of when drug therapy is initiated.^11,12 However, by alleviating the motor symptoms (i.e., bradykinesia and rigidity), drug therapy can allow patients with Parkinson disease to continue to lead relatively active lifestyles, thus improving their overall physiological and psychological well-being.

Likewise, effective drug treatment can dramatically increase the patient's ability to participate in physical rehabilitation. Antiparkinson drugs help improve motor function so that the patient can be actively involved in cardiovascular conditioning, balance training, fine motor tasks, and various other rehabilitation interventions. What follows is a brief discussion of the neurochemical changes and possible causative factors in Parkinson disease. This review will help ...