Objective
     To equip the pharmacist with the necessary knowledge for competent pharmaceutical care of the Parkinson's patient.

Goals
     Upon successful completion of this continuing education article, the pharmacist should be able to:

1. Describe the pathophysiology of Parkinson's disease.

2. Identify the symptoms.

3. List the different classes of medications used in treatment.

4. Discuss the relative merits of the different medications within each class.

5. Provide the Parkinson's patient with the information necessary for optimal therapeutic management of the condition.

Introduction

     Paralysis agitans, or Parkinson's Disease (PD), is a progressive neurological disorder affecting neurons projecting from the basal ganglia, the areas of the brain involved in motor control. It was first officially detailed in 1817 by James Parkinson, a London Physician; and the disease currently affects over a million Americans.
     It is characterized by a variety of neurological symptoms arising primarily from a progressive deficiencyof the neurotransmitter, dopamine, in areas of the brain that control motor functions. This deficiency in turn, is pursuant to degeneration and death of populations of neurons in the affected areas of the brain due to one of a number of possible ultimate causes. 2

Primary Symptoms
     Since symptoms are generally not seen until dopamine levels have been reduced by some 80%, the disease process is well under way before being detected.' Resting tremor is seen in most PD victims, manifest as rhythmic shaking in one or several body parts like hands, feet, head, face, lips, tongue, jaw, or neck at a rate of 4 to 6 cycles per second. It may be partially controllable, may vary with time of day, and may worsen with fatigue and stress.
     Rigidity is more commonly complained of as "stiffness" and may precipitate awkward or overly deliberate voluntary movements as well as immobility of certain muscle groups. A group of muscles may remain in a constant state of contraction rather than relaxing normally, and a physician will label this symptom "rigidity". Bradyinesia, or slowness of movement, may be a result of rigidity, but is itself a hallmark of the disease. Postural Instability refers to the fact that many sufferers of PD lose the normal automatic responses necessary to stand up straight, pick up their feet, and maintain balance that require no conscious thought for most normal people."

Secondary Symptoms
     Secondary symptoms may actually appear before primary symptoms in any given individual, and there may be considerable overlap in the gray areas that attempt to separate them. They are presented here to point out the many aspects of a victim's life that may be so profoundly affected by the disease.
     Gait Disturbance may be the result of bradykinesia, postural instability, and/or rigidity; but many clinicians recognize it as a distinct symptom on its own. It may be manifest by shuffling, bent posture, a tendency to propel oneself forward, or an inability to turn quickly.
     Freezing refers to sudden involuntary arrests of movement, leaving the victim unable to initiate certain movements or engage in repetitive tasks. It often affects the patient's ability to walk, causing him to literally freeze in his tracks, especially when turning or approaching a door.
     Dexterity and Coordination Difficulties may seem like the normal consequences of aging, but are nonetheless generally more pronounced in the victim of PD. Handwriting typically becomes smaller and less legible (micrographia), the ability to tie one's shoes, manipulate one's buttons, and keep the score down on the golf course may tend to deteriorate.     
     Visual Symptoms generally include difficulty reading (since the muscles of and around the eye may be affected), impairment of the normal blinking patterns (leading to dry eyes, irritation, and conjunctivitis), impaired contrast perception (making objects of similar color and lighting disappear), and blurred vision (as a side effect of anticholinergic medications actually used to treat PD).
     Tingling and numbness of extremities may be early manifestations of the disease; and though pain is generally not a direct result of PD, muscle cramps and spasms are common complaints among sufferers.      
     Speech and Swallowing Dysfunction may show up as a result of impaired automatic control of the muscles involved in speech from the lips and tongue, to glottis, palate, and diaphragm.
     Slurred speech or an unemotional monotone are common with PD, as are difficulty swallowing and choking.
     Depending upon the extent of involvement of the autonomic nervous system, the ability to control blood pressure may be affected; and eczema, an oily, scaly dermatitis, is common on the eyelids, forehead, nose, and eyebrows of sufferers.        
     Constipation is a frequent problem and may have a basic cause that lies in the neurological pathology of the disease; but diminished levels of physical activity in patients who have difficulty with motor skills is also an obvious contributory factor. Further, those with difficulty in swallowing may not intake sufficient fiber for optimal bowel function, and anti-Parkinson's medications can add to the problem as well.      
     Neurological effects on the bladder and urethral musculature may gender difficulty in urinating and in bladder emptying, while the sexual organs, similarly affected by both the disease process and its pharmacological remedies, may be sluggish to arouse, the psychological and emotional factors of sexual function must also be considered.      
     Dementia, the progressive loss of intellectual functions, memory, and personality that accompany the loss of neurons, generally affect the older Parkinson's s victim and may frequently be the result of Alzheimer' s comorbidity.
     It would be truly remarkable if a significant percentage of PD patients, with the symptomatology listed here, were not also clinically depressed. Facing the reality of any chronic illness can be enough to send many patients over the brink of depression; but the percentage of Parkinson' s patients who also suffer from depression and other serious psychological disease points to the imbalances in chemical mediators as a contributing factor here as well. Since most of the medications used to treat the symptoms of PD contraindicate the concurrent use of most traditional antidepressant and antipsychotic agents, this can be a particularly awkward manifestation to manage effectively. 6

Anatomy of Parkinson’s Disease
     The basal gangilia comprise a strategic link between the cerebral hemispheres, where thought and movement are thought to be conceived, and the spinal cord, which carries those instructions to the rest of the body. Central to motor function, are the cerebral cortex and basal ganglia, whose corpus striatum is thought to continuously and subconsciously process incoming and outgoing data on movement and body position. The complexities of sensory input as feedback for fine motor control, muscle tone maintenance, balance, and posture are continuously monitored and integrated from the corpus striatum.
     The necessary impulses for monitoring sensory input as well as outgoing impulses for motor control also depend upon the proper functioning of the substantia nigra in the midbrain below the corpus striatum. 7

Diagnosis: If it looks like a duck, quacks like a duck, and...

     To understand PD, one must recognize its impact on its victims and how it changes almost every aspect of their lives. The patient typically seeks medical advice for an imprecise collection of confusing and frightening symptoms that may include weakness in an extremity, tremor (especially when resting), slowness of movement, rigidity, perhaps a tendency to speak indistinctly and softly, a shuffling gait, or a frozen facial expression. He may have difficulty swallowing, walking, digesting, or eliminating; and finally, he may be depressed, which may or may not be related to the rest of the symptoms. Such symptoms can also be caused by a variety of more and less serious problems including Progressive Supranuclear Palsy, Shy-Drager Syndrome, serial strokes, and essential or familial tremor. In addition, he may be taking a number of medications that could be contributing to his symptoms. 8
     All this adds up to a complicated diagnosis performed best by a neurologist with extensive experience in diagnosing PD; for there are no definitive lab tests that say conclusively that this person has PD, but another does not. A neurologist will concentrate on muscle tone, resistance to passive movement, limitations in eye movement, body language and how the patient uses it, memory, mental agility, and abstract thinking. He may subject his patient to myriad diagnostic aids simply to rule out all other possibilities. Response to anti-PD medications can also contribute to the diagnosis. In fact, response to Sinemet is considered diagnostic. Thus, diagnosis is largely a process of elimination of other possible medical causes for observed symptoms, so that when nothing else can be found, it must be PD.

Synaptic Biochemistry

     Neurotransmitters are the microchemicals responsible for transmitting neuronal impulses from axon to dendrite, a process that entails precisely controlled synthesis and release of these chemicals in minute amounts from intracellular capsules in the axon to connect with specific chemoreceptor sites on the surface of the target dendrite. Once the impulse has been transmitted, the neurotransmitters must be quickly deactivated to re-arm the synapse for subsequent impulse transmission. Though dopamine is the most pervasive neurotransmitter in the areas of the brain affected by PD, acetylcholine, norepinephrine, and serotonin are recognized as having significant, but as yet incompletely defined roles in the process of motor control as well. It is becoming increasingly