McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 2 4 Antiparkinsonism agents

I n the 1990s, several prominent figures—including former heavyweight boxing champion Muhammad Ali and actor Michael J. Fox—revealed that they had Parkinson’s disease , a progressive, chronic neurological disorder. In general, Parkinson’s disease may develop in people of any age, but it usually affects those who are past middle age and entering their 60s or even later years. Therefore, the occurrence of Parkinson’s disease in these well-known individuals who were relatively young at the time of diagnosis is that much more inter- esting. The cause of the condition is not known. At this time, there is no cure for Parkinson’s disease. Therapy is aimed at management of signs and symptoms to provide optimal functioning for as long as possible. Lack of coordination is characteristic of Parkinson’s disease. Rhythmic tremors develop, insidiously at first. In some muscle groups, these tremors lead to rigidity, and in others weakness. Affected people may have trouble maintaining position or posture, and they may develop the condition known as bradykinesia , marked by difficulties in performing intentional movements and extreme slowness or sluggishness. As Parkinson’s disease progresses, walking becomes a problem; a shuffling gait is a hallmark of the condition. In addition, people may drool, and their speech may be slow and slurred. As the cranial nerves are affected, they may develop a mask-like expression. Parkinson’s disease does not affect the higher levels of the cerebral cortex, so a very alert and intelligent person may be trapped in a progressively degenerating body. Parkinsonism is a term used to describe the Parkin­ son’s disease–like extrapyramidal symptoms that are adverse effects associated with particular drugs or brain injuries. People typically exhibit tremors and bradykinesia. PARKINSON’S DISEASE AND PARKINSONISM

Pathophysiology Although the cause of Parkinson’s disease is not known, it is known that the signs and symptoms of the disease relate to damaged neurons in the basal ganglia of the brain. Theories about the cause of the degeneration of these neurons range from viral infection, blows to the head, brain infection, atherosclerosis and exposure to certain drugs and environmental factors. Even though the actual cause is not known, the mechanism that causes the signs and symptoms of Parkinson’s disease is understood. In a part of the brain called the substantia nigra , a dopamine-rich area, nerve cell bodies begin to degenerate. This process results in a reduction of the number of impulses sent to the corpus striatum in the basal ganglia. This area of the brain, in conjunction with the substantia nigra, helps to maintain muscle tone not related to any particular movement. The corpus striatum is connected to the substantia nigra by a series of neurons that use gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. The substantia nigra sends nerve impulses back into the corpus stratum using the inhibitory neurotransmitter dopamine. The two areas then mutually inhibit activity in a balanced manner. Higher neurons originating in the cerebral cortex secrete acetylcholine (an excitatory neurotransmitter) in the area of the corpus striatum to coordinate intentional movements of the body. When dopamine decreases in the area, a chemical imbalance occurs that allows the cholinergic or excitatory cells to dominate. This affects the functioning of the basal ganglia and the cortical and cerebellar components of the extrapyramidal motor system. The extrapyramidal system is one that provides coordination for unconscious muscle movements, including those that control position, posture and movement. The result of this imbalance in the motor system is apparent as the manifestations of Parkinson’s disease (Figure 24.1).

Basal ganglia

ACh +++ Corpus striatum

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GABA

Dopamine

FIGURE 24.1  Schematic representation of the degeneration of neurons that leads to Parkinson’s disease. Cells in the corpus striatum send impulses to the substantia nigra using gamma-aminobutyric acid (GABA) to inhibit activity. In turn, the substantia nigra sends impulses to the corpus striatum, using dopamine, to inhibit activity. Cortical areas use acetylcholine (ACh) to stimulate intentional movements.

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Substantia nigra

Degeneration of dopamine-releasing neurons leads to Parkinson’s disease