Parkinson's disease and its treatment

Drug Store News, Feb 19, 1990 by H. David Bergman

Parkinson's Disease and Its Treatment

H. David Bergman, Ph.D., Dean School of Pharmacy Southwestern Oklahmoma State University Feb. 19, 1990, lesson 679-401-90-02

Goals:

To provide the practicing pharmacist with current concepts regarding Parkinson's Disease.

Objectives:

1. Discuss the historical development of theories regarding causes and treatments for Parkinson's disease. 2. Discuss the various etiologies of Parkinson's disease 3. Recognize and describe the major signs and symptoms associated with Parkinson's disease. 4. For each drug or group of drugs used to treat Parkinson's disease, identify the following: mechanism of action, advantages and disadvantages, dosage range and adverse effects.

The first concise description of the disorder known today as Parkinson's disease was provided by James Parkinson, a London general practitioner, in 1817. In a monograph entitled "An Essay on Shaking Palsy," Parkinson described a chronic progressive abnormality associated with the nervous system which begins insidiously in middle age as a mild tremore and weakness on one hand and later progresses to other limbs affecting posture and gait and eventually, causes invalidism. This description later became known as paralysis agitans and was described by a variety of individuals throughout the 1800s. However, despite the clinical features of the disease being clearly defined, the etiology and pathology remained unclear.

During the 1920s, Parkinson's disease was associated with a variety of neurological and infectious disorders, such as influenza and von Economo's disease, but no clear relationships could be established.

In recent years, information concerning the etiology of Parkinson's disease has focused on biochemical basis as the primary culprit. In particular, dopamine depletion has been considered to be an important contributor to the disease.

Recently, typical parkinsonism was reported in a group of individuals who had attempted to make a narcotic drug related to meperidine but actually synthesized and then took 1-methyl-4-phenyl-1, 2,5,6-tetrahydropyridine (MPTP). This compound selectively destroys dopaminergic neurons in the substantia nigra. This unfortunate incident provided further support for dopamine depletion as being a primary cause of Parkinson's disease.

Incidences of Parkinson's

The risk of developing Parkinson's disease during one's lifetime is two percent to three percent. About one percent of the nation's population over age 50 is affected with the disease, and each year there are an additional 20 new cases per 100,000 population. Although men and women appear to be equally subject to Parkinson's disease, the number of men seeking treatment is somewhat greater than women (1.3 to 1). The disease is encountered in all races throughout the world. More than 65 percent of those afflicted (men and women) have an onset of symptoms between 50 and 69 years of age. The average age of onset is 60 years, and onset under the age of 40 is rare.

Etiology

The typical signs and symptoms of Parkinson's disease can be demonstrated by many different causes. Therefore, before the diagnosis of Parkinson's disease or idiopathic parkinsonism can be established, other causes must be examined. The major possible causes are idiopathic and chemical-induced Parkinson's disease.

The term "idiopathic" indicates an unknown cause. Many theories have been postulated, but lack of supporting evidence regarding etiologies, such as head injuries, viruses and allergic reactions, has resulted in the etiology remaining unknown. During recent years, substantial information regarding a biochemical basis for the disease has been generated.

Numerous chemicals cause symptoms resembling Parkinson's disease when large amounts are acutely ingested as well as during chronic exposure. Chronic exposure to certain heavy metals, such as lead or mercury, may result in symptoms similar to Parkinson's disease. Certain photographic dyes, carbon monoxide, carbon disulfide, cyanide and methylchloride have produced some of the signs associated with Parkinson's disease. (See Table 1)

Iatrogenic Parkinson's disease occurs with a variety of drugs, but is most commonly associated with the phenothiazine tranquilizers. These drugs produce extrapyramidal side effects which ultimately may produce a Parkinson-like disorder. The more common Parkinson-like syndrome becomes apparent after two or three months of therapy. The major symptoms of Parkinson's disease (i.e., rigidity, tremor, bradykinesia) are present. It occurs most frequently in patients over 50 years of age and responds well to conventional anticholinergic therapy (i.e., benztropine), but not to levodopa. Since phenothiazines probably reduce extrapyramidal side effects by blocking dopamine receptors, levodopa would be unable to counteract this side effect.

With regard to the phenothiazines, the piperazine compounds (i.e., trifluoperazine, prochlorperazine) can cause the highest incidence of extrapyramidal adverse effects, the aliphatic compounds (i.e., chlorpromazine) cause a moderate amount of extrapyramidal adverse effects, and the piperidine compounds (i.e., thioridazine) cause the lowest incidence of extrapyramidal adverse effects.