Parkinsonism is a movement disorder characterized by tremor, rigidity, bradykinesia, and postural instability.
Parkinsonism is a relatively common disorder that occurs in all ethnic groups, with an approximately equal sex distribution. The most common variety, idiopathic Parkinson’s disease (paralysis agitans), begins most often between 45 and 65 years of age.
Exposure to certain toxins (eg, manganese dust, carbon disulfide) and severe carbon monoxide poisoning may rarely lead to parkinsonism. Typical parkinsonism has occurred in individuals who have taken 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) for recreational purposes. This compound is converted in the body to a neurotoxin that selectively destroys dopaminergic neurons in the substantia nigra. Reversible parkinsonism may develop in patients receiving neuroleptic drugs and has also been caused by reserpine and metoclopramide. Only rarely is hemiparkinsonism the presenting feature of a brain tumor or some other progressive space-occupying lesion.
In idiopathic parkinsonism, dopamine depletion due to degeneration of the dopaminergic nigrostriatal system leads to an imbalance of dopamine and acetylcholine, which are neurotransmitters normally present in the corpus striatum. Treatment is directed at redressing this imbalance by blocking the effect of acetylcholine with anticholinergic drugs or by the administration of levodopa, the precursor of dopamine.
Tremor, rigidity, bradykinesia, and postural instability are the cardinal features of parkinsonism and may be present in any combination. There may also be a mild decline in intellectual function. The tremor of about four to six cycles per second is most conspicuous at rest, is enhanced by emotional stress, and is often less severe during voluntary activity. Although it may ultimately be present in all limbs, the tremor is commonly confined to one limb or to the limbs on one side for months or years before it becomes more generalized. In some patients, tremor is absent.
Rigidity (an increase in resistance to passive movement) is responsible for the characteristically flexed posture seen in many patients, but the most disabling symptoms of parkinsonism are due to bradykinesia, manifested as a slowness of voluntary movement and a reduction in automatic movements such as swinging of the arms while walking. Curiously, however, effective voluntary activity may briefly be regained during an emergency (eg, the patient is able to leap aside to avoid an oncoming motor vehicle).
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Clinical diagnosis of the well-developed syndrome is usually simple. The patient has a relatively immobile face with widened palpebral fissures, infrequent blinking, and a certain fixity of facial expression. Seborrhea of the scalp and face is common. There is often mild blepharoclonus, and a tremor may be present about the mouth and lips. Repetitive tapping (about twice per second) over the bridge of the nose produces a sustained blink response (Myerson’s sign). Other findings may include saliva drooling from the mouth, perhaps due to impairment of swallowing; soft and poorly modulated voice; a variable rest tremor and rigidity in some or all of the limbs; slowness of voluntary movements; impairment of fine or rapidly alternating movements; and micrographia. There is typically no muscle weakness (provided that sufficient time is allowed for power to be developed) and no alteration in the tendon reflexes or plantar responses. It is difficult for the patient to arise from a sitting position and begin walking. The gait itself is characterized by small shuffling steps and a loss of the normal automatic arm swing; there may be unsteadiness on turning, difficulty in stopping, and a tendency to fall. Canadian Antibiotics
Diagnostic problems may occur in mild cases, especially if tremor is minimal or absent. For example, mild hypokinesia or slight tremor is commonly attributed to old age. Depression, with its associated expressionless face, poorly modulated voice, and reduction in voluntary activity, can be difficult to distinguish from mild parkinsonism, especially since the two disorders may coexist; in some cases, a trial of antidepressant drug therapy may be necessary. The family history, the character of the tremor, and lack of other neurologic signs should distinguish essential tremor from parkinsonism. Wilson’s disease can be distinguished by its early age at onset, the presence of other abnormal movements, Kayser-Fleischer rings, and chronic hepatitis, and by increased concentrations of copper in the tissues. Huntington’s disease presenting with rigidity and bradykinesia may be mistaken for parkinsonism unless the family history and accompanying dementia are recognized. In Shy-Drager syndrome, the clinical features of parkinsonism are accompanied by autonomic insufficiency (leading to postural hypotension, anhidrosis, disturbances of sphincter control, impotence, etc) and more widespread neurologic deficits (pyramidal, lower motor neuron, or cerebellar signs). In progressive supranuclear palsy, bradykinesia and rigidity are accompanied by a supranuclear disorder of eye movements, pseudobulbar palsy, and axial dystonia. Creutzfeldt-Jakob disease may be accompanied by features of parkinsonism, but dementia is usual, myoclonic jerking is common, ataxia and pyramidal signs may be conspicuous, and the electroencephalographic findings are usually characteristic. In cortical-basal ganglionic degeneration, parkinsonism is accompanied by conspicuous signs of cortical dysfunction (eg, apraxia, sensory inattention, dementia, aphasia).
A. Medical Measures: Drug treatment is not required early in the course of parkinsonism, but the nature of the disorder and the availability of medical treatment for use when necessary should be discussed with the patient.
1. Amantadine–Patients with mild symptoms but no disability may be helped by amantadine. This drug improves all of the clinical features of parkinsonism, but its mode of action is unclear. Side effects include restlessness, confusion, depression, skin rashes, edema, nausea, constipation, anorexia, postural hypotension, and disturbances of cardiac rhythm. However, these are relatively uncommon with the usual dose (100 mg twice daily).
2. Anticholinergic drugs–Anticholinergics are more helpful in alleviating tremor and rigidity than bradykinesia.
Treatment is started with a small dose (Table 24–4) and gradually increased until benefit occurs or side effects limit further increments. If treatment is ineffective, the drug is gradually withdrawn and another preparation then tried.
Table 24–4. Some anticholinergic antiparkinsonian drugs.1
Drug ……………………………………………. Usual Daily Dose (mg)
Benztropine mesylate (Cogentin) ……….. 1–6
Biperiden (Akineton) ……………………….. 2–12
Chlorphenoxamine (Phenoxene) ………… 150–400
Cycrimine (Pagitane) ……………………….. 5–20
Orphenadrine (Disipal, Norflex) ……………. 150–400
Procyclidine (Kemadrin) …………………….. 7.5–30
Trihexyphenidyl (Artane) …………………….. 6–20
Common side effects include dryness of the mouth, nausea, constipation, palpitations, cardiac arrhythmias, urinary retention, confusion, agitation, restlessness, drowsiness, mydriasis, increased intraocular pressure, and defective accommodation.
Anticholinergic drugs are contraindicated in patients with prostatic hypertrophy, narrow-angle glaucoma, or obstructive gastrointestinal disease and are often tolerated poorly by the elderly.
3. Levodopa–Levodopa, which is converted in the body to dopamine, improves all of the major features of parkinsonism, including bradykinesia, but does not stop progression of the disorder. The commonest early side effects of levodopa are nausea, vomiting, and hypotension, but cardiac arrhythmias may also occur. Dyskinesias, restlessness, confusion, and other behavioral changes tend to occur somewhat later and become more common with time. Levodopa-induced dyskinesias may take any conceivable form, including chorea, athetosis, dystonia, tremor, tics, and myoclonus. An even later complication is the “on-off phenomenon,” in which abrupt but transient fluctuations in the severity of parkinsonism occur unpredictably but frequently during the day. The “off” period of marked bradykinesia has been shown to relate in some instances to falling plasma levels of levodopa.
During the “on” phase, dyskinesias are often conspicuous but mobility is increased.
Carbidopa, which inhibits the enzyme responsible for the breakdown of levodopa to dopamine, does not cross the blood-brain barrier. High blood pressure When levodopa is given in combination with carbidopa, the extracerebral breakdown of levodopa is diminished. This reduces the amount of levodopa required daily for beneficial effects, and it lowers the incidence of nausea, vomiting, hypotension, and cardiac irregularities. Such a combination does not prevent the development of the “on-off phenomenon,” and the incidence of other side effects (dyskinesias or psychiatric complications) may actually be increased.
Sinemet, a commercially available preparation that contains carbidopa and levodopa in a fixed ratio (1:10 or 1:4), is generally used. Treatment is started with a small dose—eg, one tablet of Sinemet 25/100 (containing 25 mg of carbidopa and 100 mg of levodopa) three times daily—and gradually increased depending on the response.
Sinemet CR is a controlled-release formulation (containing 50 mg of carbidopa and 200 mg of levodopa). It is sometimes helpful in reducing fluctuations in clinical response to treatment and in reducing the frequency with which medication must be taken. Response fluctuations are also reduced by keeping the daily intake of protein at the recommended minimum and taking the main protein meal as the last meal of the day. The dyskinesias and behavioral side effects of levodopa are dose-related, but reduction in dose may eliminate any therapeutic benefit.
Levodopa therapy is contraindicated in patients with psychotic illness or narrow-angle glaucoma. It should not be given to patients taking monoamine oxidase A inhibitors or within 2 weeks of their withdrawal, because hypertensive crises may result. Levodopa should be used with care in patients with suspected malignant melanomas or with active peptic ulcers.
4. Dopamine agonists–Dopamine agonists act directly on dopamine receptors, and their use in parkinsonism is associated with a lower incidence of the response fluctuations and dyskinesias that occur with long-term levodopa therapy. They were previously reserved for patients who had either become refractory to levodopa or developed the “on-off phenomenon.” However, they are now best given with a low dose of Sinemet 25/100 (carbidopa 25 mg and levodopa 100 mg), one tablet three times daily when dopaminergic therapy is first introduced; the dose of Sinemet is kept constant, while the dose of the agonist is gradually increased. The two most widely used agonists are bromocriptine and pergolide, which are equally effective. The initial dosage is 1.25 mg twice daily; this is increased by 2.5 mg at 2-week intervals until benefit occurs or side effects limit further increments. The usual daily maintenance dose in patients with parkinsonism is between 10 and 30 mg. Pergolide is similarly started in a low dose (eg, 0.05 mg daily) and built up gradually depending on the response and tolerance. Buy Generic Prozac FLUOXETINE
Side effects include anorexia, nausea, vomiting, constipation, postural hypotension, digital vasospasm, cardiac arrhythmias, various dyskinesias and mental disturbances, headache, nasal congestion, erythromelalgia, and pulmonary infiltrates.
Bromocriptine and pergolide are contraindicated in patients with a history of mental illness or recent myocardial infarction and are probably best avoided in those with peripheral vascular disease or peptic ulcers (as bleeding from the latter has been reported).
Pramipexole and ropinirole are two new dopamine agonists that will become available in the USA in 1997. They are more selective, have fewer side effects, and may produce a longer-lasting therapeutic response than existing agonists.
5. Selegiline–Selegiline is a monoamine oxidase B inhibitor that is sometimes used as adjunctive treatment for parkinsonism in patients receiving levodopa. By inhibiting the metabolic breakdown of dopamine, selegiline has been used to improve fluctuations or declining response to levodopa. In general, however, the response to treatment with it has been disappointing. The drug is taken in a standard dose of 5 mg with breakfast and 5 mg with lunch. It may increase any adverse effects of levodopa. Cheap drug online.
There are reasons to believe that selegiline may arrest the progression of Parkinson’s disease. Studies have failed to establish this conclusively, but this remains an important consideration for patients who are young or have mild disease.
B. General Measures: Physical therapy or speech therapy helps many patients. The quality of life can often be improved by the provision of simple aids to daily living, eg, rails or banisters placed strategically about the home, special table cutlery with large handles, nonslip rubber table mats, and devices to amplify the voice.
C. Surgical Measures: Thalamotomy or pallidotomy may be helpful for patients who become unresponsive to medical treatment or have intolerable side effects from antiparkinsonian agents, especially if they have no evidence of diffuse vascular disease. Surgical implantation of adrenal medullary or fetal substantia nigra tissue into the caudate nucleus has recently been reported to benefit some patients, but other investigators have failed to substantiate such claims or have found only modest benefits, and the procedure is still being evaluated. Online Canadian Pharmacy
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