Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Senile Parkinsonism can be clinically differentiated from idiopathic Parkinson's disease in younger age groups. It has a slower clinical course, an altered therapeutic response and a more widespread neuropathology. The drug of choice for senile Parkinsonism is levodopa given in low starting daily doses of 100mg, with low increments of 100mg every 4 to 7 days and low maintenance doses of 0.5 to 2.5g daily. Increased absorption of a given dose of levodopa in the elderly explains in part the lower dosage requirements. Combined therapy with a peripheral decarboxylase inhibitor is usually unnecessary in the elderly and carries a higher risk of neuropsychiatric toxicity. The use of a peripheral decarboxylase inhibitor should be reserved for those few elderly patients with significant gastrointestinal side effects and for those who respond poorly to levodopa alone. Anticholinergic agents are in general contraindicated in the elderly, either used alone or in combination with levodopa.
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PMID:Senile Parkinsonism and dopa pharmacokinetics. 692 87

Sixty patients with Parkinson's disease underwent sterotaxic surgery in Edinburgh between 1965 and 1967, and were examined every 2 years for a total follow-up period of 10 years. Although stereotaxic surgery had been extremely effective in treating tremor and rigidity, the other manifestations of Parkinson's disease were noted to progressively affect more patients at each follow-up examination. L-dopa therapy was instituted in 36 patients after 1968. The effect of L-dopa on bradykinesia was remarkable, but the long-term benefit on the other manifestations of Parkinson's disease was negligible. Furthermore in most cases L-dopa became progressively ineffective for bradykinesia after 3 to 5 years. L-dopa-induced tremor and involuntary movements were less frequently noted in limbs contralateral to the side of a previous stereotaxic procedure. It was concluded that in patients presenting with tremor and rigidity as the major problem in their parkinsonian syndrome, the most effective form of palliative therapy is stereotaxic surgery, and that L-dopa should be reserved for the management of bradykinesia.
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PMID:The long-term results of stereotaxic surgery and L-dopa therapy in patients with Parkinson's disease. A 10-year follow-up study. 699 32

The 18 patients diagnosed with Parkinson's disease were individually administered the Rorschach test. They showed less Dd%, more S%, more FC, and slightly more M responses than Japanese normal adults. These findings suggest the following personality characteristics of Parkinsonians: they are reserved, self-reliant, over-control emotionality in their inner lives, and like going their own ways. They have good common sense.
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PMID:Personality characteristics of Parkinson's disease. 725 47

Selegiline is a selective monoamine oxidase inhibitor used in the treatment of Parkinson's disease. It is estimated that approximately one-half of Parkinsonian patients will develop depression requiring antidepressant drug treatment. Recently, selegiline's package insert was revised to reflect the potential risk of adverse effects when it is used in combination with selective serotonin reuptake inhibitors and tricyclic antidepressants. The objective of our study is to assess the safety of combining selegiline with antidepressants. A retrospective chart review was performed on all 28 patients with Parkinson's disease receiving selegiline and antidepressants concurrently to identify possible drug interactions. Compliance was assessed according to prescription refill records. Suspected adverse reactions with combination therapy were documented. There was a total of 40 selegiline-antidepressant drug combinations involving tricyclic antidepressants (n = 25), selective serotonin reuptake inhibitors (n = 7), trazodone (n = 5), and bupropion (n = 3). One patient receiving fluoxetine developed a reaction consistent with the serotonin syndrome; however, it was never documented as such. No other selegiline drug interactions were found. Adverse effects noted were typical of antidepressant monotherapy. Although no selegiline drug interactions were documented in our study, the concurrent administration of selegiline and selective serotonin reuptake inhibitors should be avoided because of literature-reported interactions. We believe that bupropion, tricyclic antidepressants, and trazodone are reasonable choices in combination with selegiline, although tricyclic antidepressants and trazodone may be reserved as second-line treatments.
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PMID:Retrospective study of selegiline-antidepressant drug interactions and a review of the literature. 916 31

The initial treatment of Parkinson's disease should be addressed to improve symptoms, slow down the progression of the illness and avoid long and short term complications. Drugs currently available for symptomatic treatment are levodopa, dopaminergic agonists, anticholinergics and amantadine. Levodopa is still the goldstandard. Both the standard preparations of carbidopa/levodopa or benserazide/levodopa and the slow release preparations are suitable for initial treatment. However, when to start levodopa remains controversial. Dopaminergic agonists are useful symptomatic drugs. They can be used in monotherapy, but usually require the addition of levodopa to obtain a satisfactory long term therapeutic response. Used as adjuvant treatment to levodopa, they help lowering the dosage of levodopa. Anticholinergic drugs effectively improve symptoms such as tremor and rigidity but their use is limited by their side effects, particularly in older people. Amantadine may be a useful drug for initial treatment of Parkinson's disease when symptoms are not severe. Symptomatic treatment should be considered individually in each patient. If there is only slight disability, treatment may be started with amantadine alone or with a dopaminergic agonist. If there is greater disability, levodopa or the simultaneous use of levodopa and a dopaminergic agonist should be considered. Anticholinergic drugs should be reserved for young patients with tremor as the main symptom. The newer dopamine agonists and inhibitors of catachol-o-methyltransferase (COMT) are coming therapeutic options. Selegiline, a MAOB inhibitor with a possible neuroprotective effect, should also be considered as initial option for Parkinson's disease.
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PMID:[Initial treatment of Parkinson's disease]. 928 Jun 84

As more is learnt about the functional implications of basal ganglia connectivity, the role of the subthalamic nucleus as a target site for stereotactic procedures in the amelioration of the symptoms of Parkinson's disease is becoming clearer. A comparison of various neurosurgical procedures in the disease is discussed in relation to current thinking about circuitry. Experimental investigations involving lesioning or stimulation of the subthalamic nucleus in nonhuman primate models and in clinical studies of Parkinson's disease are compared. Neurosurgical procedures that lesion structures bilaterally are more likely to induce side effects than is deep-brain stimulation, which has the added advantage of reversibility and which is more amenable to titration in relation to medication and dosage. A small but growing number of parkinsonian patients have received subthalamic stimulation either unilaterally or bilaterally. Stimulation of the subthalamic nucleus ameliorates tremor, rigidity and hypokinesia, as opposed to thalamic stimulation which is probably best reserved for tremor-dominant patients. Such procedures also do not involve the same complex technical and ethical issues that are associated with foetal mesencephalic grafting. Although subthalamic stimulation shows great promise, it has not been developed to the point where it can be used as more than an experimental treatment. Further experimental research is required before the new strategies can be used on a larger scale.
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PMID:Targeting the subthalamic nucleus in the treatment of Parkinson's disease. 974 82

Orthostatic hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson's disease, the prevalence of symptomatic orthostatic hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen orthostatic hypotension. Secondly, Parkinson's disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson's disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic orthostatic hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson's disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson's disease and thus no specific therapeutic strategy can be recommended. The management of orthostatic hypotension in patients with Parkinson's disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, alpha1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on orthostatic hypotension.
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PMID:Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management. 1148 43

In 1891, Paul Ehrlich began investigating the possible antimalarial effects of methylene blue. His studies prompted other such studies with antimalarials, including pheno-thiazine analogues of the dye. One of these analogues, fenethazine, was found to be a potent antihistamine, and was well received by clinicians as an antiallergic drug. Homologues of fenethazine, although found to be weak antihistamines, had pronounced anticholinergic effects and were used successfully in the treatment of Parkinson's disease. Henri Laborit's search to find a drug that would be of value in preventing the traumatic consequences of shock caused by circulatory collapse during surgery led him to discover the important effects that antihistamines, particularly promethazine, had on the central nervous system. Investigations of centrally acting phenothiazines suitable to Laborit's requirements, with more sedating properties, eventually led to the development of chlorpromazine and its use as an antipsychotic drug. (c) 2002 Prous Science. All rights reserved.
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PMID:The 50th Anniversary of Chlorpromazine. 1267 84

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. This disease is mainly characterized by tremor, bradykinesia, rigidity and postural instability that results primarily from a loss of dopaminergic neurons of the nigrostriatal pathway. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is well known to damage the nigrostriatal dopaminergic pathway, as seen in Parkinson's disease. Recent evidence shows that glial-related response plays a key role in the MPTP neurotoxic process, and the blockade of glial activation may be a new therapeutic approach to treating Parkinson's disease. In view of these new insights, this article suggests that the overexpression of S100beta protein secreted by glial cells may be an exacerbating factor in the neurodegeneration of dopaminergic cells in MPTP-treated animals. (c) 2002 Prous Science. All rights reserved.
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PMID:Glial Cells as a Target for the Development of New Therapies for Treating Parkinson's Disease. 1267 99

Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.
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PMID:Treatment of psychosis in Parkinson's disease: safety considerations. 1281 32


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