Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The introduction of levodopa in the treatment of Parkinson's disease had modified both the prognosis and the current concepts of the disease, Although levodopa remains the most potent drug for the treatment of Parkinson's disease, its long-term use is associated with fluctuations in motor performance, abnormal movements and psychotic hallucinations. These late side-effects remain difficult to treat and thus raise questions as to the benefits and risks of first-time treatment with levodopa. Levodopa mainly alleviates akinesia and rigidity and to a lesser extent, tremor. Levodopa increases life expectancy. This paper reviews some recent developments in the pharmacology of Parkinson's disease. Recent findings indicate that not only central dopamine but also several other central neurotransmitter and receptor changes are involved in the pathophysiology of Parkinson's disease. New data on autonomic dysfunction in Parkinson's disease are presented. New methods of investigation (clinical rating scales, pharmacological tests, imaging techniques, etc.) are reviewed. Finally, future strategies, e.g. the development of potent new symptomatic drugs (selective D2 and D1 agonists, new formulations of apomorphine, COMT inhibitors, new routes of administration, etc.) and etiopathogenic agents (antioxidative and anti-free radical drugs, etc.) are discussed.
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PMID:Recent advances in the clinical pharmacology of Parkinson's disease. 168 24

Parkinson's disease is essentially motor. The core symptoms comprise akinesia, rigidity and tremor. Concomitantly, signs of autonomic, cognitive and affective disturbances may be found. The disease progresses slowly and, without treatment, ultimately results in disability and loss of independence. The symptoms can be controlled for a long time by pharmacotherapy. Dopaminergic drugs such as L-DOPA, dopaminreceptor agonists, and MAO-B- and COMT-blockers can essentially improve most of the symptoms. The tremor may be alleviated by central anticholinergic drugs. With time, however, unwanted side effects such as "end of dose akinesia", "on-off phenomena", hyperkinesis and exogenous psychosis come into play. Therefore, pharmacological treatment becomes very complex in the late stages of the disease and the unwanted side effects can no longer be sufficiently controlled. It is not clear whether conservative approaches will be ever able to cope with these problems. This explains the search for novel treatment strategies, e.g. neurotransplantation, stereotaxic lesion of the subthalamic nucleus or stimulation techniques.
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PMID:[Clinical aspects and conservative therapy of Parkinson disease]. 857 92

Although there is no known cure for essential tremor or Parkinson's disease (PD), medical treatment can often significantly reduce or eliminate functional disability. Mild essential tremor does not require treatment, and early treatment does not arrest or slow the natural progression in symptoms. When essential tremor interferes with daily activities, medical treatment options include beta blockers, anticonvulsants, benzodiazepines, and carbonic anhydrase inhibitors. Because of the great variability in the presentation of PD, no single approach is appropriate for all patients. Levodopa is the mainstay of pharmacologic therapy for PD, although other agents are indicated for monotherapy or in combination with levodopa. These include traditional and newer dopamine agonists, amantadine, anticholinergics, selegiline, and an emerging class of agents called COMT inhibitors.
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PMID:Medical treatment of essential tremor and Parkinson's disease. 959 79

Parkinson's disease is characterised by a variable combination of tremor, rigidity, bradykinesia and impaired righting reflexes. The cumulative life-time risk is one in 40. Levodopa remains the single most effective treatment in older patients, and the minimum dose to achieve maximum functional benefit should be employed. When fluctuations occur, controlled release preparations and selegiline can improve function. Oral dopamine agonists have a role but the combined side effect profile with levodopa should be monitored. COMT inhibitors have recently become available. Subcutaneous apomorphine can be helpful when "on-off" phenomena are marked. The concept of neuroprotection continues to be debated. Surgery is an option for fitter older people but neurotransplantation remains essentially a research tool.
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PMID:The treatment of Parkinson's disease in older people. 983 45

The recent advances in the treatment of Parkinson's disease have made for significant improvements in the quality of life and mortality rate of those who suffer from this neurodegenerative disease. At the same time, the number of options and the complexity of multi-drug regimens have posed a great challenge for the clinician caring for the patient with Parkinson's disease. Though there are still many questions to be answered in regard to the potential neuroprotective effects of several medications, a few general rational treatment plans can be outlined. In patients requiring treatment in the early stages of the disease, especially with a predominance of tremor, anticholinergics or amantadine should be considered initially. At this point, it would be reasonable to add selegiline for both therapeutic and possible neuroprotective effects. As a patient becomes more affected by the disease and additional therapy is necessary, starting either a dopamine agonist or levodopa would be a rational choice. Continuation of selegiline and, possibly, amantadine for neuroprotective reasons should be contemplated. Titration in levodopa therapy (with controlled-release or standard levodopa) to higher levels should prompt addition of a dopamine receptor agonist if one has not been started previously. Conversely, if a patient is receiving only a dopamine receptor agonist and is becoming progressively disabled, levodopa should be added to the regimen. Fluctuations in motor abilities may be improved further by the use of a COMT inhibitor. Patients with uncontrollable motor fluctuations should be considered for surgery. Undoubtedly, the coming years will bring more treatment options and more evidence on which sequences and combinations of therapies are the most beneficial. Differences in efficacy and adverse effects for each patient must be taken into consideration when outlining and carrying out a treatment plan. By using a rational approach to the treatment of Parkinson's disease, with the above guidelines in mind, the patient should be able to enjoy a good quality of life and level of function for many years.
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PMID:The treatment of Parkinson's disease: current concepts and rationale. 984 72

Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS
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PMID:Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. 1075 67

Parkinson's disease (PD) is caused by progressive degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in the deficiency of DA in the striatum. Thus, symptoms are developed, such as akinesia, rigidity and tremor. The aetiology of neuronal death in PD still remains unclear. Several possible mechanisms of the degeneration of dopaminergic neurons are still elusive. Various mechanisms of neuronal degeneration in PD have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental factors, toxic action of nitric oxide, and apoptosis. All these factors interact with each other, inducing a vicious cycle of toxicity causing neuronal dysfunction, atrophy and finally cell death. Considerable evidence suggests that free radicals and oxidative stress may play key roles in the pathogenesis of PD. However, currently, drug therapy cannot completely cure the disease. DA replacement therapy with levodopa (L-Dopa), although still being a gold standard for symptomatic treatment of PD, only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-Dopa treatment. Until now, no therapy is available to stop or at least slow down the neurodegeneration in patients. Therefore, efforts are made not only to improve the effect of L-Dopa treatment for PD, but also to investigate new drugs with both antiparkinsonian and neuroprotective effects. Here, the advantages and limitations of current and future therapies for PD were dicussed. Current therapies include dopaminergic therapy, DA agonists, MAO-B inhibitor, COMT inhibitors, anticholinergic drugs, surgical procedures such as pallidotomy and more specifically deep brain stimulation of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN), and stem cell transplantation.
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PMID:Treatment strategies for Parkinson's disease. 2010 Dec 74

The diagnosis of idiopathic Parkinson's disease is based on a thorough clinical examination with demonstration of the presence of bradykinesia, as well as tremor, rigidity, postural instability and hyposmia. Symptomatic forms and atypical Parkinson syndrome should be ruled out. Nuclear medical analyses of the dopamine metabolism and the dopamine receptors are used only in exceptions to clarify difficult cases of differential diagnoses. For young patients, dopamine-agonists and, indeed, once again increasingly MAO-B inhibitors, such as rasagiline, are mainly used for therapy. Older patients und patients in advanced stages receive levodopa and a COMT inhibitor. As supplemental therapy, amantadine is given for dyskinesia and apathy and budipine is given for tremor-dominant type of Parkinson's disease. In advanced stages with motor fluctuations, apomorphine or Duodopa pumps or deep brain stimulation are employed.
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PMID:[Diagnosis and therapy of idiopathic Parkinson's disease]. 2010 16

Levodopa combined with carbidopa is still the most effective treatment for symptoms of Parkinson's disease. Dopamine agonists, the next most effective class of drugs, can be used alone before the introduction of levodopa or as an adjunct to levodopa.Addition of a peripherally-acting COMT inhibitor or an MAO-B inhibitor to levodopa can reduce motor fluctuations in patients with advanced disease.Amantadine may have mild symptomatic benefit and can decrease levodopa-induced dyskinesias.Anticholinergics are rarely used because of their adverse effects, but can be a useful addition to levodopa for control of tremor and drooling.Subcutaneous apomorphine should be available for rescue use in patients with 'off' episodes. Deep brain stimulation is an option for patients with levodopa-induced motor complications and relatively intact cognition.
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PMID:Drugs for Parkinson's disease. 2416 88

There are many guidelines available concerning the treatment of Parkinson's disease. Most of these advocate treating young-onset patients with a dopamine agonist and older patients with levodopa. The rationale behind this recommendation has its origins in the side effects associated with each of these drug classes: whilst levodopa leads to dyskinesia, which may not be relevant for patients with a limited life-expectancy, dopamine agonists have a much longer plasma half life which probably leads to more continuous dopamine receptor stimulation and thus decreases the occurrence and severity of dyskinesia. However, the side effects associated with the use of dopamine agonists, such as sleepiness, orthostatic problems, hallucinations and impulse control disorders are a drawback. In this overview, the hypothesis will be put forward that perhaps such a strict distinction is no longer needed. A new idea may be the early combination of levodopa with a dopamine agonist which would provide good clinical efficacy and, because of the relatively low doses involved, would reduce the side effects associated with both substances. MAO-B inhibitors may be a good option for early treatment and especially for patients who experience first motor fluctuations. Similarly, and particularly if a wearing-off symptom is present, COMT inhibitors smoothen and prolong the action of levodopa. More invasive escalation therapy comes into play when patients reach the advanced stages with problems of insufficient motor control, such as bradykinesia, rigidity and resting tremor, combined with on-time dyskinesia. The use of all oral and invasive treatment has to be individualized to gain a good motor and non-motor control and especially a good quality of life.
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PMID:Modern treatment in Parkinson's disease, a personal approach. 2629 52


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