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)

Salbutamol (albuterol) is a beta 2-selective adrenoceptor agonist which accounts for its pronounced bronchodilatory, cardiac, uterine and metabolic effects. During the intervening years since salbutamol was first reviewed in the Journal (1971), it has become extensively used in the treatment of reversible obstructive airways disease. Numerous studies in this disease (including severe acute, childhood and exercise-induced asthma) have confirmed the bronchodilatory efficacy of salbutamol, and it has been shown to be at least as effective as most of the currently available bronchodilators, if not more effective. The onset of maximum effect of salbutamol is dependent on the formulation used and the route by which it is administered. In most patients inhaled salbutamol is a first-line therapy, since it offers rapid bronchodilation, usually relieving bronchospasm within minutes. Although oral salbutamol has often proved to be less efficacious than the inhaled formulation, it still affords clinically significant bronchodilation, and it is particularly useful in those patients unable to coordinate the use of inhalers. Parenteral formulations of salbutamol are generally reserved for the treatment of severe attacks of bronchospasm and they are one of the treatments of choice in these life-threatening situations. Studies of the concomitant use of salbutamol and other agents such as anticholinergics, methylxanthines and beclomethasone dipropionate have usually shown a complementary response in the majority of patients, as might be expected from the different mechanisms of action of these groups of drugs. Salbutamol is generally well tolerated and any side effects observed are a predictable extension of its pharmacology. Since the frequency of side effects is dose related, and therefore dependent on the route of administration, it is not surprising that they are much more common following intravenous and oral rather than inhalation therapy. Tremor, tachycardia and hypokalaemia are the most frequently reported adverse effects. After nearly 20 years of use, salbutamol is well established as a 'first-choice' treatment in reversible obstructive airways disease. Indeed, throughout this time many new bronchodilatory agents have been studied but none have proved more effective. Clinical evaluation of salbutamol in the treatment of premature labour, hyperkalaemia and cardiac failure awaits further studies, although to date some encouraging results have been reported.
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PMID:Salbutamol in the 1980s. A reappraisal of its clinical efficacy. 267 May 12

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

Essential tremor, including the juvenile and senile variations, may be a result of a disorder of the servomechanism that controls physiologic tremor. Hands and arms are affected most commonly, and the tremor can vary in amplitude as well as frequency. Long-term treatment with propranolol has been helpful for some patients, although older patients are less likely to benefit. Other drugs and behaviour modification therapy have been less successful. Surgical treatment is effective but should probably be reserved for severe cases. An effective instrument for measuring the subjective and objective aspects of the tremor is still needed, as is an effective long-term method of treatment.
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PMID:Essential tremor. 701 58

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

Idiopathic cervical dystonia (ICD) is the most common form of adult-onset focal dystonia. Previously, disagreement existed about whether ICD was a psychiatric illness, but the disorder is now viewed as a neurological illness and large clinical series have clarified the clinical features of the disease. At the time of diagnosis, extracervical dystonia is found in approximately 20% of patients, and there may be a concomitant head or hand tremor. Importantly, adult-onset ICD does not become generalized, although there may be segmental spread and pain may increase independently of the dystonia. While 10-20% of patients may experience remission, nearly all patients relapse within 5 years and are left with persistent disease. The aetiology of ICD is unknown, but there has been much progress in clarifying the genetic abnormality in families with inherited adult-onset cervical dystonia; linkage to chromosome 18p has been demonstrated in one family, and the DYT1 locus has been excluded in two other families. Painful trauma may be involved in the pathogenesis of ICD. Painful stimuli are received and processed by the basal ganglia, and the synaptic changes provoked by pain may lead to the abnormal physiology underlying dystonia. Consistent with this idea are experiments which demonstrate that altered sensory input leads to plasticity of the motor cortex, and those that explore the 'tonic vibration reflex' in patients with dystonia. Another theory suggests that a primary vestibular abnormality is responsible for ICD. Botulinum toxin is the most effective treatment for ICD. Roughly 75% of patients improve, and a response is generally seen within the first week. However, many questions remain regarding the optimal technique of administration. The development of neutralizing antibodies occurs in at least 5-10% of patients, and appears to be related both to dosage and to the interval between treatments. Side-effects are generally mild and result from the action of the toxin in the periphery. If the response to botulinum toxin is not adequate, anticholinergics, benzodiazepines, baclofen and other medications are used as adjunctive therapy. Surgical therapies are available for the treatment of ICD but are reserved for patients refractory to conservative measures.
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PMID:Current concepts on the clinical features, aetiology and management of idiopathic cervical dystonia. 957 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

Many data point to a pathogenetic role for IgM antibodies to the myelin-associated glycoprotein (MAG) in the neuropathy associated with IgM monoclonal gammopathy, supporting the use of immune therapies in affected patients. Almost 50% of patients have been reported to improve with these therapies, but the effect of treatment on the long-term prognosis of the neuropathy remains unclear. We analysed the outcome of 25 of the 26 patients (mean age at entry 65 years, range 45-85 years) with neuropathy and high anti-MAG IgM, first examined by us between 1984 and 1994. By January 1999, after a mean follow-up of 8.5 years (range 2-13 years) and a mean duration of neuropathy symptoms of 11.8 years (range 3-18, >10 years in 16), 17 patients (68%) (aged 58-84 years, mean 73.4) were alive, while eight (32%) (aged 69-78 years, mean 73.1) had died 3-15 years (mean 10.6) after neuropathy onset; in none of them was death caused by the neuropathy, although in three it was possibly related to the therapy for the neuropathy. By the time of last follow-up or patients' death, 11 patients (44%) were disabled by severe hand tremor, gait ataxia or both. The disability rates at 5, 10 and 15 years from neuropathy onset were 16, 24 and 50%, respectively. Of the 19 patients treated during the follow-up for 0.5-11 years (mean 4 years) with various immune therapies, five reported a consistent and four a slight improvement in the neuropathy (total 47%) after one treatment or more, but in only one patient was improvement persistent throughout, to the end of follow-up. In 10 patients (53%), severe adverse events, possibly related to therapy, occurred during treatment and were considered responsible for the patient's death in three. The neurological impairment did not differ between treated and untreated patients at the end of a similar follow-up. Our findings indicate that (i) the majority of patients with neuropathy and anti-MAG IgM have a favourable prognosis even after several years, and (ii) current immune therapies, though temporarily effective in half of the patients, are associated with considerable side effects which limit their prolonged use and efficacy, suggesting that until more effective or safer therapies become available, they should probably be reserved for patients impaired in their daily life or in a progressive phase of the disease.
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PMID:Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. 1073 2

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

The present renewal of the surgical treatment of Parkinson's disease, almost abandoned for twenty Years, arises from two main reasons. The first is the better understanding of the functional organization of the basal ganglia. It was demonstrated in animal models of Parkinson's disease that the loss of dopaminergic neurons within the substantia nigra, at the origin of the striatal dopaminergic defect, induces an overactivity of the excitatory glutamatergic subthalamo-internal pallidum pathway. The decrease in this hyperactivity might lead to an improvement in the pakinsonian symptoms. The second reason is the improvement in stereotactic neurosurgery in relation with the progress in neuroimaging techniques and with intraoperative electrophysiological microrecordings and stimulations, which help determine the location of the deep brain targets. In the 1970s chronic deep brain stimulation in humans was applied to the sensory nucleus of the thalamus for the treatment of intractable pain. In 1987, Benabid and colleagues suggested high frequency stimulation of the ventral intermediate nucleus of the thalamus in order to treat drug-resistant tremors and to avoid the adverse effects of thalamotomies. How deep brain stimulation works is not well known but it has been hypothetized that it could change the neuronal activities and thus avoid disease-related abnormal neuronal discharges. Potential candidates for deep brain stimulation are selected according to exclusion and inclusion criteria. Surgery can be applied to patients in good general and mental health, neither depressive nor demented and who are severely disabled despite all available drug therapies but still responsive to levodopa. The first session of surgery consists in the location of the target by ventriculography and/or brain MRI. The electrodes are implanted during the second session. The last session consists in the implantation of the neurostimulator. The ventral intermediate nucleus of the thalamus was the first target in which chronic deep brain stimulation electrodes were implanted in order to alleviate tremor. This technique can be applied bilaterally without the adverse effects of bilateral thalamotomies. Like pallidotomy, internal globus pallidum stimulation has a dramatic beneficial effect on levodopa-induced dyskinesia but its effects on the parkinsonian triad are less constant and opposite motor effects are sometimes observed in relation with the stimulated contact. The inconstant results, perhaps related to the complexity of the structure led to the development of subthalamic nucleus stimulation. The alleviation of motor fluctuations and the improvement in all motor symptoms allows a significant decrease in levodopa daily dose and in levodopa-induced dyskinesia. Presently, deep brain stimulation is a fashionable neurosurgical technique to treat Parkinson's disease. Subthalamic nucleus stimulation seems to be the most suitable target to control the parkinsonian triad and the motor fluctuations. Because of the possible adverse effects it must be reserved for disabled parkinsonian patients. No large randomized study comparing different targets and different neurosurgical techniques has been performed yet. Such studies, including cost benefit studies would be useful to assess the respective value of these different techniques.
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PMID:[Deep brain stimulation]. 1526 68


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