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)

Parkinson's disease (PD) is a neurodegenerative disorder that affects an estimated 1 million people in the US and tens of millions worldwide. Medication therapy has made significant advances and improvements especially over the last 10 years. A number of new treatments and new strategies have emerged and the quality of life for the average sufferer has improved. This review will describe the rationale and strategies for current medical therapies in PD, with special emphasis on the use of antipsychotic agents. Levodopa remains the most efficacious medication for the management of PD. Long-term use of levodopa, however, is associated with the development of motor fluctuations including dyskinesia. Trials with dopamine agonists have demonstrated a delay in the onset of dyskinesia with the use of this therapy. There is also active, ongoing investigation to determine whether a neuroprotective effect may be present with agonist therapy. Anticholinergics have been successfully used to treat tremor as well as sialorrhoea and urinary urgency. Catechol-O-methyltransferase inhibitors increase 'on time', decrease 'off time,' and improve motor scores. Continuous stimulation of dopamine receptors may decrease the fluctations observed with pulsatile delivery of anti-Parkinsonian medications, but this will require more study. Monoamine oxidase-B inhibitors, specifically selegiline, may provide symptomatic improvement; the question as to whether a neuroprotective benefit is present remains unanswered. Amantadine has demonstrated both symptomatic benefit and dyskinesia benefit in some patients. Selective dopamine blockers such as clozaril and quetiapine, have been shown to be effective in the treatment of psychosis. This class of medications is particularly useful as an adjunctive to levodopa and dopamine agonists. Doses of dopaminergic drugs can be escalated to treat Parkinsonian symptoms, whereas selective dopamine blockers can be added to block psychosis. Old management strategies required a reduction in dopaminergic therapy and therefore worsened Parkinsonian symptoms. Even though there have been great advances in the medical options for symptomatic management of PD, there are still many unmet needs for this patient population.
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PMID:Rationale for current therapies in Parkinson's disease. 1452 85

Diagnosis of PD can be difficult in elderly patients because some of the key PD symptoms also may be manifestations of normal aging. Asymmetrical symptom onset, resting tremor,and sustained response to levodopa are key features that suggest a diagnosis of PD. For most patients, PD progresses fairly slowly. The goal of treatment is to control symptoms, thereby allowing quality of life and functional ability to be maintained. Pharmacologic therapies are primarily targeted at stimulating dopaminergic receptors, either by increasing the levels of dopamine or by using dopamine agonists. Levodopa, the main therapy for PD and a precursor of dopamine, has a short half-life and is quickly metabolized.Accordingly, decarboxylase inhibitors, like carbidopa, are almost always administered with levodopa to prevent breakdown in the periphery. Catechol-O-methyltransferase (COMT)inhibitors, which increase dopamine levels by inhibiting the metabolism of levodopa and dopamine, recently have become available, including a tablet containing carbidopa, levodopa,and entacapone. Other pharmaceutical therapies for PD include dopamine agonists, monoamine oxidase-B (MAO-B) inhibitors, anticholinergic agents, and amantadine. Dopamine agonists, anticholinergic agents, and amantadine are associated with an increased risk of hallucinations or other adverse events in elderly patients; therefore, use of these should be avoided in this population. Surgical management, particularly deep brain stimulation(DBS), is an option for patients who are refractory to pharmaceutical therapy. Although patients may not need levodopa as an initial treatment, over time most patients will require this drug to control symptoms. With chronic levodopa therapy, patients ultimately experience a wearing off in levodopa response and other motor complications. Management of wearing off is a significant challenge in the treatment of patients with advanced PD.
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PMID:Understanding Parkinson's disease: an update on current diagnostic and treatment strategies. 1794 13

Epinephrine (E) and sympathetic nerve stimulation were described by Thomas Renton Elliott in 1905 for the first time. Dopamine (DA), norepinephrine (NE), E, and serotonin (5-HT) belong to the classic biogenic amines (or monoamines). Parkinson's disease (PD) is among the diseases in which it has been established that catecholamines may account for the neurodegeneration of central and peripheral catecholamine neural systems. PD is a chronic and progressive neurological disorder characterized by resting tremor, rigidity, and bradykinesia, affecting 2% of individuals above the age of 65 years. This disorder is a result of degeneration of DA-producing neurons of the substantia nigra and a significant loss of noradrenergic neurons in the locus coeruleus. In PD and other related neurodegerative diseases, catecholamines play the role of endogenous neurotoxins. Catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) catalyze the metabolism of monoamines. However, the monoamine transporters for DA, NE, and 5-HT namely DAT, NET, and SERT, respectively regulate the monoamine concentration. The metabolism of catecholamines and 5-HT involves common factors. Monoamine transporters represent targets for many pharmacological agents that affect brain function, including psychostimulators and antidepressants. In PD, polymorphisms of the COMT, MAO, DAT, NET, and 5- HTT genes may change the levels of biogenic amines and their metabolic products. The currently available therapies for PD improve the symptoms but do not halt the progression of the disease. The most effective treatment for PD patients is therapy with L-dopa. Combined therapy for PD involves a DA agonist and decarboxylase, MAOs and COMT inhibitors, and is the current optimal form of PD treatment maintaining monoamine balance.
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PMID:Polymorphism of the COMT, MAO, DAT, NET and 5-HTT Genes, and Biogenic Amines in Parkinson's Disease. 2453 84