Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parkinson's disease is a movement disorder resulting from neurodegeneration of the basal ganglia. Parkinson's disease is usually diagnosed at approximately 55-60 years of age and affects approximately 1% of the population over 60 years. Dopaminergic cells located in the substantia nigra and whose terminals extend to the striatum degenerate slowly such that 60% of cells are already lost when clinical motor symptoms first become evident. In addition to the classic triad of Parkinson's disease symptoms, rest tremor, muscular rigidity and bradykinesia, abnormalities in postural reflexes, dementia and depression are important comorbid conditions. Current therapies are aimed primarily at replacing dopamine with the dopamine precursor L-dopa or by the use of direct acting dopamine receptor agonists. Adjunctive treatments with monoamine oxidase inhibitors, catechol-O-methyl transferase inhibitors and amantadine are also used. While providing very effective symptomatic therapy in early stages of the disease, these agents fail to halt disease progression. Thus, while these treatments generally provide excellent results for 2-5 years, quality of life for Parkinson's disease patients becomes increasingly poor 5-10 years after diagnosis. Symptoms that become increasingly problematic with disease progression include inconsistencies in motor control (response fluctuations), gait and balance abnormalities, cognitive loss, hypophonia and dysphagia. Therefore, in order to maintain an acceptable quality of life for patients with Parkinson's disease, therapies that provide not only symptomatic improvement, but also slow or stop disease progression are greatly needed. In this review, we will discuss possible mechanisms of cell death in Parkinson's disease and related potentially disease-modifying therapies. These therapies include dopaminergic cell tranplantation and the use of growth factors. Small molecules that may act as antioxidants, nicotinic receptor agonists, nitric oxide synthase inhibitors, immunophilins, excitatory amino acid-related (iGluR and mGluR agonists and antagonists) drugs and anti-inflammatory drugs will also be discussed.
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PMID:Pharmacological approaches to disease-modifying therapies in Parkinson's disease. 1981 Sep 16

Parkinson's disease (PD) is a common neurodegenerative disease. While its cause remains elusive, much progress has been made regarding its treatment. Available drugs have a good symptomatic effect, but none has yet been shown to slow the progression of the disease in humans. The most efficacious drug is levodopa, but it remains unclear whether the symptomatic benefit is associated with neurotoxic effects and long-term deterioration. The long-term problem associated with levodopa is the appearance of dyskinesias, which is significantly delayed among patients treated with dopamine agonists as initial therapy. Less clear is the role of other drugs in PD, such as monoamine oxidase inhibitors (MAOIs), including selegiline and rasagiline, the putative N-meihyl-o-aspartaie (NMDA) receptor antagonists amantadine and memantine, and the muscarinic receptor blockers. All these may be used as initial therapy and delay the use of dopaminergic drugs, or can be added later to reduce specific symptoms (tremor or dyskinesias). Advanced PD is frequently associated with cognitive decline. To some extent, this can be helped by treatment with cholinesterase inhibitors such as rivastigmine. Similarly, hallucinations and delusions affect PD patients in the advanced stages of their disease. The use of classical neuroleptic drugs in these patients is contraindicated because of their extrapyramidal effects, but atypical drugs, and particularly clozapine, are very helpful. The big void in the therapy of PD lies in the more advanced stages. Several motor symptoms, like postural instability, dysphagia, and dysphonia, as well as dyskinesias, are poorly controlled by existing drugs. New therapies should also be developed against autonomic symptoms, particularly constipation.
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PMID:Drug treatment of Parkinson's disease. 2203 79

Neuroleptic Malignant-Like Syndrome (NMLS) is a rare, but potentially fatal complication of dopaminergic therapy in Parkinson's disease due to a sudden withdrawal of dopaminergic therapy. Here, we describe the case of a 79 years old woman, with 19 years history of Parkinson disease treated with L-dopa, dopamine agonists and MAO inhibitors, whose sudden withdrawal due to lack of therapeutic compliance, led to sudden onset of high fever, muscle rigidity, akinesia, autonomic dysfunction, impaired level of consciousness, respiratory distress and dysphagia with inability to take oral dopaminergic therapy. High blood levels of CPK and myoglobinaemia were found. The patient was treated with transdermal Rotigotine starting from a dose of 2 mg/24 hours, that was rapidly increased to 6 mg/24 hours, leading to resolution of the acute disturbances.
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PMID:A neuroleptic malignant-like syndrome (NMLS) in a patient with Parkinson's disease resolved with rotigotine: a case report. 2556 68