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

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

Studies assessing the effect of transdermal nicotine in Parkinson's disease (PD) have generated mixed results regarding its efficacy to treat motor and cognitive deficits. These studies generally reported good tolerability in nonsmoking PD patients. The authors report the tolerability data of an open trial with transdermal nicotine in PD. Twenty-two therapeutically well-controlled nonsmoking PD patients received a transdermal nicotine treatment over 25 days according to the following fixed titration schedule: 7 mg for the first 11 days, 14 mg for the next 11 days, and 21 mg for the last 3 days. Fourteen PD patients (64%) had side effects such as nausea, vomiting, and dizziness, and 10 of them withdrew from the study. Factors such as age, body mass index, disease duration, and motor disability were not related to this intolerance. Transdermal nicotine can produce unpleasant adverse effects in patients with PD. Given that similar doses of nicotine were better tolerated in previous studies, the authors suspect the pharmacokinetic profile of the transdermal delivery system to be a determining factor in the effect of nicotine treatment in PD.
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PMID:Poor tolerability of a transdermal nicotine treatment in Parkinson's disease. 1452 Jan 60

(-)-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase (MAO) B, which was discovered in 1962 and become the "golden standard" of MAO research. Like the other MAO-B inhibitors, it was synthesized as an antidepressant, but in a selective MAO-B inhibitory dose it does not act in depression. It is used in the treatment of Parkinson's disease. (-)-Deprenyl potentiates the effect of dopamine, it has antioxidant activity and prevents the toxicity of the dopaminergic (6-OH-dopamine; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)), the noradrenergic (DSP-4) and cholinergic (AF64A) neurotoxins after pre-treatment. When (-)-deprenyl was administered with levodopa in a long-term treatment of Parkinsonian patients, it induces adverse events (nausea, dizziness, confusion, hallucination, insomnia and cardiovascular changes), which could be due to dopamine potentiation in dopaminergic systems (limbic system), other than the nigrostriatal pathway. (-)-Deprenyl in much lower concentrations needed to induce MAO-B inhibition (10(-9) to 10(-13) M) potently inhibits MPTP or serum withdrawal induced apoptosis in tissue cultures of neuro-ectodermal origin (PC12, M1, M2058). The (+)-enantiomer of deprenyl lacks of this property. The anti-apoptotic activity of (-)-deprenyl can be prevented by inhibiting the metabolism of the drug with SKF-525A pre-treatment, which suggests that some of the presently unknown metabolites could be responsible for the anti-apoptotic activity. In high concentration (10(-3) M), (-)-deprenyl and its metabolites induce apoptosis in tissue cultures without serum withdrawal (biphasic action). Our findings support the view that 100, or even 1000 times lower dose of (-)-deprenyl can be offered in human therapy to protect, or slow down neuronal degeneration, than it is presently used. With low dose of the drug the dopaminergic adverse events could be avoided, while anti-apoptotic activity might be preserved.
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PMID:(-)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties. 1469 98

Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.
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PMID:Spectrum of use and tolerability of 5-HT3 receptor antagonists. 1551 6

Frequency and clinical importance of autonomic failure in idiopathic Parkinson's disease (PD) are discussed controversially. 141 patients with PD and 50 healthy age-matched control subjects were interviewed for symptoms of autonomic failure and their influence on daily life using a questionnaire. In PD patients, the prevalence of orthostatic dizziness, bladder dysfunction, erectile dysfunction and hyperhidrosis was significantly higher compared with controls. About 50% of PD patients rated the impact of the symptoms of autonomic failure on their daily lives as "a lot" or "very much" due to orthostatic dizziness, bladder dysfunction and constipation, which were more statistically significant than in age-matched controls. Prevalence and number of autonomic symptoms were not correlated with duration and severity of PD. In 32% of patients, impaired cardiovascular regulation was found by standardized cardiovascular function tests. If testing showed abnormal findings, orthostatic dizziness, bladder dysfunction, constipation and erectile dysfunction were significantly more frequent than in patients with normal regulation, but the impact on daily life due to these symptoms differed significantly only for bladder dysfunction between groups. It is concluded that autonomic failure is a clinically relevant, pervasive problem in PD and compromise patients' daily life activities in all stages of the disease. This underlines the necessity to adequately search for and treat these non-dopaminergic symptoms during the whole course of the disease.
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PMID:Symptoms of autonomic failure in Parkinson's disease: prevalence and impact on daily life. 1583 63

Levodopa, a dopamine precursor administered with a decarboxylase inhibitor, is the principal therapy for treating the symptoms of Parkinson's disease. Unfortunately, after approximately 2-5 years, it frequently loses its beneficial effects as evidenced by motor fluctuations. Entacapone (Comtan) is a selective, reversible catechol-O-methyltransferase inhibitor that dose-dependently increases the peripheral bioavailability of levodopa and prolongs its duration of action. Early studies confirmed that treatment with entacapone resulted in increased striatal uptake of levodopa after iv. administration of [18F] levodopa. Preclinical studies confirmed decreased formation of COMT-dependent metabolites, including 3-O methyldopa and homovanillic acid. Clinical studies performed in patients with motor fluctuations have shown that entacapone prolonged the duration of motor response by an average of 1-1.3 h. Parkinsonian patients receiving therapeutic doses of dopamine agonists and selegiline also experienced an incremental improvement in 'on' time when entacapone was added to their drug regimen. At present, there are no published safety studies beyond six to twelve months in duration, or studies in nonfluctuating patients. Based on the clinical trial data available, entacapone is well-tolerated in the majority of patients. Dopaminergic-related adverse effects include dyskinesias, nausea and dizziness. Non-dopaminergic adverse effects include diarrhoea, abdominal discomfort and discoloration of urine. Diarrhoea is occasionally severe and may require discontinuation of therapy. Of 406 entacapone-treated subjects, there was one incidence of elevated liver transaminases, although this was attributed to an underlying disorder. In the US, Phase III trials have been completed and a New Drug Application (NDA) has been filed. In Europe, the drug received a favourable review and is currently available.
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PMID:Entacapone, a catechol-O-methyltransferase inhibitor for treating Parkinson's disease: review and current status. 1599 91

The objective of this study was to characterize the phenotypic associations of orthostatic hypotension (OH) in Parkinson's disease (PD). One hundred fifty-nine subjects with PD underwent assessment including autonomic symptom severity scoring, disease-specific rating scales, and measurement of postural blood pressure response. Symptoms of autonomic impairment weakly correlated with disease duration and severity. A posture and gait instability (PIGD) motor phenotype was associated with greater severity of autonomic symptoms. Eighty subjects (50.3%) had OH. These subjects were older, more likely to be male, and taking larger doses of dopaminergic medications than those without OH. There was no difference in disease severity or duration between those with and those without OH. Symptomatic dizziness did not distinguish between groups, although subjects with OH had more symptoms of generalized autonomic impairment than those without. Progressive autonomic involvement may be linked to disease progression in PD, particularly in patients with a PIGD phenotype, but dichotomization into groups with and without OH is a relatively insensitive method for demonstrating this. Longitudinal studies of changes in autonomic reflex abnormalities, autonomic symptom profiles, and motor severity might clarify these associations.
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PMID:Clinical phenotype of subjects with Parkinson's disease and orthostatic hypotension: autonomic symptom and demographic comparison. 1695 96

Postprandial hypotension (PPH) is a clinical entity considered to affect above all elderly people with hypertension. It is equally common in diastolic heart failure, Parkinson's disease, diabetes mellitus and autonomic dysfunction. Diagnosis is based on a minimum of 20 mmHg drop of the systolic blood pressure oron a symptomatic systolic blood pressure decrease within 2 hours of the meal. Post-prandial dizziness, fatigue, syncope and falls must raise suspicion for this entity. Although more frequent than orthostatic hypotension, PPH is less searched for. Socio-economical repercussions associated to falls require a better screening of PPH in hospital and ambulatory conditions.
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PMID:[Postprandial hypotension: an unclear clinical entity]. 1712 Jul 14

Inhibition of acetylcholinesterase improves symptoms of dementia in patients with Parkinson's disease (PD). Dementia in PD has a cumulative incidence of up to 80% and is mainly caused by a distinct cholinergic deficit. Objectives of this investigator initiated multicenter open label trial were to confirm the efficacy of donepezil in the treatment of dementia in PD patients and to investigate the tolerability and safety of donepezil. The Mini Mental State Examination (MMSE)-score significantly increased in patients, who finished the trial. A detailed analysis of the various items of the MMSE revealed, that only task performance of orientation and recall significantly improved. Scores of the short syndrome test and the Clinical Global Impression Scale improved, motor impairment did not increase. Only 14 out of 24 PD patients finished the trial due to predominant onset of vomiting, nausea, dizziness and confusion. This may result from the titration regime of donepezil, that allows only 5 and 10 mg dosages. Participants with premature study termination had a significant longer duration of PD, less motivation and sleep disturbances at night. Treatment with donepezil was only effective in PD patients with dementia, who experience nearly no side effects from the drug.
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PMID:The DONPAD-study--treatment of dementia in patients with Parkinson's disease with donepezil. 1744 12

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that is characterized by varying degrees of parkinsonism and cerebellar, corticospinal, and autonomic dysfunction. Vocal cord abductor paralysis (VCAP) is considered a sign of a poor prognosis in MSA, because it is a life-threatening complication that may cause nocturnal sudden death. This case report presents a patient who was treated for Parkinson's disease, and complained of dizziness and sleep apnea. We examined VCAP using fiberoptic laryngoscopy as the possible cause of sleep apnea. VCAP usually occurs in the advanced stages of MSA and is accompanied by a worsening of other symptoms. Optokinetic nystagmus was severely impaired and the caloric test response was bilaterally absent. Objective findings such as VCAP and abnormal neuro-otological results led to the diagnosis of MSA.
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PMID:Vocal cord abductor paralysis in multiple system atrophy: a case report. 1834 May 90


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