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

Entacapone is one of a new class of drugs, the catechol-O-methyltransferase (COMT) inhibitors, which expand the therapeutic options for Parkinson's disease by extending the action of levodopa. Entacapone is used in conjunction with levodopa and provides benefit to patients who suffer from motor fluctuations. Side effects include worsening of the dyskinesias associated with peak doses of levodopa, hypotension, constipation and urine discoloration. Unlike tolcapone, an earlier COMT inhibitor, entacapone does not require liver function monitoring.
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PMID:Entacapone in the management of Parkinson's disease. 1208 95

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

For the assessing the incidence of mood disturbances among the neurological out-patients 3287 of them were examined by 111 neurologists during their routine practice. Early diagnosis, the type of mood disturbances and the depth of depression were estimated by the use of Beck's Depression Inventory, the questionnaire based on The Mini-International Neuropsychiatric Interview and Hamilton Depression Rating Scale, as well. Around half of the patients (50.47%) were suspected on depression, as an early diagnosis. In suspected and diagnosed depressive patients the symptoms as anxiety, low activity precordial pain, headaches, dry mouth, constipation, sleep and appetite troubles were significantly (p < 0.01) more frequent than in euthymic subjects. Among all studied patients the episode of depression were found as a final diagnose in 17.2%, recurrent depressive disorders--in 17.6% and dysthymia--in 2.8% of subjects. In finally diagnosed depressive patients the chronic neurological problems were significantly (p = 0.013) more frequent, as the cause of the visit, than in the euthymic ones. The low mood was equally frequent among the patients with Parkinson's disease, multiple sclerosis and cerebrovascular disorders, as well.
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PMID:[Prevalence of depression in neurological outpatients. DEPEND study]. 1291 Aug 52

Selegiline protects nigral dopaminergic neurons and is recommended for the treatment of patients in the early stage of Parkinson's disease (PD). We treated 112 PD patients and noted that those given selegiline had a high incidence of hallucination. Our objective was to determine which clinical therapeutic factors cause such hallucinations. The Kruskal-Wallis and chi-square test showed that in 94 patients, the severity of the hallucinations was significantly related to the duration of illness, Hoehn and Yahr stage, doses of levodopa and cabergoline, whether or not selegiline was used, and whether or not medication for constipation was required. In addition, patients who were treated with a low dose of levodopa (< or =300 mg/day), who had a low Hoehn and Yahr stage, and a short duration of illness (< or =8 years) together with a high dose of selegiline or cabergoline also tended to have hallucinations. MRI findings were not related to the incidence of hallucination. When selegiline is given to patients who have PD of long duration and a high Hoehn and Yahr stage, and who already are receiving levodopa and a dopamine agonist, the doses of levodopa and the dopamine agonists given, as well as the presence of constipation, may be related to the incidence of hallucination.
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PMID:Therapeutic factors causing hallucination in Parkinson's disease patients, especially those given selegiline. 1587 91

Both constipation and fecal incontinence are prominent lower gastrointestinal tract (LGIT) dysfunctions that occur frequently in multiple system atrophy (MSA). We investigated the mechanism of constipation and fecal incontinence in MSA. Colonic transit time (CTT), sphincter electromyography (EMG), and rectoanal videomanometry were performed in 15 patients with MSA (10 men, 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased bowel frequency [< 3 times a week] in 9; difficulty in expulsion in 11; fecal incontinence in 3) and 10 age-matched healthy control subjects (7 men and 3 women; mean age, 62 years; decreased bowel frequency in 2; mild difficulty in expulsion in 2; fecal incontinence in none). Compared to the control subjects, MSA patients had significantly prolonged CTT in the rectosigmoid segment and total colon. Sphincter EMG showed neurogenic motor unit potentials in none of control subjects but in 93% of MSA patients. At the resting state, MSA patients showed a lower anal squeeze pressure (external sphincter weakness) and a smaller increase in abdominal pressure on coughing. During rectal filling, MSA patients showed smaller amplitude in phasic rectal contraction, which was accompanied by an increase in anal pressure that normally decreased, together with leaking in 3 patients. During defecation, most MSA patients could not defecate completely and had larger postdefecation residuals. MSA patients had weak abdominal strain, smaller rectal contraction on defecation, and larger anal contraction on defecation (paradoxical sphincter contraction on defecation), although these differences were not statistically significant. These findings in MSA patients were similar to those in Parkinson's disease patients in our previous study, except for the sphincter denervation and weakness in MSA. Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain, and fecal incontinence results from weak anal sphincter due to denervation. The responsible sites for these dysfunctions seem to be both central and peripheral nervous systems that regulate the LGIT.
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PMID:Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy. 1530 Jun 57

Five studies compared polyethylene glycol (PEG), an osmotic laxative, with placebo. In two studies the comparison was lactulose and in one study two different doses of PEG 3350 and PEG 4000, respectively were evaluated. PEG is associated with an increase in bowel movement frequency when compared with placebo. There was inadequate evidence to establish whether PEG was superior to lactulose. Data from elderly patients are lacking and data from patients with constipation due to Parkinson's disease, multiple sclerosis or opioid therapy was only evaluated in two very small studies. Severe side-effects with PEG are rare. There are no convincing data regarding the superiority with PEG in flatulence. On the whole there is a real lack of research into treatment of the chronic constipation in adults as well as in the elderly.
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PMID:[The effect of polyethylene glycol in chronic constipation is not sufficiently evaluated. A systematic literature review]. 1544 95

Gastrointestinal dysfunction, especially constipation, is one of the major problems in the daily life of patients with Parkinson's disease (PD). About 60 to 80% of PD patients suffer from constipation. Several studies have proven that constipation appears about 10 to 20 years prior to motor symptoms. More recently, Abbott et al. have found from a large scale prospective study that lower frequency bowel movements predict the future risk of PD. Furthermore, Braak et al. have found that Lewy neuritis and Lewy bodies, the hallmarks of PD pathology, appear in the dorsal nucleus of vagus in the earliest stage of the disease and then extend upward through the brain stem to reach the substantia nigra in the third stage. They also hypothesize that some yet undefined toxins break through the mucosal barrier of the intestine and are incorporated into the axon terminal of the vagus nerve and transported in a retrograde manner to the vagus nucleus. In this study, we assessed bowel movements and nutritional status in Japanese patients with PD. We found that intake of water was significantly decreased in PD patients from early life and associated with their constipation. Ninety four patients with PD (M 50, F 44) were enrolled. Nutritional status was assessed using the Self-administered Diet History Questionnaire (DHQ). Total water intake was calculated from the consumption of coffee, green tea, and tea. We also questioned the behavior of water drinking from the early stage of life. The questionnaire for bowel movements concerned the frequency of defecation, age of onset of constipation, and age of onset of motor dysfunction. Less than one bowel movement in 3 days was defined as constipation. The nutritional status of PD patients did not differ significantly from those of controls though several studies have shown excess intake of animal fats or reduced consumption of coffee are risks in PD. In contrast, water intake was significantly lower in PD patients than controls (604.0+/-377.2 ml/d vs 909.5+/-531.6 ml/d; P<0.0001). Interestingly, PD patients tended not to feel thirsty and thus they had no desire to drink water throughout their life. Seventy four patients out of 94 (78.7 %) complained of constipation. Mean bowel frequency was once per 3.3+/-1.1 days and 71.1% of patients were defined as having constipation. Women suffered from constipation more frequently than men (82.4% vs 61.9 %). In 33 patients out of 74 (44.6 %), onset of constipation preceded motor disturbance by an average time of 18.1+/-18.8 years. Furthermore, the amount of water intake correlated inversely with the severity of constipation and the depletion of water intake preceded constipation in most cases. The present results support previous findings that constipation precedes the onset of motor dysfunction in PD. To our knowledge, this is the first report to point out latent water depletion in PD patients. It is not certain at present whether coffee or caffeine themselves are the protective factor for PD or alternatively the amount of water in coffee drinking is more essential. Prospective studies on a large scale are necessary to elucidate the real meaning of water depletion in PD.
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PMID:Life style risks of Parkinson's disease: association between decreased water intake and constipation. 1550 50

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

Mosapride citrate is a novel selective 5-HT4 receptor agonist. It facilitates acetylcholine release from the enteric cholinergic neurons. In contrast to cisapride, mosapride does not block K(+) channels or D2 dopaminergic receptors. The objective of this study is to perform an open study of mosapride citrate's effects on constipation, a prominent lower gastrointestinal tract disorder in parkinsonian patients. A total of 14 parkinsonian patients (7 with Parkinson's disease, 7 with multiple system atrophy; 10 men, 4 women; mean age, 67 years) with constipation (10 with bowel movement < 3 times/week; 14 with difficulty in defecation) were treated with 15 mg/day of mosapride citrate for 3 months. Pre- and posttreatment objective parameters in colonic transit time (CTT) and rectoanal videomanometry were obtained. Statistical analysis was made by Student's t test. Mosapride was well tolerated by all patients except for 1, who discontinued use of the drug because of epigastric discomfort. None had a worsening of parkinsonism or other adverse events. Thirteen patients reported subjective improvements in bowel frequency (>3 times/week, 13) and difficult defecation (13). Mosapride shortened CTT of the left colon (P < 0.01) and the total colon (P < 0.05). During rectal filling, mosapride lessened the first sensation (P < 0.05) and augmented the amplitude in phasic rectal contraction. During defecation, mosapride augmented the amplitude in rectal contraction (P < 0.05) and lessened the volume of postdefecation residuals. The present study showed for the first time that mosapride citrate augmented lower gastrointestinal tract motility, as shown in CTT and videomanometry, and thereby ameliorated constipation in parkinsonian patients without serious adverse effects.
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PMID:Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients. 1571 24

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


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