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)

Ergot alkaloids, such as ergotamine, have been associated with numerous vascular complications and with valvular heart disease. The authors describe a man who developed fibrosis of three heart valves during a 5-year treatment with bromocriptine for Parkinson disease. There were no other plausible causes. To our knowledge, such a side effect has never been described with this drug.
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PMID:Fibrotic valvular heart disease subsequent to bromocriptine treatment. 1239 Jun 88

We report on 4 new cases of valvular heart disease in Parkinson's disease patients treated with the ergot derivative dopamine agonists pergolide and cabergoline. Noninflammatory fibrotic degeneration of cardiac valves has been reported to occur in patients with carcinoid syndrome and to occasionally complicate therapies with the anti-migraine ergot alkaloid ergotamine and methysergide and with the appetite suppressants fenfluramine and dexfenfluramine. In these cases, the pathogenesis is suspected to involve serotonin-mediated abnormal fibrogenesis by means of the 5-HT2B receptors, which are expressed in the fibroblasts of heart valves. Based on strikingly similar echocardiographic and histopathological features, we strongly suspect that ergot-derived dopamine agonists may cause a valvular heart disease nearly identical to that seen in those conditions. These cases add to a rapidly growing and worrying list of similar published reports, suggesting that we may well be facing a novel, yet unrecognized, complication of this class of agents, which are widely used not only in Parkinson's disease but also in restless legs syndrome and various common endocrine dysfunctions. Therefore, until more is known about the true prevalence of this side effect, we propose that an assessment of cardiac function be performed before and in the course of a long-term therapy with ergot derivative dopamine agonists.
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PMID:Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. 1519 97

Fourteen male patients suffering from Parkinson's disease, each of whom had been treated with L-DOPA, and in whom additional treatment with oral dopamine agonist (DA) was needed, were followed for a period of one year. Pergolide mesylate (Permax) was given to each patient, and titrated to a total daily dose of 3 mg. All of the patients were taking L-DOPA. The assessments performed before the start of pergolide treatment consisted of neurological examination, unified Parkinson's disease rating scale (UPDRS) III and IV subscales scoring, mini mental state examination (MMSE) scoring, the neuropsychological examination including Zung scale scoring, biochemical and hematological examinations including prolactine serum levels; and a sexological examination during which the patients filled-in the international index of erectile function (IIEF) questionnaire. These examinations were repeated during the control assessments at months 1, 3, 6 and 12. ANOVA, non-parametric Friedmann's ANOVA and Tukey post hoc tests were used for the statistical analysis. There were statistically significant differences between the values of UPDRS III motor subscale and all subscales of IIEF when months 0 and 1 were compared with the results obtained at months 3, 6 and 12. Pergolide mesylate, when added to L-DOPA, significantly improved all sexual functions in younger male Parkinsonian patients who were still interested in sexual activities. The treatment with pergolide in these cases might be more beneficial than with short-acting PDE-5 inhibitor sildenafile. Nevertheless, the relationship between pergolide treatment and incidence of restrictive valvular heart disease must be considered.
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PMID:The long-lasting improvement of sexual dysfunction in patients with advanced, fluctuating Parkinson's disease induced by pergolide: evidence from the results of an open, prospective, one-year trial. 1599 12

The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.
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PMID:Pramipexole in the treatment of Parkinson's disease: new developments. 1616 81

Dopamine receptor agonists play an important role in the treatment of Parkinson's disease and hyperprolactinemic conditions. Proterguride (n-propyldihydrolisuride) was already reported to be a highly potent dopamine receptor agonist, thus its action at different non-dopaminergic monoamine receptors, alpha(1A/1B/1D), 5-HT(2A/2B)- and histamine H(1), was investigated using different functional in vitro assays. The drug behaved as an antagonist at alpha(1)-adrenoceptors without the ability to discriminate between the subtypes (pA(2) values: alpha(1A) 7.31; alpha(1B) 7.37; alpha(1D) 7.35) and showed antagonistic properties at the histamine H(1) receptor. In contrast, at serotonergic receptors (5-HT(2A), 5-HT(2B)) proterguride acted as a partial agonist. The drug stimulated 5-HT(2A) receptors of rat tail artery in lower concentrations than 5-HT itself but failed to evoke comparable efficacy (proterguride: pEC(50) 8.34, E(max) 53% related to the maximum response to 5-HT; 5-HT: pEC(50) 7.03). Agonism at 5-HT(2B) receptors is presently considered to be involved in drug-induced valvular heart disease. Activation of 5-HT(2B) receptors in porcine pulmonary arteries by proterguride (pEC(50) 7.13, E(max) 49%; E(max) (5-HT) 69%), however, occurred at concentrations much higher than plasma concentrations achieving dopaminergic efficacy in humans. The results are discussed focussing on the relevance of action at 5-HT(2B) receptors as well as their significance for a transdermal administration of proterguride. Since it is well accepted that pulsatile dopaminergic stimulation is associated with treatment-related motor complications in the dopaminergic therapy of Parkinson's disease, the transdermal route of administration is of great clinical interest due to the possibility to achieve constant plasma concentrations.
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PMID:Proterguride, a highly potent dopamine receptor agonist promising for transdermal administration in Parkinson's disease: interactions with alpha(1)-, 5-HT(2)- and H(1)-receptors. 1631 Aug 6

Valvular heart disease, associated with ergot derivative dopamine agonists, has been reported in patients with Parkinson's disease (PD). There are few comparative studies on the frequency, severity, and dose dependency of valvular disease associated with ergot derivatives. We analyzed these factors in 58 PD patients who were taking ergot derivatives (22 were taking bromocriptine and 36 were taking pergolide) and compared them with 20 age-matched controls based on the two-dimensional echocardiographic findings. Aortic, mitral, and tricuspid valvular thicknesses, as well as tenting areas and tenting distance of the mitral valve were measured. We also assessed the correlation between the cumulative or daily doses of ergot derivatives and each valvular parameter. There was no significant increase in the frequency of valvulopathy in the PD patients taking bromocriptine or pergolide. We identified a positive correlation between the daily dose of pergolide and the tenting area of the mitral valve (r = 0.385; P = 0.020). However, other valvular parameters were not found to correlate with the age, disease duration, treatment duration, or dosage of medication. Our study failed to uncover definitive harmful effects of ergot derivative dopamine agonists on cardiac valves; this is considering the relatively lower daily doses than other reported cases. To establish a dosage dependency with valvulopathy, a more detailed study with higher doses of ergot derivatives for longer duration of treatment may be needed.
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PMID:Valvular heart disease in Parkinson's disease treated with ergot derivative dopamine agonists. 1668 92

Ergot derivatives (EDs) are used in the treatment of Parkinson's disease, but recent reports indicate induction of valvular heart disease. This survey reviews the documentation and reports on the design of a blinded study of 160 Parkinson's patients treated with either EDs or non-EDs. The present recommendations regarding monitoring of patients treated with ED are also described.
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PMID:[Valvular heart disease associated with the treatment of Parkinson disease]. 1682 7

Pergolide is an ergot derivative dopamine agonist used in the treatment of Parkinson's disease and restless legs syndrome. Ergot derivatives are known to be associated with fibrotic conditions, including a carcinoid-like, fibrotic, valvular heart disease (VHD). Recently, pergolide was identified in association with the development of VHD. This article includes a summary of the literature published on pergolide-associated VHD, a description of the potential mechanisms of drug-induced VHD, and the clinical implications for the management of patients taking pergolide.
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PMID:Pergolide-associated valvular heart disease. 1684 52

Fibrotic valvular heart disease (VHD) has been reported in association with ergot dopamine agonists (DAs), but the current database is insufficient regarding clinical relevance and comparison to data on non-ergot DAs. We evaluated the effects of four DAs (pergolide, cabergoline, ropinirole, pramipexole) on morphology and function of heart valves in patients with Parkinson's disease (PD) to determine the frequency and clinical relevance of DA-induced VHD. A total of 85 patients treated with ergot or non-ergot DAs and 38 age-matched controls were evaluated by transthoracic echocardiography. Valvular pathology was assessed by established criteria of valvular regurgitation and a VHD scoring system. Both grading systems revealed increased frequency of VHD in ergot DA patients compared to both non-ergot DA patients and controls with 22% of ergot DA patients having moderate VHD versus 3% of non-ergot DA patients and none of controls (P = 0.001). We did not find correlations of echocardiographic findings with duration/cumulative dose of treatment, age, or vascular risk factors. Our data suggest that ergot DAs are associated with higher prevalence of VHD compared to non-ergot DAs and controls. Standard echocardiography seems sufficient to detect VHD in PD patients treated with DAs.
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PMID:Valvular heart disease in Parkinson's disease patients treated with dopamine agonists: a reader-blinded monocenter echocardiography study. 1709 87

Valvular heart disease in patients being treated with ergot-derivative dopamine agonists (Ergot-DA) for Parkinson's disease has been reported to occur as a consequence of serotonine receptor stimulation. Goal of this analysis was to estimate the incidence of those changes from recently published studies and to determine its clinical relevance. Medline searches were performed to identify cross-sectional, echocardiographic studies comparing patients treated with dopamine agonists or controls, in terms of valvular changes. Observational studies of valve changes in Parkinsonian patients were used to estimate the incidence of severe valvulopathy. The results from 7 cross-sectional studies including 477 patients treated with Ergot-DA, 127 patients with non-Ergot-DA, and 364 control patients were analyzed. Moderate-to-severe valvular changes were detected in 26% of patients treated with Ergot-DA, 10% of patients treated with non-Ergot DA, and 10% of control patients. Severe valvulopathy was less than 1% both in cross-sectional and observational studies. The high rate of moderate valvular changes in patients treated with Ergot-DA suggests that close surveillance of the patients is required. Severe valvulopathy was less than 1% in the studies analyzed.
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PMID:Meta-analysis of heart valve abnormalities in Parkinson's disease patients treated with dopamine agonists. 1765 36


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