ergoline and Pulmonary-Fibrosis

Dopamine agonists (DAs), which can be categorized as ergot derived and non-ergot derived, are used in the treatment of Parkinson's disease.. This review describes the pharmacologic and pharmacokinetic properties of selected DAs and relates these characteristics to clinical outcomes, with an emphasis on adverse events.. Relevant articles were identified through a search of MEDLINE (to May 2006) using the terms dopamine agonists (or each individual drug name) and pbarmacokinetics, metabolism, drug-drug interaction, interactions, CYP450, fibrosis, valvular heart disease, tremor, clinical trials, reviews, and meta-analyses. Abstracts from recent sessions of the International Congress of Parkinson's Disease and Movement Disorders were also examined. Clinical studies with <20 patients overall or <10 patients per treatment group in the final analysis were excluded. All DAs that were graded at least possibly useful with respect to at least 3 of 4 items connected to the treatment/prevention of motor symptoms/complications in the most recent evidence-based medical review update were included. This resulted in a focus on the ergot-derived DAs bromocriptine, cabergoline, and pergolide, and the non-ergot-derived DAs pramipexole and ropinirole.. Bromocriptine, cabergoline, pergolide, and ropinirole, but not pramipexole, have the potential for drug-drug interactions mediated by the cytochrome P450 (CYP) enzyme system. The occurrence of dyskinesia may be linked to stimulation of the dopamine D(1) receptor, for which cabergoline and pergolide have a similar and relatively high affinity; bromocriptine, pramipexole, and ropinirole have been associated with a lower risk of dyskinesias. The valvular heart disease (VHD) and pulmonary and retroperitoneal fibrosis seen with long-term use appear to represent a class effect of the ergot-derived DAs that may be related to stimulation of serotonin 5-HT(2B) (and possibly 5-HT(2A)) receptors. The incidence of valvular regurgitation was 31% to 47% with ergot-derived DAs, 10% with non-ergot-derived DAs, and 13% with controls.. As reflected in the results of the clinical trials included in this review, dyskinesia associated with DA therapy may be linked to stimulation of the D(1) receptor. Fibrosis (including VHD) seemed to be a class effect of the ergot-derived DAs. Each of the DAs except pramipexole has the potential to interact with other drugs via the CYP enzyme system.

Topics: Animals; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Interactions; Dyskinesia, Drug-Induced; Ergolines; Heart Valve Diseases; Humans; Indoles; Pergolide; Pulmonary Fibrosis; Receptors, Dopamine

Cabergoline is related to an elevated risk of fibrotic adverse reactions including cardiac valvular and pleuropulmonary fibrosis. We investigated pulmonary and cardiac valve fibrosis and immunological markers before and after 3 and 12 months of treatment with cabergoline in women with prolactinoma.. The study included thirty-two women with newly diagnosed prolactinoma and 28 healthy women. CAB cumulative dose was 7.8±5.5 mg after 3-month therapy, and 31±22 mg after 12-month follow-up. The risk of autoimmune adverse fibrotic reactions related to CAB treatment including cardiac valvulopathy and pulmonary fibrosis were assessed by a transthoracic echocardiography and pulmonary function tests, respectively. Immunological markers including Antistreptolysin O, Rheumatoid factor, Immunglobuline E, Antinuchlear antibody were also evaluated.. Before the start of CAB therapy, the total prevalence of trace grade of mitral, aortic, pulmonic, and tricuspid valve regurgitations were found as 34%, 3%, 6.3%, and 39 % respectively in women with prolactinoma. After improving of prolactin levels with CAB treatment, no change was found in the prevalence of the all valve regurgitations. There was no deterioration in pulmonary function tests. Rheumatoid factor was found higher in newly diagnosed women with prolactinoma than in healthy women (p=0.01), and this was improved by CAB therapy (p=0.005).. The prospective study indicated that sufficient cabergoline doses for a period of one year treatment of prolactinoma were not found to be related to fibrotic adverse reactions including cardiac valvular and pulmonary fibrosis or increased levels of immunological marker, apart from rheumatoid factor. For the first time Rf was found higher in newly diagnosed women with prolactinoma and was improved after cabergoline therapy.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; Heart Diseases; Humans; Prolactinoma; Prospective Studies; Pulmonary Fibrosis; Time Factors; Treatment Outcome; Young Adult

There is growing evidence that the ergot-derived dopamine agonists cabergoline and pergolide can cause fibrotic cardiac valvulopathy. Data on other fibrotic reactions and nonergot-derived dopamine agonists are sparse. Aim of this study was to investigate whether there are signals that dopamine agonists are related to cardiac and other fibrotic reactions. We identified all reports of fibrotic reactions at the heart, lung, and retroperitoneal space associated with dopamine agonists within the US Adverse Event Reporting System database. Disproportionality analyses were used to calculate adjusted reporting odds ratios (RORs). For ergot-derived dopamine agonists (bromocriptine, cabergoline, pergolide), the RORs of all reactions under study were increased, whereas no such increases were observed for nonergot-derived drugs (apomorphine, pramipexole, ropinirole, rotigotine). Fibrotic reactions due to ergot-derived dopamine agonists may not be limited to heart valves. For nonergot-derived dopamine agonists, no drug safety signals were evident.

Topics: Aged; Aged, 80 and over; Apomorphine; Benzothiazoles; Bromocriptine; Cabergoline; Databases, Factual; Dopamine Agonists; Endomyocardial Fibrosis; Ergolines; Female; Fibrosis; Heart Valve Diseases; Humans; Indoles; Male; Middle Aged; Pergolide; Pericarditis; Pleural Diseases; Pramipexole; Pulmonary Fibrosis; Retroperitoneal Fibrosis; Tetrahydronaphthalenes; Thiophenes; United States

There are a large variety of dopamine agonists available. Especially de novo patients are treated with dopamine agonists to avoid dyskinesia. Dopamine agonists can be subdivided into ergoline and non-ergoline derivatives. This distinction raises the question whether there are differences in the effects to treat symptoms, not only in the side effects between the individual dopamine agonists but also between these two groups. Pergolide is now considered a second line drug because of its particularly high tendency towards valvular heart disease. Some authors claim that all ergoline-derivatives may cause this problem, while own results do not necessarily support this view. We recommend performing echocardiography on those patients being treated with an ergot-derivative. New data support the view that all dopaminergic drugs may cause somnolence and that there is no preference for non-ergots. It may be that the number of gamblers is slightly higher among patients treated with pramipexole than in others. Dopamine agonists with a high affinity to D3 receptors have a good anti-anhedonic potency. In cell culture all dopamine agonists studied so far show neuroprotective properties in cell culture. The introduction of a slow-release formulation for ropinirole and the rotigotine and lisuride patches have opened new ways of continuous dopamine receptor stimulation. Taken together, dopamine agonists show individual properties and there are differences between ergot and non-ergot derivatives.

Topics: Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Parkinson Disease; Pulmonary Fibrosis; Retroperitoneal Fibrosis

Cardiac valvulopathy has been recently associated with the use of the ergot dopamine agonist (EDA) pergolide in Parkinson's disease (PD). Cabergoline a widely used, well-tolerated EDA which has also been recently implicated in relation to fibrotic side effects although the evidence base for this is not sound.. In PD patients on chronic cabergoline therapy, do symptoms suggestive of serosal/cardiac fibrosis imply underlying fibrotic lesions?. A retrospective data review of 234 PD cases from three UK centres, on chronic cabergoline monotherapy or adjunctive treatment to identify symptoms suggestive of pleuro-pulmonary, cardiac or retroperitoneal fibrosis. These causes were thereafter selectively examined by appropriate specialists with relevant investigations.. Out of 234 cases, 15 were identified with symptoms suggestive of respiratory, cardiac or abdominal systems involvement although subsequent investigations failed to reveal definite association with cabergoline except two cases with probable alveolitis and a possible association with cardiac murmur in one case. In spite of the deficiencies of a retrospective study, the results suggest a low risk of fibrotic side effects with cabergoline, particularly cardiac valvulopathy.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Cabergoline; Ergolines; Female; Fibrosis; Heart Valve Diseases; Humans; Male; Middle Aged; Parkinson Disease; Pulmonary Fibrosis; Retroperitoneal Fibrosis; Retrospective Studies

A 63 year old man with a six year history of Parkinson's disease presented with signs of right heart failure following a knee replacement. Constrictive pericarditis was diagnosed and a radical pericardectomy performed. Six months later, the patient remained unwell with raised inflammatory markers. An inflammatory fibrotic reaction caused by cabergoline was diagnosed. He improved after cessation of cabergoline.

Topics: Antiparkinson Agents; Cabergoline; Ergolines; Fibrosis; Humans; Male; Middle Aged; Parkinson Disease; Pericarditis, Constrictive; Pleura; Pulmonary Fibrosis

Topics: Antipsychotic Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Heart Valve Diseases; Humans; Hyperprolactinemia; Pergolide; Pulmonary Fibrosis; Risperidone

This is the first report of a histologically confirmed pleuropulmonary fibrosis (PPF) associated with the dopamine agonist dihydroergocryptine.. A 67-year-old male patient with Parkinson's disease developed a severe restrictive pulmonary disorder with dyspnea and nonproductive cough after a daily intake of 45 mg dihydroergocryptine for 2 years. After changing the dopamine agonist to the non-ergoline substance pramipexole, marked improvement of the clinical symptoms of PPF occurred, while radiological signs showed only a moderate decrease.. PPF is a possibly fatal complication. Chest X-rays and specific pneumological diagnostics should be done if typical symptoms or nonspecific signs of PPF occur while a patient is on treatment with an ergoline dopamine agonist.

Topics: Aged; Antiparkinson Agents; Benzothiazoles; Cough; Dopamine Agonists; Dyspnea; Ergolines; Humans; Male; Parkinson Disease; Pramipexole; Pulmonary Fibrosis; Thiazoles