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)

Ropinirole is a novel, nonergoline, selective D2-type dopamine agonist developed to treat Parkinson's disease. Safety data from therapeutic studies involving 1364 patients receiving ropinirole are reported (mean daily dose 8.7 mg, early therapy; 8.2 mg adjunct therapy). In early therapy, the emergent adverse experiences more common with the ropinirole group compared with placebo were nausea, somnolence, leg edema, abdominal pain, vomiting, dyspepsia, and hallucinations. In adjunct therapy, they were dyskinesia, nausea, hallucinations, and confusion. Most adverse experiences were mild and associated with a similar withdrawal rate compared with the placebo group. Except for hallucinations, the incidence of emergent adverse experiences decreased with time, despite increasing doses. Long-term adverse experiences particularly associated with ergoline-type dopamine agonists have so far not been observed with ropinirole. Only 1.2% of patients receiving ropinirole developed dyskinesia compared with 11.2% receiving L-dopa in early therapy over a mean period of 17 months. There were no clinically significant changes in cardiovascular parameters or laboratory data. The incidence of adverse experiences in the bromocriptine group was low, possibly because of a slow titration scheme and low average dose. Overall, the safety profile of ropinirole appears similar to that of other dopamine agonists. Clinical studies are continuing to assess the long-term safety and efficacy of ropinirole.
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PMID:The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson's disease. 961 8

New microvascular findings in a woman with Parkinson's disease and lower leg oedema are presented. Microlymphography showed enhanced filling of the microlymphatic network with the fluorescent contrast medium comparable to the findings in lymphoedema. The microlymphatic and interstitial pressures of the skin were increased (27 mm Hg and 16 mm Hg respectively). The increased interstitial and microlymphatic pressures are the result of insufficient venous and lymphatic drainage due to impairment of calf muscle function during walking in Parkinson's disease. Manual lymph drainage and compression therapy, in combination with improvement of calf muscle function, resulted in regression of the oedema.
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PMID:Lymphoedema, lymphatic microangiopathy and increased lymphatic and interstitial pressure in a patient with Parkinson's disease. 1021 75

Ergot derivative dopamine agonists, e.g. pergolide, bromocriptine, dihydroergocriptine used in treatment of Parkinson's disease can cause pleural, pericardial, retroperitoneal and valvular fibrotic changes. Case No 1: A 56-year-old woman with PD was treated with pergolide 3mg/24h since July 2002. In June 2003, edema of lower extremities was first noticed and echocardiography found a minor mitral regurgitation without any morphological changes of the valve. In January 2004, left- sided cardiac failure rapidly developed and echocardiography revealed multivalvular insufficiency with predominating severe mitral regurgitation. Mitral valve replacement was performed and pergolide was changed to ropinirole. Until now, neither cardiac functions nor motor status are sufficiently compensated. Case No 2: A 66-year-old-man with PD since 1996 was treated with pergolide 3 mg/day since 1999. In the beginning of 2004, leg edema appeared. On examination, bilateral hydronephrosis with ureteric strictures and incipient renal insufficiency was found. Bilateral ureteroplasty was performed and the histology showed periureteric fibrosis. Treatment with steroids was initiated and pergolide was changed to pramipexole. Despite the treatment, the fibrosis progressed, requiring ureteral stenting. Based on the literature review and on our own experience, we propose following guidelines to minimize the risk of complications: A. Not to use EAD as the first-line dopamine agonists. B. Regularly follow all patients treated with EAD, especially monitor the majorsymptoms: dyspnea, cough, fatigue, leg edema (also asymmetric), symptoms of urinary outflow obstruction, cardiac insufficiency, chest pain, heart murmur. An elevated ESR, C-reactive protein or anemia support the diagnosis. C. All symptomatic patients should undergo workup for serosal fibrosis (according to type of complication): chest X-ray or CT scan, spirometry, renal functions, renal ultrasound, CT of retroperitoneum. D. Before the introduction of EAD therapy, examine the renal functions, perform chest X-ray and echocardiography. Screening echocardiography should be performed in 3-6 months and subsequently in every 6-12 months.
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PMID:[Organ changes induced by ergot derivative dopamine agonist drugs: time to change treatment guidelines in Parkinson's disease?]. 1580

A 77-year-old woman was admitted to our department due to leg edema of 2-year duration. The patient has been suffered from Parkinson's disease for 12 years and prescribed levodopa, selegiline, and small dosage of pergolide (200 microg/day). Leg edema developed one year after she took pergolide. Bilateral peripheral effusion was shown without any findings for malignancy, infection, and heart failure. After discontinuation of pergolide, both pleural effusion and systemic edema were solved. Pergolide was reported to cause cardiac valve fibrosis, pleural effusion and fibrosis, and peritoneal fibrosis. This case suggests that low dose pergolide (200 microg/day: cumulative dose is about 200 mg) could cause severe pleural effusion and systemic edema.
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PMID:[Low dose pergolide induced systemic edema and pleural effusion in a patient with Parkinson's disease]. 1832 10

Neurologists have several choices of drugs that have been shown to be effective for the treatment of the symptoms of Parkinson's disease. Among the first options are the dopamine agonists, which are commonly used both as an early monotherapy and as an adjunct therapy to levodopa. However, before starting any treatment, the overall benefit-to-risk ratio to individual patients must be considered. For the dopamine agonists, the available evidence on their symptomatic efficacy, effect on long-term levodopa-related motor complications, putative effect on progression of disease, and adverse event profile must be taken into account. Recently, the occurrence of adverse events such as leg oedema, daytime somnolence, impulse control disorders, and fibrosis have increasingly been recognised. The risks of these potentially serious adverse events must therefore be taken into account and treatment decisions should be based on considerations of risks versus benefits for individual patients.
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PMID:A reassessment of risks and benefits of dopamine agonists in Parkinson's disease. 1970 31

Recent data suggests that isradipine, a dihydropyridine calcium channel blocker, is neuroprotective in preclinical models of parkinsonism. Isradipine has not been systematically studied in patients with Parkinson's disease (PD). The aim of this study was to evaluate safety and tolerability of isradipine controlled release (CR) in patients with early PD. Qualified subjects (n = 31) received isradipine CR, titrated from 5 to 20 mg daily dose over 8 weeks as tolerated. Eighty-one percent of subjects completed the study. Tolerability of isradipine CR was dose dependent: 94% for 5 mg dose; 87% for 10 mg; 68% for 15 mg; and 52% for 20 mg. Isradipine had no significant effect on blood pressure or PD motor disability. The two most common reasons for dose reduction were leg edema (7) and dizziness (3). There was no difference in isradipine tolerability between subjects with and without dopaminergic treatment, or with and without hypertension.
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PMID:Tolerability of isradipine in early Parkinson's disease: a pilot dose escalation study. 2081 67

Pramipexole has been a widely used dopamine agonist for the last decade. Recently an extended release formulation of pramipexole has been introduced as both monotherapy for patients with early Parkinson's disease as well as for patients with more advanced disease, as an adjunct to L-DOPA. Along with the enhanced patient compliance seen with once a day dosing, there are other potential advantages of extended release preparations of dopamine agonists. Patients initiated on pramipexole have a lower incidence of developing motor fluctuations including dyskinesia than those initiated on L-DOPA. Pramipexole requires a prolonged dose titration compared to L-DOPA, and generally does not have the efficacy of L-DOPA. The extended release form of pramipexole shows comparable mean and peak serum levels with once a day dosing as seen with three times a day dosing of the immediate release preparation. The extended release preparation has been studied in randomized multicenter clinical trial against both placebo and the immediate release preparation in the setting of early Parkinson's disease as monotherapy and in more advanced patients with motor fluctuations on L-DOPA. In both settings the extended release preparation was superior to placebo and comparable to the immediate release form in efficacy with a similar side effect profile including nausea, sleepiness, leg edema, dyskinesias, hallucinations and impulse control disorders.
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PMID:Pramipexole and its extended release formulation for Parkinson's disease. 2386 46

The main adverse effects of dopaminergic drugs used in Parkinson's disease are hypotension, somnolence, hallucinations and impulse control disorder. Less common is leg edema. We report on a 68-year-old male receiving levodopa and pramipexole consulting for severe leg edema lasting two years, whose etiology was not ascertained with multiple lab tests. This edema subsided substantially when pramipexole was discontinued and the dose of levodopa was increased to treat motor symptoms.
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PMID:[Severe leg edema associated with the use of dopaminergic drugs in Parkinson's disease. Report of one case]. 2965 61