The prescription pattern of dopamine agonists and the effect on the cardiac valvulopathy in the treatment of Parkinson’s disease

• Main Authors: Pay-Fen Lii, 李佩芬
• Other Authors: Churn-Shiouh Gau
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/94040330272442667809

碩士 === 國立臺灣大學 === 臨床藥學研究所 === 96 === Background Recently published literatures indicated that ergot-derived dopamine receptor agonists, often used in the treatment of Parkinson''s disease, have been associated with an increased risk of valvular heart disease. Objective To evaluate the safety issue of pergolide use in patients with Parkinson disease（PD）in Taiwan by analyzing the drug utilization and echocardiographic data of patients. Methods For the first part, the drug utilization and dosage distribution of dopamine agonists prescriptions treated in patients with Parkinson disease（PD）in a medical center during 2000 and 2007 were analyzed based on the hospital pharmacy database For th second part, patients with PD using ergot and non-ergot dopamine agonists were included, respectively. Forty-one subjects without PD matched with age were served as controls. All subjects underwent transthoracic echo-Doppler examinations. Aortic, mitral, tricuspid and pulmonary regurgitation and mitral valvular thicknesses as well as tenting area and distance of the mitral and tricuspid valve were assessed. Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used to assess the potential clinical presentation of valvulopathy of patients. Multiple regression anlysis was used to assess the correlation between factors. Results The amount of pergolide used during 2003-2006 did not have any significant change, since there were two other dopamine agonists available on market after year 2002. However, there was a significant decresed in pergolide drug withdrawal from the market by FDA. Among 12444 prescriptions, the most often daily dose of pergolide is 0.75 mg/day, and only 1.1% prescriptions is higher than 2.0 mg/day. Since March 2007, 78 out of 160（48.8%）patients with pergolide opted to switched to a nonergot dopamine agonist. Overall, 12 of 78 patients（15.4%）experienced adverse events suggestive of over- or unedertreatment and reverted to pergolide.The most often used dose conversion ratio in these patients was pergolide：pramipexole：ropinirole＝1：2：4. 71 patients with PD（37 were taking pergolide and 34 were taking non-ergot derivatives）and 41 controls were included in the observational study. Among 37 pergolide users ( 25 male, 12 female ), mean age was 66.8±10.0 y/o, mean duration of illness was 8.8 years, mean daily dose of pergolide was 0.85 mg/day, mean duration of treatment was 51.2 months, and mean cumulative dose was 1058.24 mg. Regurgitation (grade 2 to 3) in any valve was found with significantly higher frequency in patients taking pergolide (21.6%) but not in patients taking non-ergot dopamine agonists (2.9%), as compared with control subjects (7.3%). The mean tricuspid tenting area in Ergot group, Non-ergot group was 0.25 cm2、0.21 cm2, respectively, and both were significantly higher than that in control group ( 0.19 cm2). There was no significant correlation between cardiovalvulopathy and pergolide dose after adjusted for potential confounding factors. Mean MLHFQ score in Ergot group, Non-ergot group and control was 6.4, 4.5 and 2.8, respectively. Among the variables examined, early onset of illness and levodopa daily dose were independent factors predicting the MLHFQ scores. Conclusion Mean daily dose of pergolide using in PD patients in Taiwan is much lower than that reported in the literature. Although the use of pergolide is associated with an increased risk of cardiac valvulopathy, the symptoms caused by heart valvular regurgitation are not clinically significant in most of our study population. Before the safety issues is clarified in further large scale or prospective studies, regular echocardiography follow up is needed in PD patients using pergolide .