Albuterol improves response to levodopa and increases skeletal muscle mass in patients with fluctuating Parkinson disease.
ABSTRACT Animal studies indicate that beta(2)-adrenergic receptor agonists enhance transport of levodopa across the blood-brain barrier. Preliminary studies showed improved response to levodopa in patients with Parkinson disease (PD) who were given albuterol as adjunctive therapy. Beta(2)-adrenergic agonists may offer additional benefits to PD patients via their skeletal muscle anabolic effects, particularly those who experience decreased muscle strength and weight loss. Nondemented, fluctuating PD patients receiving levodopa but not experiencing severe dyskinesias underwent the following tests at baseline and 14 weeks after treatment with albuterol sulfate (4 mg four times a day, orally): Unified Parkinson's Disease Rating Scale motor, tapping, and stand-walk-sit tests every 30 minutes between 8 am and 5 pm; body composition analyses using whole-body plethysmography and computed tomography of the thigh; muscle strength tests; and the Parkinson's Disease Questionnaire (PDQ-39). Results were analyzed using paired t-tests (2 tailed), repeated-measures analysis of variance, and the Wilcoxon signed-rank test. Seven of 8 enrolled patients completed the study; 1 patient withdrew because of headache and anxiety. The area under the curve for all-day UPDRS motor scores improved by 9.8 +/- 9.1% (mean +/- standard deviation; P < 0.05) and tapping improved by 7.6 +/- 8.1% (P < 0.05). The effect was more pronounced when only the response to the first levodopa dose (area under the curve, 8-11 am) was analyzed: 13.0 +/- 9.8% and 9.8 +/- 9.6% respectively. Thigh muscle cross-sectional area increased significantly as measured by computed tomography (5.3 +/- 3.2%, P < 0.01), as did fat-free mass by whole-body plethysmography combined with total-body water determination (9.5 +/- 2.9%, P < 0.05). There was no significant improvement in the stand-walk-sit test, muscle strength tests, other UPDRS sections, daily OFF time, or PDQ-39. Four patients were rated as having a mild global improvement (+1 point) on a -3 to +3-point scale, and 3 of them chose to continue albuterol beyond the termination of the study. The mean heart rate increased from 78.3 +/- 9.3 beats/minute to 85.6 +/- 8.7 beats/minute (P < 0.05). No laboratory abnormalities or electrocardiographic changes were induced by albuterol in any subject. This open-label pilot study suggests that albuterol increases muscle mass and improves the therapeutic response to levodopa in patients with fluctuating PD. A double-blind, placebo-controlled study is needed to confirm the effects and safety profile of beta(2)-agonists in PD.
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ABSTRACT: The objective of this study was to examine the change of body weight (BW) among Parkinson's disease (PD) patients and controls over years and determine the predictors of weight loss among PD patients. Studies on weight loss in PD studies are cross-sectional, have a short follow-up, or lack in clinical detail. We examined the percentage of BW change over years among 49 PD patients and 78 controls. The controls were from another study on longitudinal evolution of BW and body composition in the elderly. We determined the BW, Hoehn and Yahr (HY) stage, and dyskinesia status of 49 consecutive nondemented PD patients with symptom duration of 6.1 +/- 0.7 years (mean +/- SEM) and ascertained their BW at the time of diagnosis and 2.4 +/- 0.2 years before the diagnosis from medical records. We collected data again 7.2 +/- 0.5 years after the first visit. The PD group lost 7.7% +/- 1.5% of BW over the entire symptomatic period (13.1 +/- 0.8 years), while the control group lost only 0.2% +/- 0.7% of BW over 9.9 +/- 0.1 years; weight loss was clinically significant (>5%) in 55.6% of PD patients vs. 20.5% of the controls (both P values < 0.001, adjusted for sex, baseline age, and observation period duration). PD patients lost weight in both the early and advanced phases. While worsening of parkinsonism was the most important factor, age at diagnosis, emergence of visual hallucinations, and possibly dementia were also associated with weight loss. We demonstrated significant weight loss in PD patients compared to controls over approximately 1 decade. Neurodegeneration involving both motor and nonmotor systems may be associated with weight loss in PD.Movement Disorders 07/2006; 21(7):930-6. DOI:10.1002/mds.20837 · 5.63 Impact Factor
Article: Physiological basis of fatigue.[Show abstract] [Hide abstract]
ABSTRACT: This work summarizes our knowledge of the physiological basis of fatigue and the effects of exercise and pharmacological interventions on fatigue. Fatigue may be defined as physical and/or mental weariness resulting from exertion, that is, an inability to continue exercise at the same intensity with a resultant deterioration in performance. The concept of deconditioning in patients is discussed as well as the implications for their rehabilitation and exercise. Because fatigue may result from a number of causes, including loss of muscle mass, deconditioning, nutritional deficiencies, oxygen delivery, and anemia, it should be treated comprehensively. Antifatigue therapy should be the standard of care for most chronic conditions associated with fatigue.American Journal of Physical Medicine & Rehabilitation 02/2007; 86(1 Suppl):S29-46. DOI:10.1097/PHM.0b013e31802ba53c · 2.01 Impact Factor
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ABSTRACT: Cardiac cachexia as a terminal stage of chronic heart failure carries a poor prognosis. The definition of this clinical syndrome has been a matter of debate in recent years. This review describes the ongoing discussion about this issue and the complex pathophysiology of cardiac cachexia and chronic heart failure with particular focus on immunological, metabolic, and hormonal aspects at the intracellular and extracellular level. These include regulators such as neuropeptide Y, leptin, melanocortins, ghrelin, growth hormone, and insulin. The regulation of feeding is discussed as are nutritional aspects in the treatment of the disease. The mechanisms of wasting in different body compartments are described. Moreover, we discuss several therapeutic approaches. These include appetite stimulants like megestrol acetate, medroxyprogesterone acetate, and cannabinoids. Other drug classes of interest comprise angiotensin-converting enzyme inhibitors, beta-blockers, anabolic steroids, beta-adrenergic agonists, anti-inflammatory substances, statins, thalidomide, proteasome inhibitors, and pentoxifylline.Pharmacology [?] Therapeutics 12/2008; 121(3):227-52. DOI:10.1016/j.pharmthera.2008.09.009 · 7.75 Impact Factor