Induction and reduction of muscle tremor upon acute and repeated administration of the beta 2-agonists terbutaline, salbutamol and tulobuterol.
Two single-blind placebo-controlled crossover studies on healthy volunteers were performed to compare typical adverse effects of the beta 2-adrenoceptor agonists salbutamol, terbutaline und tulobuterol in a daily period of eight h after acute oral administration of different doses. Assessments were repeated after six days of regular drug intake, to look for habituation phenomena. Finger tremor, integrated surface-EMG in relation to voluntary force, blood pressure and heart rate were measured. Tremor was recorded with a 3-dimensional accelerometer during three different states of hand extensor muscle activity: relaxed, lightly and maximally contracted. The tremor signal was submitted to power spectrum analysis (FFT). All drug effects depended on the dose and the type of drug used, 2 mg tulobuterol being about equivalent to 4 mg salbutamol and to 2.5 mg terbutaline. Cardiovascular adverse effects were weak and transient. The induction of resting tremor showed some habituation across subchronic medication, whereas cumulative and ceiling effects of the beta 2-agonists occurred in respect to tremor during both states of active muscle contraction. However, the beta 2-adrenergic effect during strong contraction consisted in a prominent reduction of tremor. This striking result did not seem to be related to a transient increase of force, relative to myoelectric activity, which was no longer seen after subchronic medication. In case of ceiling effects, the relative changes in tremor intensity decreased with continuous beta 2-sympathomimetic treatment. Therefore, tremor might become a tolerable though inevitable concomitant of bronchodilatory therapy. Its quantitative measurement seems to provide adequate means to assess dose- and time-efficacy as well as to estimate clinical benefit.
D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000328:Adult; D000420:Albuterol / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004576:Electromyography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D011897:Random Allocation; D013726:Terbutaline / Q000009:adverse effects / Q000031:analogs & derivatives; D014202:Tremor / Q000139:chemically induced* / Q000503:physiopathology
D000318:Adrenergic beta-Agonists; C010809:tulobuterol; D013726:Terbutaline; D000420:Albuterol