Deutsch Website, wo Sie Qualität und günstige https://medikamenterezeptfrei2014.com/ Viagra Lieferung weltweit erwerben.

Zufrieden mit dem Medikament, hat mich die positive Meinung cialis kaufen Viagra empfahl mir der Arzt. Nahm eine Tablette etwa eine Stunde vor der Intimität, im Laufe der Woche.

Ylh.ntuh.mc.ntu.edu.tw

EffEcts of mEphEnoxalonE and tizanidinE for acutE
painful spasm of paravErtEbral musclEs: a randomizEd
doublE-blind control study
Sheng-Mou Hou, Shu-Hua Yang2,3, Jyh-Horng Wang2 objectives: skeletal muscle relaxants are frequently used to treat low back
pain with spasm of paravertebral muscles. however, there is little comparative
efficacy and safety data of different muscle relaxants. a randomized, double-
blind study was conducted to evaluate and compare the efficacy and safety of
mephenoxalone and tizanidine in the 7-day treatment of adult patients suffering
from acutely painful and moderately severe spasm of paravertebral muscles.

methods: a total of 41 taiwanese patients were randomly allocated into
mephenoxalone and tizanidine groups. primary (muscle spasm severity,
treatment responses) and secondary efficacy variables were obtained before
and after treatments. adverse events and several safety assessments were also
recorded.

results: in a three item scale, muscle spasm severity was reduced by 0.90±0.55
and 0.95±0.67 points in the mephenoxalone and ±tizanidine groups, respectively.
there was no significant difference between the two treatment groups in all
variables for primary and secondary efficacy assessments. nine mild to moderate
adverse events were reported and one tizanidine-treated patient stopped
the medication due to drug-induced urticaria. transient slight drowsiness
experienced in four mephenoxalone-treated patients did not hinder the treatment
effect.

conclusion: this randomized, double-blind study demonstrates equivalent
treatment efficacies of mephenoxalone and tizanidine in alleviating symptoms of
acute painful paravertebral muscle spasms in taiwanese patients. both drugs
with generally well tolerated.

Received for publication: April 25, 2009.
Department of Orthopedic Surgery, Shin Kong Wo Ho-Su Memorial HospitalDepartment of Orthopedics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan2 Department of Orthopedic Surgery, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin County, Taiwan3Correspondence should be sent to: Shu-Hua Yang, MD, PhD, Department of Orthopedics, National Taiwan University Hospital Yun-Lin Branch, No. 579, Sec. 2, Yunlin Rd., Douliou City, Yunlin County 640, Taiwan.
Mephenoxalone and tizanidine for acute back pain Key words: spasm, paravertebral muscles, low back pain, mephenoxalone,
tizanidine
(J orthop Surg taiwan 27: 1-9, 2010)
introduction
that of tizanidine (4 mg TID) in the 7-day treatment of adult patients with acute and moderately severely painful Muscle spasm is defined as a sustained involun- spasm of paravertebral muscles. The study protocol and tary contraction, which is usually painful and cannot be informed consent form were approved by the Institute relieved completely by voluntary effort.9 Muscle spasm Review Board (IRB) of National Taiwan University is a typical clinical feature of acute low back pain (LBP), Hospital and the study was conducted in National and it is one of the principal factors related to the per- Taiwan University Hospital, Taipei, Taiwan. The study sistence of the pain and disability.,8,9 Skeletal muscle was conducted in full accordance with the ethical prin- relaxants are one of several classes of medications fre- ciples as laid down in the Declaration of Helsinki and/or quently used to treat LBP with spasm of paravertebral the local laws and regulations. All patients signed the muscles.4,7,8 Skeletal muscle relaxants are commonly IRB approved written informed consent form prior to used to treat spasticity from upper motor syndromes and muscular pain, or spasms from peripheral musculoskel- Selection of participantS
etal conditions.3 The use of muscle relaxants can have positive effects on the quality of life and improvement inclusion criteria
rate of patients with acute LBP.2,6,24 Drugs classified as Eligible patients were male or female adults aged 20 skeletal muscle relaxants include baclofen, carisoprodol, –65 years who had been diagnosed with spasm of para- chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, vertebral muscles related to acute LBP. Painful spasm of mephenoxalone, methocarbamol, orphenadrine, and paravertebral muscles was diagnosed when the muscle tizanidine. Because skeletal muscle relaxants are a het- tone increased at palpation and pain/tenderness was erogeneous group of medications that are not chemically induced at the palpated area. The severity of pain and related, there may be important differences in efficacy or tenderness at the lumbar region were rated as moderate safety that must be considered in choosing a medication or severe before enrollment. Before entering the study, to treat patients with muscle spasm.3 However, there patients did not take any form of skeletal muscle relax- is scant literature regarding the comparative efficacy ants. During the study, patients were required to refrain and safety of different skeletal muscle relaxants. The from using muscle relaxants other than mephenoxalone present randomized, double-blind, parallel group study and tizanidine. Patients were also required to have no was undertaken to compare the efficacy and safety of history of mephenoxalone and tizanidine hypersensi- mephenoxalone and tizanidine as skeletal muscle relax- tivity, and to refrain from the use of any pain medica- ants for treating painful spasm of paravertebral muscles tions including non-steroid anti-inflammatory drug and muscle relaxants within 7 days of the screening visit and throughout the 7-day study.
matErials and mEthods
exclusion criteria
The primary objective of this study was to evalu- Because some clinically unstable conditions might ate and compare the efficacy and safety profiles of present significant confounding factors to the evaluation mephenoxalone (200 mg three times daily; TID) with of this study, patients were excluded from the study if they had uncontrolled gastrointestinal diseases (which of movements for both cervical spine and lumbar spine, might potentially affect the absorption of the study medi- as well as overall assessment (0 = no symptoms;  = cations), confirmed evidence of hepatic disease, renal persistent moderately severe symptoms; 2 = persistent impairment, clinically relevant hematological disease, severe symptoms) made by the patient and investigator, terminal stage of malignant disease, psychological or global treatment response assessed by the investiga- mental disorders, or any other serious disease considered tor (0 = excellent;  = good; 2 = fair; 3 = poor) and the suitable for exclusion. Patients who had a history of sub- amounts of paracetamol dose required (in mg). The tests stance abuse or were currently pregnant or lactating were indicating movements of the cervical spine included flex- also excluded. Premenopausal patients were excluded ion (in cm), extension (in cm), and rotation (left/right, in if they were utilizing unreliable methods for contracep- degree) of the neck. Tests indicating movements of the tives. Patients who had participated in any investiga- lumbar spine included flexion (finger to floor distance, tional drug trial within 3 months before the start of the in cm), lateral flexion (left/right, in cm), Laseque test (left/right, positive/negative), and Schober test (in cm). All measurements or ratings were obtained before and Study deSign
after treatment except those for global assessment by This randomized, double-blind, parallel, com- the investigator and the amounts of paracetamol dose parative study finally enrolled 45 patients. During the required, which were made only at the final visit. The screening visit, information concerning demography, differences of measurements or ratings taken before and vital signs, general physical conditions, and general after the treatment and the measurements taken at final medical history and its respective current status were visit were used for the efficacy analyses.
collected. All eligible patients were randomized : to two treatment groups: mephenoxalone (200 mg TID) Safety assessments
or tizanidine (4 mg TID) for 7 days. Four subjects Throughout the study, the investigators monitored were excluded from data analysis due to failure to com- each subject for the occurrence of any laboratory and ply with treatment. Finally, 20 patients received the clinical adverse event. The safety variables consisted mephenoxalone treatment and 2 patients received the of adverse events, physical examination, laboratory assay, and vital signs. After the screening visit, adverse events were assessed at each visit and were recorded in efficacy assessments
detail, regardless of their presumed relationship to the The primary efficacy assessment was the severity investigational product. Safety profile was assessed of paravertebral muscle spasm (0 = normal;  = slightly upon a complete review of all adverse events reported increased muscle tone; 2 = markedly increased muscle during the study, summarized descriptively by treat- tone) and the response of paravertebral muscle spasm to ment group, body system, COSTART term, seriousness, the trial treatments. The secondary efficacy assessments severity, and possible relationship to the study medica- consisted of the severity and the response to the trial tions. Physical examinations were conducted before treatment in pain/tenderness (0 = no pain;  = slight pain; and after treatment by the investigators. Clinically 2 = moderate pain; 3 = severe pain), abnormal posture significant changes from baseline were monitored for (0 = slight, correction possible but slightly painful;  = marked, correction painful; 2 = very marked, correction not possible), day-to-day activity (0 = subject could carry StatiStical analySiS
out normal daily work;  = subject could do only light An intention-to-treat (ITT) population analysis physical work; 2 = subject could not do even light work was used in this study with population defined as those or exercise; 3 = subject was immobile), and restrictions randomized patients who took at least one dose of study Mephenoxalone and tizanidine for acute back pain medication. All patients receiving at least one dose of ness, abnormal posture, day to day activity, patient/inves- study medication and who had at least one post-treatment tigator overall assessments, and restriction of movement primary efficacy evaluation were considered for the at baseline are summarized in Table 2. At baseline, 65% efficacy assessment. Summary statistics were provided (n=3) of the patients in the mephenoxalone treatment for all efficacy, safety, and baseline/demographic vari- group and 7% (n=5) of the patients in the tizanidine ables. Wilcoxon rank sum test, two sample t-test, and treatment group had rating  in the severity of muscle Fisher’s exact test were used to compare the demograph- spasm, while the reminder of the subjects in either treat- ic characteristics between the two treatment groups. A ment group had rating 2. The average ratings in the p-value < 0.05 was considered statistically significant. severity of muscle spasm were .35 in the mephenoxa- Wilcoxon matched-pairs signed-ranks test and paired lone treatment group and .29 in the tizanidine treatment t-test were employed to compare the efficacy variables group. No statistical difference was evident between the before and after treatment to check whether each treat- treatment groups in all baseline values. In other words, ment medicine was effective or not. The Cochran- baseline conditions were comparable between groups. Mantel-Haenszel test, Wilcoxon rank sum test, and The percentage of subjects with at least one medical Fisher’s exact test were used to compare the differences abnormality other than muscle spasm at baseline was between the two treatment groups for the efficacy and 3.7% in the studied patient population, and the major abnormalities were gastrointestinal and musculoskeletal problems. At the end of study, treatment compliance did not show any particular difference between groups (Median/IQR: 85.7/2.4% in mephenoxalone group vs. Demographic characteristics for all studied subjects are summarized in Table . No statistically significant differences were evident between both treatment groups efficacy aSSeSSmentS
for all characteristics including age, weight, height, body After medical treatments for acute painful spasm mass index (BMI), and gender, although the mephenoxa- of paravertebral muscles, both treatment groups showed lone group tended to have a slightly larger BMI average. significant improvements of primary efficacy vari- Thirty-nine percent of patients were male (n=6) and the able, severity of muscle spasm (mephenoxalone: .35 mean age for all patients was 3.9 years. The ratings and ± 0.49 to 0.45 ± 0.60, P=3.05x0-5; tizanidine: .29 ± measurements of severity of muscle spasm, pain/tender- 0.46 to 0.33 ± 0.48, P=3.05x0-5), and several second- Table . Demographic Characteristics.
*All results represent mean (SD): Wilcoxon ranked-sum test, significant at 5 % level2: Two sample t-test, significant at 5 % level3: Fisher’s exact test, significant at 5 % level Table 2. Baseline Characteristics. Baseline Parameters *All results represent mean (SD)a: 0 = normal;  = slightly increased muscle tone; 2 = markedly increased muscle toneb: 0 = no pain;  = slight pain; 2 = moderate pain; 3 = severe painc: 0 = slight, correction possible but slightly painful;  = marked, correction painful; d: day to day activity: 0 = subject could carry out normal daily work;  = subject could do only light physical work; 2 = subject could not do even light work or exercise; 3 = subject was immobile e: 0 = no symptoms;  = persistent moderately severe symptoms; 2 = persistent severe symptoms: Cochran-Mantel-Haenszel test, significant at 5% level2: Two sample t-test, significant at 5% level3: Wilcoxon rank sum test, significant at 5% level ary efficacy variables including severity of pain/ten- 0.48 to 0.00 ± 0.00, P=.53x0-5), day-to-day activity derness (mephenoxalone: 2.5 ± 0.37 to 0.95 ± 0.60, (mephenoxalone: .05 ± 0.60 to 0.20±0.52, P=3.05x0-5; P=.53x0-5; tizanidine: 2.0 ± 0.30 to 0.7 ± 0.46, tizanidine: .00 ± 0.55 to 0.05 ± 0.22, P=7.63x0-6), P=6.4x0-5), abnormal posture (mephenoxalone: 0.80 overall assessments by patient (mephenoxalone: .5 ± 0.4 to 0.5 ± 0.37, P=2.44x0-4; tizanidine: 0.86 ± ± 0.37 to 0.60 ± 0.50, P=.95x0-3; tizanidine: .05 Mephenoxalone and tizanidine for acute back pain Table 3. Changes of efficacy variables during the study period. : Wilcoxon rank sum test, significant at 5 % level2: ANCOVA with treatment effect and covariate of baseline, significant at 5 % level ± 0.22 to 0.43 ± 0.5, P=2.44x0-4) and by investi- groups. At the final visit, the global treatment response gator (mephenoxalone: .0 ± 0.3 to 0.50 ± 0.5, rated by the investigators were excellent in one, good P=4.88x0-4; tizanidine: .00 ± 0.00 to 0.38 ± 0.50, in 4, and fair in five mephenoxalone-treated patients P=2.44x0-4). However, movements of cervical spine and were excellent in one, good in 7, and fair in three and lumbar spine did not show a significant change tizanidine-treated patients. No clear difference between before and after treatment in each group (P > 0.05).
these two groups was shown in the final global treatment Changes of primary and secondary efficacy vari- response (P = 0.464). Eight patients out of 20 in the ables in each group during the study period are sum- mephenoxalone group and nine out of 2 in the tizani- marized in Table 3. The scores representing severity dine group used paracetamol during the treatment. The of muscle spasm were reduced by 0.90 ± 0.55 in the average dose by patients who ever had paracetamol was mephenoxalone treatment group and 0.95 ± 0.67 in the 420 ± 2720 mg (range 500 – 8500) in the mephenoxa- tizanidine treatment group. There was no statistically lone treatment group and 3560 ± 2890 mg (500 – 9000) significant difference in responses to treatments in mus- in the tizanidine treatment group. There was no signifi- cant difference between the two treatment groups regard- Movements of cervical spine in the acute LBP ing numbers of patients who had ever taken paracetamol patients were not influenced by either muscle relaxant. (P = 0.872) and the dose (P = 0.736) during the study Movements of lumbar spine were enhanced in flexion and lateral bending in both treatment groups. However, the improvements in these movement directions showed Patients in both treatment groups were exposed to no significant differences between the two treatment the study medication for approximately 7 days (6.95 ± 0.94 days for the mephenoxalone group and 6.8 ± LBP and painful muscle spasm.5,0,6,2-23 Double-blinded, .08 days for the tizanidine group). Nine treatment- randomized, placebo-controlled studies have shown the related adverse events (six in the mephenoxalone group, superior treatment effects of tizanidine on acute skeletal three in the tizanidine group) in eight subjects (five muscle spasms and LBP over placebo.22,23 Tizanidine in the mephenoxalone group, three in the tizanidine appears to assist more rapid improvement, decrease mus- group). Subjects in the mephenoxalone group were at cle tension/tenderness, and lower consumption of addi- higher risk to experience adverse events compared to tional analgesics. Tizanidine is superior to diazepam, the the tizanidine group (relative risk=.66). However, the other commonly prescribed muscle relaxant, for alleviat- difference in the proportion of subjects experiencing ing symptoms and improving mobility in patients with adverse events was not statistically significant (P=0.454). In the mephenoxalone treatment group, four patients Mephenoxalone is a propanediol type of tranquil- (20%) reported slight drowsiness on the beginning of izer and a centrally acting muscle relaxant that exerts its mephenoxalone usage that soon disappeared. One effect through the suppression of polysynaptic reflexes.23 patient experienced mild urogenital distress and one The compound is also useful in the treatment of patients patient experienced mild digestive upset. In the tizani- with marked tension, anxiety, and agitation with depres- dine group, an episode of urticaria that occurred in one sion.2 Furthermore, mephenoxalone does not have any patient, and which led to stoppage of the medication was analgesic effect, but its slight sedative action might influ- considered as a significant adverse event. Two other ence the perception of pain5. The present randomized, minor disturbances of the respiratory and nervous sys- double-blind control study was conducted to evaluate the tems were also evident in the tizanidine group. No other efficacy and safety of mephenoxalone and tizanidine as significant or serious adverse events were reported. No muscle relaxants for treating acute painful spasm of para- death was reported and no subject in either group exhib- ited any significant change in laboratory parameters, vital The primary efficacy end-point regarding the response to treatment in paravertebral muscle spasm revealed that both mephenoxalone and tizanidine were discussion
equally effective in alleviating the severity of pain-ful spasm. Both compounds also showed comparable Muscle relaxants are one of the current treatments improvements in various secondary efficacy assessments commonly used in the management of LBP. Skeletal including pain/tenderness, abnormal posture, level of muscle relaxants include a wide range of drugs with dif- daily activity, movement restriction in lumbar spine, ferent mechanisms of action. Skeletal muscle relaxants amount of paracetamol dose required, and overall and are effective in the management of acute and chronic global assessments. All efficacy assessments indicated LBP by relieving pain, reducing the duration of discom- that both tested muscle relaxants exhibit equivalent treat- fort, and accelerating recovery.25 Although these relax- ment effects on painful paravertebral muscle spasm.
ants are commonly used to treat LBP, knowledge is scant Among the nine treatment-related adverse events concerning the comparative efficacy and safety of differ- reported in eight patients, only one episode of urticaria in the tizanidine group led to cessation of medication Tizanidine is a centrally acting α2-adrenergic ago- use and was considered to be significantly adverse. nist, which presumably reduces spasticity by increasing Although the occurrence rate of light drowsiness (20%) pre-synaptic inhibition of motor neurons, with effects was noteworthy in the mephenoxalone treatment group at the levels of both the brain and the spinal cord.,3,7 of the current study, this incidence was not significantly Tizanidine has been utilized as a muscle relaxant and has higher than that caused by tizanidine treatment in the been reported to be effective in the treatment of acute literature (22%).6 Furthermore, the drowsiness was tran- Mephenoxalone and tizanidine for acute back pain sient and did not stop the affected patients from ceasing identify the few who need extra attention. Postgrad use of mephenoxalone. In fact, light drowsiness could be a desirable effect, since patients with severe acute 8. Coward DM: Tizanidine: neuropharmacology and LBP are often treated with sedation, analgesics, and bed mechanism of action. Neurology 44(Suppl 9): To conclude, this randomized, double-blind control 9. Denber HC: Note on methoxydone. Am J Psychiat study has demonstrated the equivalently efficacious treat- ment effects of mephenoxalone and tizanidine in alle- 10. Deyo RA, Tsui-Wu YJ: Descriptive epidemiology viating symptoms of acute painful paravertebral muscle of low back pain and its related medical care in the spasms in Taiwanese patients. Furthermore, both com- United States. Spine 12: 264-268, 1987.
pounds are generally well tolerated.
11. Deyo RA, Bergman J, Phillips WR: Drug therapy for back pain: which drugs help which patients? The authors thank U-Chu Pharmaceutical Co., Ltd., Tao Yuan, Taiwan, for providing the study medications 12. Eskenazi J, Nikiforidis T, Livio JJ, et al. Effect of free of cost and Mr. Douglas Chen M.S. for assisting paracetamol, mephenoxalone and their combina- tion on pain following bone surgery. Eur J Clin Pharmacol 9: 411-415, 1976.
rEfErEncEs
13. Fischer AA, Chang CH. Electromyographic evi- dence of paraspinal muscle spasm during sleep in 1. Baratta RR: A double-blind study of cyclobenzap- patients with low back pain. Clin J Pain 1: 147-154, rine and placebo in the treatment of acute musculo- skeletal conditions of low back pain. Curr Ther Res 14. Fryda-Kaurimsky Z, Muller-Fassbender H: Tizanidine (DS 103-282) in the treatment of acute 2. Berry H, Hutchinson DR: A multicentre placebo- paravertebral muscle spasm: a controlled trial com- controlled study in general practice to evaluate the paring tizanidine with diazepam. J Intern Med Res efficacy and safety of tizanidine in acute low-back pain. J Intern Med Res 16: 75-82, 1988.
15. Frymoyer JW, Cats-Baril Wl: An overview of the 3. Berry H, Hutchinson DR: Tizanidine and ibuprofen incidences and costs of low back pain. Orthop Clin in acute low back pain: results of a double-blind multicenter study in general practice. J Intern Med 16. Hennies OL: A new skeletal muscle relaxant (DS 103-282) compared to diazepam in the treatment of 4. Casale R: Acute low back pain, symptomatic treat- muscle spasm of local origin. J Intern Med Res 9: ment with a muscle relaxant drug. Clin J Pain 4: 17. Ketenci A, Ozcan E, Karamursel S: Assessment of 5. Cherkin DC, Wheeler KJ, Barlow W, et al: efficacy and psychomotor performances of thiocol- Medications use for low back pain in primary care. chicoside and tizanidine in patients with acute low back pain. Int J Clin Pract 59: 764-770, 2005.
6. Chou R, Peterson K, Helfand M: Comparative 18. Kraft IA: Use of mephenoxalone in behavioral pro- efficacy and safety of skeletal muscle relaxants for blems. Am J Psychiat 118: 841-842, 1962.
spasticity and musculoskeletal conditions: a sys- 19. Lepisto P: A comparative trial of tizanidine and temic review. J Pain Symptom Manag 28: 140-175, placebo in patients with skeletal muscle spasm after operation for herniated disk. Curr Ther Res 30: 7. Connelly C: Patients with low back pain: how to 20. Malmivaara A, Hakkinen U, Aro T, et al: The treat- Efficacy and safety of tizanidine in the treatment of ment of acute low back pain – bed rest, exercise, spasticity in patients with spinal cord injury. North or ordinary activity? N Engl J Med 332: 351-355, American Tizanidine Study Group. Neurology 21. Middleton RS: A comparison of two analgesic mus- 24. van Tulder MW, Touray T, Furlan AD, et al: Muscle cle relaxant combinations in acute back pain. Br J relaxants for nonspecific low back pain: a systemic review within the framework of the Cochrane col- 22. Miettinen TJ, Kanto JH, Salonen MA, et al: The laboration. Spine 28: 1978-1992, 2003.
sedative and sympatholytic effects of oral tizanidine 25. Wagstaff AJ, Bryson HM: Tizanidine. A review of in healthy volunteers. Anesth Analg 82: 817-820, its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cere- 23. Nance PW, Bugaresti J, Shellenberger K, et al: bral and spinal disorders. Drugs 53: 435-52, 1997.

Source: http://www.ylh.ntuh.mc.ntu.edu.tw/ylh/epaper/ylh_epaper_no37/file/99017.pdf

Microsoft word - contigo somos+paz.doc

Ponencias del acto “Contigo somos + Paz” (18 noviembre 2007) 1.- Federico Mayor Zaragoza : cada ser humano es la solución 2.- Antonio Garrigues : debemos estar en posesión de la bondad, no de la verdad 3.- Alex Rovira : ¿por qué ser budistas si podemos ser Buda, por qué ser cristianos si podemos ser Cristo? 4.- Antonio Malagón : los niños necesitan que apoy

Finding relief for peripheral neuropathy

development of this neuropathy and are probably closely related to diabetic control. There are complex relationships between high blood sugar levels, the enzyme aldosereductase, the formation of You wake up in the middle of the night with sorbitol in the cells, and myoinositol in the tissues, burning and tingling in your feet. The weight of the which have been implicated in the development

Copyright © 2010-2014 Health Drug Pdf