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We assigned randomly in a double blind study 10 children treated with tizanidine (0.05 mg/kg/day) and 30 with placebo for a 6-month period, after which they were unified in the group of tizanidine. The dependent variables were spasticity, Ashworth scale, posture tone scale, reflex scale and liver function test.
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The long latency M2 electromyographic response of a suddenly stretched active muscle is stretch duration dependent of which the nature is unclear. We investigated the influence of the group II afferent blocker tizanidine on M2 response characteristics of the m. flexor carpi radialis (FCR). M2 response magnitude and eliciting probability in a group of subjects receiving 4 mg of tizanidine orally were found to be significantly depressed by tizanidine while tizanidine did not affect the significant linear relation of the M2 response to stretch duration. The effect of tizanidine on the M2 response of FCR is supportive of a group II afferent contribution to a compound response of which the stretch duration dependency originates from a different mechanism, e.g., rebound Ia firing.
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A double-blind clinical trial has been performed on 70 candidates for elective abdominal surgery undergoing general anesthesia in Educational Hospital of Ghaem, Mashhad, Iran. 35 randomly selected patients (the case group) were given 4 mg of oral Tizanidine 90 minutes before the induction of anesthesia whereas the remaining subjects (the control group) were given placebo. Blood pressure and heart rate before and after induction of anesthesia, and after intubation and extubation, existence of postoperative shivering, and the needed Propofol dosage were measured and recorded. Data analysis was done with T-test and Chi-squared test, using SPSS software version 16.
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Metanalisys results suggest that carbamazepine is more efficient than placebo. In three controlled studies comparing lamotrigine, topiramate and 0.5% proparacaine hydrochloride, only lamotrigine was superior to placebo. Dextromethorphan was compared to low-dose lorazepam, with increased pain with dextromethorphan. Three studies have compared carbamazepine to tizanidine, tocainide and pimozide, and only pimozide was superior to carbamazepine.
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Variations of blood pressure and heart rate after anesthesia induction, intubation and extubation were less in Tizanidine group generally. Postoperative shivering was reported in 28.6% and 11.4% of patients in control and case group respectively. Average propofol needed dose for anesthesia maintenance in case group was 25% less than the needed amount in the control group.
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Tizanidine, a centrally acting skeletal muscle relaxant, is metabolized mainly by cytochrome P450 (CYP) 1A2 and has a low oral bioavailability. The fluoroquinolone antibiotic ciprofloxacin is only a moderately potent inhibitor of CYP1A2. Our objective was to study the extent and mechanism of a possible interaction of ciprofloxacin with tizanidine.
Fifty healthy patients participated in this prospective clinical study. The test group received tizanidine (4 mg in the evenings for the first 2 postoperative days) in addition to antibiotic and antiinflammatory medications. Postoperatively, 1 independent investigator performed clinical examinations. Appropriate statistical analysis was used to evaluate data.
The paper considers mechanisms of action and clinical efficacy of the drug sirdalud (tizanidine) in painful musculotonic syndromes. Sirdalud is an agonist of alpha 2-adrenergic receptors effective in painful musculotonic syndromes and spasticity of various genesis. The drug exhibits myorelaxative and direct central analgetic effects, is well tolerated and has minimal side effects (drowsiness). The response can be seen as early as the first treatment days. Sirdalud is applicable as alone and in combination with non-steroid anti-inflammatory drugs.
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Twelve spastic patients received single oral doses of a new anti-spastic drug DS103-282 (Sandoz) 6 mg, baclofen 20 mg, and placebo on three separate days. Passive stretch responses were measured before administration and for four hours afterwards. DS103-282 was more effective than baclofen, and both drugs were more effective than placebo. Analysis of the recordings confirmed that DS103-282 had a specific effect upon stretch reflexes independent of its effect on resting muscle tone. Its action appeared at 30 to 45 minutes after ingestion, with maximum activity at 60-90 minutes. Unwanted effects of DS103-282 were drowsiness and (in one case) potentiation of antihypertensive therapy.
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The spectrum of antispasticity therapies is fairly broad. Familiarity with the various therapies will enable a nurse involved in the care of neurological patients to deliver the effective treatment and minimize adverse events. Referral to specialty care centers may be appropriate for selected patients who require more complex interventions for spasticity control.
Eight children and young adults from East Denmark with spasticity and 12 with dystonia aged 3-18 years (median 10.9 years) were tested, operated and treated with continuous intrathecal baclofen for a period of 2-64 months (median 22.2 months). Registration of efficacy, fillings, adjustments of baclofen and other therapies were performed in an out patient setting since 1995.
Methodological quality of studies (allocation concealment, blinding, patients characteristics, inclusion and exclusion criteria; interventions; outcomes; lost to follow up) was independently assessed by two investigators. The heterogeneity among studies did not allow quantitative combination of results.
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Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria. Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive.
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Case report and literature review.
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BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.
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At the end of the treatment period all patients had improved; 42/78 patients (53.8%) showed absence of clinical symptoms; 18/78 (23.1%) showed a good improvement, still presenting a low number of painful sites, but not satisfying RDC/TMD parameters for diagnosis of myofascial pain; 18/78 (23.1%) showed only a slight improvement, still presenting a high number of painful sites and satisfying RDC/TMD parameters for diagnosis of myofascial pain.
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Electronic MEDLINE, PubMed, Cochrane Library, and hand searches.
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The antagonistic effects of MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine at rat thoracic aorta and rabbit iliac artery alpha1-adrenoceptors were investigated in this study. Selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin dose-dependently shifted the concentration-response curves for noradrenaline to the right. Schild plots of the results obtained from the inhibition by MDL73005EF (pA2 8.30 +/- 0.04) and tamsulosin (pA2 10.51 +/- 0.06) of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta. The slopes of Schild plots obtained from the inhibition by MDL73005EF and tamsulosin of noradrenaline were significantly different from unity in rabbit iliac artery. Schild plots of the results obtained from the inhibition by clonidine and tizanidine of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta (pA2 7.08 +/- 0.04 and 7.32 +/- 0.04, respectively). These results suggest that alpha1D-adrenoceptors play a significant role in the alpha1-adrenoceptor-agonist-induced contraction of rat thoracic aorta and rabbit iliac artery, and that clonidine and tizanidine interact with the alpha1D-adrenoceptor subtype as competitive antagonists in rat thoracic aorta.
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Treatment with tizanidine was carried out with 1 mg/ day in 18 mo-7 yr old children, 2 mg/day in 7-12 yr old children as initial doses, and for those older than 12 yr similar dosing to that in adults. Tolerance was excellent in 79.3 % of children. Sedation was the most uncomfortable side- effect. Subjective assessment by 92.9 % of parents was good.
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In the studied real-life setting, we found a considerable number of MQAB users with additional risk factors for TdP but no ECG monitoring. However, adverse drug reactions were rarely found, and costs vs. benefits of ECG monitoring have to be weighted. In contrast, avoidable risk factors and selected contraindicated pharmacokinetic interactions are clear targets for implementation as automated alerts in electronic prescribing systems.
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We report a case of delirium accompanied by extrapyramidal symptoms and autonomic dysfunction in a 59-year-old man following abrupt cessation of baclofen and tizanidine. An extensive search for the etiology was undertaken, but it was only after a careful history was taken that suspicion for baclofen and tizanidine withdrawal was raised. The delirium and motor disturbances resolved within 24 h of reintroduction of baclofen. Withdrawal from muscle relaxants requires a high index of suspicion but should be considered in patients who manifest signs and symptoms of withdrawal from the medications, particularly visual hallucinations, rigidity and autonomic dysfunction.
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From 2000-2011, there was a significant increase (5.9% per year, CI 3.6, 8.2) in unintentional pediatric exposures to National Poison Data System for central alpha-2 agonists. There were 27,825 clonidine exposures (67.3% male, median age: 4 years), 6143 guanfacine exposures (69.8% male, median age: 6 years), and 856 tizanidine exposures (51.9% male, median age: 2 years). Guanfacine had the greatest proportional increase among the medications. Clonidine was associated with the most respiratory (799, 2.9%) and central nervous system symptoms (12,612, 45.3%), as well as the most episodes of bradycardia (2847, 10.2%) and hypotension (2365, 8.5%). Seven-hundred twenty-eight (2.0%) patients were intubated, and 141 patients (0.5%) were administered vasopressors. There were 7 cardiac arrests and 3 deaths from clonidine.
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The anticonvulsant activity of 5-chloro-4-(2-imidazolin-2yl-amino)-2,1,3-benzothiazole, tizanidine, was studied following intraperitoneal (i.p.) administration in DBA/2 mice (which show sound-induced seizures). Protection against sound-induced seizures was observed after tizanidine, (0.5-4 mg/kg i.p.). The ED50 values for suppression of the tonic, clonic and wild running phases of sound-induced seizures were 0.54, 0.76 and 1.43 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (25 mg/kg i.p.), yohimbine (1 mg/kg i.p.) or piperoxan (20 mg/kg i.p.). Methysergide, a serotonin antagonists, did not significantly reduce the anticonvulsant effects of tizanidine. The present experiments suggest an involvement of purinergic and adrenergic mechanisms in the anticonvulsant action of tizanidine.
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Multiple sclerosis spasticity (MSS) is a common and disabling symptom for which a number of antispastic agents are available; however, evidence-based guidelines for optimal management are lacking.