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Reflex and strength were measured before and after the administration of a single dose of each intervention agent. Electromyographic and joint torque data were collected during assessments of plantar flexor stretch reflexes, maximum contraction during motor-assisted isokinetic movements, and maximum isometric knee extension and flexion.
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This study was designed to compare the pharmacokinetic properties and tolerability of a single dose (4 mg) of an immediate-release, multiparticulate tizanidine capsule versus a commercially available tablet (reference) administered after a standardized high-fat meal.
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Spasticity is common in many neurological disorders, such as stroke and multiple sclerosis. It is part of the upper motor neurone syndrome manifesting as increased tone, clonus, spasms, spastic dystonia and co-contractions. The impact of spasticity varies from it being a subtle neurological sign to severe spasticity causing pain and contractures. Existing spasticity can be worsened by external factors such as constipation, urinary tract infections or pressure ulcers. Its management involves identification and elimination of triggers; neurophysiotherapy; oral medications such as baclofen, tizanidine and dantrolene; focal injection of botulinum toxin, alcohol or phenol, or baclofen delivered intrathecally through a pump; and surgical resection of selected dorsal roots of the spinal cord. This article reviews the current understanding of pathophysiology, clinical features and management of spasticity.
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Male Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters, and the sciatic nerve was loosely ligated. After 21-28 days after surgery, the rats received intrathecal clonidine (0.3, 1.0, and 3.0 microg) and tizanidine (1.0, 2.0, and 5.0 microg), and the antihyperalgesic effects of thermal and mechanical stimuli were examined. In addition, the changes in blood pressure and heart rate, sedation level, and other side effects after intrathecal administration of drugs were recorded.
Tizanidine (Sirdalud) was compared to baclofen (Lioresal) in a randomized, double-blind, cross-over trial. Each medication was introduced over a three week titration period and then maintained at the highest tolerated dose for five weeks. The two treatment phases were separated by a one week drug withdrawal and a two week washout period. Sixty-six patients entered the trial and forty-eight completed both treatment phases. At the end of the trial, neurologists and physiotherapists thought that baclofen was superior on the basis of perceived efficacy and tolerance (p less than or equal to 0.05). Although the efficacy of tizanidine or baclofen was judged as good to excellent by 24 and 39% of patients respectively, this difference was not statistically significant. Muscle weakness was the most common adverse effect. This was significantly more troublesome in patients treated with baclofen. Somnolence and xerostomia were more common in patients treated with tizanidine. Both baclofen and tizanidine appear to be useful adjuncts in the treatment of spasticity in patients with multiple sclerosis. Preference of either drug is tempered principally by side-effects.
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There is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.
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Severe muscle hypertonia in patients with the mixed type of tetraplegia may be associated with significant deterioration in the quality of life of the patients. Intermittent use of oral muscle relaxant drugs, for example, Tizanidine (Ternelin), which is a fast-acting muscle relaxant, can provide relief from the severe hypertonia in these patients, but only for short durations.
1. The relationship between receptor occupancies and contractile responses for some alpha 1-adrenoceptor agonists were investigated in rabbit iris dilator smooth muscles. 2. Noradrenaline acted as a full agonists, while oxymetazoline and xylometazoline behaved as partial agonists with moderately higher intrinsic activity, and tizanidine and clonidine were partial agonists with lower intrinsic activity. 3. The pD2-values of oxymetazoline and xylometazoline were practically equal to the corresponding pKB-values, the negative log of dissociation constant, estimated by the partial irreversible blockade of alpha 1-adrenoceptors with phenoxybenzamine. However, the pD2-values of tizanidine and clonidine were significantly lower than the corresponding pKB-values. 4. The threshold phenomena lay between the receptor occupations and tissue responses, therefore, the pKB-values of partial agonists with lower intrinsic activity were different from their pD2-values. 5. These results suggest that the threshold phenomena in the tissue used may be an important factor in determining the agonist sensitivity.
Approximately 90% of patients with multiple sclerosis (MS) experience spasticity during their lifetime. Tizanidine HCl is an alpha2 adrenergic agonist indicated for treating spasticity due to MS or spinal cord injury.
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Further investigations that must also include neurologists and anesthetists are required to work out effective pain relief regimens for APAM in patients with PP.
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Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies.
The use of tizanidine or cyclobenzaprine in addition to self-care management and patient education was not more effective than placebo for the management of patients with myofascial jaw pain upon awakening.
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Double-blind, placebo-controlled, crossover, before-after trial, pilot study.
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A 60-year-old female with multiple sclerosis (MS) and supranuclear palsy (PSP) was scheduled for right eye iridotomy, left eye phaco emulcification aspiration and insertion of the intraocular lens. Her medical conditions included prolonged immobility, spastic contracture, and a history of convulsion. She was administered with L-dopa, tizanidine, bacrofen, and dantrorane. Anesthesia was induced with propofol 50 mg and fentanyl 25 microg intravenously, and inhalation of oxygen and 1% sevoflurane. Tracheal intubation was performed without neuromuscular blocking agents. Anesthesia was maintained with inhalation of oxygen-air (Fi(O2) 0.4) and 1-1.5% sevoflurane, combined with regional anesthesia. Supplemental fentanyl was administered as needed. The bispectral index (BIS) was monitored and kept between 40 and 60. The operation proceeded uneventfully. After discontinuation of anesthetic agents, she awoke immediately and the BIS index returned to the pre-induction level. Neither neurological disturbances nor unexpected event were observed postoperatively. In patients with MS, it is important to remember the possibility of drugs moving into the central nervou system easily due to the disturbance of the blood-brai barrier. Patients with PSP are usually medicated wit. various medicines which have possibility of interactin with anesthetics. Therefore, we used least anesthetic as possible. In this case, monitoring of BIS seemed to be useful to maintain the minimum sevoflurane concen trations needed.
Baclofen and tizanidine are both used for the treatment of muscle spasticity of spinal origin. Their effectiveness, cost and adverse-effect profiles differ. This paper sets out to estimate the cost effectiveness of each drug, and the impact of changing from baclofen to tizanidine.