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Choosing a skeletal muscle relaxant.
Am Fam Physician. 2008 Aug 1; 78(3): 365-70
See S, Ginzburg R
Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor methodologic design. In addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the most heavily studied and has been shown to be effective for various musculoskeletal conditions. The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are consistently reported with all skeletal muscle relaxants. The potential adverse effects should be communicated clearly to the patient. Because of limited comparable effectiveness data, choice of agent should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions.
Update on tizanidine for muscle spasticity and emerging indications.
Expert Opin Pharmacother. 2008 Aug; 9(12): 2209-15
Malanga G, Reiter RD, Garay E
BACKGROUND: Tizanidine hydrochloride, an alpha(2)-adrenergic receptor agonist, is a widely used medication for the treatment of muscle spasticity. Clinical studies have supported its use in the management of spasticity caused by multiple sclerosis (MS), acquired brain injury or spinal cord injury. It has also been shown to be clinically effective in the management of pain syndromes, such as: myofascial pain, lower back pain and trigeminal neuralgia. This review summarizes the recent findings on the clinical application of tizanidine. OBJECTIVE: Our objective was to review and summarize the medical literature regarding the evidence for the usefulness of tizanidine in the management of spasticity and in pain syndromes such as myofascial pain. METHODS: We reviewed the current medical and pharmacology literature through various internet literature searches. This information was then synthesized and presented in paragraph and table form. RESULTS/CONCLUSION: Tizanidine hydrochloride is a very useful medication in patients suffering from spasticity caused by MS, acquired brain injury or spinal cord injury. It can also be helpful in patients suffering from chronic neck and/or lower back pain who have a myofascial component to their pain. Doses should be started at low dose and gradually titrated to effect.
Eur J Pharmacol. 2008 Jul 28; 589(1-3): 102-5
Tanabe M, Hashimoto M, Ono H
To explore the therapeutic potential of imidazoline I(1) receptor ligands in motor dysfunction related to the basal ganglia, rigidity was induced in mice by intraperitoneal administration of reserpine. The imidazoline I(1) receptor agonists moxonidine and tizanidine reduced rigidity in a dose-dependent manner. Although rigidity was reduced by efaroxan (an imidazoline I(1) receptor and alpha(2)-adrenoceptor antagonist) and idazoxan (an imidazoline I(1) and I(2) receptor and alpha(2)-adrenoceptor antagonist), SKF86466 and yohimbine, both of which are alpha(2)-adrenoceptor antagonists with no affinity for imidazoline receptors, also suppressed rigidity, suggesting that activation rather than blockade of imidazoline I(1) receptors contributes to reduction of reserpine-induced muscle rigidity.
[Protocol for tizanidine use in infantile cerebral palsy]
An Pediatr (Barc). 2008 May; 68(5): 511-5
Palazón García R, Benavente Valdepeñas A, Arroyo Riaño O
INTRODUCTION: Cerebral palsy is usually spastic, and baclofen, benzodiazepines and tizanidine are considered as oral treatments. The aim of this paper is to demonstrate tizanidine management in children with generalized spasticity. PATIENTS AND METHODS: Scheduled medical uses and dosing of tizanidine in our hospital are shown. It was assessed in 45 children. Appearance and repercussions of side-effects were studied using Global Tolerance to Treatment Scale, and drug tolerance was studied by subjective assessment by parents, children or therapists. RESULTS: were analysed using SPSS version 11.5. RESULTS: 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. DISCUSSION: Tizanidine shows greater capacity for binding to brain receptors, and therefore more effective for brain spasticity, better tolerance and higher approval. Therefore, it is an ideal treatment for generalised spasticity in cerebral palsy.
Ann Pharmacother. 2008 Jun; 42(6): 903-4
Caballero J, Gonzalez-Blanco M
Current management of pain associated with multiple sclerosis.
CNS Drugs. 2008; 22(4): 291-324
Pöllmann W, Feneberg W
While pain is a common problem in patients with multiple sclerosis (MS), it is not frequently mentioned by patients and a more direct approach is required in order to obtain information about pain from patients. Many patients with MS experience more than one pain syndrome; combinations of dysaesthesia, headaches and/or back or muscle and joint pain are frequent. For each pain syndrome a clear diagnosis and therapeutic concept needs to be established. Pain in MS can be classified into four diagnostically and therapeutically relevant categories: (i) neuropathic pain due to MS (pain directly related to MS); (ii) pain indirectly related to MS; (iii) MS treatment-related pain; and (iv) pain unrelated to MS. Painful paroxysmal symptoms such as trigeminal neuralgia (TN), or painful tonic spasms are treated with antiepileptics as first choice, e.g. carbamazepine, oxcarbazepine, lamotrigine, gabapentin, pregabalin, etc. Painful 'burning' dysaesthesias, the most frequent chronic pain syndrome, are treated with TCAs such as amitriptyline, or antiepileptics such as gabapentin, pregabalin, lamotrigine, etc. Combinations of drugs with different modes of action can be particularly useful for reducing adverse effects. While escalation therapy may require opioids, there are encouraging results from studies regarding cannabinoids, but their future role in the treatment of MS-related pain has still to be determined. Pain related to spasticity often improves with adequate physiotherapy. Drug treatment includes antispastic agents such as baclofen or tizanidine and in patients with phasic spasticity, gabapentin or levetiracetam are administered. In patients with severe spasticity, botulinum toxin injections or intrathecal baclofen merit consideration. While physiotherapy may ameliorate malposition-induced joint and muscle pain, additional drug treatment with paracetamol (acetaminophen) or NSAIDs may be useful. Moreover, painful pressure lesions should be avoided by using optimally adjusted aids. Treatment-related pain associated with MS can occur with subcutaneous injections of interferon-beta or glatiramer acetate, and may be reduced by optimizing the injection technique and by local cooling. Systemic (particularly 'flu-like') adverse effects of interferons, e.g. myalgias, can be reduced by administering paracetamol, ibuprofen or naproxen. A potential increase in the frequency of pre-existing headaches after starting treatment with interferons may require optimization of headache attack therapy or even prophylactic treatment. Pain unrelated to MS, such as back pain or headache, is common in patients with MS and may deteriorate as a result of the disease. In summary, a careful analysis of each pain syndrome will allow the design of the appropriate treatment plan using various medical and nonmedical options (multimodal therapy), and will thus help to improve the quality of life (QOL) of the patients.
Tizanidine-induced hypotension in patients with liver cirrhosis.
Eur J Clin Pharmacol. 2008 Mar 5;
Momo K, Homma M, Abei M, Hyodo I, Kohda Y
Pharmacotherapy. 2008 Feb; 28(2): 207-13
See S, Ginzburg R
Health care providers prescribe skeletal muscle relaxants for a variety of indications. However, the comparative efficacy of these drugs is not well known. Skeletal muscle relaxants consist of both antispasticity and antispasmodic agents, a distinction prescribers often overlook. The antispasticity agents-baclofen, tizanidine, dantrolene, and diazepam-aid in improving muscle hypertonicity and involuntary jerks. Antispasmodic agents, such as cyclobenzaprine, are primarily used to treat musculoskeletal conditions. Much of the evidence from clinical trials regarding skeletal muscle relaxants is limited because of poor methodologic design, insensitive assessment methods, and small numbers of patients. Although trial results seem to support the use of these agents for their respective indications, efficacy data from comparator trials did not particularly favor one skeletal muscle relaxant over another. Therefore, the choice of a skeletal muscle relaxant should be based on its adverse-effect profile, tolerability, and cost.
Int J Clin Pract. 2008 Feb; 62(2): 314-24
Henney HR, Runyan JD
AIMS: Tizanidine, one of the few oral antispastic therapies approved for use in the USA, has a narrow therapeutic index that can often make optimal patient dosing difficult. We surveyed the published literature for data on potential tizanidine dose relationships to pharmacokinetics, drug safety and effectiveness, as well as to provide practical drug dosing advice. RESULTS: The number of primary studies that describe tizanidine dose proportionality relationships was somewhat limited, even when including studies that used doses above those currently recommended or data from drug-drug interaction studies that resulted in supra-therapeutic tizanidine concentrations. DISCUSSION AND CONCLUSIONS: There is substantial evidence to show that plasma tizanidine concentrations are linearly related to dose in healthy subjects and patients, although there is a high degree of intersubject variability. The most common adverse events and pharmacodynamic effects are related to plasma concentrations. The clinical implications of the large interpatient variability in plasma tizanidine concentrations and its narrow therapeutic index make it necessary to individualise patient therapy. Practical advice on tizanidine dosing and/or switching between formulations is provided.
Celecoxib is a CYP1A2 inhibitor in vitro but not in vivo.
Eur J Clin Pharmacol. 2008 May; 64(5): 511-9
Karjalainen MJ, Neuvonen PJ, Backman JT
BACKGROUND AND OBJECTIVE: We recently discovered that rofecoxib is a potent mechanism-based inhibitor of CYP1A2. The effect of the widely used cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug celecoxib on CYP1A2 activity has not been reported. METHODS: The effect of celecoxib on CYP1A2 activity (phenacetin O-deethylation) was first studied in vitro using human liver microsomes. This was followed by a randomized, placebo-controlled, cross-over study in which 12 healthy volunteers were given celecoxib (200 mg twice daily) or placebo for 4 days. On day 3, a caffeine test was performed. On day 4, the subjects ingested 2 mg tizanidine. Plasma samples for the measurement of the concentrations of tizanidine, its metabolites and celecoxib were collected up to 24 h post-administration. Pharmacodynamic variables (e.g. blood pressure, subjective drowsiness and drug effect) were recorded up to 12 h post-adm. RESULTS: Celecoxib was found to be a moderately potent competitive inhibitor of CYP1A2 in vitro with a K(i) (inhibitor constant) of 25.4 microM. However, in vivo, celecoxib did not affect the caffeine test, or the peak concentration, time to peak concentration, area under the concentration-time curve or half-life of tizanidine. The pharmacodynamic variables of tizanidine also remained unchanged. CONCLUSIONS: Unlike rofecoxib, celecoxib does not clinically to significantly inhibit CYP1A2. The lack of significant in vivo inhibition of CYP1A2 can be correctly predicted on the basis of in vitro K(i) data and the free peripheral or portal plasma concentration of celecoxib.