Tramadol chemical structure
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Ultram


Tramadol is an opioid used as an analgesic for treating moderate to severe pain. It is a synthetic agent, unrelated to other opioids, and appears to have actions on the GABAergic, noradrenergic and serotonergic systems. Tramadol was developed by the German pharmaceutical company Grünenthal GmbH and marketed under the trade name Tramal®. Grünenthal has also cross licensed the drug to many other pharmaceutical companies that market it under various names, some of which are listed below. more...

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Tramadol is available in both injectable (intravenous and/or intramuscular) and oral preparations. It is usually marketed as the hydrochloride salt (tramadol hydrochloride). Dosages vary depending on the degree of pain experienced by the patient, and should be decided on the basis of need by the prescriber.

Mechanism of action

The mechanism of action of tramadol has yet to be fully elucidated, but it is believed to work through modulation of the GABAergic, noradrenergic and serotonergic systems. Tramadol have been found to bind to μ-opioid receptors (thus exerting its effect on GABAergic transmission), and to inhibit reuptake of 5-HT and noradrenaline. The second mechanism is believed to contribute since the analgesic effects of tramadol are not fully antagonised by the μ-opioid receptor antagonist naloxone.

Although irrelevant to its mechanism of action, tramadol, unlike morphine, has not been found to induce histamine release.

The serotonergic modulating properties of tramadol mean that it has the potential to interact with other serotonergic agents. There is an increased risk of serotonin syndrome when tramadol is taken in combination with reuptake inhibitors (e.g. SSRIs), agents that potentiate the effect of 5-HT (e.g., MAOIs), or 5-HT agonists.

Dependence

Some controversy exists regarding the dependence liability of tramadol. Grünenthal has promoted it as an opioid with "little" risk of dependence, claiming little evidence of such dependence in their clinical trials. They offer the theory that since the M1 metabolite is the principal agonist at μ-opioid receptors, the delayed agonist activity reduces dependence liability.

Despite these claims it is apparent, in community practice, that dependence does occur to this agent. This would be expected since analgesic and dependence effects are mediated by the same μ-opioid receptor. However, this dependence liability is considered relatively low by health authorities, such that tramadol is classified as a Schedule 4 in Australia, rather than as a Schedule 8 like other opioids (Rossi, 2004).

Proprietary preparations

Grünenthal, which still owns the patent to tramadol, has cross-licensed the agent to various pharmaceutical companies internationally. Thus tramadol is marketed under many trade names including: Adolonta, Contramal, Crispin, Nobligan, Siverol, Tiparol, Toplagic, Tradolan, Tralgit, Tramacet, Tramadin, Ultracet, Ultram, Zamadol and Zydol.

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Useful treatments for fibromyalgia syndrome
From Journal of Family Practice, 2/1/05

* CLINICAL QUESTION

What treatment modalities are most effective for fibromyalgia syndrome?

* BOTTOM LINE

Treatments for fibromyalgia syndrome with the strongest evidence for efficacy include amitriptyline (Elavil), cyclobenzaprine (Flexeril), exercise, cognitive behavioral therapy, patient education, and multidisciplinary therapy. (Level of evidence [LOE]=1a-)

* STUDY DESIGN

Meta-analysis (other)

* SETTING

Various (meta-analysis)

* SYNOPSIS

The optimal method for treating fibromyalgia syndrome is unclear. The investigators thoroughly searched multiple sources--including Medline, EMBASE, Science Citation Index, and the Cochrane Collaboration--for trials evaluating the effectiveness of treatment for fibromyalgia syndrome. A total of 505 articles were reviewed and classified according to their level of evidence. The authors don't state whether the articles were reviewed independently and do not discuss the potential for publication bias.

Evidence was ranked as strong (positive results from a meta-analysis or consistent results from more than 1 randomized controlled trial [RCT]), moderate (positive results from 1 RCT or mostly positive results from multiple RCTs or consistently positive results from non-RCT studies), or weak (positive results from descriptive and case studies, inconsistent results from RCTs, or both).

Strong evidence for efficacy was found for treatment with amitriptyline, cyclobenzaprine, exercise, cognitive behavioral therapy, and patient education. Modest evidence for efficacy was found for tramadol (Ultram), various selective serotonin reuptake inhibitors, acupuncture, hypnotherapy, and biofeedback. Weak evidence for efficacy was found for growth hormone therapy, SAM (S-adenosyl-methionine), chiropractic and massage therapy, electrotherapy, and ultrasound. No evidence of any evaluation or effectiveness was found for steroids, nonsteroidal anti-inflammatory drugs, melatonin, benzodiazepine hypnotics, or trigger-point injections.

Goldenberg DL, Burchhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA 2004; 292:2388-2395.

COPYRIGHT 2005 Dowden Health Media, Inc.
COPYRIGHT 2005 Gale Group

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