Tramadol drug is used for pain relief
Tramadol (generic for Ultram) is a prescription medication used for the management of moderate to moderately severe pain. Tramadol® has been prescribed to more than 55 million patients worldwide; Ultram® has been prescribed to more than 21 million patients in the U.S.

The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acidA, and N-methyl-D-aspartate receptors expressed in Xenopus oocytes.

Hara K, Minami K, Sata T.

Department of Anesthesiology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan. kojihara@med.uoeh-u.ac.jp

We assessed the effects of tramadol, a centrally acting analgesic, and its major metabolite, on neurotransmitter-gated ion channels. Tramadol binds to mu-opioid receptors with low affinity and inhibits reuptake of monoamines in the central nervous system. These actions are believed to primarily contribute to its antinociceptive effects. However, little is known about other sites of tramadol's action. We tested the effects of tramadol and its M1 metabolite (0.1-100 microM) on human recombinant neurotransmitter-gated ion channels, including glycine, gamma-aminobutyric acid(A) (GABA(A)), and N-methyl-D-aspartate (NMDA) receptors, expressed in Xenopus oocytes. Tramadol and M1 metabolite did not have any effects on glycine receptors. GABA(A) receptors were significantly inhibited only at large concentrations (100 microM). NMDA receptors were inhibited in a concentration-dependent manner. Tramadol and M1 metabolite inhibited the glutamate-concentration response curve without changing the half-maximal effective concentration or the Hill coefficient, indicating a noncompetitive inhibition. This study suggests that glycine receptors do not provide the antinociceptive effect of tramadol and that the inhibition of GABA(A) receptors at large concentration might correlate with convulsions. The inhibitory effect on NMDA receptors may contribute to the antinociceptive effect of tramadol at relatively large concentrations.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15845694&query_hl=2

[Side effects of tramadol: 12 years of experience in the Netherlands]

[Article in Dutch]

Kabel JS, van Puijenbroek EP.

Nederlands Bijwerkingen Centrum Lareb, Goudsbloemvallei 7, 5237 MH 's-Hertogenbosch. j.kabel@lareb.nl

Tramadol is a synthetic opioid that has been available in the Netherlands since 1992 and is usually used as a centrally-acting analgesic when paracetamol or an NSAID provides insufficient relief. In the period 1 January 1992--30 November 2003, the Netherlands Pharmacovigilance Centre Lareb received 299 reports concerning 522 adverse drug reactions associated with the use of tramadol. Some of the frequently reported side effects with a high reporting odds ratio were nausea, constipation and withdrawal symptoms. These side effects are very similar to those of the other opioids due to the affinity of tramadol for the micro-opioid receptor. Because tramadol is often not recognised as an opioid, it is important that such opiate effects be recognised as an adverse drug reaction on time.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15835626&query_hl=2

Tramadol produces outward currents by activating mu-opioid receptors in adult rat substantia gelatinosa neurones.

Koga A, Fujita T, Totoki T, Kumamoto E.

[1] 1Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan [2] 2Department of Anesthesiology & Critical Care Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.

An action of a tramadol metabolite, mono-O-dimethyl-tramadol (M1), on substantia gelatinosa (SG) neurones in adult rat spinal cord slices was examined by using the whole-cell patch-clamp technique.In 41% of the neurones examined, superfusing M1 produced an outward current at -70 mV; this response reversed at a potential close to the equilibrium potential for K(+). M1 current hardly declined and persisted for >30 min after its washout.M1 current correlated in amplitude with current produced by mu-opioid receptor agonist DAMGO in the same neurone, and largely reduced in amplitude in the presence of mu-opioid receptor antagonist CTAP but not alpha2-adrenoceptor antagonist yohimbine. In a neurone where M1 had no effect on holding currents, noradrenaline produced an outward current at -70 mV.The amplitude of the M1 response, relative to that of the DAMGO response, exhibited an EC(50) value of 300 muM.We conclude that M1 produces a persistent hyperpolarization by activating mu-opioid receptors in adult rat SG neurones. This could contribute to at least a part of pain alleviation produced by tramadol.British Journal of Pharmacology advance online publication, 18 April 2005; doi:10.1038/sj.bjp.0706225.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15834442&query_hl=2

Appropriate use of medicines in patients with rheumatoid arthritis, osteoarthritis and osteoporosis--pharmacists' role]

[Article in French]

Spinewine A.

Aspirante FNRS, Universite catholique de Louvain, Bruxelles. anne.spinewine@facm.ucl.ac.be

The care of patients with osteoarthritis, rheumatoid arthritis and osteoporosis often requires a pharmacologic approach. The co-prescription of several medicines is regularly needed in order to optimise treatment. Several recent studies, however, have identified instances of inappropriate medicines use in these patients. This mainly includes "misuse" (inappropriate medicines use in terms of dosing, choice of drug, treatment modalities, treatment duration, interactions,...) and "underuse" (omission of drug therapy that is indicated for the treatment or prevention of a disease or condition). The following examples are discussed: insufficient or inappropriate pain control, use of codeine and tramadol in CYPD2D6 poor metabolisers, underuse or delayed use of disease-modifying anti-rheumatic drugs, medication errors with methotrexate, underuse of medicines for the treatment of osteoporosis. By being aware of these events of inappropriate medicines use, the pharmacist should be better able to deliver pharmaceutical care to these patients. The aim is to improve patients' quality of life.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15828488&query_hl=2

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