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.

Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives.

Lotsch J, Skarke C, Liefhold J, Geisslinger G.

Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. j.loetsch@em.uni-frankfurt.de

This review uses a candidate gene approach to identify possible pharmacogenetic modulators of opioid therapy, and discusses these modulators together with demonstrated genetic causes for the variability in clinical effects of opioids.Genetically caused inactivity of cytochrome P450 (CYP) 2D6 renders codeine ineffective (lack of morphine formation), slightly decreases the efficacy of tramadol (lack of formation of the active O-desmethyl-tramadol) and slightly decreases the clearance of methadone. MDR1 mutations often demonstrate pharmacogenetic consequences, and since opioids are among the P-glycoprotein substrates, opioid pharmacology may be affected by MDR1 mutations. The single nucleotide polymorphism A118G of the mu opioid receptor gene has been associated with decreased potency of morphine and morphine-6-glucuronide, and with decreased analgesic effects and higher alfentanil dose demands in carriers of the mutated G118 allele. Genetic causes may also trigger or modify drug interactions, which in turn can alter the clinical response to opioid therapy. For example, by inhibiting CYP2D6, paroxetine increases the steady-state plasma concentrations of (R)-methadone in extensive but not in poor metabolisers of debrisoquine/sparteine.So far, the clinical consequences of the pharmacogenetics of opioids are limited to codeine, which should not be administered to poor metabolisers of debrisoquine/sparteine. Genetically precipitated drug interactions might render a standard opioid dose toxic and should, therefore, be taken into consideration. Mutations affecting opioid receptors and pain perception/processing are of interest for the study of opioid actions, but with modern practice of on-demand administration of opioids their utility may be limited to explaining why some patients need higher opioid doses; however, the adverse effects profile may be modified by these mutations. Nonetheless, at a limited level, pharmacogenetics can be expected to facilitate individualised opioid therapy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15530129&query_hl=2

Opioid neurotoxicity: comparison of morphine and tramadol in an experimental rat model.

Atici S, Cinel L, Cinel I, Doruk N, Aktekin M, Akca A, Camdeviren H, Oral U.

Department of Anesthesiology & Reanimation, Mersin University School of Medicine, Mersin, Turkey. atici@mersin.edu.tr

Histopathologic changes in rat brain due to chronic use of morphine and/or tramadol in progressively increased doses were investigated in this study. Thirty male Wistar rats (180-220 g) were included and divided into three groups. Normal saline (1 ml/kg) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4 mg/kg/day for the first 10 days, 8 mg/kg/day between 11-20 days, and 12 mg/kg/day between 21-30 days. The tramadol group (n = 10) received the drug intraperitoneally at doses of 20, 40, and 80 mg/kg/day in the first, second, and the third 10 days of the study, respectively. All rats were decapitated on the 30th day and the brain was removed intact for histology. The presence and the number of red neurons, which are a histologic marker of apoptosis, were investigated in the parietal, frontal, temporal, occipital, entorhinal, pyriform, and hippocampal CA1, CA2, CA3 regions. Red neurons were found in morphine and tramadol groups but not in the control group. The total number of red neurons was not different in morphine and tramadol groups, but the numbers of red neurons were significantly higher in the temporal and occipital regions in tramadol group as compared with the morphine group (p < .05). In conclusion, chronic use of morphine and/or tramadol in increasing doses is found to cause red neuron degeneration in the rat brain, which probably contributes to cerebral dysfunction. These findings should be taken into consideration when chrome use of opioids is indicated.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15527204&query_hl=2

Probable ischemic colitis caused by pseudoephedrine with tramadol as a possible contributing factor.

Traino AA, Buckley NA, Bassett ML.

The Prince of Wales Hospital, Randwick, Sydney, Australia.

OBJECTIVE: To report a case of acute self-limiting ischemic colitis in a patient who was self-medicating with a proprietary over-the-counter oral decongestant containing pseudoephedrine. CASE SUMMARY: A 46-year-old white man developed clinical, endoscopic, and histologic features of acute ischemic colitis after taking a proprietary oral decongestant containing pseudoephedrine 240 mg/day for one week. The total daily dose was at the upper limit of recommended doses for pseudoephedrine (as a single drug or in combination products). The patient was also taking tramadol 150 mg/day for chronic back pain. He made a complete recovery. There were no other explanations for the episode of ischemic colitis. DISCUSSION: An objective causality assessment based on the Naranjo probability scale revealed pseudoephedrine to be a probable cause of ischemic colitis in our patient. Pseudoephedrine occasionally causes vascular insufficiency due to intense vasoconstriction, even at standard doses. Although our patient was not taking an excessive dose of pseudoephedrine, it is possible that the concurrent use of pseudoephedrine and tramadol may have increased adrenergic vasoconstriction, predisposing to ischemic colitis. CONCLUSIONS: Prolonged or intensive use of medications containing pseudoephedrine should be avoided, and the package information should contain advice that the medication should be ceased if abdominal pain or other ischemic symptoms occur.

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