The efficacy of epidurally administered tramadol hydrochloride, a weak centrally acting analgesic, was studied for the relief of postoperative pain. Sixty patients undergoing abdominal surgery were randomly allocated to three treatment groups to be given the following agents by the epidural route: group 1 tramadol 50 mg; group 2 tramadol 100 mg; group 3 10 ml of bupivacaine 0.25%. The drugs were administered at the patients' request with each patient being allowed four doses in the first 24 h following surgery. Blood pressure, pulse rate, respiratory rate, arterial blood gas analyses, pain scores, the interval between doses and the occurrence of any side effects were recorded. Pain scores (assessed using a visual analogue scale) were significantly less (p < 0.05) at 3, 12, and 24 h in patients receiving tramadol 100 mg than in those receiving tramadol 50 mg or bupivacaine. The mean interval between doses for groups 1, 2 and 3 was 7.40 h, 9.36 h and 5.98 h respectively. The mean interval in group 2 was significantly longer than in group 3 (p < 0.05). The incidence of nausea and vomiting in group 2 was significantly higher than in group 3 (p < 0.05).
CYP2D6 polymorphisms show large geographical and interethnic differences. Variations in CYP2D6 activity may impact upon a patient's pain level and may contribute to interindividual variations in the response to opioids. This paper reviews the evidence on how CYP2D6 polymorphisms might influence pain sensitivity and clinical response to codeine and tramadol. For example, it is shown that (1) CYP2D6 poor metabolizers (PMs) may be less efficient at synthesizing endogenous morphine compared with other metabolizers. In contrast, ultra-rapid metabolizers (UMs) may be more efficient than other metabolizers at synthesizing endogenous morphine, thus strengthening endogenous pain modulation. Additionally, for codeine and tramadol that are bioactivated by CYP2D6, PMs may undergo no metabolite formation, leading to inadequate analgesia. Conversely, UMs may experience quicker analgesic effects but be prone to higher mu-opioid-related toxicity. The literature suggested the potential usefulness of the determination of CYP2D6 polymorphisms in elucidating serious adverse events and in preventing subsequent inappropriate selection or doses of codeine and tramadol. Notably, even though many studies investigated a possible role of the CYP2D6 polymorphisms on pain sensitivity, pharmacokinetics and pharmacodynamics of these drugs, the results of analgesia and adverse effects are conflicting. More studies are required to demonstrate genetically determined unresponsiveness and risk of developing serious adverse events for patients with pain and these should involve larger numbers of patients in different population types.