Abstract
The antinociceptive effect of morphine and oxycodone is mediate preferentially at and κ receptors. Respectively. This study aime to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain. Buy Oxycodone online compare to the standard administration of morphine alone.
Controll-release formulations of oxycodone (CRO) and morphine (CRM) were compare in 26 patients. The study start with an open-label randomize titration phase to achieve stable pain control for seven days. follow by a double-mask. Randomize crossover phase in two periods. 14 days each. At any point.
patients were allow to use oral immediate-release morphine (IRM) as need to keep the visual analog scale ⩽4. Pain, satisfaction. adverse effects. And number of daily rescue morphine tablets were assess. A total of 22 patients were evaluate. The weekly upload consumption ratio in morphine/oxycodone was 1: 1.8 (1.80, 1.83, 1.76, 1.84). The weekly IRM consumption was higher in patients have CRM compare to patients have CRO (ratio morphine/oxycodone: 1.6, 1.6, 1.6, 1.7) (P<0.05).
Patients receive oxycodone complain of less nausea and vomiti. The rescue morphine analgesic consumption was 38% higher in patients receive only morphine than patients receive g morphine and oxycodone. The results suggest that combine morphine/oxycodone (opioids with differential preferential sites of action) can be a valuable alternative to morphine alone, result in a better analgesia profile and less emesis.
Materials and methods
The Ethical Committee of the University of São Paulo’s Teach Hospital, Ribeirão Preto, approv the study protocol. Controll-release formulations of oxycodone and CRM were evaluate in 26 patients with chronic cancer pain of the visceral and somatic type (either oropharynx, lung, colon, gastric, ovary, or prostate gland, as describe in Table 1) after inform consent of the patients.
The visual analog scale (VAS) consist of a 10 cm line with 0 equal ‘no pain at all’ or ‘no nausea,’ and ten equalling ‘the worst possible pain’ or ‘worst possible nausea’ was introduced previously. Before enrolling in this study, patients receive 3–4 mg kg−1 tramadol, plus nonsteroidal anti-inflammatory drugs; however.
They still complain of pain VAS ⩾4 cm. As part of the protocol. all patients took oral 25 mg amitriptyline at bedtime. The study start with an open-label, randomize titration phase to achieve seven-day pain control. At this initial phase. Patients use only IRM and had free access to it to keep pain VAS <4 cm. After stable pain relief.
This was follow by a double-mask crossover phase in two periods. 14 days each. Each patient acts as their control to minimize the interindividual variability of response in this group of patients. And no period of washout was allow for ethical reasons. Patients did not know which treatment they were enroll in at this phase. The optimum opioid dosage was calculate daily. and the consumption ratio of oxycodone to morphine was set at 1 1.8 as part of the study protocol.
Discussion
The study’s results have demonstrated that patients suffering from cancer pain receiving the combination of morphine and oxycodone consumed significantly fewer escape doses of IRM, which was 38% higher in patients receiving morphine only. The data suggest that the combination of morphine/oxycodone (Ross and Smith, 1997; Nielsen et al., 2000) can be a valuable alternative to morphine alone, resulting in a better analgesia profile by animal studies.
Coadministration of sub-antinociceptive doses of oxycodone with morphine to rats by both intracerebroventricular and systemic routes (intraperitoneal and subcutaneous) resulted in synergistic levels of antinociception (Ross et al., 2000). Behaviourally, rats coadministered sub-antinociceptive doses of oxycodone and morphine were not different from control rats related to sedation while showing antinociception (Ross et al., 2000).
Under the World Health Organisation guidelines for cancer pain relief, when initiating treatment, controlled-release preparations of opioids are generally favored. They are combined with IRM to prevent or treat breakthrough pain.
Method
Despite the preferential action at κ receptors (Ross and Smith, 1997; Nielsen et al., 2000), oxycodone is an opioid analgesic that closely resembles morphine.
morphine, the active metabolite of oxycodone, is formed in a reaction catalyzed by the cytochrome isoenzyme CYP2D6, Buy Oxycodone which is under polymorphic genetic control and severely impaired by liver dysfunction. However, the role of oxymorphone in the analgesic effect of oxycodone is not yet clear (Heiskanen et al., 2000).
Although gender differences exist in response to oxycodone either due to pharmacodynamics or differences in metabolism related to reduced CYP2D6 in females (Davis et al., 2003), in the present study, each patient participated in both study groups and acted as their control, minimizing any analgesic tendency in the female population. In addition, an unidentified metabolite other than oxymorphone appears to be a potent μ agonist (Poyhia et al., 1993), and the intrinsic efficacy of oxycodone that may not correlate with binding affinity is not known (Duttaroy and Yoburn, 1995).
