Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column. These compounds have a very similar chemical structure to morphine. Unlike morphine, which is metabolized chiefly through conjugation reactions with uridine diphosphate glucuronosyl transferase (UGT) enzymes, these five drugs are metabolized both through oxidative reactions by the cytochrome P450 (CYP450) enzyme and conjugation by UGT enzymes. There is controversy as to whether codeine, dihydrocodeine, and hydrocodone are actually prodrugs requiring activation by the CYP450 2D6 enzyme or UGT enzymes. Oxycodone and buprenorphine, however, are clearly not prodrugs and are metabolized by the CYP450 2D6 and 3A4 enzymes, respectively. Knowledge of this metabolism assists in the understanding for the potential of drug-drug interactions with these drugs. This understanding is important so that clinicians can choose the proper dosages for analgesia and anticipate potential drug-drug interactions.
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PMID:Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II. 1459 88

Studies addressing pain management after pediatric spinal fusion surgery have focused on the use of patient-controlled or epidural analgesia during the immediate postoperative period. Controlled-release (CR) analgesics have been found to be safe and effective in adults. The purpose of this study was to describe the use of oxycodone-CR in pediatric patients after the immediate postoperative period. A retrospective chart review of 62 postoperative spinal fusion patients (10-19 years) was conducted. The mean initial oxycodone-CR dose was 1.24 mg/kg/day. The mean ratio of conversion from parenteral morphine equivalents to oxycodone-CR was 1:1. Mean pain scores decreased from 4.2/10 to 3.7/10 with the transition to oxycodone-CR. Common side effects included dizziness, constipation, and nausea. Oxycodone-CR was used for an average of 13.3 days, which included an average wean time of 6 days. Results of this study demonstrate safe and effective use of oxycodone-CR in the pediatric spinal fusion population.
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PMID:Controlled-release oxycodone for the management of pediatric postoperative pain. 1511 83

Our objective in this study was to compare the analgesic effects of etoricoxib and oxycodone/acetaminophen in a postoperative dental pain model. Patients experiencing moderate to severe pain after extraction of two or more third molars were randomized to single doses of etoricoxib 120 mg (n = 100), oxycodone/acetaminophen 10/650 mg (n = 100), or placebo (n = 25). The primary end-point was total pain relief over 6 h. Other end-points included patient global assessment of response to therapy; onset, peak, and duration of effect; and rescue opioid analgesic use. Active treatments were statistically significantly superior to placebo for all efficacy measures. Total pain relief over 6 h for etoricoxib was significantly more than for oxycodone/acetaminophen (P < 0.001). Patient global assessment of response to therapy at 6 and 24 h was superior for etoricoxib. Both drugs achieved rapid onset, although the time was faster for oxycodone/acetaminophen by 5 min. The peak effect was similar for both drugs. Compared with oxycodone/acetaminophen patients, etoricoxib patients experienced a longer analgesic duration, had a smaller percentage requiring rescue opioids during 6 and 24 h, and required less rescue analgesia during 6 and 24 h. Oxycodone/acetaminophen treatment resulted in more frequent adverse events (AEs), drug-related AEs, nausea, and vomiting compared with etoricoxib treatment. In conclusion, etoricoxib 120 mg provided superior overall efficacy compared with oxycodone/acetaminophen 10/650 mg and was associated with significantly fewer AEs.
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PMID:The analgesic efficacy of etoricoxib compared with oxycodone/acetaminophen in an acute postoperative pain model: a randomized, double-blind clinical trial. 1533 15

Postpartum bilateral tubal ligation (PPBTL) causes postoperative pain. We designed this study to determine the efficacy of 50 microg intrathecal morphine for analgesia after PPBTL. Sixty-five women received spinal anesthesia with 12.75 mg hyperbaric bupivacaine, 20 microg of fentanyl, and either 50 microg of morphine (morphine group) or 0.05 mL of saline (control group). Postoperative analgesia was provided with regular naproxen 500 mg and oxycodone 5 mg/acetaminophen 325 mg mixture as needed. Overall, satisfaction was higher (P=0.003) and pain was less intense at rest (P=0.008) and on movement (P <0.0001) in the morphine group. There was no significant overall difference in nausea, pruritus, or sedation scores, but vomiting occurred more frequently in the morphine group (21.4% versus 3.5%; P=0.052). In post hoc comparisons, pain at rest within the morphine group was significantly less at 4 h (P=0.006), pain on movement was significantly less at 4 h (P=0.002) and 12 h (P=0.0004), and pruritus was significantly more frequent at 12 h (P=0.002) compared with the control group. Oxycodone 5 mg/acetaminophen 325 mg mixture consumption was significantly smaller (P=0.006) and the time to first request of analgesia was significantly longer (P=0.006) in the morphine group. We conclude that the addition of 50 microg of morphine to intrathecal hyperbaric bupivacaine and fentanyl provides improved postoperative analgesia in women undergoing PPBTL.
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PMID:Intrathecal morphine for analgesia after postpartum bilateral tubal ligation. 1603 93

Oxycodone/ibuprofen 5 mg/400 mg (Combunox) is an oral fixed-dose combination tablet with analgesic, anti-inflammatory and antipyretic properties. It is approved in the US for the short-term (up to 7 days) management of acute, moderate-to-severe pain and is the first and only fixed-dose combination containing ibuprofen and oxycodone. A single dose of oxycodone/ibuprofen 5 mg/400 mg provided better analgesia than low-dose oxycodone or ibuprofen administered alone in most trials and appears to be more effective than a single dose of some other fixed-dose combination analgesics. It is generally well tolerated after single or multiple doses and short-term use is not expected to produce any of the serious adverse effects typically associated with the long-term use of opioids or NSAIDs. Thus, oxycodone/ibuprofen 5 mg/400mg is an effective, convenient treatment option for the short-term management of acute, moderate-to-severe pain.
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PMID:Oxycodone/Ibuprofen combination tablet: a review of its use in the management of acute pain. 1626 3

Intravenous lidocaine, a nonspecific Na-channel blocker, was used to assess the dental impaction model for evaluation of neuropathic pain drugs. Sixty patients, experiencing moderate or severe pain after removal of > or = 2 third molars, were randomized (2:2:1:1) to lidocaine (4 mg/kg; maximal dose 300 mg), oxycodone/acetaminophen (10/650 mg), placebo, and active placebo (diphenhydramine, 50 mg). Lidocaine provided a modest degree of pain relief. Predefined endpoints of total pain relief and sum of pain intensity at 2, 4, and 6 hours showed numerically, not statistically significantly, greater pain relief versus placebo. A significantly greater effect over placebo was observed in peak effect and at shorter time points (30 minutes and 1 hour), consistent with the pharmacokinetic profile (plasma concentration of approximately 2 mug/mL). Oxycodone/acetaminophen provided significantly greater analgesia versus placebo, validating study conduct, and significantly greater pain relief was observed versus lidocaine, which is consistent with a smaller portion of dental extraction pain being of neuropathic origin.
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PMID:Dental impaction pain model as a potential tool to evaluate drugs with efficacy in neuropathic pain. 1685 76

Postoperative pain is now a critical focus of perioperative patient care. The current perioperative analgesic strategy is a "balanced-multimodal analgesia". Cornerstones of this treatment approach are patient controlled neuraxial administration of local anesthetics and opioids or patient controlled intravenous administration of opioids. However, systemic opioids are limited by side effects. Thus, adjuvants like anticonvulsants, NMDA receptor antagonists, alpha-2 adrenergic agonists and other non-Opioid analgesics are considered to reduce pain and opioid requirements in the perioperative period. In the present review we discuss recent findings about the effectiveness of different systemic administered adjuvants including ketamine, lidocaine, gabapentin, pregabalin and corticosteroids for postoperative pain treatment. Furthermore a nurse based oral analgesic concept using controlled released Oxycodon for all postoperative patients without a patient controlled analgesia device will be introduced.
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PMID:[Systemic analgesia: an update]. 1725 34

Oral opioids are the treatment of choice for chronic cancer pain. Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines from the World Health Organization (WHO). This recommendation by the WHO was derived from availability, familiarity to clinicians, established effectiveness, simplicity of administration, and relative inexpensive cost. It was not based on proven therapeutic superiority over other options. Patients who experience inadequate pain relief or intolerable side effects with one opioid may often be successfully treated with another agent or with the same agent administered by a different route. Opioid rotation, or switching to an alternative opioid, helps some patients achieve better pain control with fewer associated adverse effects. Oxycodone is a mu-opioid receptor specific ligand, with clear agonist properties. It is an active potent opioid, which is in part a kappa-receptor agonist. Like morphine and other pure agonists, there is no known ceiling to the analgesic effects of oxycodone. The active metabolites of oxycodone (eg, oxymorphone) could be important in oxycodone-mediated analgesia. The main pharmacokinetic difference between oxycodone and morphine is in oral bioavailability. The bioavailability of oxycodone is >60% and the bioavailability of morphine is 20%. Controlled-release oxycodone is absorbed in a bi-exponential fashion. There is a rapid phase with a mean half-life of 37 min, accounting for 38% of the dose, and a slow phase with a half-life of 6.2 h, which accounts for the residual 62%. Oxycodone elimination is impaired by renal failure because there are both an increased volume of distribution and reduced clearance. A lot of studies prove that the efficacy of controlled-release oxycodone in cancer-pain control is at least the same as morphine, immediate-release oxycodone and hydromorphone. Its toxicity profile seems better than that of morphine. There are actually several illustrations of a lower incidence of side-effects in the central nervous system. It is therefore possible to conclude that oxycodone represents a valid alternative to morphine in the management of moderate to severe cancer pain, also as first-line treatment.
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PMID:Oxycodone controlled release in cancer pain management. 1836 May 98

Analgesia from most opioids is mediated by mu receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia. Twenty-four healthy subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal, and electrical pain tests were performed in the skin and viscera. Blood samples and pain measurements were taken at baseline and after 15, 30, 60, 90, and 120 minutes. Pharmacokinetic/pharmacodynamic profiles were modeled using a 2-stage, nonlinear, mixed-effects approach with an effect compartment to represent the concentration-analgesia delay. Morphine kinetics was best described by a 2-compartment model, whereas oxycodone kinetics was best described with a 1-compartment model. Generally the analgesic effects of morphine were best related to plasma concentration by introducing a delay via an effect compartment. However, for oxycodone, this was only the case for analgesia in the somatic pain measures, whereas the plasma concentration correlated better to the course of the analgesia with no delay in the visceral pain measures. Oxycodone and morphine showed different pharmacodynamic/pharmacokinetic relationships for the visceral analgesia, whereas relationships were alike for somatic analgesia.
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PMID:Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. 1844 Sep 21

Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P = 0.037, a difference of 10%, CI: 1%-20%) for PM compared with EM. In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM compared with EM (P < 0.001). Oxycodone analgesia seems to depend both on oxycodone itself and its metabolite oxymorphone.
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PMID:The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism. 1928


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