Oxycodone

For thousands of years, opioids have been used to treat pain, and they continue to be one of the most commonly prescribed medications for pain. It is estimated that 90% of patients presenting to pain centers and receiving treatment in such facilities are on opioids. Opioids can be considered broad-spectrum analgesics that act at multiple points along the pain pathway. Unfortunately, opioids also have the potential for great harm, with multiple side effects and potential complications, some of which are lethal. They are also uniquely addictive, which can lead to misuse and diversion. We reviewed the relevant English literature and did thorough manual searches of the bibliographies of known primary and review articles. We utilized pain relief as the primary outcome measure. Other outcome measures were functional improvement, improvement of psychological status, improvement in work status, and evidence of addiction. Short-term use and improvement was defined as less than 6 months and l...

Objective: Emerging data are demonstrating that tamper-resistant opioids may play an important role in changing prescription opioid abuse behaviors. This study was a chart review to examine if the reformulation of OxyContin ® into a version with tamper-resistant properties (OxyNEO ®) had an impact on oxycodone-positive urine drug screens (UDSs) in opioid-dependent patients receiving methadone maintenance therapy (MMT). Design: The historical element of this study examined 250 eligible charts from patients on MMT who had data during the time periods when only OxyContin was available (baseline period), during the transition to OxyNEO, and when only OxyNEO was available. The prospective element included an exploratory questionnaire regarding retrospective opioid use. Setting: The study was conducted at three methadone clinics, in Oshawa, Peterborough, and Scarborough in Ontario, Canada. Participants: Male and female patients were eligible if they had a diagnosis of opioid dependency, received MMT, and had at least one oxycodone-positive UDS during the baseline period. Intervention: This was a noninterventional study. Main outcome measure: The main outcome was the number of oxycodone-positive UDSs. Results: The results demonstrated a marked reduction in oxycodone-positive UDSs that showed stepwise, statistically significant decreases during the transition and post-OxyContin periods relative to baseline. While the oxycodone-positive UDS results were decreasing, morphine-related-positive UDSs remained relatively stable during the same periods. There were no significant gender differences noted. Conclusions: The introduction of OxyNEO was associated with a statistically significant reduction in oxycodone exposure in a population of methadone-maintained patients.

OxyContin (Purdue Pharma L.P., Stamford, Conn) was approved by the Food and Drug Administration (FDA) in 1995 as a sustained-release preparation of oxycodone hydrochloride and was thought to have much lower abuse potential than immediate-release oxycodone because of its slow-release properties. However, beginning in 2000, widespread reports of OxyContin abuse surfaced. In response, Purdue Pharma L.P. sponsored the development of a proactive abuse surveillance program, named the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system. In this paper, we describe results obtained from one aspect of RADARS--the use of drug abuse experts (ie, key informants)--as a source of data on the prevalence and magnitude of abuse of prescription drugs. The results indicate that prescription drug abuse has become prevalent, with cases reported in 60% of the zip codes surveyed. The prevalence of abuse was rank ordered as follows: OxyContin >or= hydrocodone > other oxycodone > methadone > morphine > hydromorphone > fentanyl > buprenorphine. In terms of the magnitude of abuse (>or=5 cases/100,000 persons in a 3-digit zip code), modest growth was seen with all analgesics over the 10 calendar quarters we monitored, but was most pronounced with OxyContin and hydrocodone. These results indicate that OxyContin abuse is a pervasive problem in this country, but that it needs to be considered in the context of a general pattern of increasing prescription drug abuse. Over the past 5 years, there have been reports, frequently anecdotal, that opioid analgesic abuse has evolved into a national epidemic. In this study, we report systematic data to indicate that opioid analgesic abuse has in fact increased among street and recreational drug users, with OxyContin and hydrocodone products the most frequently abused. Steps need to be taken to reduce prescription drug abuse, but very great care needs to be exercised in the nature of these actions so the legitimate and appropriate use of these drugs in the treatment of pain is not compromised as a result.

The modern approach to the management of pain involves optimizing all aspects of the process. This includes utilization of pharmacologic and non-pharmacologic modalities, consideration of patient characteristics, proper matching of the physiology of the pain with the analgesic's mechanism of action (pharmacodynamics, PD), and the onset and duration of action (pharmacokinetics, PK). No single agent or formulation satisfies all of the requirements for all patients. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are effective options for inflammatory pain and, as is acetaminophen, for mild pain. Specialized agents are helpful for particular pains, such as for migraine headache. Opioids remain the standard option for severe pain. Although they are generally a safe and effective option, opioids can produce dose-limiting adverse effects and have abuse potential. The goal of pain therapy is thus to achieve the maximum pain relief with the least amount of opioid exposu...

Abstract:  In recent years, drugs including flunitrazepam, gamma-hydroxybutyrate, ketamine, and ethanol, have become popularly associated with drug-facilitated sexual assault. Other drugs are also candidates as factors in “drug facilitated sexual assault” (DFSA). The true extent of DFSA is not known, and is difficult to estimate. We recruited sexual assault complainants at four clinics in different parts of the U.S. to anonymously provide urine and hair specimens, and to answer questions about suspected drugging, drug use, and the sexual assault incident. Urine and hair specimens were tested for 45 drugs, including ethanol, and those pharmacologically capable of inducing sedation, amnesia, or impairment of judgment. Analytical test results were used to estimate the proportion of subjects, and the proportion of all complainants to the clinic in the same time period, who were victims of DFSA. Overall, cases of 43% of 144 subjects, and 7% of 859 complainants, were characterized as DFSA. Subjects underreported their use of drugs. The role of toxicological results and history in characterizing DFSA cases is discussed.

The Transient Receptor Potential (subfamily M, member 8), TRPM8, is a non-selective cation channel localized in primary sensory neurons and a candidate for cold thermosensing, mediation of cold pain and bladder over-activity. Studies with TRPM8 knock-out mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models (Xing et al., 2007; Su et al., 2011). Furthermore, TRPM8 blockers significantly lower body temperature (Gavva et al., 2012; Almeida et al., 2012). We have identified a moderately potent (IC50 = 103nM), selective TRPM8 antagonist PF-05105679 ((R)-3-[(1-(4-Fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid) WO/2012/120398). It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200nM and also reduced core body temperature in the rat (at concentrations >1219nM). PF-05105679 was suitable for acute administration to humans and was evalu...

A case is presented of a fatal drug interaction caused by ingestion of oxycodone (Oxycontin) and clonazepam (Klonapin). Oxycodone is an opium alkaloid used in long-term pain management therapy. Clonazepam is a benzodiazepine used for the treatment of seizures and panic disorders. The Drug Abuse Warning Network (DAWN) has reported an increase of 108% in the last two years of emergency department episodes related to Oxycontin. Six billion prescriptions were written for Oxycontin in the year 2000, an 18-fold increase from four years previous (1). Oxycontin has recently gained enormous notoriety at the local and national levels; however, there are very few previously documented cases of lethal drug interactions between oxycodone and clonazepam. Synergistic effects between these two drugs are postulated to arise from different agonistic mechanisms producing similar physiological changes. It is also theorized that clonazepam may inhibit the metabolism of oxycodone. A 38-year-old white fem...

Our previous studies indicate that oxycodone is a putative kappa-opioid agonist, whereas morphine is a well documented micro-opioid agonist. Because there is limited information regarding the development of tolerance to oxycodone, this study was designed to 1) document the development of tolerance to the antinociceptive effects of chronically infused i.v. oxycodone relative to that for i. v. morphine and 2) quantify the degree of antinociceptive cross-tolerance between morphine and oxycodone in adult male Dark Agouti (DA) rats. Antinociceptive testing was performed using the tail-flick latency test. Complete antinociceptive tolerance was achieved in 48 to 84 h after chronic infusion of equi-antinociceptive doses of i.v. oxycodone (2.5 mg/24 h and 5 mg/24 h) and i.v. morphine (10 mg/24 h and 20 mg/24 h, respectively). Dose-response curves for bolus doses of i.v. and i.c.v. morphine and oxycodone were produced in naive, morphine-tolerant, and oxycodone-tolerant rats. Consistent with o...

The effect of intrapleural bupivacaine in the treatment of post–thoracotomy pain was evaluated. Bupivacaine, 0.5% 20 ml, with adrenaline (5 μg/ml) was given through an indwelling intrapleural catheter, at 4–h intervals four times daily for 2 days. No pleural suction was applied during and 10 min after each injection. A control group received intramuscular oxycodone on request. A visual analogue scale (VAS), a pain questionnaire (PQ) and registration of the need for supplementary analgesics were used for the assessment of postoperative analgesia. Blood–gas analyses showed elevated Pacoz values in both groups on the day of operation and on the first postoperative day, without differences between the groups. Plasma concentrations of bupivacaine did not reach toxic values, and no symptoms of central nervous toxicity or any other untoward reactions were found during the study period. Clinically, there was some pain relief after the intrapleural bupivacaine. The VAS and PQ scores 30 min after bupivacaine instillations diminished to an extent similar to that after oxycodone treatment. The need for analgesics during the day of operation was less in the bupivacaine group than in the control group (P < 0.001). The number of oxycodone supplementation doses during 48 h postoperatively was, however, not smaller in the bupivacaine group than in the control group.

This study&amp;#39;s purpose was to determine the effectiveness of adding a preoperative interscalene brachial plexus block to standard postoperative management, including oral narcotics and a subacromial bupivacaine infusion pump, after arthroscopic shoulder surgery. After performing a prospective power analysis and obtaining institutional board approval, we conducted a randomized placebo-controlled trial of 53 patients separated into a preoperative interscalene brachial plexus group and a control group. Group 1 received an interscalene block with 30 mL of 0.5% ropivacaine. Group 2 received a placebo with 10 mL of saline solution. All patients postoperatively received an arthroscopically placed subacromial infusion pump catheter for 72 hours and oral narcotics. Pain scores on a visual analog scale (VAS) and narcotic pill use were recorded at 6, 12, 20, 32, 40, 52, 60, 72, and 80 hours. Preoperative pain scores between groups were not significant (P &amp;gt; .05). A statistically significant difference was found for decreased pain scores at 6 hours after discharge in patients receiving an interscalene block (P = .001) (VAS of 30.9 in group 1 v 61.8 in group 2). There was also a decrease in the number of narcotic pills taken at the 6-hour time interval (P = .1) (0.6 pills v 1.1 pills). Group 1 had a rebound phenomenon 20 hours after discharge. Pain scores spiked as the effects of the block wore off (P = .08) (net change in VAS score increase, 25.0 v 10.3). No other statistical or clinical differences were observed. The addition of a preoperative interscalene block to a postoperative subacromial infusion pump provided significant improvement of pain control only at 6 hours after discharge. Twelve hours after discharge, this benefit had disappeared. A rebound phenomenon of increased pain at 20 hours was seen after the interscalene block had worn off. After 20 hours, no statistically significant or clinically applicable differences were found. Level I, randomized controlled trial.

To quantify the potential impact of reductions in positive subjective measures from human abuse liability studies on real-world rates of nonmedical use of prescription drugs and associated healthcare resource utilization and costs. Positive subjective endpoints &quot;overall drug liking,&quot; in-the-moment &quot;drug liking,&quot; and &quot;drug high&quot; Emaxs (peak effects) were recorded from published studies. Nonmedical use data were obtained from the 2010 National Survey on Drug Use and Health (NSDUH) and Drug Abuse Warning Network surveys. Multivariate regressions evaluated the association between the positive subjective endpoints and nonmedical use rates, controlling for prescription volume, whether the drug is an opioid, and controlled substance schedule. A published budget-impact model was used to assess healthcare resource utilization and cost impacts of abuse-deterrent opioid formulations. A five-point reduction in overall drug liking/drug liking/drug high Emax was asso...

Objective  Oxycodone is widely used for the treatment of cancer pain, but little is known of its pharmacokinetics in cancer pain patients. The aim of this study was to explore the relationships between ordinary patient characteristics and serum concentrations of oxycodone and the ratios noroxycodone or oxymorphone/oxycodone in cancer patients. Methods  Four hundred and thirty-nine patients using oral oxycodone for cancer pain

The utilization of high-potency opioids is an important component of chronic pain management, and appropriate utilization of these medicines is a common concern of payers. Two of the most commonly prescribed oral long-acting opioids, oxycodone controlled-release (CR) and oxymorphone extended-release (ER), are FDA-approved for twice-daily dosing, which equates to a theoretical average consumption (DACON) of 2 tablets per day. DACON values greater than 2 have budget and policy implications for managed care pharmacists. To assess from the perspective of the pharmacy benefit decision maker the DACONs of oxycodone CR and oxymorphone ER. The main outcome measure for the analysis was DACON. Pharmacy and medical claims data from a large commercially insured population (i3 InVision Data Mart database) were analyzed to identify patients with at least 1 pharmacy claim for either oxycodone CR or oxymorphone ER from July 1, 2007, to September 30, 2009. After an initial 30-day titration period, a...