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Clinical Infectious Diseases : An... May 2019Although evidence from animal and human studies indicates opioid analgesics increase susceptibility to infections, it is unclear whether the risk varies by specific...
BACKGROUND
Although evidence from animal and human studies indicates opioid analgesics increase susceptibility to infections, it is unclear whether the risk varies by specific opioid. We compared the risk of serious infection among patients initiating long-acting opioid analgesics with and without previously reported immunosuppressive properties.
METHODS
We conducted a retrospective cohort study of Tennessee Medicaid enrollees age ≥18 years initiating long-acting opioids (1995-2015). Hospitalizations for serious infection were identified using validated coding algorithms. We used multivariable Poisson regression models to calculate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) to compare the infection risk among patients using long-acting opioids with known immunosuppressive properties (morphine, fentanyl, methadone) to the infection risk among patients using long-acting opioids without known immunosuppressive properties (oxycodone, oxymorphone, tramadol) accounting for demographics, opioid dose, comorbidities and pain conditions, medication use, frailty indicators, and healthcare encounter history using exposure propensity scores. We further compared users of individual long-acting opioids to long-acting morphine users (considered the prototypical immunosuppressive opioid).
RESULTS
Among the 61 240 patients initiating opioids with immunosuppressive properties and 22 811 patients initiating opioids without immunosuppressive properties, we identified 1906 serious infections. Nonimmunosuppressive opioid users had a lower rate of infections than immunosuppressive opioid users (aIRR:0.78 [CI: 0.66-0.91]). Among individual opioids, oxycodone users had a lower rate of infection than morphine users (aIRR:0.73 [CI: 0.60-0.89]). There were no significant differences in the infection risk between other opioids and morphine.
CONCLUSION
The risk of serious infections among long-acting opioid users varies by opioid type. Providers should carefully consider the risk of serious infections when making pain management decisions.
Topics: Adult; Aged; Analgesics, Opioid; Chronic Pain; Female; Fentanyl; Hospitalization; Humans; Immunosuppressive Agents; Infections; Male; Medicaid; Methadone; Middle Aged; Morphine; Opioid-Related Disorders; Retrospective Studies; Risk Factors; Tennessee; United States
PubMed: 30239630
DOI: 10.1093/cid/ciy809 -
Drug and Alcohol Dependence Sep 2018For a number of fiscal and practical reasons, data on heroin use have been of poor quality, which has hampered the ability to halt the growing epidemic. Internet search...
BACKGROUND
For a number of fiscal and practical reasons, data on heroin use have been of poor quality, which has hampered the ability to halt the growing epidemic. Internet search data, such as those made available by Google Trends, have been used as a low-cost, real-time data source for monitoring and predicting a variety of public health outcomes. We aimed to determine whether data on opioid-related internet searches might predict future heroin-related admissions to emergency departments (ED).
METHODS
Across nine metropolitan statistical areas (MSAs) in the United States, we obtained data on Google searches for prescription and non-prescription opioids, as well as Substance Abuse and Mental Health Services Administration (SAMHSA) data on heroin-related ED visits from 2004 to 2011. A linear mixed model assessed the relationship between opioid-related Internet searches and following year heroin-related visits, controlling for MSA GINI index and total number of ED visits.
RESULTS
The best-fitting model explained 72% of the variance in heroin-related ED visits. The final model included the search keywords "Avinza," "Brown Sugar," "China White," "Codeine," "Kadian," "Methadone," and "Oxymorphone." We found regional differences in where and how people searched for opioid-related information.
CONCLUSIONS
Internet search-based modeling should be explored as a new source of insights for predicting heroin-related admissions. In geographic regions where no current heroin-related data exist, Internet search modeling might be a particularly valuable and inexpensive tool for estimating changing heroin use trends. We discuss the immediate implications for using this approach to assist in managing opioid-related morbidity and mortality in the United States.
Topics: Adult; Analgesics, Opioid; Emergency Service, Hospital; Female; Forecasting; Heroin Dependence; Humans; Internet; Linear Models; Male; Patient Admission; Pilot Projects; Predictive Value of Tests; Public Health; United States; United States Substance Abuse and Mental Health Services Administration
PubMed: 30036853
DOI: 10.1016/j.drugalcdep.2018.05.009 -
American Journal of Ophthalmology Case... Sep 2018To report the only known case, to our knowledge, of bilateral exudative retinal detachments in the setting of thrombotic microangiopathy associated with intravenous...
PURPOSE
To report the only known case, to our knowledge, of bilateral exudative retinal detachments in the setting of thrombotic microangiopathy associated with intravenous abuse of extended-release oxymorphone (Opana ER).
OBSERVATIONS
A 35-year-old male presented with headaches and acute, painless vision loss in the context of daily IV abuse of crushed oral Opana ER. The patient was found to have microangiopathic hemolytic anemia (MAHA), acute kidney injury in conjunction with hypertensive crisis and bilateral exudative retinal detachments.
CONCLUSIONS AND IMPORTANCE
Bilateral exudative retinal detachments are rare ophthalmic complications that have been reported with thrombotic thrombocytopenic purpura (TTP). Non-TTP thrombotic microangiopathy, initially described as a "TTP-like illness" consisting of MAHA and thrombocytopenia, has been associated with the IV abuse of Opana ER. We report a case of bilateral exudative retinal detachments due to thrombotic microangiopathy in the setting of IV abuse of Opana ER.
PubMed: 29998206
DOI: 10.1016/j.ajoc.2018.06.001 -
Scandinavian Journal of Pain Jan 2010Oxycodone is a strong opioid and it is increasingly used in the management of acute and chronic pain. The pharmacodynamic effects of oxycodone are mainly mediated by the...
Oxycodone is a strong opioid and it is increasingly used in the management of acute and chronic pain. The pharmacodynamic effects of oxycodone are mainly mediated by the μ-opioid receptor. However, its affinity for the μ-opioid receptor is significantly lower compared with that of morphine and it has been suggested that active metabolites may play a role in oxycodone analgesia. Oxycodone is mainly metabolized by hepatic cytochrome (CYP) enzymes 2D6 and 3A4. Oxycodone is metabolized to oxymorphone, a potent μ-opioid receptor agonist by CYP2D6. However, CYP3A4 is quantitatively a more important metabolic pathway. Chronic pain patients often use multiple medications. Therefore it is important to understand how blocking or inducing these metabolic pathways may affect oxycodone induced analgesia. The aim of this study was to find out whether blocking CYP2D6 would decrease oxycodone induced analgesia in chronic pain patients. The effects of the antidepressant paroxetine, a potent inhibitor of CYP2D6, on the analgesic effects and pharmacokinetics of oral oxycodone were studied in 20 chronic pain patients using a randomized, double-blind, placebo-controlled cross-over study design. Pain intensity and rescue analgesics were recorded daily, and the pharmacokinetics and pharmacodynamics of oxycodone were studied on the 7th day of concomitant paroxetine (20 mg/day) or placebo administration. The patients were genotyped for CYP2D6, 3A4, 3A5 and ABCB1. Paroxetine had significant effects on the metabolism of oxycodone but it had no statistically significant effect on oxycodone analgesia or use of morphine for rescue analgesia. Paroxetine increased the dose-adjusted mean AUC0-12h of oxycodone by 19% (-23 to 113%; P = 0.003), and that of noroxycodone by 100% (5-280%; P < 0.0001) but decreased the AUC0-12 h of oxymorphone by 67% (-100 to -22%; P < 0.0001) and that of noroxymorphone by 68% (-100 to -16%; P < 0.0001). Adverse effects were also recorded in a pain diary for both 7-day periods (placebo/paroxetine). The most common adverse effects were drowsiness and nausea/vomiting. One patient out of four reported dizziness and headache during paroxetine co-administration, whereas no patient reported these during placebo administration (P = 0.0471) indicating that these adverse effects were due to paroxetine. No statistically significant associations of the CYP2D6 or CYP3A4/5 genotype of the patients and the pharmacokinetics of oxycodone or its metabolites, extent of paroxetine-oxycodone interaction, or analgesic effects were observed probably due to the limited number of patients studied. The results of this study strongly suggest that CYP2D6 inhibition does not significantly change oxycodone analgesia in chronic pain patients and that the analgesic activity of oxycodone is mainly due to the parent compound and that metabolites, e.g. oxymorphone, play an insignificant role. The clinical implication of these results is that induction of the metabolism of oxycodone may lead to inadequate analgesia while increased drug effects can be expected after addition of potent CYP3A4/5 inhibitors particularly if combined with CYP2D6 inhibitors or when administered to poor metabolizers of CYP2D6.
PubMed: 29913934
DOI: 10.1016/j.sjpain.2009.09.003 -
Acta Obstetricia Et Gynecologica... Oct 2018There are limited data on oxycodone pharmacokinetics during pregnancy and on fetal exposure after maternal administration. The present study describes the...
INTRODUCTION
There are limited data on oxycodone pharmacokinetics during pregnancy and on fetal exposure after maternal administration. The present study describes the pharmacokinetics of intravenous (i.v.) oxycodone in pregnant sheep and fetal exposure after intravenous and epidural administration.
MATERIAL AND METHODS
Ten pregnant sheep received 0.1 mg·kg oxycodone intravenously, and blood samples were collected up to 24 hours. Seven days later, the ewes were randomized to receive 0.5 mg·kg oxycodone intravenously (n = 5) or epidurally (n = 5) as a single bolus, before laparotomy for placement of catheters into the fetal superior vena cava and carotid artery. Paired maternal and fetal blood samples were taken when the fetal arterial catheter was in place and at the end of surgery. Maternal blood samples were taken up to 24 hours.
RESULTS
After 0.1 mg·kg oxycodone intravenously, the median clearance was 5.2 L·h ·kg (range 4.6-6.2), but the volume of distribution varied between 1.5 and 4.7 L·kg . The area under the curve was 17 h·ng·mL (range 14-19) and the plasma concentration at 2 minutes 60 ng·mL (range 50-74). Following administration of 0.5 mg·kg intravenously or epidurally, oxycodone concentrations were similar in the maternal and the fetal plasma. Accumulation of oxymorphone in the fetus occurred; fetal-to-maternal ratios were 1.3-3.5 (median 2.1) in the i.v.-group and 0.9-3.0 (1.3) in the Epidural-group.
CONCLUSIONS
We determined the pharmacokinetics of oxycodone in pregnant sheep. We showed accumulation of oxymorphone, which an active metabolite of oxycodone, in the fetus. Further studies in human pregnancies are required to evaluate the safety of oxycodone.
Topics: Analgesics, Opioid; Animals; Female; Fetal Blood; Fetus; Injections, Intravenous; Maternal-Fetal Exchange; Oxycodone; Pregnancy; Pregnancy, Animal; Sheep
PubMed: 29772054
DOI: 10.1111/aogs.13378 -
Deutsches Arzteblatt International Mar 2018Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or...
BACKGROUND
Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it.
METHODS
This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route.
RESULTS
9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best.
CONCLUSION
Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.
Topics: Analgesics, Opioid; Buprenorphine; Cancer Pain; Chronic Pain; Fentanyl; Germany; Humans; Hydromorphone; Morphine; Neoplasms; Oxycodone; Pain Management
PubMed: 29563006
DOI: 10.3238/arztebl.2018.0135 -
Journal of Investigative Medicine High... 2018Oxymorphone is a semisynthetic extended release opiate used to treat moderate to severe chronic pain. The Food and Drug Administration approved the oral form of...
Oxymorphone is a semisynthetic extended release opiate used to treat moderate to severe chronic pain. The Food and Drug Administration approved the oral form of oxymorphone available as Opana and Opana ER (extended release) since 2006. The Food and Drug Administration and the Centers for Disease Control and Prevention issued warning against intravenous use of Opana ER. We are presenting a case report of a 37-year-old female with a history of active intravenous drug abuse who presented to our hospital with acute kidney injury. Urinalysis showed red blood cell sediments, many dysmorphic red blood cell casts along with nephrotic range proteinuria of 12 g/deal per day. Kidney biopsy showed microscopic thrombotic microangiopathy (TMA) involving glomeruli and vessels. Further workup was undertaken for TMA, and apart from mildly elevated lactate dehydrogenase of 380 (normal <243), active hepatitis C, and slightly low ADAMTS-13 (55%), there was no other laboratory evidence of TMA. On literature search, we found that intravenous injection of chronic Opana ER has been reported to cause TMA resulting in chronic kidney disease. Our patient also admitted to use of intravenous Opana ER abuse for the past 5 years. She had a normal platelet count and an absence of schistocytes, which makes it an atypical presentation of TMA resulting in chronic kidney disease in an opiate user. We strongly urge physicians to avoid prescribing opiates for chronic pain, especially Opana ER, which if injected intravenously for recreational purposes can lead to serious side effects like TMA. Treatment is mainly supportive and avoidance of drug in future.
PubMed: 29435466
DOI: 10.1177/2324709618756423 -
The International Journal on Drug Policy Feb 2018Misuse of prescription opioid analgesics (POA) has increased dramatically in the US, particularly in non-urban areas. We examined injection practices among persons who...
BACKGROUND
Misuse of prescription opioid analgesics (POA) has increased dramatically in the US, particularly in non-urban areas. We examined injection practices among persons who inject POA in a rural area that experienced a large HIV outbreak in 2015.
METHODS
Between August-September 2015, 25 persons who injected drugs within the past 12 months were recruited in Scott County, Indiana for a qualitative study. Data from in-depth, semi-structured interviews were analyzed.
RESULTS
All 25 participants were non-Hispanic white and the median age was 33 years (range: 19-57). All had ever injected extended-release oxymorphone (Opana ER) and most (n=20) described preparing Opana ER for multiple injections per injection episode (MIPIE). MIPIE comprised 2-4 injections during an injection episode resulting from needing >1mL water to prepare Opana ER solution using 1mL syringes and the frequent use of "rinse shots." MIPIE occurred up to 10 times/day (totaling 35 injections/day), often in the context of sharing drug and injection equipment.
CONCLUSIONS
We describe a high-risk injection practice that may have contributed to the rapid spread of HIV in this community. Efforts to prevent bloodborne infections among people who inject POA need to assess for MIPIE so that provision of sterile injection equipment and safer injection education addresses the MIPIE risk environment.
Topics: Adult; Analgesics, Opioid; Disease Outbreaks; Female; HIV Infections; Humans; Indiana; Interviews as Topic; Male; Middle Aged; Needle Sharing; Opioid-Related Disorders; Oxymorphone; Risk-Taking; Rural Population; Substance Abuse, Intravenous; Substance-Related Disorders; Syringes; Young Adult
PubMed: 29278838
DOI: 10.1016/j.drugpo.2017.12.003 -
Journal of Medicinal Chemistry Jan 2018An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation of 1 was described in the route in the...
A Stable Heroin Analogue That Can Serve as a Vaccine Hapten to Induce Antibodies That Block the Effects of Heroin and Its Metabolites in Rodents and That Cross-React Immunologically with Related Drugs of Abuse.
An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation of 1 was described in the route in the synthesis of 2 (DiAmHap). A scalable procedure was developed to install the C-3 amido group. Using the Boc protectng group in 18 allowed preparation of 1 in an overall yield of 53% from 4 and eliminated the necessity of preparing the diamide 13. Hapten 1 was conjugated to tetanus toxoid and mixed with liposomes containing monophosphoryl lipid A as an adjuvant. The 1 vaccine induced high anti-1 IgG levels that reduced heroin-induced antinociception and locomotive behavioral changes following repeated subcutaneous and intravenous heroin challenges in mice and rats. Vaccinated mice had reduced heroin-induced hyperlocomotion following a 50 mg/kg heroin challenge. The 1 vaccine-induced antibodies bound to heroin and other abused opioids, including hydrocodone, oxycodone, hydromorphone, oxymorphone, and codeine.
Topics: Animals; Antibodies; Cross Reactions; Female; Haptens; Heroin; Humans; Mice; Opioid-Related Disorders; Vaccines
PubMed: 29236495
DOI: 10.1021/acs.jmedchem.7b01427 -
The Journal of Pain Apr 2018Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute...
UNLABELLED
Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted.
PERSPECTIVE
This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol.
Topics: Analgesics, Opioid; Chronic Pain; Female; Humans; Male; Opioid-Related Disorders; Oxycodone; Retrospective Studies; Substance-Related Disorders; Tapentadol
PubMed: 29224919
DOI: 10.1016/j.jpain.2017.11.007