Non-oral Routes Of Administration Research Articles

Sources for prescription stimulant misuse: A person-centered approach to understanding links to substance use and psychiatric impairment.

Prescription stimulant misuse (PSM) is most prevalent among college students and is associated with numerous negative academic and psychosocial outcomes. A large body of literature has identified predictors of PSM in this population, however few studies have utilized a person-centered approach to examine how the sources from which students procure prescription stimulants are associated with substance-related and psychiatric impairment. We used latent class analysis (LCA) to classify a geographically and racially/ethnically diverse sample of U.S. undergraduates (N = 538) who misused prescription stimulants into groups based on their endorsement of nine sources of medication. We selected a five-group classification from the LCA with classes of peer/dealer, given by friend, own prescription, lower multiple sources (i.e., relatively infrequent endorsement of multiple sources), and any source. Compared to the reference group (given by friend), the own prescription class was less likely to report marijuana use, simultaneous alcohol and marijuana use, alcohol or marijuana consequences, and nonoral routes of administration. On the other hand, the own prescription class was more likely to screen positive for anxiety, anger, and suicidality. Similarly, the lower multiple sources group was more likely to screen positive for depression, anxiety, anger, and suicidality. Prevention and intervention efforts focused on PSM may be tailored differently for students who are misusing their own medication and/or endorsing multiple sources. Specifically, these students may need broader assistance with comorbid psychiatric conditions, particularly suicidality, while students who obtain stimulants from peers or a dealer may benefit more from substance-focused interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Structural Insight into Privileged Heterocycles as Anti-Trypanosoma cruzi and brucei Agents.

Trypanosomiasis is caused by parasitic protozoan trypanosomes in vertebrates. T. cruzi and T. brucei are causative agents of Chagas disease (CD) and Human African Trypanosomiasis (HAT), respectively. These life-threatening diseases are a serious threat to public health, with considerable incidence in sub-Saharan African and continental Latin America countries. Although WHO validated mitigated number of HAT cases in Togo (June 2020) and Cote d'Ivoire (December 2020), serious efforts need to be performed for the elimination of the disease. Antigenic variation of trypanosomal parasites provides a major bottleneck for developing effective vaccines. In the absence of human vaccines or chemoprophylaxis, the control of trypanosomatid infections may be envisaged through the eradication of vectors, management of animal reservoirs, and chemotherapy. A small number of chemical agents are currently available for antitrypanosomal treatments, and most of them are associated with toxicity, lack of efficacy, and non-oral route of administration. Given the restricted applicability of current medications, numerous efforts have been made for the synthesis and biological evaluation of heterocyclic scaffolds as antitrypanosomal candidates. In light of the above considerations, we were prompted to describe chemical diversity within privileged 5- membered heterocycles (imidazoles, thiazoles, triazoles and tetrazoles) as antitrypanosomal agents. The main purpose of the study was to throw light on the structure-activity relationship (SAR) of the relevant structures. To capture the recent structural diversity within reported cases, small molecules that belonged to the recent 7-year period (2015-2021) have been discussed. The available medications have also been briefly reviewed.

The Oral Proteasome Inhibitor Ixazomib, Alone and in Combination with Ibrutinib, Induces Lethality in Waldenstrom Macroglobulinemia Cells That Are Resistant to Ibrutinib

Introduction: Dysregulated B-cell receptor (BCR) signaling drives proliferation of Waldenstrom macroglobulinemia (WM) cells, which characteristically secrete excessive IgM. To maintain IgM production and preserve cellular homeostasis, WM cells rely on optimally functioning proteasomes to degrade and recycle proteins. This biological dependence has been clinically exploited using the proteasome inhibitor (PI), bortezomib (Btz), which is capable of inducing remission in 85% of WM patients (Treon et al Clin Canc Res, 2007) as a single agent. Despite, its activity, Btz use is associated with a high incidence of sensory and autonomic neuropathies as well as its cumbersome dosing schedule and non-oral route of administration. Thus, new agents that 1.) build on the activity of Btz, 2.) have a more favorable toxicity profile and 3.) can be combined with standard of care agents such as, ibrutinib (Ibr), are highly attractive and should be prioritized for investigation. Here we describe the preclinical activity of ixazomib (Ixa), a PI that is administered orally and is associated with significantly less peripheral neuropathy; in combination with Ibr, in WM cells.Methods: WM cell lines (BCWM.1 and RPCI.WM1) and their drug-resistant subclones were used. Genomic data including whole exome sequencing (WES) and copy number variations (CNV) was used in creation of digital simulation avatars of RPCI-WM1 and RPCI-WM1/IR (Ibr-resistant, Ibr-R variant), where the salient and prominently dysregulated cellular pathways were identified. Ixa +/- Ibr was tested in digital avatars and dose-dependent impact on simulated disease growth was assessed (Fig 1A). The predictive results were experimentally validated. Cell viability was measured using trypan blue or CellTiter Glo. Apoptosis was examined by annexin-V/PI staining of drug-treated cells followed by flow cytometry analysis. Mitochondrial membrane permeability (MOMP) was determined by TMRM staining of drug-treated cells followed by flow cytometry.Results: We first profiled the growth inhibitory action of Ixa in WM cell lines (n=9); all of which were sensitive to Ixa irrespective of acquired resistance to Btz, Ibr or carfilzomib with a median IC50 of 95.59nM. We then tested whether Ixa could cooperate with Ibr to enhance WM cell kill. Indeed, the Cellworks modeling tool, predicted a significant loss of viability and induction of apoptosis in both wildtype and Ibr-R cells treated with Ibr + Ixa, as compared to either single agent (Fig 1B-D). We confirmed this in vitro, where viability of wildtype WM cells treated with Ixa (20nM), Ibr (5uM) or Ibr + Ixa for 6h significantly decreased; most notable with Ixa + Ibr (25.5% viable cells). And this effect was similar in Ibr-R cell lines (30.3% viable cells) after combination treatment. Further confirming in silico predictive modeling results, we noted a significant increase in annexin-V/PI positivity in Ixa treated wildtype (24.5%) and Ibr-R WM cell lines (33.1%). Whereas Ibr alone exhibited minimal apoptosis in WM cell lines (~11 - 15%), the combination of with Ixa + Ibr enhanced programmed cell death in wildtype (40.2%) and Ibr-R cells (50.5%). As intrinsic apoptosis is triggered through mitochondrial disruption, we also examined mitochondrial transmembrane permeability (MOMP) in cells treated with Ibr, Ixa or Ixa + Ibr. In wildtype cells, mean MOMP induced by single agent Ixa was 23.5% and in Ibr-R cells 33%; increasing to 39% and 50.4%, respectively, after treatment with Ibr + Ixa. Mechanistic studies revealed changes in proteins regulated by the ubiquitin proteasome system and those associated with BTK signaling. While Ixa alone downregulated Bcl-2 and Mcl-1 levels, this effect was more marked in cells (both wildtype and Ibr-resistant) treated with Ixa + Ibr combination. Similar effects were noted in pPLCg2, albeit with some variability between the cell lines.Conclusion: Using a combination of in silico modeling and experimental approaches, we provide first preclinical evidence on the antitumor effects of Ibr combined with the oral PI, Ixa, in WM cells, including those resistant to Ibr. Whereas further investigation on the precise molecular mechanisms of how Ibr + Ixa cooperate to induce apoptosis in WM cell is ongoing, our studies provide the basis for clinical testing of the Ibr + Ixa regimen; with a phase II clinical study in development. [Display omitted] DisclosuresSingh:Cellworks Research India Pvt. Ltd: Employment. Kumar:Cellworks: Employment. Basu:Cellworks: Employment. Trivedi:Cellworks: Employment. Majumdar:Cellworks: Employment. Abbasi:Cellworks Group Inc.: Employment. Vali:Cellworks Group Inc.: Employment. Martin:Janssen: Consultancy, Honoraria, Other: travel expenses; Genentech: Consultancy; Celgene: Consultancy; Teva: Research Funding; Novartis: Consultancy; Gilead: Consultancy, Other: travel expenses. Ansell:Bristol-Myers Squibb: Research Funding; Merck: Research Funding; Celldex: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding. Ailawadhi:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pharmacyclics: Research Funding; Takeda: Consultancy, Honoraria.

Substance Use Trajectories: Nonmedical Use (NMU) of Prescription Stimulants via Non-Oral Routes of Administration Among Adults Recruited from Reddit

NMU of prescription stimulant medications (RxStim) intended for treatment of attention deficit/hyperactivity disorder (ADHD) is a growing public health concern, particularly when used via non-oral routes of administration. However, the role of non-oral routes of administration for RxStim NMU in the larger substance abuse pathway is less well studied. The purpose of this study was to characterize RxStim NMU and investigate substance use trajectories among adults who reported non-oral RxStim NMU recruited from Reddit.Eligible participants must have been located in the US, English speaking, age 18 y, and have reported RxStim NMU via a non-oral route (any route other than ingestion) within the past 5 y. Participants were recruited from Feb-Sep 2019 using banner ads on Reddit, the 5th most visited website in the US. Participants completed an online survey which captured demographics, lifetime RxStim NMU and illicit substance use; they were compensated for their time. For purposes of this study, NMU included ANY of the following: (1) use for any reason, even once, without their own prescription, (2) use in ways other than prescribed, and (3) use for the feeling or experience the medication caused.Respondents (n=225) were primarily male (86.2%), 18-24 (48.0%) or 25-34 (43.1%) years of age, and Caucasian (78.2%), Black (7.1%) or Hispanic (5.3%). Lifetime diagnosis of ADHD was reported by 27.6%, with 53.2% diagnosed at age 11-19 and 35.5% at age 20+ years. RxStim NMU via snorting was reported by 99.1%, smoking 3.6% and injecting 6.2% (multiple routes could be reported). Almost all (n=222; 98.7%) also reported lifetime illicit drug use, among whom 182 (82.0%) initiated substance use by using an illicit drug (77.9% marijuana, 1.8% cocaine/crack, 0.9% inhalants, 0.9% hallucinogens, 0.5% methamphetamine/amphetamines) prior to RxStim NMU. Forty (18.0%) respondents initiated with RxStim NMU; 14.4% then initiated marijuana use, 0.9% initiated cocaine/crack use, 0.9% initiated barbiturate use, and 0.5% initiated heroin, inhalant, methamphetamine/amphetamine, and hallucinogen use. Average age of initial RxStim NMU was 18.7 (SD 3.7) years and most often was via swallowing (89.1%) followed by snorting (10.9%). Respondents began using marijuana at age 15.9 (SD 2.5), cocaine or crack at 19.7 (SD 3.3), and heroin at 20.9 (SD 5.5).Engagement in RxStim NMU via a non-oral route of administration is most often preceded by marijuana use. Among this Reddit-recruited population of non-oral RxStim nonmedical users, only 1 in 4 reported an ADHD diagnosis and <1 in 5 reported RxStim NMU as their first substance use experience; most of these then added marijuana and few moved toward cocaine/crack or methamphetamine. RxStim NMU via non-oral routes is associated with a larger pattern of risky substance use behaviors. Nearly all non-oral RxStim NMU is associated with concomitant drug use, especially marijuana.Funding. Arbor Pharmaceuticals, LLC.

Nanosuspension As An Innovative Nanotechnology Trend Drug Delivery System: A Review

Solubility, the freedom of the drug from its route of administration, is the key factor for drug efficacy. Most of recently discovered drugs are insoluble in water and hence poorly absorbed with reduced bioavailability that lead to more production efforts. Due to their flexible characteristics and specific advantages, nanosuspensions has introduced as promising technique for effective hydrophilic drugs delivery. The reduction into the submicron range of drug particles leads to a major increase in rate dissolution and thus improves bioavailability of the drug. Nanosuspension involves colloidal dispersed submicron particles of the pharmaceutical active drug ingredient in liquid-phase stabilized with a surfactant. By oral and non-oral route of administration, nanosuspensions can be administered. Study focuses on different preparation methods with advantages and disadvantages, characterization techniques, and implementations.

Sex differences in benzodiazepine misuse among adults with substance use disorders

Women are more likely than men to be diagnosed with anxiety disorders and to be prescribed benzodiazepines. People with substance use disorders are at a heightened risk for the misuse of benzodiazepines, yet little is known about sex differences in the prevalence, correlates or patterns of benzodiazepine misuse in this population. The aim of this study was to characterize sex differences in benzodiazepine misuse in a sample of adults receiving substance use disorder treatment (N = 352). Almost half of the sample had been prescribed a benzodiazepine and more than 40% had misused a benzodiazepine. Women were more likely to have a lifetime prescription than men, but were not more likely to report misuse or regular misuse. Consistent with data for other substances, women were more likely to report misusing benzodiazepines to cope and reported greater anxiety sensitivity. The vast majority (97%) of participants reported co-use of benzodiazepines with other substances and 65% of women reporting misusing benzodiazepines via a non-oral route of administration (e.g., intranasal). Although benzodiazepine misuse prevalence was not substantively different between men and women, several sex differences in clinical characteristics and patterns of use were identified. Further research on the nature of sex differences in benzodiazepine misuse is needed to inform targeted treatment for both men and women with substance use disorders.

Abstract B007: OKI-179 is a novel, oral, class I specific histone deacetylase inhibitor in phase 1 clinical trials

Abstract Multiple histone deacetylase (HDAC) inhibitors are approved for use as single agents in hematological cancers, including T-cell lymphomas and multiple myeloma. However, these compounds have failed to address unmet needs in other hematological malignancies and solid tumors, due in part to the promiscuous inhibitory properties of pan inhibitors, a lack of suitable therapeutic indices for combination therapy, and, in some cases, a non-oral route of administration. Of the approved agents, romidepsin is the most potent and selective, but is limited by its need for IV infusion and therapeutic index. With these challenges in mind, our team designed OKI-179, a novel, oral pro-drug analog of largazole, a compound reminiscent of the romidepsin-depsipeptide class of natural products. OKI-179 demonstrates potent inhibition of the Class 1 HDACs, HDAC 1,2,3 (IC50 = 1.2, 2.4, 2.0 nM, respectively), with no significant inhibition of Class IIa HDACs. It shows potent antiproliferative and apoptotic effects against a wide range of cell lines, activity in xenograft cancer models, and good oral PK properties in mouse, rat and dog models. OKI-179 inhibits the growth in mice of colorectal (HCT-116) and triple negative breast (MDA-MB-231) xenograft models potently and dose-dependently as a single agent. OKI-179 potently and dose-dependently causes the upregulation of MHC Class 1 in B16F10 murine melanoma cells; patients with low MHC presentation respond poorly to checkpoint inhibitors. Importantly, the combination of OKI-179 and a murine anti-PD1 agent demonstrates significant synergistic tumor growth inhibition in the syngeneic CT26 murine CRC model and in a genetic model of DLBCL. OKI-179 is currently being investigated in a first-in-human phase 1 dose-escalation trial, with the goals of determining safety, MTD, RP2D, PK, PD, and preliminary efficacy signals. In the first dosing cohorts, the drug was well-tolerated, achieved good exposure following oral administration, and preliminary signs of on-target PD effects were observed. An update of the clinical experience will be presented and discussed, along with translational data that will guide subsequent clinical development. Citation Format: Jennifer R Diamond, Jodi A Kagihara, Xuedong Liu, Gilad Gordon, Amy M Heim, James Winkler, John A DeMattei, Anthony D Piscopio, S. Gail Eckhardt. OKI-179 is a novel, oral, class I specific histone deacetylase inhibitor in phase 1 clinical trials [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B007. doi:10.1158/1535-7163.TARG-19-B007

2.37 Prevalence and Consequences of Amphetamine Abuse Among Adolescents and Adults Calling US Poison Control Centers

Amphetamine formulations (AMP) are one of the most effective treatments for ADHD. However, AMP are also associated with liability for abuse and dependence. This study evaluated the consequences of nonmedical AMP use via oral and nonoral routes of administration.

Relative Oral Bioavailability of an Abuse-deterrent, Extended-release Formulation of Morphine Versus Extended-release Morphine: A 2-period, Single-dose, Randomized Crossover Study in Healthy Subjects

PurposeMorphine ARER is a novel oral, abuse-deterrent, extended-release (ER) formulation of morphine sulfate with physical and chemical properties that deter misuse and abuse by nonoral routes of administration. Here we evaluate the relative bioavailability of morphine ARER and extended-release morphine. MethodsThis single-dose, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy adult subjects compared the relative bioavailability of morphine ARER 100 mg to that of ER morphine 100 mg in the fasted condition. At 12 and 1.5 hours before dosing and 12 hours after dosing, all subjects received a 50-mg oral naltrexone tablet to minimize opioid-related side effects. Pharmacokinetic parameters including the AUC0–t, AUC0–∞, and Cmax of morphine and its metabolite morphine-6-glucuronide (M6G) were determined at various times up to 48 hours postdose. The bioequivalence of morphine ARER and ER morphine was determined using an ANOVA of the least-squares mean values of morphine and M6G bioavailability. FindingsForty-nine subjects completed the study. Both morphine ARER and ER morphine exhibited peak plasma morphine and M6G concentrations of ∼30 ng/mL and ∼200 ng/mL, respectively, at 3 hours postdose. The 90% CIs of the ln-transformed values of morphine AUC0–t, AUC0–∞, and Cmax were within the 80% to 125% range for bioequivalence. M6G values also indicated bioequivalence of morphine ARER and ER morphine. The most common adverse events were nausea and somnolence. ImplicationsThese data show that, in these subjects, morphine ARER was bioequivalent to ER morphine, a treatment for pain with well-established efficacy and safety profiles.

Oral and non-oral routes of administration among prescription opioid users: Pathways, decision-making and directionality

Oral and non-oral routes of administration among prescription opioid users: Pathways, decision-making and directionality

CYP3A pharmacogenetic association with tacrolimus pharmacokinetics differs based on route of drug administration.

Tacrolimus is prescribed to the majority of transplant recipients to prevent graft rejection, and although patients are maintained on oral administration, nonoral routes of administration are frequently used in the initial post-transplant period. CYP3A5 genotype is an established predictor of oral tacrolimus dose requirements, and clinical guideline recommendations exist for CYP3A5-guided dose selection. However, the association between CYP3A5 and nonoral tacrolimus administration is currently poorly understood, and differs from the oral tacrolimus relationship. In addition to CYP3A5, other pharmacogenes associated with CYP3A activity, including CYP3A4, CYP3A7 and POR have also been identified as predictors of tacrolimus exposure. This review will describe the current understanding of the relationship between these pharmacogenes and tacrolimus pharmacokinetics after oral and nonoral administration.

Seizure Bootcamp: Everything You Ever Needed to Know to Manage Seizures in End Stage Disease (FR455)

•Describe common clinical presentations of seizures in advanced illness.•Implement strategies for appropriate use of antiepileptics in end stage illness.•Develop a framework for management of acute seizure activity in home and inpatient hospice settings. Seizures are a common occurrence in end stage disease, occurring in a wide range of conditions, including dementia, stroke, AIDS, end stage renal disease, and both primary brain tumors and metastatic disease. Not only are uncontrolled seizures a significant source of distress to both patient and families, but they present a significant management challenge to the hospice team, who are often faced with controlling seizures in the face of advancing disease, increasing seizure risk factors, and declining ability of the patient to take oral medications. Through use of current evidence, case studies, and interactive discussion, this session will present participants with the opportunity to establish a framework to effectively assess and manage seizures in the end stages of illness, with particular attention to management of seizures in the hospice setting. Participants will develop the bedside clinical skills necessary to detect subtle presentations of seizures and to distinguish them from common seizure mimics. Participants will also develop increased comfort with use of antiepileptics in end stage disease, including facility with non-oral routes of administration, and with treatment of acute seizures in both the home and inpatient settings. In addition, participants will develop techniques to effectively educate families and other caregivers about the safe management of acute seizures at home.

Relative Abuse of Crush-Resistant Prescription Opioid Tablets via Alternative Oral Modes of Administration.

ObjectiveSome crush-resistant tablet formulations (CRTs) reduce prescription opioid abuse by nonoral routes of administration (ROAs), especially insufflation and injection, while oral abuse increases. Oral abuse involving product manipulation vs swallowing whole for CRTs and comparators was examined.MethodsAbuse by oral modes of administration (e.g., swallowing whole, chewing, dissolving in the mouth), was examined using the ASI-MV, a computerized, clinical interview for adults in substance abuse treatment from January 2009 to March 2015. CRTs (reformulated oxycodone extended-release [ER], reformulated oxymorphone ER, and tapentadol ER) were compared with non-CRT versions, morphine ER, and oxycodone immediate-release single entity. Analyses employed descriptive statistics and logistic regression.ResultsAmong 364,329 unique assessments, 18,135 patients reported oral abuse of the CRTs and comparators examined. CRTs had a higher prevalence of oral abuse involving product manipulation than comparators (P < 0.0001) among all abusers of product. Oral abuse involving product manipulation for CRTs was greater among the subset of patients reporting oral abuse and significantly higher than comparators (P < 0.003). CRTs were significantly less likely than comparators to be swallowed whole (P < 0.0001) and significantly more likely to be chewed (P < 0.003). CRTs were more likely to be dissolved in the mouth than most comparators.ConclusionsResults suggest the need for abuse-deterrent formulations designed to reduce abuse by oral administration with product manipulation, such as chewing. Advances in this area may reduce the overall abuse of prescription opioids and interrupt the progression from abuse by swallowing whole to oral administration involving product manipulation and other ROAs.

Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration

BackgroundPrescription opioid abuse and misuse is a serious and growing public health issue. While the most common form of abuse is swallowing intact tablets/capsules, some abusers manipulate, or tamper with, these medications by altering the dosage form to allow for non-oral routes of administration (e.g., injection, inhalation) in order to achieve more rapid or enhanced psychoactive effects. Because administration of opioids via non-oral routes results in greater systemic availability and more rapid central nervous system penetration, we hypothesized that death and major medical outcomes occur more frequently with non-oral routes compared to oral route alone. MethodsThis retrospective cohort study analyzed data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center Program to investigate relative risk of prescription opioid abuse via oral and non-oral routes. ResultsWhile the oral route was the most commonly reported route of abuse (64.0%), non-oral routes were reported in 14.6% exposures and unknown routes in 21.4% exposures. The relative risk of an exposure resulting in death or major effect was 2.43 (95% CI 1.97, 2.99) if non-oral routes were reported compared to exposures involving oral route only. ConclusionAnalysis of acute health events recorded by poison centers indicates that death or major effects are twice as likely to occur with intentional abuse of prescription opioids via non-oral routes of administration than ingestion alone. Effective interventions to prevent abuse via non-oral routes of solid dosage forms of prescription opioids, such as abuse-deterrent formulations could have a significant public health impact.

Nanosuspension Technologies for Delivery of Poorly Soluble Drugs-A Review

Solubility is the crucial factor for drug effectiveness, independence of the route of administration. Large proportion of newly discovered drugs are water insoluble and therefore poorly bioavailable contributing to desert development effort. Nanosuspensions have emerged as a promising strategy for the efficicent delivery of hydrophilic drugs because of their versatile features andunique advantages. The reduction of drug particles into submicron range leads to a significant increase in dissolution rate and therefore enhances bioavailability. Nanosuspension contain submicron colloidal dispersion of the pharmaceutical active ingredient particles in a liquid phase stabilised by surfactant. Nanosuspensions can be delivered by oral and non-oral route of administration. Study is focused on various methods of preparation with advantages and disadvantages, characterization properties, applications.

Abuse Rates and Routes of Administration of Reformulated Extended-Release Oxycodone: Initial Findings From a Sentinel Surveillance Sample of Individuals Assessed for Substance Abuse Treatment

Oxycodone hydrochloride controlled-release, also known as extended-release oxycodone (ER oxycodone), was reformulated with physicochemical barriers to crushing and dissolving intended to reduce abuse through nonoral routes of administration (ROAs) that require tampering (eg, injecting and snorting). Manufacturer shipments of original ER oxycodone (OC) stopped on August 5, 2010, and reformulated ER oxycodone (ORF) shipments started August 9, 2010. A sentinel surveillance sample of 140,496 individuals assessed for substance abuse treatment at 357 U.S. centers between June 1, 2009, and March 31, 2012, was examined for prevalence and prescription-adjusted prevalence rates of past-30-day abuse via any route, as well as abuse through oral, nonoral, and specific ROAs for ER oxycodone and comparators (ER morphine and ER oxymorphone) before and after ORF introduction. Significant reductions occurred for 8 outcome measures of ORF versus OC historically. Abuse of ORF was 41% lower (95% CI: −44 to −37) than historical abuse for OC, with oral abuse 17% lower (95% CI: −23 to −10) and nonoral abuse 66% lower (95% CI: −69 to −63). Significant reductions were not observed for comparators. Observations were consistent with the goals of a tamper resistant formulation for an opioid. Further research is needed to determine the persistence and generalizability of these findings. PerspectiveThis article presents preliminary findings indicating that 8 outcome measures of abuse of a reformulated ER oxycodone were lower than that for original ER oxycodone historically, particularly through nonoral ROAs that require tampering (ie, injection, snorting, smoking), in a sentinel sample of individuals assessed for substance use problems for treatment planning.

Stick It to Me: Topical and Transdermal Analgesics at End of Life (524)

1.Describe the evidence regarding efficacy and toxicity of topical analgesics, and proposed roles in caring for patients with advanced illness.2.Describe patient- and agent-related variables that affect the selection and use of transdermal opioids (eg., fentanyl and buprenorphine), including equianalgesic conversions and timing considerations when switching to and from a transdermal opioids.3.Given an actual or simulated case of a patient with an advanced illness, assess for the appropriateness of a topical or transdermal analgesic, and recommend dosing and monitoring strategies. Topical and transdermal analgesics are frequently used to provide an opioid-sparing effect, or serve to facilitate analgesic delivery by a non-oral route of administration. However, most practitioners are unaware of the role in therapy for these analgesics. Specifically, practitioners are not clear on the patient- and drug-related variables that influence product selection, and realistic expectations for patient outcomes. Participants in this session will learn about the efficacy and toxicity of topical analgesics including commercially available products such as capsaicin, salicylates, counterirritants, nonsteroidal anti-inflammatory drugs, and lidocaine and compounded topical opioids for wound care pain. By using a case-based active-learning approach, participants will learn which patient scenarios are amenable to topical analgesic therapy. Transdermal opioid therapy (fentanyl and buprenorphine) are not appropriate for every pain patient. Consideration of formulation- and patient-specific variables is key to success. Participants will learn about the appropriate indications for therapy, how to transition to and from these products, how to titrate these products, the impact of patient-specific variables such as fever, low body weight and a rapidly changing pain pattern. Participants will learn the appropriate role of topical and transdermal analgesics through a case-based approach.

Alternate Routes of Administration and Risk for HIV Among Prescription Opioid Abusers

ABSTRACT Route of administration is an important contributor to the adverse health consequences of prescription medication abuse. The current study examines characteristics associated with non-oral routes of administration among a large sample of prescription opioid abusers and explores needle-related human immunodeficiency virus (HIV) risk behaviors as well. In the study, 791 opioid abusers completed a one-time structured interview, including complete histories of illicit and prescription drug abuse and route of drug administration. The most common method of pill use was oral (91%), followed by intranasal (53.1%), injection (23.8%), and smoking (14.5%). The youngest prescription opioid abusers, ages 18–24, displayed significantly higher odds of using alternate routes of administration and of reusing nonsterile needles for injection. HIV prevention programming should be developed for young prescription opioid injectors.

Triptans for acute cluster headache.

Cluster headache is an uncommon, but severely painful and disabling condition, with rapid onset. Validated treatment options are limited, and first-line therapy includes inhaled oxygen. Alternative therapies such as intranasal lignocaine and ergotamine are not as commonly used and are less well studied. Triptans are successfully used to treat migraine attacks and, because of this, they may also be useful for cluster headache. To determine the efficacy and tolerability of triptans for the acute treatment of cluster headaches. We searched Cochrane CENTRAL, MEDLINE and EMBASE for studies through 22 January 2010. Randomised, double-blind, placebo-controlled studies of triptans for acute treatment of cluster headache episodes. Two review authors independently assessed study quality and extracted data. Numbers of participants with different levels of pain relief, requiring rescue medication and experiencing adverse events and headache-associated symptoms in treatment and control groups were used to calculate relative risk and numbers needed to treat (NNT) and harm (NNH). All six included studies used a single dose of triptan to treat an attack of moderate to severe pain intensity. In total 231 participants received zolmitriptan 5 mg, 223 received zolmitriptan 10 mg, 131 received sumatriptan 6 mg, 88 received sumatriptan 12 mg, and 326 received placebo. Zolmitriptan was administered either orally or intranasally, and sumatriptan either subcutaneously or intranasally.Overall, the triptans studied were better than placebo for headache relief and pain-free responses, with an NNT of 2.4 for 15 minute pain relief with subcutaneous sumatriptan 6 mg (75% with sumatriptan and 32% with placebo), and 2.8 for 30 minute pain relief with intranasal zolmitriptan 10 mg (62% with zolmitriptan and 26% with placebo). Fewer participants need rescue medication with triptan than with placebo, but more experienced adverse events. Zolmitriptan and sumatriptan are effective in the acute treatment of cluster headaches and may provide a useful treatment option, potentially offering convenience over oxygen therapy and a better safety and tolerability profile than ergotamine. Non-oral routes of administration are likely to provide better and more rapid responses.

Nonmedical use of prescription stimulants and depressed mood among college students: Frequency and routes of administration

Studies demonstrate associations between nonmedical use of prescription stimulants (NMUPS) and depressed mood; however, relevance of NMUPS route of administration and frequency of use have not been examined. We hypothesized frequent NMUPS and nonoral routes would be significantly associated with depressed mood. A Web survey was self-administered by a probability sample of 3,639 undergraduate students at a large U.S. university. The survey contained substance use (e.g., frequency, route of administration) and depressed mood measurement. Past-year prevalence of NMUPS was 6.0% ( n = 212). Approximately 50% of frequent or nonoral NMUPS reported depressed mood. Adjusted odds of depressed mood were over two times greater among frequent monthly NMUPS (adjusted odds ratio [AOR] = 2.3, 95% confidence interval [CI] = 1.01–5.15) and nonoral routes of administration (AOR = 2.2, 95% CI = 1.36–3.70), after controlling for other variables. Nonmedical users of prescription stimulants should be screened for depressed mood, especially those who report frequent and nonoral routes of administration.