Non-opioid Drugs Research Articles

Efficacy of Intravenous Infusion of Acetaminophen for Intrapartum Analgesia.

The intensity of pain experienced by women in labour, has been found to affect the progress of labour, foetal well-being and maternal psychology. Adverse effects associated with commonly used opioids for providing intrapartum analgesia have created a need for an alternative non-opioid drug. To evaluate the efficacy of an intravenous infusion of 1000 mg of acetaminophen as an intrapartum analgesic. The present prospective single-centre, single blind, placebo-controlled randomized interventional study was conducted in Department of Obstetrics and Gynaecology in Vardhaman Mahavir Medical College & Safdarjung Hospital over a period of six months from September 2014 to March 2015. After receiving the ethical clearance and written informed consent. The first 200 consecutive parturients fulfilling the inclusion criteria were recruited into the study. Women were then randomised to receive either intravenous 1000 mg (100ml) of acetaminophen (Group A, n=100) or 100 ml normal saline (Group B, n=100). Primary outcome assessed was effectiveness of acetaminophen to provide an adequate amount of analgesia, as measured by a change in Visual Analogue Scale (VAS) pain intensity score at various times after drug administration. Secondary outcomes measured were duration of labour, need for additional rescue analgesia and presence of adverse maternal or foetal effect. There was pain reduction at 1 and 2 hours in both groups (p<0.001). However, it was more significant in the acetaminophen group, especially at 1 hour. Duration of labour was shortened in both the groups, without any maternal and foetal adverse effects. Intravenous acetaminophen is an efficacious non-opioid drug for relieving labour pain without any significant maternal and foetal adverse effects.

Prevalence of Pain. and analgesic therapy adequacy in patients hospitalized in a university hospital

Objectives: To evaluate the prevalence of Pain. and adequacy of analgesic therapy administered to patients at a university hospital, as well to assess the agreement between the painful self-reporting and data from medical records regarding Pain. manifestation. Methods: Observational and cross-sectional study, from structured interviews with adult patients who expressed a complaint of Pain. up to 24 hours prior to hospital admission or at any time after admission to the Lauro Wanderley University Hospital (LWUH) interviews. Socio-demographic and clinical characteristics of patients, type of analgesics, treatment regimens, intensity and characteristics of Pain. were evaluated. The medical records of medication use were collected through the notes in the medical report and lists of prescriptions. Pain. was assessed by visual analogue scale (VAS ) and the Multidimensional Pain. Scale (EMADOR). To assess the adequacy of analgesia used the Index of Pain. Management (IMD). The Analgesic Ladder of the World Health Organization was used in evaluating requirements. Results: In the period of the study, 480 patients admitted up to 18 years or more wards for adults of the LWUH. Of these, 115 (24%) complained of Pain. and were included in the sample. The age of the 115 participants ranged from 18 to 90 years, with a mean of 48,7 (± 17,7). It was found that 60 (52,2 %) had severe Pain. and 39 ( 33,9% ) had moderate pain. The assessment of agreement between the painful self-reporting and data from medical records regarding Pain. showed that only 45 (39,1% ) and 42 ( 36,1 %) of the times of admission and in the hospital course respectively, were recorded information about pain. Concerning the adequacy of analgesic therapy, it was found negative IMD in 85 (82,6 % ) patients. There was inappropriate prescribing in 78,3% of patients. The use of monotherapy use of non-opioid analgesics (dipyrone / acetaminophen) and nonsteroidal anti-inflammatory drugs in 87,8 % of patients was predominant, while opiates were used in only 14,7% of patients. Conclusions: The initial assumptions of this research were partially supported. The prevalence of Pain. in hospitalized patients was not high as assumed, but the analgesic adequacy was unsatisfactory. Moreover, there was no agreement between self-reported Pain. and records data, indicating that doctors do not to ask about this symptom or register it in the records. It has been shown inadequate treatment regimens and the need for greater knowledge of the analgesics use in Pain. therapy in the LWUH

Pain Symptoms Associated with Opioid Use among Vulnerable Persons with HIV: An exploratory study with implications for palliative care and opioid abuse prevention.

Current or former injection drug users with human immunodeficiency virus (HIV) are at high risk for pain, which adversely affects their quality of life and may increase their risk for illicit drug use or relapse. We explored associations between pain symptoms and substance use among injection-drug-using study participants with HIV who had histories of heroin use. Using generalized estimating equations and controlling for prior substance use, we found that pain in each six-month period was associated with the use of heroin and prescription opioids, but not the use of nonopioid drugs or alcohol. Routine clinical assessment and improved management of pain symptoms may be needed for persons with HIV and a history of injection drug use, particularly those with chronic pain, for whom there is increased risk for heroin use.

Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding.

Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for the justification of alternative pain therapies. This study systematically examined the antihyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. Von Frey and Hargreaves tests were used to examine the antihyperalgesic effects of drugs in complete Freund's adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. 2-BFI (3.2-17.8mg/kg, i.p.), phenyzoline (17.8-100mg/kg, i.p.), and acetaminophen (56-178mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. Quantitative analysis of the antihyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen.

Impact of Illicit Drug Use on Health-Related Quality of Life in Opioid-Dependent Patients Undergoing HIV Treatment.

To assess the impact of illicit drug use on health-related quality of life (health utility) among opioid-dependent HIV-infected patients. Secondary analyses of data from the Buprenorphine-HIV Evaluation and Support cohort of HIV-infected patients with opioid dependence in 9 US HIV clinics between 2004 and 2009. Health status [short form-12 (SF-12)], combination antiretroviral treatment (ART) status, CD4 cell count, hepatitis C virus antibody status, current drug use, and demographics were assessed at the initial visit and quarterly follow-up visits until 1 year. The SF-6D health utility scores were derived from the SF-12. Multivariate mixed-effects regression models were used to assess the impact of illicit drug use on health utility controlling for demographic, clinical, and social characteristics. Health utility was assessed among 307 participants, 67% male, with a median age of 46 years at 1089 quarterly assessments. In multivariate analyses, illicit opioid use, nonopioid illicit drug use, not being on ART, and being on ART with poor adherence were associated with lower health utility. The observed decrement in health utility associated with illicit opioid use was larger for those on ART with good adherence (beta = -0.067; P < 0.01) or poor adherence (-0.049; P < 0.01) than for those not on ART. Illicit opioid and nonopioid drug use are negatively associated with health utility in patients with HIV; however, the relative effect of illicit opioid use is smaller than that of not being on ART. Postponing ART until initiation of opioid substitution therapy or abstinence may have limited benefits from the perspective of maximizing health utility.

Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse

Purpose:This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use.Method:We followed ...

An Audit of Changes in Outcomes of Acute Pain Service: Evolution Over the Last 2 Decades.

Acute pain services (APS) have evolved over time. Strategies nowadays emphasize multimodal analgesic regimes using a combination of nonopioid adjuvant analgesic drugs, peripheral nerve blocks, and local anaesthetic wound infiltration where appropriate. APS should be assessed over time to evaluate changes in outcomes which form the basis for future development.In this audit, data of patients under APS care in Queen Mary hospital, Hong Kong, between 2009 and 2012 were analyzed and compared with data from a previous audit between 1992 and 1995. The use of patient-controlled analgesia (PCA) was increased (from 69.3% to 86.5%, P < 0.001), while the use of epidural analgesia reduced (from 25.3% to 8.3%, P < 0.001) significantly. Although postoperative pain scores did not improve, PCA opioid consumption and the incidence of analgesia-related side effects were significantly less (all P < 0.001). More patients graded their postoperative analgesic techniques used as good when the results from these 2 audit periods were compared (P < 0.001 and P = 0.001 for PCA and epidural analgesia, respectively). In conclusion, there has been a change in analgesic management techniques, but there has been no improvement in overall pain relief. While changes over time have led to improvement in important parameters such as the incidence of side effects and patient satisfaction, further and continuous efforts and improvements are warrant to reduce acute pain relief and suffering of the patients after the surgery.

The effect of prescription opioid injection on the risk of non-fatal overdose among people who inject drugs

ObjectivesPrescription opioid (PO) use by people who inject drugs (PWID) is a growing public health concern. Non-fatal overdose remains a leading source of morbidity among PWID, however, little is known about the relationship between PO injection and non-fatal overdose in this population. In this study we sought to examine the impact of PO injection on non-fatal overdose among PWID from Vancouver, Canada. MethodsData were derived from two open prospective cohorts of PWID for the period of December, 2005 to May, 2014. Multivariable generalized estimating equations were used to examine the odds of overdose among those who injected: POs; heroin; and POs and heroin. ResultsIn total, 1660 PWID (33.7% women) participated in this study. In multivariable analyses, in comparison to those who were injecting non-opioid drugs, exclusive PO injection was not significantly associated with non-fatal overdose (adjusted odds ratio [AOR]: 1.17, 95% confidence interval [CI]: 0.74–1.86). The odds of non-fatal overdose were elevated for heroin injection (AOR: 1.72, 95% CI: 1.31–2.27), but were greatest for those who injected both heroin and POs (AOR: 2.46, 95% CI: 1.83–3.30). DiscussionCompared to injecting non-opioids, injecting POs exclusively did not increase risk of non-fatal overdose; however, injecting both POs and heroin doubled the risk. This may reflect consistencies in drug potency and composition when POs are used, as well as unique characteristics of exclusive PO injectors. Our findings call for the continued scale-up of evidence-based overdose prevention interventions for people who inject opioids, including POs.

Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice

Objective:To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice.Research design and methods:This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician’s global impression (PGI) during the 12 week observation period.Results:A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by −2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12.Conclusion:This is a first report to evaluate the risk–benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk–benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs.Trial registration:This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).

Advanced formulations for improving therapies with anti-inflammatory or anaesthetic drugs: A review

The development of new more effective therapeutic treatments for pain relief is essential for enhancing the patient quality of life and safety and avoiding or limiting risks of abuse, addiction or serious injuries posed by some of the present pain therapies. With this aim, in the last years, several advanced delivery systems have been developed to increase bioavailability, therapeutic efficacy and safety of well known analgesics, overcoming limits and drawbacks of traditional formulations. Among the different kinds of drugs used in the treatment of pain, non-opioid drugs such as local anaesthetics, corticosteroids and non steroidal anti-inflammatory drugs are preferred in the treatment of mild or moderate pain. However, each of these classes is associated with different adverse events and inconveniences, most of which could be reduced or overcome by appropriate drug carrier systems. This review is focused on recent drug delivery strategies based on micro- and nano-technologies developed for improving the effectiveness in pain management through non-opioid agents, exploiting different approaches such as: cyclodextrin complexation, solid dispersions with hydrophilic polymers, mechano-chemically activated systems, micro and nanoparticles, micro and nano-emulsions, vesicular systems. Combined approaches, simultaneously exploiting the relative advantages of such systems in a single drug delivery device, were also reviewed.

Pharmacokinetics and disposition of flupirtine in the horse

Flupirtine (FLU) is a non-opioid analgesic drug, with no antipyretic or anti-inflammatory effects, used in the treatment of a wide range of pain states in human beings. It does not induce the side effects associated with the classical drugs used as pain relievers. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy horses. Six mixed breed adult mares were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, paired, cross-over design (2 × 2 Latin-square). Group 1 (n = 3) received a single dose of 1 mg/kg of FLU injected IV into the jugular vein. Group 2 (n = 3) received FLU (5 mg/kg) via nasogastric tube. The animals then swapped groups after a 1-week wash-out period and the doses were repeated. Blood samples (5 mL) were collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36 and 48 h and plasma was then analysed by a validated HPLC method.Some mild and transient adverse effects (that spontaneously resolved within 5 min) were observed in 2/6 animals after IV administration. No adverse effects were noticed in the PO administration group. After IV and PO administrations, FLU was detectable in plasma for up to 36 h. The mean elimination half-life was longer after PO (10.27 h) than after IV (3.02 h) administration. The oral bioavailability was 71.4 ± 33.1%. After compartmental simulation/modelling, an oral dose of 2.6 mg/kg was calculated to give Cmax and AUC values in horses similar to those reported in humans after a clinical dose administration with a theoretical FLU effective plasma concentration of 187 ng/mL. These findings may form the basis for further studies concerning this active ingredient in equine medicine.

Characteristics of Non-Opioid Substance Misusers Among Patients Enrolling in Opioid Treatment Programs: A Latent Class Analysis

Using latent class analysis, this study examined the pattern of non-opioid substance misuse among 19,101 enrollees into 85 opioid treatment programs. The most frequent non-opioid drugs were cannabis, anti-anxiety medications, and cocaine. Four non-opioid drug use latent classes were identified: low-use (73%), prescription drug use (16%), marijuana and cocaine use (8.5%), and poly-drug use (2.5%). Compared to the low-use class, participants in the other classes were more likely to be female, Caucasian, use tobacco, have chronic pain, and use prescription opioids either with or without heroin. Recognition of characteristics derived from these classes can improve opioid treatment program services.

Opioid abuse and depression in adolescents: Results from the National Survey on Drug Use and Health

ObjectiveTo investigate the association of major depressive episode (MDE) with nonmedical prescription opioid use (NMPOU) and opioid abuse/dependence among adolescents aged 12 to 17. MethodsWe analyzed 5 years of data from the National Survey on Drug Use and Health (NSDUH). We used logistic regressions to study the relationship between MDE and NMPOU among all adolescents, as well as the relationship of MDE with opioid abuse/dependence among adolescents with NMPOU. Other covariates included: sociodemographics, alcohol abuse/dependence, nonopioid drug abuse/dependence, delinquency, school performance, religious services attendance, and family support/supervision. ResultsIn the sample of all adolescents, 6% reported past year NMPOU, and 8% reported past year MDE. When NMPOU and MDE were comorbid, MDE usually preceded the NMPOU. In the sample of adolescents with NMPOU, 15% reported past year opioid abuse/dependence, and 20% reported past year MDE. In adjusted logistic regression, MDE was associated with both NMPOU (OR=1.51, p<0.001) among all adolescents and opioid abuse/dependence (OR=2.18, p<0.001) among adolescents with NMPOU. ConclusionMDE occurs commonly in adolescents and is associated with NMPOU and opioid abuse/dependence. In terms of population attributable risk, which is a function of both the prevalence and the strength of the association, MDE is an important risk factor for NMPOU among adolescents and opioid abuse/dependence among adolescents with NMPOU. Preventive and clinical programs to decrease NMPOU and opioid abuse/dependence among adolescents should consider the prominent role of depression.

Anesthesia and pain management during pregnancy

During the perioperative and postoperative care of pregnant women it is prudent to pay close attention to the changed physiology of these patients. The main principles of care are the preservation of maternal and fetal homeostasis as well as avoidance of any substances with toxic effects on the fetus. In order to provide pregnant patients with good quality care, all relevant disciplines should be involved as early as possible. Modern anesthetic drugs can be used as they seem to be without teratogenic effects. Adequate perioperative surveillance and assessment of the fetus is also important.The mainstay of pain management during pregnancy is the World Health Organization (WHO) pain ladder. It is of the utmost importance to use only substances without teratogenic or fetotoxic properties. Considering non-opioid drugs, the use of paracetamol is a viable option, whereas non-steroidal anti-inflammatory drugs (NSAID) should only be used with rigorous restrictions. Tramadol is a first-line drug when using opioids with low potency, whereas morphine can be used as an opioid with a higher potency after careful consideration of the risk-benefit ratio. If possible anticonvulsives should not be used as an adjunct in pain management during pregnancy. The use of thoroughly investigated antidepressants seems to be a better alternative. Apart from drug therapy it is important to use all available conservative pain treatment options.

Intravenous nonopioid analgesic drugs in chronic low back pain patients on chronic opioid treatment: A crossover, randomised, double-blinded, placebo-controlled study: Retraction.

The authors of the 2014 article "Intravenous nonopioid analgesic drugs in chronic low back pain patients on chronic opioid treatment: A crossover, randomised, double-blinded, placebo-controlled study" wish to retract the article as Dr Kozek-Langenecker did not consent to its submission and publication.

Oral analgesia for relieving post-caesarean pain.

Oral analgesia for relieving post-caesarean pain.

Flupirtine: Preliminary Pharmacokinetics in the Donkey

Flupirtine (FLU) is a nonopioid analgesic drug with no antipyretic or antiphlogistic effects labeled for humans. It does not induce the side effects associated with the classical drugs used as pain relievers (Non steroidal antiinflammatory drugs and opioids) in human beings. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administrations in healthy donkeys. Six Amiata breed adult jennies were randomly assigned to two treatment groups using an open, 2 × 2 Latin-square crossover study design. Group 1 (n = 3) received a single dose of 1 mg/kg of FLU injected IV into the jugular vein. Group 2 (n = 3) received FLU (5 mg/kg) via nasogastric tube. The washout period was 1 week. Blood samples (5 mL) were collected at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36, and 48 hours, and plasma was then analyzed by a validated high-performance liquid chromatography method. No adverse effects were noticed in either administration group. After IV and PO administrations, FLU was detectable in plasma for up to 24 hours. The mean elimination half-life was longer after PO (10.81 hours) than after IV (0.90 hours) administration. The clearance was fast, and the area under the plasma concentration–time curve was small, findings consistent with a low PO bioavailability of about 20%. The pharmacokinetic trend of FLU in donkeys was different from those earlier reported in cats and dogs. Further studies are needed to understand if this active ingredient may be used in donkeys.

Clinical perspective on the Clinical Pharmacogenetics Implementation Consortium Updated 2014 guidelines for CYP2D6 and codeine.

As pharmacogenomics makes further advances into clinical practice, the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provide considerable assistance in clinical decision making. The new 2014 CPIC guidelines on CYP2D6 and codeine (1) have an update on considerations for clinicians and healthcare providers. The previous CPIC guidelines provided recommendations primarily on codeine and tramadol. The new guidelines maintain the dosing recommendations for codeine—specifically, to avoid codeine in both CYP2D6 poor and ultrarapid metabolizers; however, the guidelines take another step forward by noting that, not only may tramadol be problematic, but hydrocodone and oxycodone are also not considered good analgesic alternatives when metabolic concerns exist with CYP2D6. Additionally, this update recommends alternatives with the following statement: “To avoid treatment complications, opioids that are not metabolized by CYP2D6, including morphine, oxymorphone, buprenorphine, fentanyl, methadone, and hydromorphone, along with nonopioid analgesics, may be considered as alternatives for use in CYP2D6 poor metabolizers and in ultrarapid metabolizers….” Although appropriate from a CYP2D6 metabolic standpoint, these recommendations may present some challenges to healthcare providers when applied to some clinical settings. Pain is one of the leading reasons a patient presents to healthcare providers, which includes physicians, dentists, physician assistants, and nurse practitioners in both inpatient hospital and outpatient clinic community settings. Many healthcare providers follow a WHO ladder “type” approach for the treatment of pain (2). In this paradigm, depending on the severity of the pain, a nonopioid drug is considered as a first step in pain management (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs). The second step employs an opioid commonly used for moderate pain (e.g., tramadol, codeine, hydrocodone, and possibly oxycodone), often in combination with acetaminophen or nonsteroidal anti-inflammatory drugs. The third step includes the use of an opioid usually reserved for severe pain presentation (e.g., morphine, oxymorphone, fentanyl, methadone, and hydromorphone). Of concern, the new …

Bioanalytical Method Validation and Quantification of Flupirtine in Canine Plasma by HPLC with Spectrofluorimetric Detection

Flupirtine (FLU) is a non-opioid analgesic drug belongs to the class of N-Methyl-D-Aspartate (NMDA) antagonist without antipyretic or antiphlogistic properties. No analytical method to detect FLU in canine plasma samples through a fluorimetric detector has been published to date. The analytical method described in this work provides a selective and accurate quantification of FLU. The mobile phase consisted of ACN:AcONH4 (20 mM) pH 6.8 (60:40, v/v) at a flow rate of 1 mL min−1 in isocratic mode. Excitation and emission wavelengths were set at 323 and 370 nm, respectively. The recoveries of FLU and IS (trazodone) were about 89 and 77%. Typical retention times for FLU and IS was 4.6±0.2 and 5.8±0.2 min, respectively. Limits of quantification and detection were 1 and 0.3 ng/mL, respectively. The described method was validated according to international guidelines on the bioanalytical method validation. The applicability of this method was verified by determining FLU in canine plasma after single oral treatment with 5 mg kg−1 of Efiret®. The low LOQ showed that the present method could be useful for the FLU measurement even when administered in sub-clinical doses.

Impairment of aspirin antiplatelet effects by non-opioid analgesic medication.

Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin, resulting in impaired aspirin antiplatelet effects. Additionally, non-opioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used non-opioid analgesics, interactions with aspirin medication and impact on cardiovascular risk.