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Analgesic Drugs (analgesic + drug)

Distribution by Scientific Domains

Medical Sciences	77%
Life Sciences	16%

Selected Abstracts

Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumption

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2009
Sabine Gaubert
Abstract Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half-lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization-days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (,8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital-based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene. [source]

Evaluation of tramadol and its main metabolites in horse plasma by high-performance liquid chromatography/fluorescence and liquid chromatography/electrospray ionization tandem mass spectrometry techniques

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 2 2009
Marinella De Leo
Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat pain in humans. The clinical response of tramadol is strictly correlated to its metabolism, because of the different analgesic activity of its metabolites. O -Desmethyltramadol (M1), its major active metabolite, is 200 times more potent at the µ -receptor than the parent drug. In recent years tramadol has been widely introduced in veterinary medicine but its use has been questioned in some species. The aim of the present study was to develop a new sensible method to detect the whole metabolic profile of the drug in horses, through plasma analyses by high-performance liquid chromatography (HPLC) coupled with fluorimetric (FL) and photodiode array electrospray ionization mass spectrometric (PDA-ESI-MS) detection, after its sustained release by oral administration (5,mg/kg). In HPLC/FL experiments the comparison of the horse plasma chromatogram profile with that of a standard mixture suggested the identification of the major peaks as tramadol and its metabolites M1 and N,O -desmethyltramadol (M5). LC/PDA-ESI-MS/MS analysis confirmed the results obtained by HPLC/FL and also provided the identification of two more metabolites, N -desmethyltramadol (M2), and N,N -didesmethyltramadol (M3). Another metabolite, M6, was also detected and identified. The present findings demonstrate the usefulness and the advantage of LC/ESI-MS/MS techniques in a search for tramadol metabolites in horse plasma samples. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Inhibition of Cyclooxygenases by Dipyrone

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2007
S C Pierre
Background and Purpose: Dipyrone is a potent analgesic drug that has been demonstrated to inhibit cyclooxygenase (COX). In contrast to classical COX-inhibitors, such as aspirin-like drugs, dipyrone has no anti-inflammatory effect and a low gastrointestinal toxicity, indicating a different mode of action. Here, we aimed to investigate the effects of dipyrone on COX. Experimental approach: The four major metabolites of dipyrone, including the two pharmacologically active metabolites, 4-methyl-amino-antipyrine (MAA) and amino-antipyrine (AA), were used to characterise their binding to COX and haem as well as their effects on the biochemical properties of COX. Mass spectrometry, UV and visible photometry were used to study binding and prostaglandin production. Levels of anti-oxidant enzymes were assessed by Western blotting. Key results: The pharmacologically active metabolites of dipyrone, MAA and AA, did not inhibit COX activity in vitro like classical COX inhibitors, but instead redirected the prostaglandin synthesis, ruling out inhibition of COX through binding to its active site. We found that MAA and AA formed stable complexes with haem and reacted with hydrogen peroxide in presence of haem, ferrous ions (Fe2+) or COX. Moreover, MAA reduced Fe3+ to Fe2+ and accordingly increased lipid peroxidation and the expression of anti-oxidant enzymes in cultured cells and in vivo. Conclusions and implications: Our data suggest that the pharmacologically active metabolites of dipyrone inhibit COX activity by sequestering radicals which initiate the catalytic activity of this enzyme or through the reduction of the oxidative states of the COX protein. British Journal of Pharmacology (2007) 151, 494,503; doi:10.1038/sj.bjp.0707239 [source]

Addiction Research Centres and the Nurturing of Creativity The Chinese National Institute on Drug Dependence, Peking University: past, present and future

ADDICTION, Issue 9 2010
Xi Wang
ABSTRACT In the 25 years since drug abuse re-emerged in China in the 1980s, the National Institute of Drug Dependence (NIDD) has made many contributions to China's antidrug campaign. This present paper offers an account of the history, current status and future of drug dependence research at NIDD. NIDD was originally a research centre at Beijing Medical University, founded by the Chinese Ministry of Health to address the rapid spread of drug abuse in China. Originally, the main task of NIDD was to complete the commissions assigned by the government and university. Further developments transformed NIDD into a national research institute in the field of drug addiction that began to conduct its own research. NIDD has now created a professional team spread across several independent departments involved in neurobiological mechanisms, epidemiological surveys and monitoring, pre-clinical and clinical evaluation of new drugs (mainly analgesic drugs and detoxification drugs) and informatics and data analysis. As a university-based research institute, NIDD's funding derives mainly from grants provided by the government and financial support from international organizations. Its past and present research has a gained NIDD a reputation with both practitioners and policy makers in the field of drug addiction. In the future, NIDD will continue to engage in various aspects of drug addiction research and will enter the field of brain function. [source]

Lumbosacral spinal cord somatosensory evoked potentials for quantification of nociception in horses

EQUINE VETERINARY JOURNAL, Issue 3 2010
J. P. A. M. Van LOON
Summary Reasons for performing study: There is a need for objective evaluation and quantification of the efficacy of analgesic drugs and analgesic techniques in horses. Objectives: To determine whether lumbosacral spinal cord somatosensory evoked potentials (SSEP) can be a useful and reliable tool to assess nociception in equines. Methods: SSEPs and electromyograms (EMG) from the epaxial muscles were recorded simultaneously, following electrical stimulation applied to the distal hindlimb in lightly anaesthetised Shetland ponies (n = 7). In order to validate the model, the effect of increasing stimulus intensity was documented and the conduction velocities (CV) of the stimulated nerves were calculated. The effect of epidurally applied methadone (0.4 mg/kg bwt) in a randomised, crossover design was investigated. Results: Two distinct complexes (N1P1 and N2P2) were identified in the SSEP waveform. Based on their latency and conduction velocity and the depressant effect of epidurally applied methadone, the SSEP N2P2 was ascribed to nociceptive A,-afferent stimulation. The SSEP N1P1 originated from non-nociceptive A,-afferent stimulation and was not influenced by epidurally applied methadone. Conclusions and potential relevance: The nociceptive A, component of the SSEP, the N2P2 complex, is presented as a valid and quantitative parameter of spinal nociceptive processing in the horse. Validation of the equine SSEP model enables the analgesic effects of new analgesics/analgesic techniques to be quantified and analgesia protocols for caudal epidural analgesia in equidae improved. [source]

Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumption

Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve patient psychomotor skills

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010
E. GALVIN
Background: Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia. Methods: Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment. Results: Sixty-seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p>0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p<0.05. Conclusion: Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills. [source]

RNA interference in pain research

JOURNAL OF NEUROCHEMISTRY, Issue 2 2006
Thomas Röhl
Abstract Within the course of only the last few years, RNA interference (RNAi) has been established as a standard technology for investigation of protein function and target validation. The present review summarizes recent progress made in the application of RNAi in neurosciences with special emphasis on pain research. RNAi is a straightforward method to generate loss-of-function phenotypes for any gene of interest. In mammals, silencing is induced by small interfering RNAs (siRNAs), which have been shown to surpass traditional antisense molecules. Due to its high specificity, RNAi has the potential for subtype selective silencing of even closely related genes. One of the major challenges for in vivo investigations of RNAi remains efficient delivery of siRNA molecules to the relevant tissues and cells, particularly to the central nervous system. Various examples will be given to demonstrate that intrathecal application of siRNAs is a suitable approach to analyse the function of receptors or other proteins that are hypothesized to play an important role in pain signalling. Intensive efforts are currently ongoing to solve remaining problems such as the risk of off-target effects, the stability of siRNA molecules and their efficient delivery to the CNS. RNAi has thus demonstrated that it is an extremely valuable tool for the development of new analgesic drugs. [source]

Induction of Glycerol Phosphate Dehydrogenase Gene Expression During Seizure and Analgesia

JOURNAL OF NEUROCHEMISTRY, Issue 4 2000
Wolfgang A. Link
Abstract: Using mRNA differential display, we found that the gene for NAD+ -dependent glycerol phosphate dehydrogenase (GPDH; EC 1.1.1.8) is induced in rat brain following seizure activity. Northern blot and in situ hybridization analysis confirmed the differential display results; they also showed, in a separate model of neuronal activation, that after thermal noxious stimulation of the hind-paws, a similar increase in GPDH mRNA occurs in the areas of somatotopic projection in the lumbar spinal cord. Surprisingly, administration of analgesic doses of morphine or the nonsteroidal antiinflammatory drugs aspirin, metamizol (dipyrone), and indomethacin also increased GPDH mRNA levels in rat spinal cord. The opioid receptor antagonist naloxone completely blocked morphine induction of GPDH but had no effect on GPDH induction by noxious heat stimulation or metamizol treatment, implicating different mechanisms of GPDH induction. Nevertheless, in all cases, induction of the GPDH gene requires adrenal steroids and new protein synthesis, as the induction was blocked in adrenalectomized rats and by cycloheximide treatment, respectively. Our results suggest that the induction of the GPDH gene upon peripheral noxious stimulation is related to the endogenous response to pain as it is mimicked by exogenously applied analgesic drugs. [source]

Hyperalgesic effects of ,-aminobutyric acid transporter I in mice

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003
Jia-Hua Hu
Abstract The present study focused on the involvement of ,-aminobutyric acid transporter I (GAT1) in pain. We found that GABA uptake was increased in mouse spinal cord at 20 min and 120 min after formalin injection and in mouse brain at 120 min, but not 20 min, after formalin injection. In addition, the antinociceptive effects of GAT1-selective inhibitors were examined using assays of thermal (tail-flick) and chemical (formalin and acetic acid) nociception in C57BL/6J mice. The GAT1-selective inhibitors, ethyl nipecotate and NO-711, exhibited significant antinociceptive effects in these nociceptive assays. To study further the effects of GAT1 on pain, we used two kinds of GAT1-overexpressing transgenic mice (under the control of a CMV promoter or a NSE promoter) to examine the nociceptive responses in these mice. In the thermal, formalin, and acetic acid assays, both kinds of transgenic mice displayed significant hyperalgesia after nociceptive stimuli. In addition, the , opioid receptor antagonist naloxone had no influence on nociceptive responses in wild-type and transgenic mice. The results indicate that GAT1 is involved in the regulation of pain processes, and point to the possibility of developing analgesic drugs that target GAT1 other than opioid receptors. © 2003 Wiley-Liss, Inc. [source]

Pain management in horses and farm animals

JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2005
Alexander Valverde DVM, DACVA
Abstract Objective: This review discusses the different analgesic drugs and routes of administration used in large animals for acute pain management. General guidelines and doses are given to assist in choosing techniques that provide effective analgesia. Etiology: Noxious stimuli are perceived, recognized, and localized by specialized sensory systems located at spinal and supraspinal levels. Diagnosis: Localizing the source of the noxious stimulus as well as understanding the behavioral aspects and physiological changes that result from such insult is important to adequately diagnose and treat pain. Pain assessment is far from being definite and objective; not only are there species differences, but also individual variation. In addition, the behavioral and physiological manifestations vary with the acute or chronic nature of pain. Therapy: Pain management should include (1) selecting drugs that better control the type of pain elicited by the insult; (2) selecting techniques of analgesic drug administration that act on pathways or anatomical locations where the nociceptive information is being processed or originating from; (3) combining analgesic drugs that act on different pain pathways; and (4) provide the best possible comfort for the animal. Prognosis: Providing pain relief improves the animal's well being and outcome; however, interpreting and diagnosing pain remains difficult. Continuing research in pain management will contribute to the evaluation of the pathophysiology of pain, pain assessment, and newer analgesic drugs and techniques. [source]

,Protective premedication': an option with gabapentin and related drugs?

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2004
A review of gabapentin, pregabalin in the treatment of post-operative pain
Substantial progress has been made during the last decades in our understanding of acute pain mechanisms, and this knowledge has encouraged the search for novel treatments. Of particular interest has been the observation that tissue injury initiates a number of modulations of both the peripheral and the central pain pathways, which convert the system from a ,physiological' to a ,pathological' mode of processing afferent information. Gabapentin, which binds to the ,2, subunit of the voltage-dependent calcium channel, is active in animal models of ,pathological' but not in models of ,physiological' pain. Consequently, attention has so far been focused on neuropathic pain as a target for the clinical use of gabapentin and analogues. Recently, several reports have indicated that gabapentin may have a place in the treatment of post-operative pain. This article presents a brief summary of the potential mechanisms of post-operative pain, and a systematic review of the available data of gabapentin and pregabalin for post-operative analgesia. It is concluded that the results with gabapentin and pregabalin in post-operative pain treatment published so far are promising. It is suggested that future studies should explore the effects of ,protective premedication' with combinations of various antihyperalgesic and analgesic drugs for post-operative analgesia. [source]

Experiences of intensive care nurses assessing sedation/agitation in critically ill patients

NURSING IN CRITICAL CARE, Issue 4 2008
Stephanie Weir
Abstract Background:, Patients admitted to the intensive care unit (ICU) will more often than not require sedative and analgesic drugs to enable them to tolerate the invasive procedures and therapies caused as a result of their underlying condition and/or necessary medical interventions. Aim:, This article reports a study exploring the perceptions and experiences of intensive care nurses using a sedation/agitation scoring (SAS) tool to assess and manage sedation and agitation amongst critically ill patients. The principle aims and objectives of this study were as follows: ,,to explore nurse's everyday experiences using a sedation scoring tool; ,,to explore and understand nurse's attitudes and beliefs of the various components of assessing and managing sedation among critically ill patients. Method:, Using a descriptive qualitative approach, semistructured interviews were carried out with a purposive sample of eight ICU nurses within a district general hospital ICU. The interviews focused on nurse's own experiences and perceptions of using a sedation scoring tool in clinical practice. Burnard's 14-stage thematic content analysis framework was employed to assist in the data analysis process. Results:, Three key themes emerged that may have implications not only for clinical practice but for further research into the use of the SAS tool. ,,Benefits to patient care as a direct result of using a sedation scoring tool. ,,The concerns of nursing staff. ,,The implications of using such a tool in clinical practice. Conclusion:, This paper reinforces the potential benefits to patients as a direct result of implementing the SAS scoring tool and clinical guidelines. Furthermore, it highlights the reluctance of a number of staff to adhere to such guidelines and discusses the concerns regarding less experienced nurses administering sedative agents. Attention was also drawn to the educational requirements of nursing and medical staff when using the SAS scoring tool. [source]

Collagen-induced arthritis as a model of hyperalgesia: Functional and cellular analysis of the analgesic actions of tumor necrosis factor blockade

ARTHRITIS & RHEUMATISM, Issue 12 2007
Julia J. Inglis
Objective There is a disparity in the animal models used to study pain in rheumatoid arthritis (RA), which tends to be acute in nature, and models used to assess the pathogenesis of RA. The latter models, like human RA, are lymphocyte-driven and polyarthritic. We assessed pain behavior and mechanisms in collagen-induced arthritis (CIA), the model of preclinical arthritis used most commonly in the field of immunology. We then validated the model using anti,tumor necrosis factor (anti-TNF) therapy, which has analgesic effects in models of inflammation as well as in human RA. Methods CIA was induced in DBA/1 mice by immunization with type II collagen at the base of the tail. Swelling and mechanical and thermal hyperalgesia were assessed before and for 28 days after the onset of arthritis. Spontaneous behavior was assessed using an automated activity monitor. Glial activity was assessed by glial fibrillary acidic protein expression, and nerve damage was evaluated by activating transcription factor 3 expression. The actions of anti-TNF therapy on nociception were then evaluated. Results Arthritis resulted in a decrease in the threshold for thermal and mechanical stimuli, beginning on the day of onset. Decreased spontaneous activity was also observed. A significant increase in the number of hyperplasic spinal cord astrocytes was observed beginning 10 days after the onset of arthritis. Anti-TNF therapy was profoundly analgesic, with an efficacy similar to that of cyclooxygenase 2 inhibition, and reduced astrocyte activity in CIA. Conclusion This study shows that the CIA model is suitable for testing not only antiinflammatory but also analgesic drugs for potential use in RA, and highlights the importance of using appropriate disease models to assess relevant pain pathways. [source]

Postoperative analgesic requirements , total laparoscopic hysterectomy versus vaginal hysterectomy

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2005
Marcelo Carraro NASCIMENTO
Abstract Background:, There is limited information available on the requirement for postoperative analgesic drugs in patients submitted to total laparoscopic hysterectomy (TLH) compared with patients undergoing vaginal hysterectomy (VH). Aim:, To compare the postoperative analgesic requirements in patients who underwent a TLH with patients who had a VH. Methods:, Chart review of 53 patients who had TLH and 47 who had VH and were seen postoperatively by an acute pain management service in order to assess postoperative analgesic requirements. Patient controlled analgesia (PCA) was part of the standard protocol for postoperative pain management. Analgesic requirement was recorded as the mean doses of morphine and number of days that patients used non-steroidal anti-inflammatory drugs (NSAIDs), oxycodone and tramadol. Results:, The requirement for total morphine was approximately half the dose in patients who had a TLH (10.8 ± 12.6 mg) compared with patients who had a VH (19.4 ± 21.9 mg) (P 0.017). The length of use of NSAIDs was significantly reduced in patients who had undergone a TLH (2.0 ± 0.95 days) as compared with patients who had a VH (2.85 ± 1.1 days) (P < 0.0001). Conclusions:, Patients submitted to TLH require less postoperative analgesic drugs when compared with patients who had VH. Prospective randomised trials are warranted to compare analgesic requirements between patients submitted to TLH and VH. [source]

Calotropis procera latex-induced inflammatory hyperalgesia , effect of bradyzide and morphine

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2007
Vijay L. Kumar
Summary 1,The milky white latex of the plant Calotropis procera induces inflammatory response upon accidental exposure and on local administration that could be effectively ameliorated by antihistaminic and standard anti-inflammatory drugs. 2,The aim of the present study was to evaluate the anti-oedematogenic and analgesic effect of the bradykinin antagonist, bradyzide (BDZ) and the opioidergic analgesic, morphine (Mor) against inflammatory hyperalgesia induced by the dried latex (DL) of C. procera in the rat paw oedema model. 3,An aqueous solution of DL (0.1 ml of 1% solution) was injected into the sub-plantar surface of the rat paw and the paw volume was measured at different time intervals. The inhibitory effect of bradyzide and morphine on oedema formation and hyperalgesic response was compared with that of cyproheptadine (CPH), a potent inhibitor of DL-induced oedema formation. 4,The hyperalgesic response was evaluated by the dorsal flexion pain test, compression test and by observing motility, stair-climbing ability, and the grooming behaviour of the rats. 5,The effect of these drugs was also evaluated against DL-induced writhings in the mouse model. 6,Both bradyzide and morphine inhibited DL-induced oedema formation by 30,40% and CPH was more effective in this regard (81% inhibition). The antihyperalgesic effect of both the drugs was more pronounced than that of CPH. Both bradyzide and morphine markedly inhibited the grooming behaviour and the effect of morphine could be reversed by pretreatment with naloxone. 7,Thus, our study shows that DL-induced oedema formation is effectively inhibited by antihistaminic/antiserotonergic drug and associated hyperalgesia by analgesic drugs. [source]

Antinociceptive Activity of a New Benzofuranone Derived from a Chalcone

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009
Pâmela Padaratz
The aim of this work was the synthesis of a new benzofuranone compound and evaluation of its antinociceptive potential in mice. The new benzofuranone 4 was synthesized from chalcone 3. The antinociceptive activity of 4 was determined by writhing, formalin, capsaicin, and glutamate and hot-plate tests. Compound 4 caused potent and dose-related inhibition against the writhing test with ID50 6.1 (5.1,7.6) ,mol/kg, i.p., being about 15 times more active than the reference drugs, acetyl salicylic acid and acetaminophen. It was also effective in a dose-dependent manner in significantly reducing the painful stimulus in both phases of formalin, in the capsaicin and in the glutamate test with ID50 values of 27.3 (24.5,30.6) and 18.9 (18.5,19.4) ,mol/kg (first and second phase), 12.6 (9.8,16.2) and 24.5 (20.4,29.6) ,mol/kg respectively. The results showed that the studied compound exhibits both central and peripheral antinociceptive activities and might be further used as a model to obtain new and more potent analgesic drugs. [source]