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PubMed1982

Cortical-evoked potentials and saliva levels as basis for the comparison of pure analgesics to analgesic combinations.

Cortical-evoked potentials, pain ratings and thresholds of sensation were monitored after tooth pulp stimulation under the influence of marketed mixtures of analgesics. Simultaneously the saliva levels of the individual pharmacological active components of these mixtures were measured by high-performance thin-layer chromatography. The action of the mild analgesics in the mixtures was calculated from the linear correlations of changes in cortical-evoked potential with saliva levels of the analgesics. The ineffectiveness of low doses of salicylamide in the combinations was demonstrated by this method. None of the investigated combination products was superior to the same doses of either acetylsalicylic acid, paracetamol or phenazone.

Adult↗
PubMed1985

[Skin testing with the components of analgesics in patients with anaphylactoid hypersensitivity reactions to mild analgesics].

In 282 patients presenting with adverse reactions to mild analgesics, prick tests were performed with components of analgesic drugs; in some of them, commercial preparations were also tested. In 19 patients (7%), a total of 40 conclusively positive immediate reactions was found: there were 22 reactions to pyrazolone derivatives, 14 reactions to commercial preparations, and one singular reaction to phenacetin, phenobarbital, carbromal and vitamin B1, respectively. Cross-sensitivity to different pyrazolone derivatives was observed in only 5 of 15 patients with a positive reaction to at least one of these substances. One of the patients with a positive immediate reaction and 2 further individuals developed positive test reactions after 4 to 24 h. Within 117 patients who gave a clear-cut history of anaphylactoid reactions to mild analgesics, there were conclusive immediate prick test results in 15 cases (13%). In these patients, the diagnostic relevance of the prick test increased with the severity of symptoms in the history, and a conclusive immediate reaction was obtained in 25% of those with full shock in the history.

Adolescent↗
PubMed1987

[Skin side effects of non-steroidal anti-inflammatory analgesics and so-called minor analgesics. Report from the Berne Comprehensive Hospital Monitor].

9118 of 19,653 inpatients of two internal medicine divisions were treated with analgesics and nonsteroidal antiinflammatory drugs including minor analgesics (NSAID). In the first part of the study all generalized skin reactions (gsr) considered to be probably or definitely due to a drug were evaluated clinically. In 23 out of 91 patients with a drug induced skin reaction, this was judged to be mainly related to an NSAID drug rather than any other drug (= 0.3% of patients exposed to an NSAID). The 26 reactions of the 23 patients were as follows: 15 maculo-papular exanthemas, 6 urticarias, 2 angioedema, 2 serum sickness syndromes and 1 erythema nodosum. In the second part we did statistical calculations only on the basis of the time/exposure relationship to ascertain the rate of gsr with chemotherapeutics and antibiotics (group B), with NSAID including minor analgesics (group A) and with all other drugs. 10.8% occurred with B, 1.8% with A without B and 0.9% without A and without B. The difference between 1.8% (A without B) and 0.9% (neither A nor B) is significant (p less than 0.05).

Analgesics↗
PubMed1972

Renal disease due to analgesics. I. Recognition of the problem of analgesic nephropathy.

The incidence of renal impairment secondary to the abuse of analgesic compounds now accounts for a significant proportion of patients requiring renal replacement therapy. The clinical features of 100 cases of analgesic nephropathy are described; essentially these consist of otherwise unexplained renal impairment, urinary tract symptoms, radiological changes and sterile pyuria, often associated with dyspepsia, anemia and psychiatric disturbances. The classical pathological changes consist of interstitial nephritis and progressive reduction in renal size, secondary to repeated episodes of papillary necrosis. Cessation of analgesic abuse usually arrests the deterioration in renal function, and indeed some recovery of function may occur.

Analgesics↗
PubMed1995

Evaluation of diagnostic criteria for analgesic nephropathy in patients with end-stage renal failure: results of the ANNE study. Analgesic Nephropathy Network of Europe.

It was found that in Belgium, renal imaging techniques, demonstrating a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications, were the only methods to reliably diagnose analgesic nephropathy (AN) in patients with end-stage renal failure. However, these criteria were selected in an area with a high prevalence of this disease (15.6% of the dialysis population at December 1990). To evaluate the criteria selected to diagnose AN in populations with lower or unknown prevalences of AN, the Analgesic Nephropathy Network of Europe (ANNE) was formed, consisting of 23 dialysis units from 14 European countries and Brazil. During 1991-1992, 598 new patients with equivocal diagnosis of renal disease (excluding biopsy-proven glomerulonephritis, polycystic disease, diabetic nephropathy and other systemic diseases) and who began renal replacement therapy in the ANNE centres were evaluated by a short questionnaire and two renal imaging techniques: sonography and either tomography or computed tomography (CT) scan. A comparison of 82 abusers (daily use of analgesic mixtures for at least 5 years) and 495 controls corroborated the excellent diagnostic performance of the renal imaging techniques for AN. We recommend the use of these renal imaging criteria in all patients without a clear renal diagnosis in order to obtain a more reliable insight into the magnitude of the AN problem in different countries.

Adult↗
PubMed2005

Good evidence for effectiveness of analgesics most commonly prescribed by UK dentists. What is the relative efficacy of single-dose oral analgesics after third molar extraction?

DATA SOURCES: Dental trials were sought among systematic reviews of randomised, double-blind studies of analgesics in acute pain, which were identified from the Cochrane Library, Biological Abstracts, MEDLINE, PubMed and the Oxford Pain Relief database. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by two reviewers. Dichotomous information from active and placebo treatments was used, first to calculate the statistical significance using relative risk, and then to evaluate the clinical relevance using number-needed-to-treat (NNT). RESULTS: Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase (COX)-2 inhibitors had the lowest (best) NNT for the outcome of pain at least halved over 4-6 h compared with placebo. With the best performing analgesics, 50-70 patients out of 100 had good pain relief compared with about 10 out of 100 with placebo. Only paracetamol (600/650 mg) plus codeine (60 mg) was associated with any significant increase in any patient experiencing an adverse event. CONCLUSIONS: NSAID and COX-2 inhibitors have the lowest (best) NNT. These may also have fewer adverse effects after third molar surgery, but conclusive evidence is lacking. At least 80% of analgesic prescribing by UK dentists is in line with the best available evidence on efficacy and safety.

Comment↗
PubMed2001

Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705].

BACKGROUND: About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). METHODS/DESIGN: This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. CONCLUSION: We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain.

Journal Article↗
PubMed1985

Prediction of human analgesic dosages of nonsteroidal anti-inflammatory drugs (NSAIDs) from analgesic ED50 values in mice.

The oral analgesic activities (ED50's) of 15 NSAIDs were determined in the phenylquinone-induced writhing test in mice. ED50 values (mg/kg) were: acetylsalicylic acid (182), fenclofenac (168), phenylbutazone (129), ibuprofen (82.2), diflunisal (55.6), benoxaprofen (25.4), naproxen (24.1), mefenamic acid (20.7), indomethacin (19.0), meclofenamate sodium (9.60), sulindac (7.20), fenoprofen calcium (3.70), tolmetin (1.30), zomepirac sodium (0.70), and piroxicam (0.44). Significant linear correlations were found between mouse ED50 values and the various recommended human analgesic or anti-inflammatory dosages. Thus, analgesic ED50 values (mg/kg p.o.) in mice (X) may be used to predict human dosages (Y) of NSAIDs according to the equation Y = 8.26X + 535, where Y is the projected human daily dosage (mg).

Administration, Oral↗
PubMed2003

The analgesic effect of interscalene block using clonidine as an analgesic for shoulder arthroscopy.

UNLABELLED: Used as the sole analgesic, clonidine produces analgesia after central neural blockade and intraarticular injection but not after axillary block. In this study, we sought to determine whether interscalene clonidine induces analgesia for shoulder arthroscopy. Forty patients scheduled for shoulder arthroscopy were prospectively included in this double-blinded study. Using a nerve stimulator technique, an interscalene catheter was inserted. The patients were randomly divided into two groups. The interscalene group (n = 20) received clonidine 150 micro g in 15 mL of saline through the catheter and 1 mL of subcutaneous saline, and the systemic group (n = 20) received 15 mL of saline through the catheter and clonidine 150 micro g (1 mL) subcutaneously. All patients underwent general anesthesia for surgery. On completion of arthroscopy, all patients received, via a patient-controlled analgesia, on demand a bolus of 8 mL of ropivacaine 0.2% through the catheter with a 1-h lockout period. Postoperative pain was measured every 4 h using the visual analog scale (VAS) for 24 h. Additional postoperative analgesia was available with parenteral nalbuphine if required until VAS < 3. VAS scores in the recovery room were significantly higher in the systemic group compared with the interscalene group (P < 0.0001). Analgesic duration was significantly longer in the interscalene group (P < 0.00001), and ropivacaine consumption was significantly less than in the systemic group (P < 0.0001). No significant difference was observed between groups for nalbuphine consumption. Side effects were comparable in the two groups. IMPLICATIONS: Clonidine administered via an interscalene catheter enhanced analgesia compared with systemic administration. Nevertheless, the adverse effect of clonidine at this dose limits its use for routine management for postoperative analgesia.

Adrenergic alpha-Agonists↗
PubMed2003

Tolerance and inverse tolerance to the hyperalgesic and analgesic actions, respectively, of the novel analgesic, F 13640.

5-HT(1A) receptor activation by the very-high-efficacy, selective 5-HT(1A) receptor agonist F 13640 [(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-([(5-methyl-pyridin-2-ylmethyl)-amino]-methyl)piperidin-1-yl]-methanone] was recently discovered to constitute a novel central mechanism of broad-spectrum analgesia that, remarkably, grows rather than decays with chronicity. However, in rodents not exposed to nociception, F 13640 induces its analgesic effect only after having initially induced hyperalgesia. Numerical simulations implementing a signal transduction theory here show that the progressive increase in the intensity of nociceptive stimulation which F 13640 presumably mimics should eventually produce a large analgesic effect without initially causing marked pain. In vivo studies examined the effects of progressively increasing doses of F 13640 on the threshold of mechanically induced vocalization and, also, on the 5-HT syndrome in rats. The infusion of increasing (0.04-0.63 mg/rat/day) doses of F 13640 over a 5-week period induced a large analgesia preceded by a hyperalgesic effect that was small and comparable to that induced by initial exposure to a low, 0.04 mg/rat/day dose. Furthermore, increasing the dose of F 13640 induced tachyphylaxis to the 5-HT syndrome. Producing the mirror opposite of morphine's neuroadaptive actions, F 13640 causes an analgesia that becomes more powerful with chronic administration, and this at the expense of the initial hyperalgesia which it may also produce.

Algorithms↗
PubMed1998

Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice.

Analogs of A-98593 (1) and its enantiomer ABT-594 (2) with diverse substituents on the pyridine ring were prepared and tested for affinity to nicotinic acetylcholine receptor binding sites in rat brain and for analgesic activity in the mouse hot plate assay. Numerous types of modifications were consistent with high affinity for [3H]cytisine binding sites. By contrast, only selected modifications resulted in retention of analgesic potency in the same range as 1 and 2. Analogs of 2 with one or two methyl substituents at the 3-position of the azetidine ring also were prepared and found to be substantially less active in both assays.

Alkaloids↗
PubMed1992

Analgesic dipeptide derivatives. 7. 3,7-Diamino-2-hydroxyheptanoic acid (DAHHA) containing dipeptide analogues of the analgesic compound H-Lys-Trp(Nps)-OMe.

A series of diastereomeric dipeptides, analogues of the analgesic compound H-Lys-Trp(Nps)-OMe (2), containing 3,7-diamino-2-hydroxyheptanoic acid (DAHHA) and 2-[(o-nitrophenyl)sulfenyl]tryptophan [Trp(Nps)] has been synthesized. These compounds were tested as enkephalin-degrading aminopeptidases (APs), AP-M and AP-B inhibitors, and analgesics. The inhibitory potencies and the antinociceptive effects depended on the stereochemistry of the compounds. (2S,3R)-DAHHA-L-Trp(Nps)-OMe (26d) was a highly potent and selective enkephalin-degrading APs inhibitor, with an IC50 value in the 10(-8) M range. Although this derivative was about 10(3)-fold more potent than 2 against these enzymes, their antinociceptive effects were completely similar. These results indicate that the inhibitory capacity of this series of Trp(Nps)-containing dipeptides against enkephalin-degrading enzymes is not an important factor for their antinociceptive effects.

Aminopeptidases↗
PubMed1985

Diversity of underlying mechanisms in the production of analgesic and pentobarbital-hypnosis prolonging effects of various analgesic drugs and stresses.

Stressful stimuli, electric footshock (FS), immobilized-water immersion (IW), and cold-water swimming (CWS), produced analgesia and prolonged the pentobarbital hypnosis as well as morphine and clonidine. Naloxone completely antagonized the analgesic effects of morphine and FS and partially that of IW; however, that of clonidine and CWS were not reversed by naloxone. Naloxone eliminated the hypnosis prolonging effect of morphine and FS, but failed to reverse the effect of clonidine, IW and CWS. Differences in the analgesic and hypnosis prolonging effects and also the respective naloxone sensitivity of each drug and stress suggest the diversity of the underlying mechanisms.

Analgesics↗
PubMedDate not supplied

From analgesic intolerance to analgesic induced asthma: are there some determinants?

BACKGROUND: Analgesic intolerance (AI) sometimes appear alone and sometimes with bronchial asthma affecting about 10% of asthmatics and sometimes before and the other times after asthma. OBJECTIVE: We investigated the possible clinical risk factors which might be affecting the transition from isolated AI to analgesic induced asthma (AIA). METHODS: A total of 344 patients admitted to Hacettepe University Hospital Adult Allergy Unit between January 1991 and March 1999 and diagnosed with AI were enrolled in this survey. Patients having AIA (group I) (n = 191) were compared with the patients having AI without asthma (group II) (n = 153). The diagnosis of AI and AIA were made by history and oral provocation tests. A standard questionnaire was filled-in for all the patients. RESULTS: The risk of AIA was increased with nasal polyp, and rhinosinusitis via OR's of 2.75 (95% CI: 1.09, 6.91), and 18.58 (95% CI: 9.86, 35.01), respectively. Having a pet, and ever smoking decreased the risk of AIA in the patients with AI via OR's of 0.53 (95% CI: 0.24, 1.17), and 0.37 (95% CI: 0.17, 0.80), respectively. The association of AIA and smoking was slightly modified by food intolerance (OR for ever smoked and food intolerance: 1.31, 95% CI: 0.40, 4.30). CONCLUSION: There may be two different phenotypes of AI with different clinical features: one developing AIA (having nasal polyp and/or rhinosinusitis, and smoking if food allergy/intolerance is present), and the other AI without asthma (having pet, and could smoke). Findings of this study should be confirmed by further investigations.

Adult↗
PubMedDate not supplied

[Standards, options and recommendations for the use of medical analgesics for the treatment of pain arising from excess nociception in adults with cancer (update 2002): opioid analgesics with the exception of morphine by mouth and the rotation].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the federation of French Cancer Centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the use of opioid analgesics with the exception of oral morphine and for opioid rotation related to the treatment of nociceptive pain in adults with cancer according to the definitions of the Standards, Options and Recommendations project. METHODS: In 1996, a working group, set up by the FNCLCC published clinical practice guidelines for pain management in adult and paediatric patients with cancer: In the light of the evolution of knowledge, and practice these guidelines need to be updated The section on "médical analgesic treatments" in the document published in 1996 was examined by the working group to identify which questions should be updated. These questions and the relevant key words were used to develop a search strategy which was used to search Medline, and for particular questions, Embase, from January 1994 to March 1999, for relevant references, published in English or French. RESULTS: For this update, only a few randomised clinical trials were identified, and their conclusions were generally weak. Thus much of the information in this document is based on the World Health Organisation (WHO) guidelines and represents the "state of the art" on this subject in France and is supported by expert agreement. Some changes to the original SOR are presented, particularly for the prescription of new opioids and opioid rotation. The full text of this SOR is available on the FNCLCC web site (http ://www.fnclcc.fr).

Analgesics, Opioid↗
PubMedDate not supplied

[A comparative study of the effectiveness of the analgesic effect of electropuncture stimulation and nonnarcotic analgesics in therapy patients in an emergency dental care office].

Analysis of patients' subjective sensations, of rheography and electro-odontometry data has lead the authors to a conclusion that the analgesic effect of rengasil was higher than that of ibuprofen and that rengasil combination with electropuncture was still more effective. The analgesic effect was the most marked in alveolitis and periodontitis, less so in inflammations of the pulp, and no effect could be achieved in acute purulent pulpitis. The authors suppose that pain syndrome alleviation after electropuncture stimulation and after administration of anti-inflammatory drugs is explained mainly by changed hemodynamics at the site of inflammation, this resulting in reduction of the edema and in diminished effects of biochemical substances released in the course of inflammation.

Acupuncture Points↗