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PubMed2003

Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo.

This study confirmed the oral anti-inflammatory, analgesic and antihistamine properties of mature fresh leaves (MFL) of Vitex negundo L. (Verbenaceae) claimed in the Ayurveda medicine by orally treating a water extract of the leaves to rats. The early phase (2h) of carrageenan-induced rat paw oedema was significantly (P<0.01) suppressed in an inversely does-dependent (r(2)=1, P<0.01) manner by MFL. The EC(50) was 2g/kg of MFL. In the formaldehyde-induced rat paw oedema test, the 2.5 and 5g/kg leaves significantly (P<0.05) suppressed the inflammation on days 4-6 of the test. In the hot plate test, 2.5 and 5g/kg of MFL showed a significant (P<0.05) and directly dose-dependent analgesic activity at 1h of treatment while the activity was absent in the tail flick test in rats. The EC(50) for the analgesic activity was 4.1g/kg. In the formalin test, 1.25, 2.5 and 5g/kg of MFL significantly (P<0.05) suppressed the pain in both the phases of the test like aspirin. The leaves showed an inversely dose-dependent in vivo antihistamine and in vitro prostaglandin (PG) synthesis inhibition, membrane stabilising and antioxidant activities. Naloxone did not abolish the analgesic activity in the hot plate test. A 5g/kg of MFL did not impair muscle strength and co-ordination and did not induce sedation. The treatment of 5g/kg of MFL did not show signs of acute toxicity or stress. Fourteen-day oral treatment of 5g/kg of MFL significantly increased the serum activity of AST. Flowering of the tree did not abolish the analgesic and anti-inflammatory activities of the leaves. These observations revealed that the fresh leaves of Vitex negundo have anti-inflammatory and pain suppressing activities possibly mediated via PG synthesis inhibition, antihistamine, membrane stabilising and antioxidant activities. The antihistamine activity can produce the anti-itching effect claimed in Ayurveda medicine.

Analgesics↗
PubMedDate not supplied

The use of analgesics in patients with acute abdominal pain.

Analgesics in patients with acute abdominal pain are often withheld for fear that they may change physical examination findings and thus may be unsafe. We conducted a randomized, prospective, placebo-controlled trial to investigate changes in physical examination following the administration of placebo, 5 mg, or 10 mg of morphine to 49 patients with acute abdominal pain. One patient was withdrawn secondary to inadequate documentation. Of the 48 patients who completed the trial, a statistically significant change in physical examination was noted in both groups receiving analgesics, but not in the placebo group. No adverse events or delays in diagnosis were attributed to the administration of analgesics. We conclude that physical examination does change after the administration of analgesics in patients with acute abdominal pain and that a larger study is needed to evaluate analgesic safety in this subpopulation of emergency department patients.

Abdominal Pain↗
PubMed2000

Variability of analgesic practices for hospitalized children on different pediatric specialty units.

This study examined the differences in the prescription and administration of analgesics in eight pediatric specialty units. Medical records of patients (n = 153) who were reported by nurses to be having pain were reviewed. Results showed that there were variations in the type of analgesics prescribed and administered in the different units. Mean doses of opioids were slightly subtherapeutic. The mean doses of the nonsteroidal anti-inflammatory drugs and adjuvants were all within the therapeutic range. There were large intervals between doses of medications. Because few patients had pain scores recorded before and after analgesic administration, evidence of relief was inconclusive, and the actual effectiveness of analgesics could not be consistently evaluated. Undertreatment of pain may result from administration of subtherapeutic analgesic doses, long intervals between administrations of doses, lack of proper documentation to guide practice, or a combination of these reasons.

Analgesics↗
PubMed2002

Chronic pain prevalence and analgesic prescribing in a general medical population.

In order to better understand the prevalence of chronic pain and the frequency of analgesic use in the U.S. veteran general medical population, a review of 300 randomly selected charts was conducted. This review revealed that 50% of patients suffered from at least one type of chronic pain. A review of the corresponding pharmacy records indicated that approximately 75% of patients with chronic pain were prescribed at least 1 analgesic, and most received 2 or more. While nonsteroidal anti-inflammatory drugs were the most commonly prescribed class of analgesics, 44% of those receiving an analgesic received opioids. Examination of clinic notes revealed that the prescribing physicians documented physical examination infrequently, and commented on a specific opioid treatment plan or follow-up of that plan in a minority of cases. It appears that chronic pain is common among U.S. veterans, and that analgesics, including opioids, are commonly prescribed. Documentation of the efficacy of opioids for treating chronic pain is often scant.

Adult↗
PubMed1998

Determination of the analgesic dose-response relationship for epidural fentanyl and sufentanil with bupivacaine 0.125% in laboring patients.

STUDY OBJECTIVE: To establish the analgesic effective doses as defined as a visual analog pain scale (VAS) of at least 10 for 95% of parturients (ED95) receiving either epidural fentanyl or sufentanil with bupivacaine 0.125% for labor analgesia. DESIGN: Double-blind, randomized controlled study. SETTING: Two tertiary-care teaching hospitals. PATIENTS: 100 female patients, at full-term pregnancy, in active early labor (< 5 cm cervical dilation) and requesting obstetric anesthesia services for labor analgesia. INTERVENTIONS: Patients were randomized and equally distributed to receive one of ten epidural dosing regimens of bupivacaine 0.125% alone or with either fentanyl 25, 50, 75, or 100 micrograms or sufentanil 5, 10, 15, 20, or 25 micrograms in a 10-ml bolus after a 3-ml test dose of bupivacaine 0.25%. MEASUREMENTS AND MAIN RESULTS: VAS scores were obtained from each parturient using a 10-cm plastic VAS slide rule at times 0, 1, 5, 10, 15, 20, 25, and 30 minutes, and then again when the patient requested additional analgesia. Analgesic duration and demographic and obstetric data also were obtained. Using a log-probit dose-response analysis, analgesic success as defined as a VAS of at least 10 with each opioid dose was plotted and an ED95 value of 8 micrograms and 50 micrograms was established for sufentanil and fentanyl, respectively, in bupivacaine 0.125%. No statistical difference was detected for analgesic duration or incidence of side effects between analgesic groups. CONCLUSIONS: Epidural analgesia with fentanyl and sufentanil in bupivacaine 0.125% behaves in a dose-response fashion allowing for the determination of equipotent dose of each.

Adult↗
PubMed2002

Analgesic effect of calcitonin in osteoporosis.

Bone pain is the most common symptom in osteoporotic patients. To date, there is mounting evidence that calcitonin significantly reduces bone pain in osteoporosis, and that the analgesic effect can be evident as soon as the second week of treatment. The limitations to the use of calcitonin, which are parenteral administration and side effects, can now be overcome by the availability of the nasal spray preparation. At present, controlled studies have demonstrated the analgesic activity of calcitonin given by nasal spray in patients with vertebral crush fractures and bone pain. The mechanism for the analgesic effect of calcitonin is yet to be clarified. In humans, similarities between calcitonin and morphine-induced analgesia, and reports of calcitonin-induced elevation of plasma beta-endorphin levels, suggest the possible involvement of the endogenous opiate system in mediating the analgesic action of calcitonin. However, the demonstration of calcitonin binding sites in areas of the brain involved in pain perception and a series of animal studies have raised the possibility that calcitonin may directly modulate nociception in the central nervous system. In support of this hypothesis are some observations of an analgesic effect obtained by direct epidural or subaracnoidal injection of calcitonin in humans.

Analgesics↗
PubMed1995

Stereoisomers of N-[1-hydroxy-(2-phenylethyl)-3-methyl-4-piperidyl]- N-phenylpropanamide: synthesis, stereochemistry, analgesic activity, and opioid receptor binding characteristics.

N-[1-(2-Hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (ohmefentanyl,1) is an extremely potent analgesic agent with high affinity and selectivity for opioid mu receptors. There are three chiral carbons in 1, so eight optically active isomers are possible. Respective reaction of optically active 3-methyl-N-phenyl-4 -piperidinamines (5a-d) with (R)- or (S)-styrene oxide produced eight optically active intermediates which were subsequently converted to eight optically active isomers of 1 (1a-h). The absolute configurations of 1a-h were determined by X-ray analysis of (3R,4S,2'R)-(-)-cis-1a and (3R,4R,2'S)-(-)-trans-1g. The analgesic activity (mice, ip, hot plate) revealed their extreme stereodifferences; the ED50 values of (3R,4S,2'R)-(-)-cis-1a and (3R,4S,2'S)-(+)-cis-1b, which are the most potent isomers among eight isomers, were 0.004 65 (2990 times that of morphine) and 0.001 06 mg/kg (13 100 times that of morphine), respectively, while the corresponding antipodes 1d,c were the least potent compounds among the eight isomers. In agreement with pharmacological results, both 1a,b also had the highest receptor affinity and selectivity for the opioid mu receptor. The ratio of K(i)(DPDPE)&K(i)(DAMGO) was 22 800 for 1a and 22 500 for 1b. All isomers except 1c,d strongly inhibited the electrically evoked smooth muscle contraction of GPI and MVD but not that of RVD, and the inhibitory effects could be reversed by naloxone, which indicated that these compounds were potent mu agonists in GPI and MVD. There was a good linear correlation between the analgesic potencies (ED50) and the receptor affinities (K(i)(DAMGO)) or inhibitory effects (IC50) to GPI and MVD. These results suggested that the analgesic effects of ohmefentanyl are mediated by interaction between the agents and opioid mu receptors in the central nervous system and the 3R,4S configuration at the piperidine 3- and 4-carbon atoms and the S configuration at the phenylethyl 2-carbon atom are beneficial for analgesic potency and inhibitory effects in GPI and MVD and the same for an S or R configuration at the phenylethyl 2-carbon atom besides the 3R,4S configuration for receptor mu affinity and selectivity.

Analgesics↗
PubMed1990

Synthesis and pharmacological evaluation of a series of new 3-methyl-1,4-disubstituted-piperidine analgesics.

The synthesis and intravenous analgesic activity of a series of 3-methyl-4-(N-phenyl amido)piperidines, entries 34-79, is described. The methoxyacetamide pharmacophore produced a series of compounds with optimal analgesic potency and short duration of action. cis-42 was 13,036 times more potent than morphine and 29 times more potent than fentanyl; however, the corresponding diastereomer 43 was only 2778 and 6 times more potent, respectively. Compounds 40, 43, 47, and 57 are extremely short acting; all had durations of action of about 2 min, which was about 1/5 of that of fentanyl in the mouse hot-plate test at a dose equivalent to 2 times the ED50 analgesic dose. Among the many compounds that displayed exceptional analgesic activity, duration of action was one of the main factors for choosing a candidate for further pharmacological investigation. At present, cis-1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-3-meth yl-4- [N-in equilibrium 2-fluorophenyl)methoxyacetamido]piperidine hydrochloride (40) (Anaquest, A-3331.HCl, Brifentanil) is in clinical evaluation. Opiate analgesics that possess short duration of action are excellent candidates for short surgical procedures in an outpatient setting where a rapid recovery is required.

Analgesics↗
PubMed1980

4-Anilidopiperidine analgesics. 3. 1-Substituted 4-(propananilido)perhydroazepines as ring-expanded analogues.

A study of ring-expanded analogues of the 4-(propananilido)piperidine analgesics has been undertaken in order to evaluate the influence of this structural modification on both analgesic activity and physical-dependence capacity. Thus, a series of 1-substituted 4-(propananilido)perhydroazepine derivatives was synthesized and pharmacologically evaluated in mice for analgesic activity and physical-dependence capacity. The results of this study indicate that the ring-expanded analogues of the 4-(propananilido)piperidines retain a relatively high degree of analgesic potency, except in the case of the 1-phenylethylated analogue which is approximately 150-fold less potent than the correspondingly 1-substituted piperidine analgesic. Evaluation of physical-dependence capacity of the most potent 1-substituted 4-(propananilido)perhydroazepines reveals no significant difference for these compounds as compared with morphine. The 4-(propananilido)perhydroazepines having 1-substitutents in common with known opiate antagonists failed to exhibit antagonism of morphine analgesia.

Analgesics↗
PubMed2001

Effect of preincisional ilioinguinal and iliohypogastric nerve block on postoperative analgesic requirement in day-surgery patients undergoing herniorrhaphy under spinal anaesthesia.

BACKGROUND: By choosing spinal anaesthesia instead of general anaesthesia, and by infiltrating the wound area with local anaesthetic the need for postoperative analgesics may be reduced. An ilioinguinal and iliohypogastric nerve block (IINB) in inguinal herniorrhaphy was, therefore, studied in a day surgery setting in combination with a spinal block. METHODS: One hundred ASA I-II adult patients scheduled for inguinal herniorrhaphy were given spinal anaesthesia with hyperbaric 0.5% bupivacaine. In a randomized and blinded fashion half of them received an IINB 5 min before the surgical incision with 10 ml of 0.5% bupivacaine (B-IINB) and the other half with saline (S-IINB). All patients received ketoprofen 100 mg i.v. during surgery and another 100 mg 2-3 h postoperatively. The patients were observed for about 6 h in the day surgery unit before discharge. RESULTS: The results showed that in comparison with the S-IINB group, significantly fewer patients in the B-IINB group needed analgesics (P<0.01) and the amount required was also significantly less postoperatively, before discharge (about 6 h postoperatively) (P<0.05). The latency to the need for the first postoperative analgesic was shorter in the S-IINB patients (P<0.01). At home the VAS scores and the need for analgesics (oral ketoprofen 100 mg) were low with no differences between the groups. No complications occurred. CONCLUSION: It is concluded that no long-term analgesia could be demonstrated by a preincisional IINB performed during spinal anaesthesia in day-surgery inguinal herniorrhaphy patients. Thus, reduced analgesic requirement was seen only for about 6 h postoperatively.

Adult↗
PubMed2000

The analgesic potential of intraventricular polymer-encapsulated adrenal chromaffin cells in a rodent model of chronic neuropathic pain.

Adrenal chromaffin cells reportedly produce analgesic effects when implanted in the periaqueductal gray and the intrathecal space near the spinal cord. Chromaffin cells implanted in the cerebral ventricles may also produce analgesic effects, and the availability of the cerebral ventricles as a potential implant site could be advantageous for some patients. In fact, some of the first patients were implanted in the intraventricular site, even though the analgesic potential of that site had never been demonstrated. The present study was conducted to assess the analgesic potential of intraventricular, polymer-encapsulated calf adrenal chromaffin cells in the Bennett model. Sciatic nerve ligations produced substantial, long-lasting pain-related behaviors. However, there was no evidence that polymer-encapsulated adrenal chromaffin cells implanted in the cerebral ventricles produce analgesic effects in this model of chronic neuropathic pain.

Adrenal Glands↗
PubMed2004

Relative efficacy of oral analgesics after third molar extraction.

OBJECTIVES: To compare the relative efficacy of analgesics after third molar extraction from systematic reviews of randomised, double blind studies. DATA SOURCES: Dental trials from systematic reviews of randomised, double-blind studies of analgesics in acute pain. DATA SELECTION: Number of patients with moderate or severe pain achieving at least half pain relief over 4 to 6 hours after a single oral dose of analgesic. DATA EXTRACTION: Independently by two reviewers. DATA SYNTHESIS: Use of dichotomous information from active and placebo treatments, first to calculate the statistical significance using relative risk, and then to evaluate the clinical relevance using number needed to treat (NNT). Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2) inhibitors had the lowest (best) NNTs for the outcome of at least half pain relief over 4-6 hours 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: NSAIDs and COX-2 inhibitors have the lowest (best) NNTs. They may also have fewer adverse effects after third molar surgery, though 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.

Acetaminophen↗
PubMed1980

Influence of N-terminal acetylation and C-terminal proteolysis on the analgesic activity of beta-endorphin.

Removal of one, two and four amino-acid residues from the C-terminus of beta-endorphin ('lipotropin C-Fragment', lipotropin residues 61--91) led to the formation of peptides with progressively decreased analgesic potency; there was no change in the persistence of the analgesic effects. The four C-terminal residues are thus important for the activity of beta-endorphin, but not for the duration of action. Removal of eight amino-acid residues from the N-terminus provided a peptide that had no specific affinity for brain opiate receptors in vitro and was devoid of analgesic properties. The N-terminal sequence of beta-endorphin is therefore necessary for the production of analgesia, whereas the C-terminal residues confer potency. The N alpha-acetyl form of beta-endorphin had no specific affinity for brain opiate receptors in vitro and possessed no significant analgesic properties. Since lipotropin C'-Fragment (lipotropin residues 61--87) and the N alpha-acetyl derivative of beta-endorphin occur naturally in brain and pituitary and are only weakly active or inactive as opiates, it is suggested that proteolysis at the C-terminus and acetylation of the N-terminus of beta-endorphin may constitute physiological mechanisms for inactivation of this potent analgesic peptide.

Acetylation↗
PubMed2002

The analgesic efficacy of preoperative high dose (40 mg x kg(-1)) oral acetaminophen after bilateral myringotomy and tube insertion in children.

BACKGROUND: The purpose of this study was to measure the plasma levels and analgesic effectiveness of a dose of 40 mg x kg(-1) of preoperative oral acetaminophen. METHODS: Thirty children aged 55 (17-72) months undergoing bilateral myringotomy and tube insertion (BMT) received acetaminophen 40 mg x kg(-1) p.o. preoperatively. Plasma levels were measured, at 29 (10-51) min and at 60 min in the postanaesthesia care unit (PACU). Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), for all subjects and the Poker Chip Tool (PCT) a self-report scale for subjects aged > 4 years, were used. After discharge, 24-h analgesic efficacy was evaluated using an observer Visual Analogue Scale (VAS) score and further acetaminophen use was recorded. RESULTS: Plasma concentrations were 259 (60-391) micromol x l(-1) and 250 (135-450) micromol x l(-1), respectively. All 60 min plasma concentrations were > or = 70 micromol x l(-1) (ED50 for adenotonsillectomy) and less than 800 micromol x l(-1) (associated with toxicity). Twenty-six subjects (87%) had adequate analgesia (CHEOPS < or = 8). The PCT was only understood in the PACU by 13 of the 21 children > 4 years (62%). The median worst 24-h observer VAS was 0.5 (0-5.5) (27 subjects). No further analgesic was required after discharge in 16/28 (57%). A higher plasma level was associated with fewer doses of acetaminophen after discharge (r = -0.36, P=0.05). CONCLUSIONS: No relationship was evident between age, the 60 min plasma acetaminophen level and the CHEOPS carried out at the same time. Acetaminophen 40 mg x g(-1) p.o. results in 60 min plasma levels of 250 (135-450) micromol x l(-1). The in-hospital analgesic efficacy was 87% (CHEOPS < 9, no further analgesics) and the 24-h efficacy was 57% (need for further acetaminophen).

Acetaminophen↗
PubMed1996

Analgesic use in cluster headache.

Cluster headache is a brutal affliction characterized by excruciating pain with relatively brief, but frequent attacks. Because of the short duration of the attacks and the tremendous intensity of pain, symptomatic analgesics are often not effective. However, inhalation oxygen, while being cumbersome, is reported to be effective in the majority of sufferers. To assess the practical effectiveness and use of analgesics and/or oxygen, a review of 60 cluster patients was conducted. At initial evaluation, 48 patients had accepted oral analgesics and 51 patients accepted inhalation oxygen for breakthrough headaches. After acceptable prophylactic treatment was established, 65% of patients who accepted analgesics continued their use, although most reported only minimal relief. Only 31% of patients who accepted oxygen continued its use, in spite of the fact that most sufferers reported significant relief. From this brief study, it appears that cluster headache patients prefer to use analgesics for reasons that are not solely for relief of pain, and that patients decline the use of oxygen for reasons other than lack of effectiveness.

Adult↗
PubMed1997

Analgesic drug taking: beliefs and behavior among headache patients.

OBJECTIVE: To explore beliefs and behavior with respect to analgesic drug taking in headache patients. To compare episodic headache to chronic headache sufferers. METHODS: A consecutive series of 280 headache patients, newly admitted to the Headache Center of the University of Modena, all referred by their general practitioner, were asked to fill out a brief questionnaire, specially compiled for this survey. The questionnaire invited patients to indicate how they themselves thought they should best cope with their headache, and how they actually did so in practice. RESULTS: The majority of our patients had a positive attitude towards the over-the-counter analgesics, which they believed to be more adequate than prescription drugs for acute treatment of their headache. They handled analgesics very carefully, believing it correct to take the drug only when the pain became unbearable, if it was not possible for them to stop work. Chronic headache patients tended to consume more prescription drugs than episodic headache sufferers. Furthermore, the majority of chronic sufferers, as opposed to episodic sufferers, took the analgesic even when not at work. CONCLUSIONS: The use of over-the-counter drugs is considered the best way to treat acute headache even by subjects suffering from severe idiopathic headache and seeking professional care in specialized clinics. Prescribed analgesics are underused by patients with serious episodic headache, which is precisely the group for which they are principally intended.

Adolescent↗
PubMed2002

Behavioral and pharmacologic treatment of transformed migraine with analgesic overuse: outcome at 3 years.

OBJECTIVE: To determine whether combined treatment using medication and biofeedback would be more effective than drug treatment alone for treating transformed migraine complicated by analgesic overuse. BACKGROUND: Headaches that are chronic, daily, and aggravated by medication overuse are particularly difficult to treat. METHODS: Sixty-one consecutive patients with transformed migraine and analgesic overuse were treated with inpatient pharmacologic therapy alone or with inpatient pharmacologic therapy combined with biofeedback-assisted relaxation. All patients then were followed prospectively for 3 years. RESULTS: Both treatment groups exhibited similar levels of improvement immediately following treatment and for 1 year thereafter. At year 3, participants receiving combined treatment showed greater sustained improvement on two of three outcome measures assessed (ie, fewer days of headache and reduced consumption of analgesic medication). In addition, a greater number of patients assigned to pharmacologic treatment alone relapsed (ie, resumed overuse of analgesics) compared to patients receiving combined treatment. CONCLUSIONS: These results suggest that a combination of pharmacologic and behavioral treatment is more effective than drug therapy alone in the long-term management of transformed migraine with analgesic overuse. Confirmation of these findings, as well as extension to other forms of behavioral and cognitive-behavioral treatment, is required.

Adult↗
PubMed1998

Analgesic nephropathy.

Many questions about analgesic nephropathy (AN) lack clear-cut answers. We present available evidence for and against proposed answers to many of these questions. These include: (1) Is acetaminophen (AC) nephrotoxic when taken as the sole analgesic? (2) Is the combination of acetylsalicylic acid (ASA) and AC more nephrotoxic than AC taken alone, and if so, why? (3) What are the minimum doses and durations of ingestion required to produce analgesic nephrotoxicity? (4) Is the combination of ASA and AC (a major metabolite of phenacetin) less nephrotoxic than that of phenacetin and ASA combined? (5) Does caffeine in combination with analgesics contribute to nephrotoxicity? (6) What is the incidence of end-stage renal disease (ESRD) due to AN? (7) What uniform diagnostic criteria should be established for AN? (8) What are the earliest anatomic and biochemical abnormalities? (9) What are the mechanisms of renal injury? (10) Does AC cause uroepithelial neoplasia? (11) What research might be most beneficial? Based mainly on associations, some strong, we suggest that AN still exists as a cause of ESRD in the United States, where AC/ASA combinations are available over the counter, and in Canada, where they are not. We also suggest that the evidence needed to recommend that the AC/ASA combination be excluded from over-the-counter analgesic preparations still has limitations. A prospective multicenter study comparing incidence related to AC/ASA in the United States and to AC in Canada and the United States may be needed to answer this question. For such a study to be worthwhile, an adequate incidence in both countries is required.

Acetaminophen↗