Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.
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PMID:Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults? 1032 37

For many reasons, nonopioid analgesics have proven to be of immense benefit in postoperative pain relief. Consideration of the limitations and side effects of opioids confirms the need for alternative, complementary analgesics. The current understanding of pain pathophysiology recognizes that many tissue and neuronal factors and changes are invoked by tissue damage, producing peripheral and central sensitization, and some of these may be modulated by the use of NSAIDs, NMDA antagonists, and local anesthetic agents. If successful preemptive analgesic techniques are developed, they will likely include the use of NSAIDs and perhaps NMDA antagonists. Nonopioids are of benefit in multimodal analgesia and allow acute rehabilitation of surgical patients. Acetaminophen, NSAIDs, alpha 2-antagonists, and NMDA antagonists are in routine use as components of multimodal analgesia, in combination with opioids or local anesthetic techniques. Tramadol is interesting because it has nonopioid and opioid actions that can be attributed to the two isomers found in the racemic mixture. Spinal neostigmine and the use of adenosine represent completely different mechanisms of nonopioid analgesia being investigated. Nonopioids, including lidocaine, ketamine, the anticonvulsants, and the antidepressants, are necessary for the treatment of patients with the difficult clinical problem of neuropathic pain that can present in the postoperative period.
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PMID:Analgesic agents for the postoperative period. Nonopioids. 1035 55

Acetaminophen is one of the most widely used analgesic drugs. Although the mechanism of analgesic action of acetaminophen is still not known, the involvement of the central serotonin (5-hydroxytryptamine: 5-HT) system is one possibility. In the present study, we examined the antinociceptive effect of acute and chronic intraperitoneally (i.p.) administered acetaminophen by tail flick latency measurements in the rat. A significantly increased tail flick latency was observed in acute and 15-day acetaminophen-treated rats, but not in 30-day acetaminophen-treated rats, at a dose of 400 mg/kg/day. To investigate the plasticity of receptors at postsynaptic membrane, we conducted a series of experiments by radioligand binding method on frontal cortex and brainstem membrane. The technique involved radioligand binding with [phenyl-4-3H]spiperone and ketanserin for studying 5-HT(2A) receptor characteristics. A significant decrease in the maximum number of 5-HT(2A) binding sites (Bmax) was demonstrated in all treatment groups with acetaminophen 300 and 400 mg/kg on frontal cortex membrane, whereas the value of the dissociation equilibrium constant (Kd) remained unchanged. The down-regulation of 5-HT(2A) binding sites in frontal cortex was of a lesser magnitude after 30 days of treatment and the tail flick latency was as in the control animals. These results suggest that down-regulation of 5-HT(2A) receptor in response to 5-HT release is a major step in the mechanism underlying analgesia produced by this agent. On the contrary, chronic use of acetaminophen may result in 5-HT depletion, which in turn produces re-adaptation of postsynaptic 5-HT(2A) receptors. These data provide further evidence for a central 5-HT-dependent antinociceptive effect of acetaminophen.
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PMID:Acetaminophen-induced antinociception via central 5-HT(2A) receptors. 1040 24

Oxycodone is a strong opioid that has been available for at least 70 years. At present, commercially prepared parenteral oxycodone is only available in Finland. We report in this paper our experience of administering oxycodone s.c. From 21 October 1996 to 31 July 1998, 63 advanced cancer patients received intermittent s.c. injections of oxycodone via the Edmonton Injector, a simple, low-cost mechanical device. Local tolerance and systemic toxicity were followed prospectively. Only 2 patients developed s.c. injection site intolerance, and in both cases doses of 50 mg/ml or more were being administered. Most of the patients in this study were rotated to oxycodone because of opioid toxicity, and in 34% of those patients their delirium subsided. A subgroup of 19 patients who underwent rotation to oxycodone SC from morphine and hydromorphone were studied for equivalent analgesia with oxycodone. We found a ratio (mean +/- SD) of 1.2+/-0.4 for morphine s.c. to oxycodone s.c. and a mean ratio of 0.5+/-0.4 for hydromorphone s.c. to oxycodone s.c. When hydromorphone s.c. was converted to a morphine s.c. equivalent dose and the results for these patients were added to those for the morphine s.c. group, the mean and median overall ratios of morphine s.c. equivalent dose to oxycodone were 1.9+/-1.5 and 1.4, respectively. The cost of the oxycodone s.c. was also evaluated and was found to be comparable to that of morphine s.c. and lower than that of hydromorphone s.c. We conclude that s.c. oxycodone can be an effective, safe and inexpensive alternative opioid agonist.
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PMID:The use of intermittent subcutaneous injections of oxycodone for opioid rotation in patients with cancer pain. 1042 53

The pharmacokinetics of paracetamol in adults after cardiac surgery have not been described. Twenty patients were randomized to receive either paracetamol 2 g through a nasogastric tube and as a suppository eight hours later or vice versa. Arterial blood samples were taken at 0.5, one, two, four, six and eight hours after dosing. Each patient was studied for 16 h. There were 16 males and three females. One patient was excluded because of sampling errors. The mean age was 59 (SD 8) years and the mean weight 84 kg (16). The time-concentration profiles for each individual were used to estimate pharmacokinetic parameters using a non-linear mixed effects model (NONMEM). Population parameter estimates with coefficient of variation (CV%), standardized to a 70 kg person, for a one-compartment model with first order input, lag time and first order elimination were volume of distribution 127l (28) and clearance 26.4 l/h (29) Rectal paracetamol had an absorption half-life (Tabs) of 2.02 h (31) with a lag time of 0.28 h. The absorption half-life for the oral preparation was 1.49 h (81) with a lag time of 0.17 h. The relative bioavailability of the rectal compared to the oral formulation was 0.98 (18). Concentrations after either nasogastric or rectal paracetamol 2 g were below a target concentration of 10 mg/l, which is associated with analgesia. Absorption after nasogastric administration was slow compared to healthy adults (Tabs 0.06 to 0.7 h) and the bioavailability was half that expected, due to nasogastric loss. Parameter estimates had large variability. Paracetamol is unlikely to have useful clinical impact in the majority of patients when standard doses (6 g/day) are given on day 1 after cardiac surgery.
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PMID:Pharmacokinetics of paracetamol in adults after cardiac surgery. 1063 16

Although significant improvement has been made in the treatment of pain in the postoperative period, many patients still experience unnecessary discomfort resulting in distress, higher morbidity and prolonged stay in hospital. The standard pillar of postoperative treatment of severe pain is the use of opioids. However, adverse reactions to opioids make their use unfavourable. A better understanding of the pathophysiology of pain has helped clinicians to a more balanced approach to postoperative pain treatment. The development of the multimodal approach to postoperative analgesia, with the use of different drugs acting via different routes to give good analgesia, with minimal side-effects, represents a major development in the treatment of postoperative pain. Early, aggressive mobilisation and feeding must follow in order to restore normal conditions quickly. Alternatives to opioids should be used as extensively as possible. Local anaesthesia, used as regional blocks or as wound infiltration, is most beneficial. Paracetamol has good basic analgesic properties, and should probably be used in dosages higher than recommended today. The combination with a NSAID results in better and longer-lasting analgesia. The intravenous form propacetamol will increase the possibilities of its use. The new concept of selective COX-2 inhibiting NSAIDs will result in analgesic and anti-inflammatory drugs with fewer side-effects. The well-known inexpensive group of corticosteroids have good analgesic and anti-emetic properties, and are especially interesting to use in patients who do not tolerate NSAIDs. The alpha2-receptor agonists like clonidine, when administered epidurally or intrathecally, are useful adjuncts, but their adverse effects on sedation and hypotension limit their use. NMDA-receptor antagonists are of limited value in the postoperative period. Adenosine and neostigimine are still on a research level but may lead to new, clinically useful analgesic drugs. In the future, cannabinoids, cholecystokinin-receptor antagonists and neurokinin-1 antagonists may become important analgesic drugs.
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PMID:Non-opioid postoperative analgesia. 1106 98

Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.
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PMID:Morphine or oxycodone in cancer pain? 1120 1

Paracetamol (acetaminophen) has a unique role in children because it is the first-line choice for the treatment of both fever and pain. When used in the recommended doses, it has few side effects and is remarkably well tolerated. While fever alone requires no treatment, when associated with discomfort or pain, paracetamol offers relief. Also, for mild to moderate pain, paracetamol, either alone or in combination with another drug, is effective. Even in severe pain, paracetamol offers a significant additive analgesic effect to opiates. Globally, the pediatric dose varies between 10 and 15 mg/kg. In the United Kingdom, 10 mg/kg is given every 4 hours, up to a maximum of four doses per day; in Australia, 15 mg/kg is administered 4-hourly up to a total dose of 60 mg/kg/day. In overdose, paracetamol is hepatotoxic. Single ingestions of more than ten times the recommended dose are potentially toxic. The development of specific antidotes and the universal availability of the Rumack-Matthew Nomogram have made the early treatment of overdose effective without long-term sequelae. There are sporadic case reports of chronic overdosing resulting in liver failure. Although the specific predictors are still being defined, exposures greater than 140 mg/kg/day for several days carry a risk of serious toxicity. In children, aspirin use has almost disappeared with the concurrent decline in Reye Syndrome. Less clinical experience has accumulated with ibuprofen, and it remains the second-line treatment for fever and pain. In conclusion, paracetamol remains the first-choice over-the-counter treatment for analgesia and antipyresis in children.
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PMID:Paracetamol efficacy and safety in children: the first 40 years. 1131 81

Seven hundred three subjects completed a randomized, double-blind, parallel-group, single-center study comparing the single-dose efficacy of ketoprofen 12.5 mg, ketoprofen 25 mg, acetaminophen 1000 mg, and placebo in the treatment of tension headache. For the primary efficacy variable, 4-hour sum of pain relief intensity differences, ketoprofen 25 mg was significantly superior to placebo. Ketoprofen 25 mg also demonstrated superior pain relief in the first hour after dosing, and the time to meaningful pain relief was significantly shorter for the ketoprofen 25-mg group. Ketoprofen 12.5 mg proved to be significantly superior to placebo for pain relief intensity difference and pain relief at 3 hours, global assessment of medication at 4 hours, and for time to onset of meaningful pain relief. The data suggest a dose response for ketoprofen 12.5 mg and 25 mg. Acetaminophen 1000 mg proved to be numerically more favorable than placebo in most variables, but could not be separated from placebo with statistical significance. In spite of possible inflation of the placebo response due to sensitivity limits of the study, ketoprofen 25 mg demonstrated a more rapid onset of analgesia compared to acetaminophen 1000 mg, and patients' global assessment rated ketoprofen 25 mg higher than acetaminophen 1000 mg.
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PMID:Ketoprofen, acetaminophen, and placebo in the treatment of tension headache. 1139

Providing intraarticular analgesia with a continuous infusion of local anesthetic via a disposable infusion pump has gained popularity. Despite the prevalence of this technique, data comparing this method of analgesia to conventional regional anesthesia are not available. We present a prospective study that compared a single-dose interscalene block with a single-dose interscalene block plus continuous intraarticular infusion of local anesthetic. Forty patients scheduled for shoulder arthroscopy were entered in this prospective, double-blinded study. All patients received an interscalene brachial plexus block as their primary anesthetic. Patients were randomly assigned to 1 of 2 groups: 1. interscalene block with 1.5% mepivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.5% ropivacaine at 2 mL/h, or 2. interscalene block with 0.5% ropivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.9% saline (placebo) at 2 mL/h. Postoperative infusions were maintained for 48 h. Visual analog scale pain scores and postoperative oxycodone consumption were measured for 48 h. Visual analog scale scores at rest and with ambulation in the Mepivacaine/Intraarticular Ropivacaine group were reduced when compared with the Ropivacaine/Saline group (rest: P = 0.003, ambulation: P = 0.006). Oxycodone consumption was also decreased (28 +/- 21 mg vs 44 +/- 28 mg, P = 0.046), respectively. We conclude that a brachial plexus block with 1.5% mepivacaine and a continuous intraarticular infusion of 0.5% ropivacaine at 2 mL/h provides improved analgesia for minor surgery at 24 and 48 h versus a single-injection interscalene block with 0.5% ropivacaine.
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PMID:Interscalene brachial plexus block with continuous intraarticular infusion of ropivacaine. 1214 84


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