Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain is the main reason prompting patients to consult their physicians. In acute conditions, pain has a very particular significance as a warning sign, enabling the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon the individual (even in the case of acute pain) and its cost to society are now widely acknowledged. There can be no doubt about the physical component of pain, but the psychological and social aspects should not be ignored, particularly in the case of chronic pain. There is no single therapeutic approach to pain and, more often than not, successful treatment comprises a combination of several. Pharmacological treatments are undeniably the most common approach. In clinical practice, recent advances have been based upon an improved understanding of 'old' substances such as morphine and, at the same time, research continues in the hope of finding the 'ideal' analgesic-effective in most situations but without adverse effects: this appears to be a somewhat utopian arm at present, considering the number of different causes of pain. An improved understanding of the physiological mechanisms of pain has led, within the field of clinical practice, to several methods of differentiating pain. These depend on whether or not pain responds to morphine, or on the type of pain: pain due to an excess of nociception, pain resulting from deafferentation (caused by damage to nerve pathways) in the central or peripheral nervous system and psychogenic (idiopathic) pain. Likewise, there are several different ways of classifying analgesic treatments: according to the intensity of pain, as with use of the WHO ladder (which is based on the notion of steps) for the treatment of cancer pain; according to the presumed physiopathological mechanism and, in particular, the response to morphine, and according to the presumed central or peripheral mechanism of the drugs. In reality, peripherally acting drugs can also have a central mechanism of action, just as drugs known to have a central mechanism of action can also have peripheral activity. As a result, several therapeutic classes have been identified. Firstly NSAIDs, which act by inhibiting the enzymes that synthesise prostaglandins, cyclooxygenases (COX-1, COX-2), but which also act upon lipo-oxygenases: Their efficacy is interesting, although somewhat limited by both their ceiling effect and the frequent adverse gastrointestinal reactions they produce. Specific inhibitors of COX-2 could well reduce the risk of adverse effects. Opioids constitute the first-line treatment for pain, particularly severe pain. There are several classifications for these drugs. Firstly, weak opioids (such as codeine) and strong opioids (such as morphine) are differentiated. Secondly, a distinction is made between pure agonists (such as morphine), partial agonists (such as buprenorphine), agonist-antagonists (such as nalbuphine) and antagonists (such as naloxone). Finally, agents are distinguished on the basis of their chemical structure (synthetic, semi-synthetic or natural derivatives). These molecules act upon different receptors (mu, delta, kappa, sigma) and, although peripheral mechanisms have been described, their activity occurs mainly at spinal and supraspinal levels. They provide a potent analgesic effect but are also responsible for various adverse effects-nausea, vomiting, sedation, constipation and respiratory depression-which seriously limit their use. As long as the indication is appropriate, these drugs should not be withheld because of fear of dependence or abuse. It has been observed that other adjuvant therapeutic approaches, generally used to treat conditions other than pain, provide pain relief in certain situations. These include corticosteroids, which are-widely used in rheumatology and oncology, and antidepressants, which are frequently used to treat chronic pain, especially that with a neuropathic component. Anti-epileptics are also used, particularly for excrutiating
 ...
PMID:[Review of current pharmacologic treatment of pain]. 919 Mar 20

Rofecoxib (Vioxx, Merck & Co., Inc.) is a new orally-effective non-steroidal anti-inflammatory drug (NSAID) approved for treatment of acute pain, fever, primary dysmenorrhea and pain and inflammation in osteoarthritis (OA). It is also being evaluated for treatment of rheumatoid arthritis and adenomatous polyps of the colon. Rofecoxib is a specific inhibitor of cyclooxygenase-2 (COX-2), thereby inhibiting prostanoid synthesis in cells that express COX-2, including inflammatory cells. As cells in the gastrointestinal (GI) tract principally express COX-1, a different isoform of cyclooxygenase, it is predicted that rofecoxib will have less GI toxicity than other less selective NSAIDs. In clinical trials, rofecoxib was found to be as effective as other NSAIDs for management of pain and inflammation. In trials that compare rofecoxib with ibuprofen, diclofenac and indomethacin, less GI toxicity has been observed, as assayed by a decrease in lesions visible on endoscopy, by GI blood loss and, in a meta-analysis, by frequency of serious adverse GI events. The presence of COX-2 in cells other than inflammatory cells results in side effects common among NSAIDs, including peripheral oedema and hypertension. These side effects are dose-dependent. Rofecoxib, together with other branded NSAIDs, are relatively expensive, which has led to concern regarding costs versus benefits. There is also concern regarding potential risks associated with the use of rofecoxib by populations that would otherwise not tolerate NSAIDs.
 ...
PMID:Rofecoxib. 1124 95

Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. In the treatment of patients with osteoarthritis, rofecoxib was more effective in providing symptomatic relief than placebo, paracetamol (acetaminophen) and celecoxib and was similar in efficacy to ibuprofen, diclofenac, naproxen and nabumetone. Overall, both the physician's assessment of disease status and the patient's assessment of response to therapy tended to favour rofecoxib. In patients with postsurgical dental pain, pain after spinal fusion or orthopaedic surgery, or primary dysmenorrhoea, rofecoxib provided more rapid and more sustained pain relief and reduced requirements for supplemental morphine use after surgery than placebo. Rofecoxib was more efficacious than celecoxib in patients with acute dental pain and pain after spinal fusion surgery, although celecoxib may have been used at a subtherapeutic dose. In comparison with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac and naproxen sodium, rofecoxib was similar in efficacy in the treatment of acute pain. Although naproxen sodium provided more rapid pain relief than rofecoxib in patients with primary dysmenorrhoea, the reverse was true after orthopaedic surgery: rofecoxib provided more rapid pain relief and less supplemental morphine was needed. Rofecoxib was as effective as naproxen in providing symptomatic relief for over 8700 patients with rheumatoid arthritis. Compared with traditional NSAID therapy, rofecoxib had a significantly lower incidence of endoscopically confirmed gastroduodenal ulceration and, in approximately 13,000 patients with osteoarthritis and rheumatoid arthritis, a lower incidence of gastrointestinal (GI) adverse events. Rofecoxib was generally well tolerated in all indications with an overall tolerability profile similar to traditional NSAIDs. The most common adverse events in rofecoxib recipients were nausea, dizziness and headache. In conclusion, rofecoxib is at least as effective as traditional NSAID therapy in providing pain relief for both chronic and acute pain conditions. Rofecoxib provides an alternative treatment option to traditional NSAID therapy in the management of symptomatic pain relief in patients with osteoarthritis. Initial data from patients with primary dysmenorrhoea and postoperative pain are promising and further trials may confirm its place in the treatment of these indications. Rofecoxib has also shown promising results in patients with rheumatoid arthritis and is likely to become a valuable addition to current drug therapy for this patient population. Importantly, rofecoxib is associated with a lower incidence of GI adverse events than traditional NSAIDs making it a primary treatment option in patients at risk of developing GI complications or patients with chronic conditions requiring long term treatment.
 ...
PMID:Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. 1139 14

While non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain and rheumatoid arthritis, toxicity associated with chronic administration limits their benefit-to-risk relationship in many patients. A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective cyclooxygenase (COX)-2 inhibitor (celecoxib) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac). Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E2 (PGE2; a product of both COX-1 and COX-2) and thromboxane B2 (as a biomarker for COX-1 activity) with parallel assessments of pain. The time course of PGE2 production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with COX-2 expression. Ketorolac 30 mg at pain onset suppressed both pain and peripheral PGE2 levels. Ketorolac 1 mg either at the site of injury or intramuscularly also produced analgesia but without any effect on peripheral PGE2 levels. Celecoxib selectively suppressed PGE2 but not TxB2 at time points consistent with COX-2 activity, while producing analgesia. These studies demonstrate the ability to assess the time course and selective effects of COX-2 inhibitors in vivo and suggest that suppression of COX-2 mediated PGE2 is temporally related to NSAID analgesia.
 ...
PMID:Analgesia and COX-2 inhibition. 1169 55

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in urticaria and angioedema, is being observed with increasing frequency. Prevalence rates range from 0.1-0.3%, which is partly due to the large size of the exposed (at risk) population. Some predisposing factors for these cutaneous reactions have been identified, among them atopic diathesis, female sex, young adulthood, a history of chronic urticaria and the use of the NSAID for the relief of acute pain. The description of two different arachidonic acid cyclo-oxygenases (COX) about a decade ago, designated COX-1 and COX-2, and the incorporation into the therapeutic armamentarium of more selective enzyme inhibitors for the control of inflammation and pain, has led to an improved understanding of the pathogenesis of adverse reactions to NSAIDs. This has allowed investigators to study 'sensitive' individuals to see if they can safely receive these new pharmaceutical compounds. The reasons why some people react to NSAIDs are not completely clarified. The prevalent theory about the pathogenesis of urticaria and angioedema due to NSAIDs in cross-reactive patients assumes that the inhibition of COX-1 leads to a shunting of arachidonic acid metabolism towards the 5-lipoxygenase pathway, which results in an increased synthesis and release of cysteinyl leukotrienes. Although COX-2 inhibitors are well tolerated by the majority of classic NSAID-sensitive patients, cutaneous reactions to highly selective inhibitors of COX-2 have been described in some of these individuals, casting some doubts about the relevance of such hypotheses. On the other hand, in patients who react to a single NSAID and chemically similar products (single-reactors), specific immunoglobulin E antibodies to haptenated NSAID metabolites have been suspected, although these metabolites are not easily demonstrated by means of routine in vivo or in vitro techniques. Facial (periorbital) angioedema constitutes the most common form of clinical presentation, and one-third of the patients show a mixed clinical pattern of cutaneous (urticaria and/or angioedema) and respiratory symptoms which include upper respiratory tract edema, rhinorrhea, cough, breathlessness and tearing. When necessary, diagnosis is confirmed by means of controlled peroral drug challenges done by experienced physicians in the hospital setting and test results are helpful for clinical management, which will be based on strict avoidance, and the use of alternative tolerated medications. This approach is specially indicated in hypersensitive patients with chronic medical conditions who require continuous NSAID therapy, such as those with arthritis and coronary heart disease.
 ...
PMID:NSAID-induced urticaria and angioedema: a reappraisal of its clinical management. 1244 2

The role of the coxibs in the management of osteoarthritis and rheumatoid arthritis has been widely discussed, but there are other potential applications for the coxibs that have received less attention. Here we consider the use of the coxibs in acute pain syndromes such as primary dysmenorrhea and the pain associated with dental extraction, as well as considering their application in chronic low back pain and cancer pain. Another area where the coxibs may prove particularly beneficial is in the management of post-surgical pain. Traditional post-surgical analgesia has involved the use of non-selective NSAIDs and opioids, but these agents can be associated with side effects such as post-operative bleeding, gastrointestinal problems, nausea, and constipation. Because the coxibs do not inhibit COX-1 dependent platelet aggregation like traditional NSAIDs, the risk of post-surgical bleeding is reduced. The careful application of coxibs as part of a multi-modal approach to pain management in the perioperative period can reduce the requirement for opioid medications and thus reduce the risk of post-operative complications such as ileus. In the future, coxibs are likely to play an important role in multi-modal perioperative analgesic regimens with the aim of reducing post-operative periods of convalescence.
 ...
PMID:Strategies in pain management: new and potential indications for COX-2 specific inhibitors. 1260 54

Non-steroidal anti-inflammatory drugs (NSAIDs) suppress the activity of both isoforms of cyclo-oxygenase (COX). Inhibition of COX-1, the constitutive isoform, is primarily responsible for the adverse gastrointestinal effects of the NSAIDs whereas inhibition of COX-2, the inducible isoform, accounts for their therapeutic effects. COX-2 inhibitors such as celecoxib and rofecoxib appear to be as effective as non-selective NSAIDs in the treatment of chronic inflammatory disease but their analgesic efficacy and their safety at the higher doses required for analgesia are less certain. There is consistent evidence that COX-1 plays a major role in the early pain response following injury and that analgesia is increased when both COX-1 and COX-2 are inhibited simultaneously. Early postoperative nociception may cause hyperalgesia at a later time by a process of central plasticity. In an experimental model of pain, ibuprofen promptly suppresses prostaglandin E2 concentrations whereas celecoxib has no discernible effect until 90-120 minutes postoperatively, when COX-2 activity is induced. Both drugs significantly reduce pain compared with placebo but celecoxib appears to have a slower onset of action. The analgesic effect of ibuprofen is well characterised for acute pain and short-term treatment is well tolerated.
 ...
PMID:Relative efficacy of selective COX-2 inhibitors compared with over-the-counter ibuprofen. 1272 42

Slow, time-dependent, irreversible, highly selective inhibitors of COX-2 (coxibs) have been used for the treatment of osteoarthritis and rheumatoid arthritis, as well as other disease entities such as acute pain, fever, neoplastic changes, and Alzheimer's disease, the pathomechanism of which is dependent on the coexisting inflammatory process or overexpression of cyclo-oxygenase (COX) genes. The article presents current state of knowledge about the clinical efficacy of coxibs (celecoxib, rofecoxib) compared to non-selective COX inhibitors. The physiology and pathophysiology of both COX isoforms (COX-1, COX-2) are also discussed.
 ...
PMID:[Coxibs: highly selective cyclooxygenase-2 inhibitors. Part I. Clinical efficacy]. 1286

The discovery of cyclooxygenase (COX)-2 has provided the rationale for the development of a new class of nonsteroidal antiinflammatory drugs (NSAIDs), the selective COX-2 inhibitors (denominated coxibs), with the aim of reducing the gastrointestinal (GI) toxicity associated with the administration of NSAIDs by virtue of COX-1 sparing. Rofecoxib and celecoxib are the first selective COX-2 inhibitors approved by the FDA and EMEA for the treatment of rheumatoid arthritis (RA), osteoarthritis (OA) and for relief of acute pain. Rofecoxib has been shown to spare COX-1 activity ex vivo, in platelets and gastric mucosa, when administered at therapeutic doses or above. In a large clinical trial, COX-2 inhibitors have been demonstrated to halve the incidence of serious upper GI events vs a nonselective NSAID. Recently, other selective COX-2 inhibitors with different COX-1/COX-2 selectivity and pharmacokinetic features have been developed, i.e. valdecoxib, parecoxib, etoricoxib and lumiracoxib. The improved biochemical selectivity of valdecoxib vs celecoxib in vitro (COX-1/COX-2 ratio: 60 vs 30, respectively) may be clinically relevant leading to an improved GI safety. Interestingly, parecoxib, a pro-drug of valdecoxib, is the only injectable coxib. Etoricoxib, showing only a slightly higher COX-2 selectivity than rofecoxib in vitro (COX-1/COX-2 ratio: 344 vs 272, respectively), has been reported to cause a similar specific COX-2 inhibition ex vivo that should translate into comparable GI safety. Lumiracoxib, the most selective COX-2 inhibitor in vitro (COX-1/COX-2 ratio: 400), is the only acidic coxib. It has been hypothesized that this pecular chemical feature may lead to an enhanced concentration in inflammatory sites that may translate into an improved clinical efficacy. The results of clinical trials have shown that coxibs have a comparable clinical efficacy and renal toxicity and an improved GI safety vs nonselective NSAIDs. Whether the different pharmacodynamic and pharmacokinetics features of the various coxibs will produce detectable differences in efficacy and toxicity remains to be evaluated in appropriate comparative randomized clinical studies.
 ...
PMID:Clinical pharmacology of selective COX-2 inhibitors. 1455 4

Novel coxibs (i.e. etoricoxib, valdecoxib, parecoxib and lumiracoxib) with enhanced biochemical cyclooxygenase (COX)-2 selectivity over that of rofecoxib and celecoxib have been recently developed. They have the potential advantage to spare COX-1 activity, thus reducing gastrointestinal toxicity, even when administered at high doses to improve efficacy. They are characterized by different pharmacodynamic and pharmacokinetics features. The higher biochemical selectivity of valdecoxib than celecoxib, evidenced in vitro, may be clinically relevant leading to an improved gastrointestinal safety. Interestingly, parecoxib, a pro-drug of valdecoxib, is the only injectable coxib. Etoricoxib shows only a slightly improved COX-2 selectivity than rofecoxib, a highly selective COX-2 inhibitor that has been reported to halve the incidence of serious gastrointestinal toxicity compared to nonselective nonsteroidal antiinflammatory drugs (NSAIDs). Lumiracoxib, the most selective COX-2 inhibitor in vitro, is the only acidic coxib. The hypothesis that this chemical property may lead to an increased and persistent drug accumulation in inflammatory sites and consequently to an improved clinical efficacy, however, remains to be verified. Several randomized clinical studies suggest that the novel coxibs have comparable efficacy to nonselective NSAIDs in the treatment of osteoarthritis, rheumatoid arthritis and acute pain, but they share similar renal side-effects. The apparent dose-dependence of renal toxicity may limit the use of higher doses of the novel coxibs for improved efficacy. Large-size randomized clinical trials are ongoing to define the gastrointestinal and cardiovascular safety of the novel coxibs.
 ...
PMID:Clinical pharmacology of novel selective COX-2 inhibitors. 1496 22


1 2 3 Next >>