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

Ketorolac tromethamine is the first injectable nonsteroidal anti-inflammatory drug approved for the management of acute pain. In analgesic potency and ability to relieve postoperative pain, it is comparable to morphine. The advantages of ketorolac over opiates are the absence of respiratory depression and lack of drug abuse potential. Ketorolac has a longer duration of action than morphine, but it has less effect on the central nervous system. Ketorolac should not be used for obstetric analgesia.
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PMID:Ketorolac: an injectable NSAID. 198 89

Ketorolac tromethamine is a pyrrolo-pyrrole nonsteroidal antiinflammatory drug (NSAID) with potent analgesic effects when administered intramuscularly for the treatment of acute pain. Ketorolac is well absorbed and has a rapid onset of action. Maximum plasma concentrations are achieved in 45-50 minutes and peak analgesic effects in about one to two hours following intramuscular injection. Ketorolac is more than 99 percent bound to plasma proteins and has a mean apparent volume of distribution of 0.11-0.25 L/kg. About 91 percent of a dose is excreted in urine, mostly as inactive metabolites, and approximately 6 percent is eliminated in feces. The elimination half-life, approximately four to six hours, increases in elderly patients and those with renal impairment. Its analgesic effectiveness was similar or superior to that of morphine, meperidine, or pentazocine in single-dose studies of patients with postoperative pain or renal colic and greater than that of placebo in patients with chronic cancer pain. The adverse effects are generally mild to moderate, self-limiting, and similar to those seen with other prostaglandin inhibitors. Ketorolac has a reversible inhibitory effect on platelet aggregation. It can cause dose-related gastric ulcerations, even when administered parenterally. Ketorolac is a promising parenteral alternative to oral NSAIDs and a nonnarcotic alternative to opioid analgesics. Additional multiple-dose studies are needed to more clearly define its place in therapy.
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PMID:Ketorolac: a parenteral nonsteroidal antiinflammatory drug. 227 36

Ketorolac tromethamine (Toradol) is a nonsteroidal antiinflammatory drug (NSAID) available in intramuscular (IM) and oral formulations for the management of acute pain. Intramuscular ketorolac is the only parenteral NSAID available for analgesic use in the US. The clinical profile is reviewed, and clinical studies most applicable to a postoperative patient are discussed in detail. The results of a clinical study performed at Emory University School of Medicine are presented. In this single-dose study, 176 patients received either 10 mg of oral ketorolac, 5 mg or 10 mg of IM morphine, or placebo after orthopedic surgery. The analgesic efficacy of ketorolac was comparable to both doses of morphine and significantly superior to placebo. Ketorolac, when administered intramuscularly or orally, is a safe and effective analgesic agent for the short-term management of acute postoperative pain and can be used as an alternative to opioid therapy.
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PMID:The use of ketorolac in the management of postoperative pain. 819 Jun 79

Systemic and intrathecally administered ketorolac produced antinociception in the p-phenylquinone test, but not in the tail-flick or hot-plate tests. Antagonists of the subtypes of opioid receptors were used to evaluate the interaction of ketorolac with these receptors. Intrathecally administered kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride blocked the antinociceptive effects of systemic ketorolac and intrathecally administered ketorolac. Naloxone and ICI 174,864 failed to block the effects of ketorolac. Activation of nor-binaltorphimine-sensitive receptors appears to be an integral element in the mechanism of antinociception of ketorolac at the spinal level. Ketorolac did not precipitate withdrawal jumping in morphine-tolerant mice demonstrating that ketorolac does not act as a mixed agonist-antagonist at the opioid receptor. We suggest that neuraxial placement of ketorolac may prove useful in the clinical setting for the management of acute pain in humans.
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PMID:Antinociceptive activity of intrathecal ketorolac is blocked by the kappa-opioid receptor antagonist, nor-binaltorphimine. 822 36

Ketorolac is a nonsteroidal anti-inflammatory drug, available in both oral and parenteral forms, that possesses significant analgesic potency. Its analgesic efficacy has been studied extensively for the treatment of moderate-to-severe pain in many clinical settings. Although ketorolac possesses significant analgesic potency, it has limited utility as an analgesic for the acute treatment of moderate-to-severe pain in the emergency department. Oral ketorolac has been shown to provide analgesia that is the same or better than aspirin, acetaminophen, and dextropropoxyphene with acetaminophen, and equal analgesia to most other commonly available oral analgesics, including ibuprofen and acetaminophen with codeine. Intramuscular ketorolac provides analgesia equivalent to commonly used doses of meperidine and morphine. However, its utility in acute pain, when rapid relief is necessary, is limited due to a prolonged onset to analgesic action (30-60 min) and a significant number of patients who exhibit little or no response, more than 25% in most studies. The use of intravenous ketorolac has been less well studied. It has analgesic potency but its utility in patients with moderate-to-severe pain is also limited because there is a significant percentage of patients who fail to obtain adequate relief. Ketorolac may be most useful in supplementing parenteral opiates.
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PMID:The analgesic efficacy of ketorolac for acute pain. 865 40

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that is indicated for the short-term management of moderately severe, acute pain, that causes analgesia equivalent to that caused by morphine. It has been shown experimentally that the analgesia produced by ketorolac in mice can be diminished by pretreatment with naloxone. This observation suggests that ketorolac produces some of its analgesia by interacting with opioid receptors. However, ketorolac does not directly interact with opioid receptors (Lopez et al., 1987). The present experiments demonstrate that the analgesia produced by ketorolac may be caused by the release of the endogenous opioid, methionine-enkephalin.
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PMID:Ketorolac causes the release of methionine-enkephalin in rats. 883 17

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with strong analgesic activity. The analgesic efficacy of ketorolac has been extensively evaluated in the postoperative setting, in both hospital inpatients and outpatients, and in patients with various other acute pain states. After major abdominal, orthopaedic or gynaecological surgery or ambulatory laparoscopic or gynaecological procedures, ketorolac provides relief from mild to severe pain in the majority of patients and has similar analgesic efficacy to that of standard dosages of morphine and pethidine (meperidine) as well as less frequently used opioids and other NSAIDs. The analgesic effect of ketorolac may be slightly delayed but often persists for longer than that of opioids. Combined therapy with ketorolac and an opioid results in a 25 to 50% reduction in opioid requirements, and in some patients this is accompanied by a concomitant decrease in opioid-induced adverse events, more rapid return to normal gastrointestinal function and shorter stay in hospital. In children undergoing myringotomy, hernia repair, tonsillectomy, or other surgery associated with mild to moderate pain, ketorolac provides comparable analgesia to morphine, pethidine or paracetamol (acetaminophen). In the emergency department, ketorolac attenuates moderate to severe pain in patients with renal colic, migraine headache, musculoskeletal pain or sickle cell crisis and is usually as effective as frequently used opioids, such as morphine and pethidine, and other NSAIDs and analgesics. Subcutaneous administration of ketorolac reduces pain in patients with cancer and seems particularly beneficial in pain resulting from bone metastases. The acquisition cost of ketorolac is greater than that of morphine or pethidine; however, in a small number of studies, the higher cost of ketorolac was offset when treatment with ketorolac resulted in a reduced hospital stay compared with alternative opioid therapy. The tolerability profile of ketorolac parallels that of other NSAIDs; most clinically important adverse events affect the gastrointestinal tract and/or renal or haematological function. The incidence of serious or fatal adverse events reported with ketorolac has decreased since revision of dosage guidelines. Results from a large retrospective postmarketing surveillance study in more than 20,000 patients demonstrated that the overall risk of gastrointestinal or operative site bleeding related to parenteral ketorolac therapy was only slightly higher than with opioids. However, the risk increased markedly when high dosages were used for more than 5 days, especially in the elderly. Acute renal failure may occur after treatment with ketorolac but is usually reversible on drug discontinuation. In common with other NSAIDs, ketorolac has also been implicated in allergic or hypersensitivity reactions. In summary, ketorolac is a strong analgesic with a tolerability profile which resembles that of other NSAIDs. When used in accordance with current dosage guidelines, this drug provides a useful alternative, or adjuvant, to opioids in patients with moderate to severe pain.
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PMID:Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. 901 Jun 53

The management of severe pain may require "balanced analgesia," involving the use of analgesics with different modes of action. Clonidine, an alpha(2)-adrenoreceptor agonist produces analgesia by itself as well as when given with morphine and local anesthetics. Ketorolac is indicated for the management of moderately severe acute pain and causes analgesia equivalent to morphine. This study was designed to investigate whether the addition of ketorolac promotes antinociception produced by intrathecal administration of clonidine in male Sprague-Dawley rats. Intrathecal injection of clonidine (1-30 microg) induced a dose-dependent increase in antinociception as measured by the tail flick (TF) and hot plate tests. Ketorolac alone (150-600 microg) increased the antinociception by 50%-60% only in the TF test. Ketorolac (10 microg) decreased clonidine (10 microg)-induced antinociception from 69.1% +/- 7.8% to 23.5% +/- 1. 6% (P < 0.05) in the TF test and 35.7% +/- 4.7% to 4.5% +/- 0.1% (P < 0.05) maximum possible effect in the hot plate test. Ketorolac also antagonized the effect of 30 microg of clonidine. The opioid receptor antagonist naloxone antagonized the antinociceptive effect of clonidine and ketorolac, indicating the involvement of the opioid system in the antinociception produced by clonidine or ketorolac. However, neither clonidine nor ketorolac (10(-8) to 10(-3) M) inhibited the binding of specific ligands to mu-, delta-, and kappa-opioid receptors, indicating a lack of direct interaction of clonidine and ketorolac with opioid receptors. These results suggest that intrathecal injection of ketorolac antagonizes the antinociception produced by clonidine.
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PMID:Antagonism of antinociception produced by intrathecal clonidine by ketorolac in the rat: the role of the opioid system. 1078 70

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.
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PMID:Analgesia and COX-2 inhibition. 1169 55

Spinal prostaglandin synthesis has been implicated in acute pain processes and in generation and maintenance of central sensitization, and intrathecal injection of cyclo-oxygenase (COX) inhibitors produce antinociception and reduce hypersensitivity in animals. We herein report a Phase I safety assessment of intrathecal injection of the COX inhibitor, ketorolac, in healthy volunteers, and demonstrate no serious side effects. Preclinical studies suggest a major site of action of COX inhibitors for analgesia lies in the central nervous system, especially the spinal cord. For example, COX isoenzymes are expressed in the spinal cord, acute noxious stimuli and inflammation increase spinal prostaglandin production, and spinally administered prostaglandins excite dorsal horn projection neurons, induce release of excitatory neurotransmitters, and cause nociceptive behavior. Intrathecal injection of COX inhibitors increases thermal and mechanical withdrawal threshold in animals with inflammation or nerve injury at doses several 100-fold less than those required systemically. Following pre-clinical neurotoxicity screening and regulatory agency approval, we examined the safety of intrathecal injection of a preservative-free formulation of the COX inhibitor, ketorolac. In an open label, dose-escalating design, 20 healthy volunteers received intrathecal ketorolac, 0.25, 0.5, 1, or 2mg (n=5 per group). Ketorolac did not alter blood pressure, although there was small (10-12%), dose-independent reduction in heart rate for the first hour after injection when data from all subjects were pooled. Ketorolac did not affect sensory or motor function or deep tendon reflexes, and there were no subjective sensations, neurologic or otherwise, reported by the volunteers. Ketorolac did not reduce pain report to heat stimuli applied to the lateral calf. One subject had a mild headache 24h after study, resolving the next day. There were no long-term side effects 6 months after study. These data suggest that intrathecal ketorolac does not produce a high incidence of serious adverse events, and they support further investigation for analgesia.
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PMID:Phase I safety assessment of intrathecal ketorolac. 1240 36


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