Disease relevance of ketorolac

• METHODS: In protocol 1, urine volume, urinary excretion of sodium and prostaglandins, glomerular filtration rate, and renal plasma flow were measured before and after administration of SC-236 (n = 12) or ketorolac (n = 10) to rats with cirrhosis [1].
• OBJECTIVE: To compare the risk for acute renal failure associated with ketorolac with that associated with opioids [2].
• Compared with opioids, ketorolac administered for 5 days or less did not increase the rate of renal failure [2].
• OBJECTIVE: To compare intramuscular ketorolac troinethamine with intravenous chlorpromazine hydrochloride in treating acute migraine [3].
• METHODS: Patients (n = 522) received a single oral or intramuscular administration of placebo or a single intramuscular dose of 10, 30, 60, or 90 mg ketorolac for postoperative pain relief [4].

Psychiatry related information on ketorolac

• RESULTS: Pretreatment with ketorolac had a selective effect on the postburn injury hyperalgesia, reducing the increase in pain intensity (P<0.05) but not the decline in pain threshold [5].
• RESULTS: For all treatment groups, there was no significant difference in extent or adequacy of sedation, incidence of oxygen desaturation, patient amnesia, time of procedure, or vital signs (except for a relative procedural tachycardia in the ketorolac and placebo groups as compared to baseline) [6].
• No significant differences between eyes treated with ketorolac 0.4% and placebo were observed in patient cooperation, and ocular pain or discomfort during or immediately after surgery [7].
• RESULTS: No significant decrease in corneal sensory thresholds was found with diclofenac or ketorolac compared with control at baseline (P = .50), 7 minutes (P = .41), or 15 minutes (P = .82) [8].
• There was a significant difference between the groups in the average and daily pain rating, with the ketorolac therapy group reporting significantly less pain [9].

High impact information on ketorolac

• A COX-1-preferential inhibitor, ketorolac, was also evaluated [10].
• Parenteral ketorolac: the risk for acute renal failure [2].
• No effect was observed with other NSAIDs, at concentrations that inhibit cyclooxygenase, such as ketorolac (10 micromol/mL), NS-398 (100 micromol/mL), or indomethacin (20 micromol/mL), thus suggesting the involvement of cyclooxygenase-independent mechanisms in aspirin-induced cytotoxicity [11].
• The pan-COX inhibitor ketorolac continuously and significantly decreased PGE(2) production and IL-6 and IL-8 levels in all OPC cell lines tested, but did not affect IL-1alpha, GM-CSF levels, or in vitro tumor cell growth [12].
• Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs [13].

Chemical compound and disease context of ketorolac

• 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) [14].
• Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac [15].
• In the class of topical NSAIDs, ketorolac has been promoted for ocular itching but has been found to be inferior for relief of allergic conjunctivitis when compared with olopatadine and emedastine [16].
• Anterior subconjunctival and topical ketorolac were compared to control as well as topical and anterior subconjunctival steroid treatments in uveitis induced by the intravitreal injection of tumor necrosis factor [17].
• Double-blind evaluation of short-term analgesic efficacy of orally administered dexketoprofen trometamol and ketorolac in bone cancer pain [18].

Biological context of ketorolac

• Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children [19].
• Ketorolac produced a modest prolongation of the bleeding time, from 4.9 +/- 1.1 minutes (mean +/- SD) to 7.8 +/- 4.0 minutes (p less than 0.005) [20].
• OBJECTIVE: To investigate the bioavailability (extent and rate of absorption) of ketorolac from two cutaneous absorption sources, active electrotransport and passive transdermal, and to examine the enantiomeric selectivity of bioavailability for each source [21].
• Ketorolac did not affect the prothrombin time or partial thromboplastin time but was associated with clinically insignificant change in the platelet count from 303 +/- 57 X 10(3)/m3 to 277 +/- 56 X 10(3)/mm3 [20].
• The authors conducted a prospective randomised double-blind comparison of patient-controlled analgesia (PCA), with a combination of morphine and ketorolac versus morphine alone and ketorolac alone in the management of postoperative pain after orthopaedic surgery [22].

Anatomical context of ketorolac

• Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: immunologic challenges in cancer therapy [23].
• 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 [24].
• In altering the production of key prostaglandins that are involved in the control of hypothalamic-pituitary-adrenal axis, ketorolac may have proinflammatory properties in the central nervous system during systemic immune stimuli [25].
• PURPOSE: To compare the corneal analgesic efficacy of the nonsteroidal anti-inflammatory drugs (NSAIDs) nepafenac, diclofenac, and ketorolac, and to evaluate the possibility that their inhibitory effects on corneal polymodal nociceptor fiber activity are partly mediated by a decrease in sodium currents [26].
• Although ketorolac is excreted into the breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure [27].

Associations of ketorolac with other chemical compounds

• Other nonspecific NSAIDs, diclofenac and ketorolac, also inhibited HIF-1alpha and HIF-2alpha [28].
• S(-)- and R(+)-ketorolac were measured in plasma; S(-)- and R(+)-ketorolac and ketorolac glucuronide were measured in urine by chiral HPLC separation [19].
• Prolonged treatment with rofecoxib but not with ketorolac caused an upregulation of COX-2 expression while COX-1 mRNA abundance remained unchanged [29].
• Increased lithium serum and red blood cell concentrations during ketorolac coadministration [30].
• The present study investigated the role of non-selective (ketorolac or indomethacin) or specific inhibitors of COX-1 (SC-560) and COX-2 (NS-398) in these effects [31].

Gene context of ketorolac

• RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/COX-2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism [1].
• These findings suggest that (R)- ketorolac may possess analgesic activity that is independent of COX inhibition and may be associated with reduced ulcerogenic potential compared to effects exhibited by (S)- ketorolac [32].
• RESULT(S): Postoperative adhesion scores were significantly reduced in all groups of animals treated with IL-10 or ketorolac [33].
• To extend these observations, we examined the (R)- and (S)- enantiomers of RS- ketorolac, (S)- ketorolac exhibited potent COX1 and COX2 enzyme inhibition, whereas (R)- ketorolac was > 100-fold less active on both COX subtypes [32].
• 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) [34].

Analytical, diagnostic and therapeutic context of ketorolac

• Analgesia after intravenous ketorolac developed more slowly but was sustained better than morphine [35].
• In this randomized, double-blind study, 26 volunteers received ketorolac, 30 mg intramuscularly four times a day for 5 days, and placebo, two capsules orally four times a day for at the last 2 study days [20].
• METHODS: Based on a crossover study in 12 healthy volunteers, the extent and rate of absorption of ketorolac, delivered by a patch, were found by estimating the input rate function of the drug [21].
• Ninety-two children from 3 to 12 years of age were given intravenous morphine or ketorolac by titration, or ketorolac by bolus injection for moderate or severe postsurgical pain in a double-blind randomized parallel-group study [35].
• NSAIDs for the chemoprevention of oral cancer: promise or pessimism?: Commentary re J. L. Mulshine et al., randomized, double-blind, placebo-controlled, phase IIB trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia. Clin. Cancer Res., 10: 1565-1573, 2004 [36].

References