ABSTRACT
Background: Epithelioid hemangioendothelioma (EHE) patients can experience severe pain. Nonsteroidal anti-inflammatory drugs, including ketorolac tromethamine, can effectively treat cancer-related pain, provide an opioid-sparing effect, and may be particularly effective for EHE pain. There are limited data describing prolonged (>5 days) continuous intravenous (IV) ketorolac infusion for cancer-related pain and no data on its use in EHE. Case Description: A 67-year-old woman with metastatic hepatic EHE suffered from chronic intractable pleuritic pain unresponsive to trials of nonopioid, opioid, adjuvant medications, and nonpharmacological interventions. In the hospital, continuous IV ketorolac infusion at 3.8 mg/hour (91.2 mg/day) effectively managed pain. With thorough monitoring, the patient was discharged on continuous IV ketorolac infusion at 3 mg/hour (72 mg/day). Infusion continued for 79 days without clinical or laboratory evidence of ketorolac toxicity. Conclusion: Ketorolac tromethamine as a long-term infusion is a potentially viable analgesic for patients with intractable EHE-related pain unresponsive to standard therapies.
Subject(s)
Hemangioendothelioma, Epithelioid , Pain, Intractable , Tolmetin , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal , Child , Double-Blind Method , Female , Hemangioendothelioma, Epithelioid/complications , Hemangioendothelioma, Epithelioid/drug therapy , Humans , Ketorolac/therapeutic use , Ketorolac Tromethamine/therapeutic use , Pain, Intractable/drug therapy , Pain, Intractable/etiology , Pain, Postoperative/drug therapy , Tolmetin/therapeutic useABSTRACT
Three novel series of diarylpyrazole 10b-d and triarylpyrazole derivatives 11a-d &12a-d were synthesized through Vilsmier-Haack condition. The structures of prepared compounds were determined through IR, 1H NMR, 13C NMR, Mass spectral and elemental analysis. Docking of the synthesized compounds over COX-2 active site ensure their selectivity. Moreover, the target compounds were evaluated for both in vitro and in vivo inhibitory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and with excellent anti-inflammatory activity. Compounds 11b, 11d and 12b showed the highest anti-inflammatory activity (67.4%, 62.7%, 61.4% respectively), lower ulcerogenic liability (UIâ¯=â¯2.00, 2.75, 3.25 respectively) than indomethacin (UIâ¯=â¯14) and comparable to celecoxib (UIâ¯=â¯1.75) which were confirmed from the histopatholgical study.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Celecoxib/therapeutic use , Cyclooxygenase 2 Inhibitors/therapeutic use , Inflammation/drug therapy , Tolmetin/therapeutic use , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/metabolism , Catalytic Domain , Celecoxib/analogs & derivatives , Celecoxib/metabolism , Celecoxib/pharmacology , Cyclooxygenase 2/chemistry , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/metabolism , Drug Design , Gastric Mucosa/pathology , Humans , Indomethacin/pharmacology , Molecular Docking Simulation , Protein Binding , Rats , Tolmetin/analogs & derivatives , Tolmetin/metabolismABSTRACT
BACKGROUND: Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID). It is most often used for treating pain of dysmenorrhoea in the short term (seven days or less), as well as mild to moderate pain including headache, dental pain, postoperative and postpartum pain. It is widely available in many countries worldwide. OBJECTIVES: To assess the efficacy of single dose oral mefenamic acid in acute postoperative pain, and any associated adverse events. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. SELECTION CRITERIA: Single oral dose, randomised, double-blind, placebo-controlled trials of mefenamic acid for relief of established moderate to severe postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Four studies with 842 participants met the inclusion criteria; 126 participants were treated with mefenamic acid 500 mg, 67 with mefenamic acid 250 mg, 197 with placebo, and 452 with lignocaine, aspirin, zomepirac or nimesulide. Participants had pain following third molar extraction, episiotomy and orthopaedic surgery. The NNT for at least 50% pain relief over 6 hours with a single dose of mefenamic acid 500 mg compared to placebo was 4.0 (2.7 to 7.1), and the NNT to prevent use of rescue medication over 6 hours was 6.5 (3.6 to 29). There were insufficient data to analyse other doses or active comparators, or numbers of participants experiencing any adverse events. No serious adverse events or adverse event withdrawals were reported in these studies. AUTHORS' CONCLUSIONS: Oral mefenamic acid 500 mg was effective at treating moderate to severe acute postoperative pain, based on limited data. Efficacy of other doses, and safety and tolerability could not be assessed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Mefenamic Acid/administration & dosage , Pain, Postoperative/drug therapy , Acute Disease , Administration, Oral , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/administration & dosage , Aspirin/therapeutic use , Humans , Mefenamic Acid/therapeutic use , Randomized Controlled Trials as Topic , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use , Tolmetin/administration & dosage , Tolmetin/analogs & derivatives , Tolmetin/therapeutic useABSTRACT
Idiopathic chondrolysis of the hip is a rare condition occurring mainly in adolescents and is characterised by a rapidly progressive destruction of the articular cartilage in the coxofemoral joint. Patients report intense pain, motion restriction and often limping due to shortening of the limb. The aetiology is not elucidated. Medical imaging techniques form the cornerstone for differential diagnosis. Additionally biological markers for inflammation and infections should be studied. Conservative treatment focuses on pain control and preservation of joint mobility. Because published results of surgical treatment are not conclusive and arthroplasty in young patients is controversial, there is up till now no consensus on the treatment algorithm. Some authors advocate conservative treatment until spontaneous fusion. A case of idiopathic chondrolysis conventionally managed is reported.
Subject(s)
Acetabulum/pathology , Cartilage Diseases/pathology , Cartilage, Articular/pathology , Femur Head/pathology , Hip Joint/pathology , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cartilage Diseases/diagnostic imaging , Cartilage Diseases/therapy , Combined Modality Therapy , Crutches , Female , Hip Joint/diagnostic imaging , Humans , Radiography , Tolmetin/therapeutic use , Weight-BearingABSTRACT
BACKGROUND: The arthritis of rheumatic fever is very responsive to treatment with salicylates, but there are many adverse reactions, especially hepatotoxicity, due to aspirin (acetylsalicylic acid) therapy. These side-effects change the course and duration of rheumatic fever. Other non-steroidal anti-inflammatory drugs may be equally effective, although no reports are available. METHODS: We studied 72 patients with rheumatic fever who were admitted to Dr Sami Ulus Children's Hospital between 1995 and 1999. Twenty patients with arthritis were treated with tolmetin (25 mg/kg per day; group I) and 52 patients with arthritis and/or mild carditis were put on aspirin therapy (75-100 mg/kg per day) for 4-6 weeks (group II). Arthritis had disappeared at the same time in both the aspirin and tolmetin groups (P = 0.675). RESULTS: The erythrocyte sedimentation rates of patients upon admission, at the first week and at the end of therapy were not different in the two groups (P > 0.05). No adverse effect of tolmetin therapy was observed, whereas side-effects of salicylate were observed in 19 patients (36.5%) in the aspirin group. Hepatotoxicity, gastric irritation and salicylism were found in 16, four and three patients, respectively. Renal toxicity and Reye syndrome were not demonstrated. Because of these side-effects of aspirin, therapy had to be stopped for 10-20 days and the duration of hospitalization in this group was lengthened unnecessarily. CONCLUSION: Tolmetin was safe and effective treatment for arthritic rheumatic fever patients without carditis. Tolmetin can be used particularly in patients who cannot tolerate aspirin.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Rheumatic Fever/drug therapy , Tolmetin/therapeutic use , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Child , Child, Preschool , Female , Humans , Infant , Male , Tolmetin/adverse effectsABSTRACT
BACKGROUND: The novel non-steroidal anti-inflammatory drug amtolmetin guacyl has been shown to possess markedly reduced ulcerogenic effects and nitric oxide-mediated gastroprotective activity against the damage induced by ethanol in the rat. AIMS: To investigate, in the rat, the role of nitric oxide and of inducible nitric oxide synthase isoform in the protective effect of amtolmetin guacyl against the gastric damage induced by ethanol. METHODS: The effects of amtolmetin guacyl on gastric transmucosal potential difference and on gastric mucosal blood flow were investigated in the anaesthetised rat; myeloperoxidase activity, inducible and endothelial nitric oxide synthase protein content were determined in rat gastric mucosal homogenates. The anti-inflammatory drug tolmetin and the bacterial lipopolysaccharide from Escherichia coli were studied for comparison. RESULTS: In the anaesthetised rat, amtolmetin guacyl, but not tolmetin, reduced by approximately 50% the fall in gastric potential difference and, to a lesser extent, the macroscopic damage induced by ethanol. The effect of amtolmetin guacyl on transmucosal potential difference was prevented by the selective inducible nitric oxide synthase inhibitor 1400W. In amtolmetin guacyl-treated rats, 1400W decreased gastric mucosal blood flow, whereas it was inactive in vehicle- and tolmetin-treated animals. In gastric mucosal homogenates, both amtolmetin guacyl and lipopolysaccharide, but not tolmetin, increased inducible, but not endothelial, nitric oxide synthase protein content, as revealed by Western immunoblotting. CONCLUSIONS: These data confirm that amtolmetin guacyl is a non-steroidal anti-inflammatory agent devoid of gastrolesive properties, that can actually reduce the damaging effects of ethanol through the increase in nitric oxide production, via the inducible isoform of nitric oxide synthase.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Gastric Mucosa/drug effects , Glycine/analogs & derivatives , Glycine/therapeutic use , Pyrroles/therapeutic use , Animals , Ethanol/adverse effects , Lipopolysaccharides/therapeutic use , Male , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/metabolism , Peroxidase/metabolism , Rats , Rats, Wistar , Tolmetin/therapeutic useABSTRACT
OBJECTIVE: To evaluate whether ketorolac ophthalmic drops prescribed four times a day can be associated with improved visual acuity and prompt resolution of edema for patients with pseudophakic cystoid macular edema identified more than 24 months after cataract surgery. DESIGN: Prospective, nonrandomized, comparative (subject self-controlled) trial. PARTICIPANTS: The records of nine patients who had pseudophakic cystoid macular edema more than 24 months after cataract surgery at the time treatment commenced were identified at the Wilmer Retinal Vascular Center from September 1, 1996, through March 1, 1997. MAIN OUTCOME MEASURES: Best-corrected visual acuities measured on a retroilluminated Bailey-Lovie chart approximately every 3 months, contact lens biomicroscopy, and fluorescein angiography following ketorolac. INTERVENTION: Commercially available ketorolac ophthalmic drops 0.5% were prescribed for the affected eye four times a day for at least 3 months and continued until edema resolved. RESULTS: Ten eyes of nine patients were identified more than 24 months after cataract extraction (median, 59 months). Seven eyes (70%) improved (mean, +3.2 lines; range, +1 to +13 lines), including six by 2 or more lines 3 months after treatment initiation. Two eyes (20%) were unchanged, and one eye (10%) was 1 line worse. All seven eyes that improved 1 line or more had some or complete angiographic resolution of fluorescein dye leakage. In these seven eyes, ketorolac was discontinued when dye leakage completely resolved or failed to continue to improve on periodic 3-month follow-up examinations. In all seven eyes, recurrence of edema was noted within 3 months after ketorolac was stopped. CONCLUSIONS: Chronic pseudophakic cystoid macular edema identified more than 24 months after cataract surgery can improve with topical ketorolac but probably requires persistent use.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cataract Extraction/adverse effects , Macular Edema/drug therapy , Pseudophakia/drug therapy , Tolmetin/analogs & derivatives , Aged , Aged, 80 and over , Chronic Disease , Female , Fluorescein Angiography , Fundus Oculi , Humans , Ketorolac , Macular Edema/diagnosis , Macular Edema/etiology , Male , Ophthalmic Solutions/therapeutic use , Prospective Studies , Pseudophakia/etiology , Pseudophakia/pathology , Time Factors , Tolmetin/therapeutic use , Visual AcuitySubject(s)
Randomized Controlled Trials as Topic/methods , Acetaminophen/administration & dosage , Acetaminophen/analogs & derivatives , Acetaminophen/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dose-Response Relationship, Drug , Humans , Ketorolac , Pain, Postoperative/drug therapy , Placebos , Research Design , Tolmetin/administration & dosage , Tolmetin/analogs & derivatives , Tolmetin/therapeutic useABSTRACT
PURPOSE: To compare the 2 most popular commercially available topical nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of ocular pain following radial keratotomy (RK). SETTING: Multicenter clinical trial. METHODS: Ninety-seven RK patients were randomly assigned to 1 of 3 treatment groups: ketorolac tromethamine, diclofenac sodium, and moist drops as a control. The patients used 1 drop of the masked medication and 1 drop of ofloxacin 3 times a day for 3 days prior to surgery. They received 1 drop of the masked medication 1 hour before surgery, immediately after surgery, and 4 times a day thereafter. Patients were given a written questionnaire preoperatively and were also instructed to call a central computerized telephone system to answer prerecorded questions about ocular comfort. The calls were placed 30 minutes and 1, 2, 3, 4, 5, 6, 24, and 48 hours after surgery. RESULTS: Two hundred ten statistical values were calculated to compare symptoms in the unoperated eye at baseline with symptoms in the operated eyes at each of 9 postoperative time points. Only 7 of the 210 values (3.3%) were significantly different among patient groups (operated versus unoperated eyes) by psychometric testing. CONCLUSIONS: Both ketorolac tromethamine and diclofenac sodium were more effective in reducing post-RK discomfort than the control (moist artificial tears). Given the large number of tests and the small number that tested as significant, the significant differences (7 of 210 measurements) observed among the 3 treatment groups probably occurred by chance, although the improved foreign-body sensation, functionality, and compliance scores in the ketorolac group during the first 4 hours might be clinically important.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diclofenac/therapeutic use , Keratotomy, Radial/adverse effects , Pain, Postoperative/drug therapy , Tolmetin/analogs & derivatives , Tromethamine/analogs & derivatives , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Diclofenac/administration & dosage , Double-Blind Method , Female , Humans , Ketorolac Tromethamine , Male , Middle Aged , Myopia/surgery , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/therapeutic use , Pain, Postoperative/etiology , Prospective Studies , Surveys and Questionnaires , Tolmetin/administration & dosage , Tolmetin/therapeutic use , Tromethamine/administration & dosage , Tromethamine/therapeutic use , Visual AcuityABSTRACT
BACKGROUND: The aim was to compare the efficacy and safety of a combination of intramuscular ketorolac and chlorpromazine for the treatment of acute exacerbations of chronic pain with the more commonly used regimen of intramuscular meperidine and promethazine. METHODS: Use-effective case series were drawn from a real-life, rural emergency department practice, in which 200 consecutive patients coming to a rural emergency department with acute exacerbations of chronic pain syndromes were assigned on an every-other basis in a single-blind fashion to one of the two treatment conditions. Patients were given intramuscular doses of either 60 mg of ketorolac plus 50 mg of chlorpromazine (75 mg of chlorpromazine for patients weighing more than 100 kg), or 50 mg of meperidine plus 25 mg of promethazine (50 mg of promethazine for patients weighing more than 75 kg); patients weighing more than 100 kg were given 1.5 doses. Patients older than 65 years or whose blood pressure at the time of injection was less than 110/70 mmHg were given half-doses. Patients could receive one additional half-dose injection if they had no results within 30 to 60 minutes after the first injection. Patients were assessed on self-report and on a verbal and visual analog scale of pain rating. Temperature, blood pressure, heart rate, and respirations were monitored every 15 minutes. RESULTS: Both regimens performed well, with more than 90 percent of patients reporting good or excellent improvement on acute exacerbations of chronic pain. Ketorolac-chlorpromazine offered significant advantages compared with meperidine-promethazine when patients rated their pain on a visual analog pain scale (P < 0.05) but not on a verbal scale. Adverse reactions were minimal and consisted of more respiratory tract depression with meperidine and more vertigo or dizziness with chlorpromazine. There was no difference in incidence of hypotension between the two groups. CONCLUSIONS: The combination of ketorolac and chlorpromazine is a safe and efficacious alternative to meperidine plus promethazine for the treatment of exacerbations of chronic pain in the rural emergency department setting.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Chlorpromazine/therapeutic use , Dopamine Antagonists/therapeutic use , Hypnotics and Sedatives/therapeutic use , Meperidine/therapeutic use , Narcotics/therapeutic use , Pain/drug therapy , Promethazine/therapeutic use , Tolmetin/analogs & derivatives , Adolescent , Adult , Aged , Aged, 80 and over , Chronic Disease , Drug Therapy, Combination , Female , Humans , Ketorolac , Male , Middle Aged , Single-Blind Method , Tolmetin/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Ketorolac is a parenteral, nonsteroidal analgesic that does not have a narcotic's risks of respiratory depression, hypotension, or dependence. Its usefulness in providing pain relief in pediatric patients with acute vaso-occlusive crisis of sickle cell disease has not been studied to date. METHODS: Twenty-nine patients with sickle cell disease between the ages of 5 and 18 years who presented to The Children's Hospital of Alabama emergency department (ED) with 41 distinct episodes of acute vaso-occlusive pain crisis were enrolled prospectively and randomized to receive either 0.9 mg/kg intravenous (IV) ketorolac or placebo in a double-blind fashion. All patients also received IV fluids and an initial 0.1 mg/kg of IV morphine. Subsequent standardized doses of morphine were given every 2 hours over a 6-hour observation period based upon severity of pain as scored by a 10-cm linear visual analog scale (VAS). Vital signs and pain severity were recorded initially and assessed hourly. Disposition was made at the end of the observation period. RESULTS: Patients receiving ketorolac and those receiving placebo were of similar age, weight, gender, number of prior ED visits, number of prior hospital admissions, duration of pain prior to presentation, and initial pain score. The total dose of morphine received, reduction in severity of pain as measured by VAS, rate of hospital admission, and rate of return to the ED for discharged patients did not differ significantly between the two groups. CONCLUSION: We were unable to demonstrate a synergistic analgesic effect for ketorolac in the treatment of pain from acute vaso-occlusive crisis in pediatric sickle cell disease. Further investigations involving larger samples of sickle cell patients may be needed to further define a role for ketorolac in the acute management of sickle cell vaso-occlusive pain.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Anemia, Sickle Cell/drug therapy , Pain/drug therapy , Tolmetin/analogs & derivatives , Adolescent , Adult , Anemia, Sickle Cell/physiopathology , Blood Vessels/physiopathology , Child , Double-Blind Method , Female , Hospitalization/statistics & numerical data , Humans , Infant , Ketorolac , Male , Morphine/administration & dosage , Narcotics/administration & dosage , Pain/classification , Pain/etiology , Pain Measurement , Prospective Studies , Tolmetin/therapeutic useABSTRACT
The possible role of spinal prostanoids in the tactile allodynia and thermal hyperalgesia associated with an experimental model of neuropathic pain was investigated. Neuropathic pain was induced by tight ligation of the L5 and L6 spinal nerves. Tactile allodynia was assessed 7 days after the surgery by measuring hindpaw withdrawal threshold to probing with von Frey filaments. Thermal hyperalgesia and nociception were determined by the 52 degrees C warm-water tail-flick test and by applying radiant heat to the plantar aspect of the hindpaw ipsilateral to the ligation. Minimal antiallodynic effect was produced by intrathecal (i.th.) administration of ketorolac or morphine up to the highest testable dose (100 microg) or by the (R)- or (S)-enantiomers of ketorolac (up to 6 microg) when administered alone. However, i.th. administration of a fixed ratio (1:1) of morphine plus racemic ketorolac or of morphine plus the (S)-enantiomer of ketorolac (S-ketorolac) produced a dose- and time-related antiallodynic effect: ED50 114 +/- 35.9 microg (total dose) for morphine plus ketorolac and 70.5 +/- 21.0 microg (total dose) for morphine plus S-ketorolac. The combination of i.th. morphine plus the (R)-enantiomer of ketorolac (R-ketorolac) (up to 200 microg total dose) was without effect. Similar antiallodynic activity was obtained for the co-administration of i.th. morphine and intravenous (i.v.) racemic ketorolac. In order to investigate the role of cyclooxygenase (COX) isozymes, relatively selective COX1 (piroxicam) and COX2 N-[2-cyclohexyloxy-4-nitrophenyl] metanesulfonamide (NS-398) inhibitors were administered i.th. (60 microg) alone or together with i.th. morphine. Piroxicam, NS-398, morphine and vehicle (90% DMSO) were without significant antiallodynic effect when administered alone, but moderate antiallodynic effects were produced by i.th. administration of fixed ratio (1:1) combinations of morphine with 60 microg each (highest soluble dose) of piroxicam (%MPE = 40.8 +/- 10.2) or NS-398 (%MPE = 32.4 +/- 9.5). Further, the combined i.th. administration of morphine, piroxicam and NS-398 in fixed 1:1:1 ratio (60 microg each) resulted in a supraadditive antiallodynic effect (%MPE = 70.4 +/- 10.8). Finally, morphine, but not ketorolac, given i.th. produced dose-dependent anti nociception in either the tail-flick or the paw-flick tests. However, there was no synergy between morphine and ketorolac against thermal nociception in either of the tests. These findings suggest that spinal prostanoids produced via both COX1 and COX2 pathways may play a role in neuropathic pain states and suggest the clinical utility of opioid plus COX-inhibitor combination therapy.
Subject(s)
Analgesics, Opioid/therapeutic use , Cyclooxygenase Inhibitors/therapeutic use , Morphine/therapeutic use , Neuralgia/drug therapy , Pain Threshold/drug effects , Tolmetin/analogs & derivatives , Animals , Drug Synergism , Hyperalgesia/drug therapy , Injections, Spinal , Isoenzymes/antagonists & inhibitors , Ketorolac , Male , Nitrobenzenes/therapeutic use , Piroxicam/therapeutic use , Rats , Rats, Sprague-Dawley , Spinal Nerves/injuries , Sulfonamides/therapeutic use , Tolmetin/therapeutic useABSTRACT
AIM: To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug, ketorolac (Toradol, Recordati spa, Milan) 10 mg p.o. (t.i.d.) with diclofenac (Voltaren, Novartis Farma, Origglo, VA) 50 mg p.o. (t.i.d.) in cancer patients with moderate to severe chronic pain. METHODS AND STUDY DESIGN: The study was a multicenter randomized double-blind cross-over trial. Each treatment lasted 7 days, after which the patients crossed over to the other drug. Pain intensity was evaluated by the visual analogue scale (VAS) after the first dose and by the 5-point verbal rating scale (VRS) by the patient and by the physician following the 7-day treatment. RESULTS AND CONCLUSIONS: A total of 138 advanced cancer patients were enrolled in the study. Overall 251 single-dose administrations (117 cross-over observations) and 257 multiple treatments (127 cross-over experiments) were assessable. After a single administration of ketorolac and diclofenac, no significant difference could be observed in analgesic activity, as indicated by the area under the pain-intensity time curve (AUC0-8), in the maximum efficacy, or the duration of efficacy of the two drugs. The Westlake confidence intervals of the AUC0-8 ratio (ketorolac: diclofenac) (1.07; 90% CI, 0.94-1.19), of the maximum efficacy ratio (1.03; 90% CI, 0.92-1.14), and the duration of efficacy ratio (1.05; 90% CI, 0.97-1.11) showed the bioequivalence of the two drugs. Satisfactory pain relief was reported for multiple 7-day treatments, with no significant differences between the two therapies: according to the physician's evaluation, in 93/128 (73%; 95% CI, 65-80%) ketorolac treatments and 91/129 (71%; 95% CI, 63-78%) diclofenac treatments; according to the patient's evaluation, in 83/128 cases (65%; 95% CI, 57-73%) after ketorolac and in 74/129 cases (57%; 95% CI, 49-66%) after diclofenac. Adverse symptoms were acceptable with both drugs. Interestingly, a pronounced sequence effect was found: gastric disturbances after ketorolac were observed mainly (10 out of 15 observed events) when the drug was given to patients pretreated with diclofenac.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diclofenac/therapeutic use , Neoplasms/complications , Pain/drug therapy , Tolmetin/analogs & derivatives , Administration, Oral , Adult , Aged , Analgesics, Non-Narcotic/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Area Under Curve , Cross-Over Studies , Diclofenac/adverse effects , Double-Blind Method , Drug Administration Schedule , Female , Humans , Ketorolac Tromethamine , Male , Middle Aged , Pain/etiology , Therapeutic Equivalency , Tolmetin/adverse effects , Tolmetin/therapeutic useABSTRACT
This multicenter, double-masked, randomized, parallel study compared the efficacy and safety profile of ketorolac tromethamine 0.5% ophthalmic solution with that of its vehicle in the maintenance of pupillary mydriasis during cataract surgery. A total of 176 adult patients scheduled to undergo unilateral extracapsular cataract extraction and posterior-chamber intraocular lens implantation received either ketorolac tromethamine 0.5% (n = 89) or vehicle (n = 87), starting 2 hours before surgery. One drop of study medication was instilled every 30 minutes for a total of 4 drops. No epinephrine was used in the intraoperative irrigating solution. Pupil diameter was measured with a caliper at 3 time points during surgery. To ensure participant safety, biomicroscopy, ophthalmoscopy, intraocular pressure, adverse events, and preoperative and postoperative visual acuity and refractive error were also monitored. The mean change in horizontal and vertical pupil diameter from the time of the first incision to after cortical irrigation and aspiration was significantly less with active ketorolac than with vehicle (P < or = 0.014). Consequently, mean pupil diameter after cortical irrigation and aspiration was significantly greater with ketorolac than with vehicle (P < or = 0.030). No significant between-group differences were observed in the change in pupil diameter between the end of surgery and postoperative administration of a miotic agent, safety variables, or occurrence of adverse events. In this study, ketorolac tromethamine 0.5% ophthalmic solution provided effective and well-tolerated inhibition of surgically induced miosis during cataract surgery.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cataract Extraction , Miosis/prevention & control , Postoperative Complications/prevention & control , Tolmetin/analogs & derivatives , Tromethamine/analogs & derivatives , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Double-Blind Method , Female , Humans , Ketorolac Tromethamine , Male , Middle Aged , Ophthalmic Solutions , Tolmetin/administration & dosage , Tolmetin/therapeutic use , Tromethamine/administration & dosage , Tromethamine/therapeutic useABSTRACT
Analysis of many-year experience gained in the use of a variety of methods and means for treating the painful syndrome in victims and patients after planned and urgent surgery allowed the authors to determine the optimal approaches to postoperative analgesia. Special attention is paid to introduction of new drugs and methods of analgesia with differentiated approach to prevention and treatment of the painful syndrome. A conclusion on the necessity of pathogenetically based and strictly individual postoperative analgesia is made; such analgesia is often to be multilevel and multicomponent, with consideration for the complex origin of painful reaction (including the components of the painful syndrome) and the armory of available means.
Subject(s)
Analgesics/therapeutic use , Pain, Postoperative/drug therapy , Analgesics/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/therapeutic use , Butorphanol/therapeutic use , Humans , Ketorolac Tromethamine , Promedol/therapeutic use , Time Factors , Tolmetin/analogs & derivatives , Tolmetin/therapeutic use , Tromethamine/analogs & derivatives , Tromethamine/therapeutic useABSTRACT
Oxadol (nefopam hydrochloride), a central analgesic, was used for postoperative pain relief in patients operated on the abdominal and pelvic organs for cancer. The analgesic effect of oxadol was sufficient for arresting moderate postoperative pain. Although the drug exerts rather many side effects, none of them notably deteriorated the clinical status of patients.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Nefopam/therapeutic use , Pain, Postoperative/drug therapy , Adult , Aged , Aged, 80 and over , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Butorphanol/administration & dosage , Butorphanol/therapeutic use , Female , Gastrointestinal Neoplasms/surgery , Genital Neoplasms, Female/surgery , Humans , Hydrocortisone/blood , Ketorolac Tromethamine , Male , Middle Aged , Nefopam/administration & dosage , Pain, Postoperative/blood , Tolmetin/administration & dosage , Tolmetin/analogs & derivatives , Tolmetin/therapeutic use , Tromethamine/administration & dosage , Tromethamine/analogs & derivatives , Tromethamine/therapeutic useABSTRACT
We studied intensity of pain, cumulative morphine consumption, ventilatory and renal function, and haemostasis in patients undergoing video-assisted thoracoscopic surgery and receiving a 2-day i.v. infusion of diclofenac, ketorolac or saline. Plasma concentrations of the two NSAID were also measured. The study was randomized, double-blind and placebo-controlled, with 10 patients in each group. Patients experienced mainly moderate pain. Mean consumption of i.v. morphine during the first day after operation was 57 (SEM 11) mg in the placebo group. Diclofenac and ketorolac were equally effective in reducing total morphine consumption (61% and 52%, respectively). Adverse events were similar and minor. Greater variability in plasma concentrations of ketorolac were detected compared with diclofenac.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Diclofenac/therapeutic use , Endoscopy , Pain, Postoperative/drug therapy , Thoracic Surgical Procedures , Tolmetin/analogs & derivatives , Adolescent , Adult , Aged , Analgesics, Opioid/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Double-Blind Method , Female , Forced Expiratory Volume/drug effects , Hemostasis/drug effects , Humans , Ketorolac , Kidney/drug effects , Male , Middle Aged , Morphine/administration & dosage , Thoracoscopy , Tolmetin/therapeutic useABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase Inhibitors/therapeutic use , Pain, Postoperative/drug therapy , Tonsillectomy , Adolescent , Adult , Diclofenac/therapeutic use , Double-Blind Method , Female , Humans , Ketoprofen/therapeutic use , Ketorolac , Male , Middle Aged , Pain Measurement , Patient Satisfaction , Tolmetin/analogs & derivatives , Tolmetin/therapeutic useABSTRACT
BACKGROUND: Thoracic epidural analgesia (TEA) is reported to provide effective analgesia following cardiac surgery. We compared the effect of buprenorphine (BN) through the lumbar and thoracic epidural routes for postoperative analgesia following coronary artery bypass graft surgery (CABG). METHODS: Forty patients with normal left ventricular ejection fraction scheduled for CABG were randomly divided into two groups, the TEA group (n = 19) and the lumbar epidural analgesia (LEA) group (n = 20). For postoperative pain relief they received epidural BN 0.15 mg at the first demand for pain relief following extubation. A top-up dose of BN 0.15 mg was administered in cases where visual analogue scale (VAS) score was > 3 at 1 h after first dose. Subsequent breakthrough pain was treated with 30 mg intramuscular ketorolac tromethamine (ketorolac). Pain assessed by VAS score on a 0-10 scale, respiratory rate, FEV1, FVC, mean arterial blood pressure, cardiac index, PaO2 and PaCO2 were measured at frequent intervals. Side effects of epidural opioids were noted. RESULTS: Both groups were comparable in demographic characteristics, had similar VAS scores from 1 to 24 h postoperatively, required similar amounts of intramuscular ketorolac for break-through pain and had comparable pulmonary functions and side effects. CONCLUSION: This study shows that BN by the lumbar epidural route for analgesia after CABG compares favourably with the same drug through the thoracic route in terms of quality of analgesia and incidence of side effects.
Subject(s)
Analgesia, Epidural/methods , Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Coronary Artery Bypass , Pain, Postoperative/drug therapy , Adult , Aged , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Blood Pressure/drug effects , Buprenorphine/administration & dosage , Buprenorphine/adverse effects , Carbon Dioxide/blood , Cardiac Output/drug effects , Coronary Artery Bypass/adverse effects , Female , Forced Expiratory Volume/drug effects , Humans , Injections, Intramuscular , Ketorolac Tromethamine , Lumbar Vertebrae , Male , Middle Aged , Oxygen/blood , Pain Measurement , Respiration/drug effects , Stroke Volume , Thoracic Vertebrae , Tolmetin/administration & dosage , Tolmetin/analogs & derivatives , Tolmetin/therapeutic use , Tromethamine/administration & dosage , Tromethamine/analogs & derivatives , Tromethamine/therapeutic use , Ventricular Function, Left , Vital Capacity/drug effectsABSTRACT
PURPOSE: To compare the anti-inflammatory and analgesic efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution with those of prednisolone acetate 1% in patients having cataract surgery. SETTING: Shawnee Mission Eye Care, Shawnee Mission, Kansas, USA. METHODS: This double-blind, randomized, single-site study comprised 59 healthy men and women with a clinical diagnosis of routine ocular cataract requiring surgical removal. All patients had extracapsular cataract extraction and posterior chamber intraocular lens implantation. After surgery, patients were randomized to receive ketorolac tromethamine 0.5% or prednisolone acetate 1%, self-instilled in the treated eye, according to the following schedule: 1 to 2 drops 4 times daily (week 1); 3 times daily (week 2); 2 times daily (week 3); once daily (week 4). Patients were examined postoperatively on days 1, 7, and 28. Intraocular anti-inflammatory efficacy was assessed by lid edema, lid injection, conjunctival injection, corneal edema, ciliary flush, and anterior chamber cells. Analgesic efficacy was assessed by patient self-rated pain severity, pain frequency, total symptom sum, and overall global improvement. RESULTS: Both treatments produced comparable reductions in intraocular inflammation and pain after cataract surgery and were well tolerated by patients. No adverse events were reported, and there were no significant changes in intraocular pressure in either group. Improvements in visual acuity were also similar in both groups. CONCLUSION: Ketorolac tromethamine 0.5% ophthalmic solution was as effective and well-tolerated as prednisolone acetate 1% solution in controlling postoperative inflammation and pain after cataract surgery.