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The Journal of Emergency Medicine 1996Ketorolac is a nonsteroidal anti-inflammatory drug, available in both oral and parenteral forms, that possesses significant analgesic potency. Its analgesic efficacy has... (Review)
Review
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.
Topics: Acute Disease; Analgesics, Non-Narcotic; Humans; Ketorolac; Pain; Tolmetin; Treatment Outcome
PubMed: 8655940
DOI: 10.1016/0736-4679(95)02052-7 -
Scientific Reports Jan 2022Understanding the drug solubility behavior is likely the first essential requirement for designing the supercritical technology for pharmaceutical processing. Therefore,...
Understanding the drug solubility behavior is likely the first essential requirement for designing the supercritical technology for pharmaceutical processing. Therefore, this study utilizes different machine learning scenarios to simulate the solubility of twelve non-steroidal anti-inflammatory drugs (NSAIDs) in the supercritical carbon dioxide (SCCO). The considered NSAIDs are Fenoprofen, Flurbiprofen, Ibuprofen, Ketoprofen, Loxoprofen, Nabumetone, Naproxen, Nimesulide, Phenylbutazone, Piroxicam, Salicylamide, and Tolmetin. Physical characteristics of the drugs (molecular weight and melting temperature), operating conditions (pressure and temperature), and solvent property (SCCO density) are effectively used to estimate the drug solubility. Monitoring and comparing the prediction accuracy of twelve intelligent paradigms from three categories (artificial neural networks, support vector regression, and hybrid neuro-fuzzy) approves that adaptive neuro-fuzzy inference is the best tool for the considered task. The hybrid optimization strategy adjusts the cluster radius of the subtractive clustering membership function to 0.6111. This model estimates 254 laboratory-measured solubility data with the AAPRE = 3.13%, MSE = 2.58 × 10, and R = 0.99919. The leverage technique confirms that outliers may poison less than four percent of the experimental data. In addition, the proposed hybrid paradigm is more reliable than the equations of state and available correlations in the literature. Experimental measurements, model predictions, and relevancy analyses justified that the drug solubility in SCCO increases by increasing temperature and pressure. The results show that Ibuprofen and Naproxen are the most soluble and insoluble drugs in SCCO, respectively.
PubMed: 35058504
DOI: 10.1038/s41598-022-04942-4 -
Journal of Pharmaceutical Investigation 2018The objective of the present study was to develop rectal mucoadhesive hydrogels loaded with Tolmetin Sodium, a non-steroidal anti-inflammatory drug, for prolonged...
The objective of the present study was to develop rectal mucoadhesive hydrogels loaded with Tolmetin Sodium, a non-steroidal anti-inflammatory drug, for prolonged duration of action and increased bioavailability. Fourteen formulae were prepared with different types and concentrations of polymers as hydroxypropylmethyl cellulose, hydroxylethyl cellulose, carboxymethyl cellulose and sodium alginate. Each formulation contain Tolmetin Sodium equivalent to 5% w/w active drug. The effect of the employed gel bases on pH, gel strength, mucoadhesion, viscosity and the in vitro release profile of drug was examined. In addition, hydrogel formulations were subjected to rheological and stability studies. The physicochemical characterization revealed that all hydrogels had a suitable pH (6.64-7.75) and gel strength (15.5-65.29 s) for rectal application. The in-vitro drug release from the formulations showed a controlled drug release pattern, reaching 72-92.6% after 8 h. The kinetic analysis of the release data revealed that the drug release from all tested hydrogel bases obeyed the diffusion mechanism. The degradation of Tolmetin Sodium from its rectal hydrogel formulations was found to be a zero-order reaction. All formulations except sodium alginate hydrogel were quite stable. Considering the in-vitro release, rheological properties and shelf life, (CMC; 2%w/w) hydrogel formula was the best among the studied formulations. Therefore, further histopathological and bioavailability studies were carried out to detect different pharmacokinetic parameters of the established formulations compared with commercially available capsules. Formula containing 2% CMC showed relative bioavailability 357.93%. Finally, good correlation was observed between in-vitro and in-vivo profile.
PubMed: 30595939
DOI: 10.1007/s40005-017-0365-1 -
CMAJ : Canadian Medical Association... May 1993
Topics: Advertising; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Drug Combinations; Humans; Ketorolac Tromethamine; Practice Patterns, Physicians'; Product Surveillance, Postmarketing; Tolmetin; Tromethamine
PubMed: 8485672
DOI: No ID Found -
British Journal of Anaesthesia Oct 1990
Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Combinations; Humans; Ketorolac Tromethamine; Pain, Postoperative; Tolmetin; Tromethamine
PubMed: 2248811
DOI: 10.1093/bja/65.4.445 -
The Annals of Thoracic Surgery Mar 1997
Topics: Analgesics, Non-Narcotic; Endoscopy; Humans; Ionophores; Ketorolac; Pain, Postoperative; Prospective Studies; Thoracic Surgery; Thoracoscopy; Tolmetin; Transcutaneous Electric Nerve Stimulation
PubMed: 9066371
DOI: 10.1016/s0003-4975(97)00005-2 -
Osteoarthritis and Cartilage Jul 1999Osteoarthritis is increasingly recognized as a complex illness in which interrelationships between the different tissues of the joint are important. We are still some... (Review)
Review
Osteoarthritis is increasingly recognized as a complex illness in which interrelationships between the different tissues of the joint are important. We are still some way from a complete understanding of the pathophysiologic and temporal relationships between bone, synovial tissue and cartilage. Recent evidence points to a significant role for cytokines and growth factors in osteoarthritis that leads to a preponderance of catabolic processes in the joint. In-vitro culture of human cartilage has been used as a model to measure the effects of drugs used in the treatment of osteoarthritis on anabolic and catabolic processes. On this basis, the nonsteroidal antiinflammatory drugs can be categorized into one of three classes depending on whether they are inhibitory (e.g., indomethacin and naproxen), neutral (e.g., diclofenac, aspirin and piroxicam) or stimulatory (e.g., aceclofenac, tenidap and tolmetin) of glycosaminoglycan synthesis in chondrocytes. The marked differences between these nonsteroidal antiinflammatory drugs suggest that a mechanism other than cyclooxygenase inhibition is involved in their effects on glycosaminoglycan synthesis. Inhibition of IL-1beta and the stimulation of growth factors are suggested as possible mechanisms. Although the significance of these properties of nonsteroidal antiinflammatory drugs awaits confirmation in in-vivo and clinical situations, they do provide the clinician with a new parameter with which to choose therapy in osteoarthritis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Disease Progression; Glycosaminoglycans; Growth Substances; Humans; Osteoarthritis
PubMed: 10419771
DOI: 10.1053/joca.1998.0215 -
Yakugaku Zasshi : Journal of the... 2013The pharmaceutical effects of non-steroidal anti-inflammatory drugs (NSAIDs) occur through the inhibition of prostaglandin H synthase (PGHS). Prostaglandin H2 is... (Review)
Review
The pharmaceutical effects of non-steroidal anti-inflammatory drugs (NSAIDs) occur through the inhibition of prostaglandin H synthase (PGHS). Prostaglandin H2 is produced from arachidonic acid via peroxidase and cyclooxygenase cycles in PGHS. NSAIDs exhibit different levels of reactivity in these reaction cycles. To prevent the development of side effect while maintaining the beneficial effects of drugs, a therapeutic strategy should be used. A new classification of NSAIDs has been proposed based on reactivity to peroxidase. Class 1 includes the majority of NSAIDs, which react with horseradish peroxidase (HRP) compounds I and II. Also, their drugs exhibit spectral changes induced by PGHS peroxidase and diminished ESR signals of the tyrosyl radical of metmyoglobin. They reduce compounds I and II of HRP and scavenge tyrosyl radicals. The branched chain mechanism by which the porphyrin radical is transferred to the tyrosine residue of the protein might be blocked by these NSAIDs. Class 2 includes salicylic acid derivatives that react only with the porphyrin radical and do not react with HRP compound II (oxoferryl species). Class 3 includes aspirin, nimesulide, tolmetin, and arylpropionic acid derivatives, including ibuprofen and the coxibs such as celecoxib and rofecoxib, which are not substrates for HRP or PGHS peroxidase. It seems that the selectivity of NSAIDs to PGHS1 and PGHS2 depends on their reactivity with cyclooxygenase rather than with the peroxidase of PGHS. The best drug for each inflammatory disease should therefore be selected for therapy.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Humans; Inflammation; Peroxidase; Prostaglandin H2; Prostaglandin-Endoperoxide Synthases
PubMed: 23474686
DOI: 10.1248/yakushi.12-00277 -
Indian Journal of Pharmaceutical... Jan 2010The aim of this study was to evaluate microencapsulated controlled release preparations of tolmetin sodium using ethylcellulose as a retardant material. Microspheres...
The aim of this study was to evaluate microencapsulated controlled release preparations of tolmetin sodium using ethylcellulose as a retardant material. Microspheres were prepared by using water-in-oil-in-oil (W/O(1)/O(2)) double-emulsion solvent diffusion method, using different ratios of ethylcellulose to tolmetin sodium. Span 80 was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties, drug content, loading efficiency, production yield, and particle size. Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy were used to characterize microparticles. The in vitro release studies were performed in pH 1.2 and 7.4. The prepared microspheres were spherical in shape. The drug-loaded microspheres showed near to the theoretical of entrapment and release was extended up to 24. The X-ray diffractogram and differential scanning thermographs showed amorphous state of the drug in the microspheres. It was shown that the drug: polymer ratio, stirring rate, volume of dispersing medium and surfactant influenced the drug loading, particle size and drug release behavior of the formed microparticles. The results showed that, generally, an increase in the ratio of drug: polymer (0.5:1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The in vitro release profile could be modified by changing various processing and formulation parameters to give a controlled release of drug from the microparticules. The release of tolmetin was influenced by the drug to polymer ratio and particle size and was found to be diffusion and erosion controlled. The best-fit release kinetic was achieved with Peppas model.
PubMed: 20582193
DOI: 10.4103/0250-474X.62251 -
British Journal of Anaesthesia Jan 1993
Topics: Analgesics; Humans; Ketorolac; Orthopedics; Pain Measurement; Pain, Postoperative; Time Factors; Tolmetin
PubMed: 8431319
DOI: 10.1093/bja/70.1.112-d