Evaluation of the analgesic activity and safety of ketorolac in whole body fractionated gamma irradiated animals

Aly, Sara; Mahmoud, Mona F.; Hassan, S; Fahmy, Aly A.

doi:10.1016/j.fjps.2015.05.002

Cited by 4 publications

(5 citation statements)

References 25 publications

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“…Results obtained in the present study revealed mild alterations in the kidney function, reflected as a significant increase in urea of KT/WR-treated rats and a significant decrease in the creatinine level of both WR and KT/WR-treated groups. These altered parameters were in accordance with several reports reflecting a disturbed kidney function (Aly et al, 2015;Hörl, 2010;Kim & Joo, 2007;Pelligand et al, 2015) More recently, Lucas et al (2018) reported that NSAIDs increase the risk of developing nephrotoxicity and acute tubular necrosis and they recommended that this condition be well evaluated. The authors concluded that NSAIDs, selective and non-selective, directly interfere with renal function due to prostaglandin inhibition, and suggested acute sodium retention, which is the main cause of the overfilling effect due to arterial hypertension and edema (Chana et al, 2014).…”

Section: Discussionsupporting

confidence: 90%

“…Ketorolac is considered a potent analgesic with moderate anti-inflammatory effects (Schwier & Tran, 2016), although it has certain harmful effects on vital body organs such as the liver, kidney, and gastrointestinal tract (Aly et al, 2015;Bally et al, 2017;Tomic et al, 2008). During the recent years, an increasing number of studies have been published concerning the nephrotoxic effects of NSAIDs and anticoagulants (Chana et al, 2014;Lanas & Chan, 2017;Ozcan et al, 2012;Sriuttha, Sirichanchuen, & Permsuwan, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The vigorous development of their uses reflects the great clinical need they address to control of pain and fever, the two common manifestations of broad spectrum of diseases (Utzeri & Usai, 2017). Among these drugs, ketorolac tromethamine being a potent NSAID analgesic inhibits the synthesis of prostaglandins and may relate to adverse effects which can be serious, such as gastrointestinal ulcers and bleeding, heart attack, liver toxicity, and kidney disease (Aly, Mahmoud, Hassan, & Fahmy, 2015;Bally et al, 2017;Ilic et al, 2011;Lanas & Chan, 2017;Tomic et al, 2008). There are interactions between NSAIDs and several classes of anti-thrombotic drugs, including WR being under interest.…”

Section: Introductionmentioning

confidence: 99%

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Ketorolac- and warfarin-induced renal toxicity: ultrastructural and biochemical study

Othman

Abdel-Ghaffar

Mahmoud

2019

JoBAZ

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Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drug classes worldwide. Although, these drugs have a potent analgesic and anti-inflammatory effects associated with nephrotoxicity. Factors such as advanced age and comorbidities may contribute to increase the risk of NSAID-related nephrotoxicity. The current study was designed to study the dual effect of non-NSAIDs and anticoagulants on the rat kidney. Methods: Thirty-two adult male albino rats were divided into four groups (n = 8): first, served as the control group which was orally administered with distilled water; second, served as the ketorolac (KT) group which received a daily intramuscular injection of ketorolac tromethamine (3 mg/kg/day); third, served as the warfarin (WR) group which was orally administered with racemic warfarin (0.3 mg/kg/day); and fourth, served as the combined (KT/WR) group which received an oral administration of WR (0.3 mg/kg/day) followed by an intramuscular injection of KT (3 mg/kg/day). After six consecutive days of daily treatment, all animals were sacrificed and their blood and tissue samples were collected.Results: A significant decrease in serum level of creatinine was observed in WR-and KT/WR-treated groups. However, urea increased significantly in the serum of the combined group, KT/WR. Furthermore, both WRand KT/WR-treated groups showed a significant increase in malondialdyhed (MDA) level; however, WR treatment induced a significant decrease in reduced glutathione (GSH) level. The total antioxidant capacity (TAC) of rat kidney showed a significant decrease in all treated groups. Electron microscopic investigations of kidney cortex localized variable degrees of focal degeneration, vacuolation, and vascular congestion in KTand WR-treated groups that are more vigorously attacking the cortical tissues in KT/WR-treated rats. Conclusions: We can conclude that the combined therapy of anti-inflammatory and anticoagulant drugs must be avoided or at least minimized, particularly in the elderly people, who mostly had other complications, in order to avoid the severe side effects on kidney structure and function.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ketorolac- and warfarin-induced renal toxicity: ultrastructural and biochemical study

Othman

Abdel-Ghaffar

Mahmoud

2019

JoBAZ

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“…There was no liver damage, and impaired metabolism and function may be attributed to the ketorolac treatment in the chicks which is in accordance with another study in the animals (Aly 2015).…”

supporting

confidence: 91%

Analgesic, antipyretic and anti-inflammatory efficacy of ketorolac in the chicks

Mousa

2019

Indian J of Anim Sci

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Now-a-days, there is a need for newly, non-addicted and effective analgesics with less side effects. Therefore, the present study evaluated the analgesic, antipyretic and anti-inflammatory efficacy of ketorolac in 7â€“21 days old broiler chicks and its possible application in the related field. The analgesic median effective dose (ED50) of ketorolac that caused analgesia in 50% of the chicks was 9.1 mg/kg, intramuscular (IM). Ketorolac caused analgesic and antipyretic effects at multiple doses (5, 10 and 20 mg/kg, IM) in a dose dependent manner, whereas these percentages were significantly higher when ketorolac was injected @ 10 and 20 mg/kg, IM. All times recorded (15, 30, 60 and 120 min) for evaluating the analgesic effect of ketorolac produced analgesia while the higher and better analgesic efficacy was observed at 15 min after ketorolac injection. The injection of ketorolac @ 20 mg/kg, IM exerted anti-inflammatory activity by significantly reducing the right paw thickness of the chicks as a result of formaldehyde injection in comparison to control. There was no liver damage, impaired metabolism and function may be attributed to the ketorolac treatment in the chicks which was evaluated through estimation of serum AST and ALT concentrations. The study suggests the benefit of using ketorolac as an analgesic, antipyretic and antiinflammatory drug in the field of veterinary medicine due to its good, reliable and efficient efficacy.

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“…Ketorolac is a non‐steroidal anti‐inflammatory drug developed by Syntex . With clinical preparation form of tromethamine, Ketorolac possesses the pharmacological activity of being antipyretic, analgesic and anti‐inflammatory . Its analgesic effect is similar to aspirin, but antipyretic properties 20 times that of aspirin .…”

Section: Introductionmentioning

confidence: 99%

Separation of Ketorolac enantiomers on polysaccharide‐based chiral stationary phases using a polar organic mobile phase

Cheng

et al. 2018

Separation Science Plus

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Ketorolac has been widely applied in clinical medicine for its antipyretic, analgesic and anti‐inflammatory pharmacological activity. Research showed that the analgesic effect of the S enantiomer is 230 times stronger than that of the R enantiomer. Getting the high‐purity S enantiomer of Ketorolac has profound significance but still remains a challenging topic. In this work, the separation of the R and S enantiomers of Ketorolac was investigated on polysaccharide‐based chiral stationary phases. Chiralcel AD‐H, OD‐H, OJ‐H and AS‐H columns were evaluated using polar organic and normal phase mode, respectively, in which the OJ‐H column showed the best performance with high selectivity and resolution for Ketorolac with α = 2.43 and RS = 9.04 by using methanol/formic acid (100:0.1, v/v) as the mobile phase. The influences of acid additive, composition of mobile phase and temperature were examined. The coating amount of cellulose tris‐(4‐methylbenzoate) has significant influence on the sample loadability. The high loadability of chiral stationary phases coated with 40% of cellulose tris‐(4‐methylbenzoate) allows preparative separation up to 16 mg on an analytical column of 250 × 4.6 mm id in a single run for Ketoroac using methanol/formic acid (100:0.1, v/v) as mobile phase, which shows a potential application in industrial preparation.

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Evaluation of the analgesic activity and safety of ketorolac in whole body fractionated gamma irradiated animals

Cited by 4 publications

References 25 publications

Ketorolac- and warfarin-induced renal toxicity: ultrastructural and biochemical study

Ketorolac- and warfarin-induced renal toxicity: ultrastructural and biochemical study

Analgesic, antipyretic and anti-inflammatory efficacy of ketorolac in the chicks

Separation of Ketorolac enantiomers on polysaccharide‐based chiral stationary phases using a polar organic mobile phase

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