The objective designated to discover the analgesic effect of nefopam in the normal (non-stressed) chickens and its possible alteration due to hydrogen peroxide (H2O2)-induced oxidative stress (OS) in ...7-14 day old chickens. The analgesia of nefopam has been increased by 47% in the stressed chickens by measuring the analgesic Median Effective Dose (ED50) value. This value was 9.10 mg/kg, IM in the normal chickens where it became 4.80 mg/kg, IM in stressed chickens. There is a significant rise in the antinociceptive action of nefopam 18 mg/kg, IM by 88% in the stressed group of chickens in comparison with the normal one elicited by an electro-stimulation and formaldehyde 0.05 ml of 0.1% tests for induction of nociception. The observations showed several significant stimulatory modifications in the neurobehaviour when nefopam treated with a subtle dosage 1 mg/kg, IM in the stressed chickens concerning the latency to move, squares crossed and time of the tonic immobility response test. Significant damage was detected in the liver function when nefopam injected at 18 mg/kg, IM in stress chickens in comparison to normal one by 28, 33 and 65% as estimated through Alkaline phosphatase (ALP), Aspartate trans-aminase (AST) and Alanine trans-aminase (ALT) concentrations in the serum, respectively. The sum of data findings indicated that H2O2-inducedOS increased the analgesic activity of nefopam in the chickens; despite the changes occur on the neurobehaviour and liver function. The dose of nefopam should be reduced when preparing the therapeutic regimen in the stressed animals.
No former studies are dealing with the pharmacological (pharmacodynamics and pharmacokinetics) interaction between nefopam and tramadol in the chicks' model. The median effective doses (ED50s) for ...nefopam and tramadol produces analgesia has been estimated each alone as 9.24 and 0.83 mg/kg, IP, respectively. The interaction concerning nefopam and tramadol combination was estimated by isobolographic analysis to be 2.91 and 0.25 mg/kg, IP. The kind of interaction between nefopam and tramadol was synergistic as indicated by the interaction index 0.61. The analgesic efficacy of the combination was significantly different from nefopam and tramadol administered alone. Nefopam plasma concentration 18.48 mg/kg, IP for different measured times 0.5, 1, 2, 4, and 24 hours 33.25, 27.10, 15.05, 13.61, and 2.45 µg/ml while the concentration was increased once coadministered with tramadol 1.66 mg/kg, IP by 22, 26, 43, 45, and 81% been 40.72, 34.27, 21.53, 19.76, and 4.43 µg/ml, respectively. Nefopam pharmacokinetic profile comprised of area-under-curve (AUC), area-under-moment-curve (AUMC), mean-residence-time (MRT), half-life (t1/2β), maximal concentration (Cmax) amplified after tramadol is coadministered with nefopam by 52, 260, 23, 15, and 22%. The elimination constant (Kel), distribution volume (VD), clearance (Cl) were diminished 13, 25, and 29%, similarly. The sum results suggested a synergistic interaction between nefopam and tramadol along with a modification in nefopam pharmacokinetic parameters which improve the therapeutic efficacy of nefopam in the chickens besides, advocate using these two drugs as preanesthetics in veterinary medicine.
The rats model has never thoroughly investigated the influence of tramadol on plasma pethidine concentration besides pethidine pharmacokinetics. Individually, analgesic ED50s for pethidine and ...tramadol are estimated as 3.55 and 24.21 mg/kg, i.p. Subsequently, their measures decreased to 1.65 and 11.27 mg/kg, i.p., when both were given in combination at 1:1 from ED50s. Tramadol and pethidine have a form of synergistic analgesic interaction, which is therefore classified as a pharmacodynamic interaction. Pethidine (7.1mg/kg, i.p.) reveals the plasma concentration of 369.00, 493.33, 373.33, 305.33, 306.33 and 247.67 µg/ml that was measured over distinctive times of 0.25,0.5,1,2,4, and 24 hours. At the same time, the concentration of plasma levels of tramadol and pethidine (48.42 and 7.1mg/kg, i.p., correspondingly) declined to 229.33, 268.33, 233.00, 198.33, 195.67 and 180.33 µg/ml by 38, 46, 38, 35, 36 and 27%, respectively. Tramadol affected the pethidine pharmacokinetics through an elevation in the area-under-curve (AUC0-∞) 49%, area-under-moment-curve (AUMC0-∞) 343%, mean-residence-time (MRT) 137%, half-life (t1/2β) 136%, and the distribution volume (Vss) 64%. Other estimated pharmacokinetic measures were reduced which included maximal concentration (Cmax) 47% and elimination rate constant (Kel) 60%. In general, the findings revealed a synergism as a mode of pharmacological interaction between pethidine and tramadol, in addition to a change in pethidine pharmacokinetics, which could improve pethidine effectiveness in the rat’s model.
Little works of literature studied the anesthetic effect of ketamine in different ages of broiler chickens, hence this study intended to examine these alterations in chickens at different ages. The ...doses of ketamine that causes hypnosis in 50% of the chickens (hypnotic ED50) were 7.90, 7.90 and 6.80 mg/kg, intramuscular (IM) at 10, 20 and 40-day-old chickens, respectively, whereas the doses that resulted in analgesia in 50% of the chickens (analgesic ED50) were 12.92, 12.92 and 6.50 mg/kg, IM. The onset, duration and recovery from ketamine hypnosis were in an age-dependent manner and significantly longer at 40-day-old, although the depth and sensitivity of chickens to ketamine hypnosis rises as the age advancing forward. Ketamine analgesia is more effective at 40-day-old. There are neurobehavioral deficits, according to the age of chickens when injecting ketamine in a subtle dose of 1 mg/kg, IM. The concentrations related to alanine transaminase (ALT) and aspartate transaminase (AST), tested in the serum, reveal that the 40-day-old chicken group differs significantly from 10 and 20-day-old chicken’s groups which all treated with single ketamine dose (25 mg/kg, IM). In conclusion, the present work discovered that ketamine’s efficacy, including hypnosis, analgesia and neurobehavioral activity will be increased as the age is progressing, suggesting that the veterinarians need to take it into account when preparing the dose regimen of ketamine anesthesia for different ages of animals.
Ciprofloxacin (CFX) and ketoprofen (KPN) are used widely in combination in veterinary interventions for bacterial infections, so in this study the effect of KPN was studied on the efficacy of CFX, by ...measuring its plasma concentration and pharmacokinetic parameters in 7-10 day-old chickens. The analgesic median effective dose (ED50) of KPN was determined to be 1.62 mg/kg, IM, in the chickens. The preferable analgesic dose of KPN to be used with CFX was 4 mg/kg, IM, which differs significantly from KPN 2 mg/kg, IM,. The CFX plasma concentrations alone (8 mg/kg, IM) measured at different times (0.5, 1, 2, 4 and 24 hours) were 3.31, 3.60, 3.21, 2.70 and 0.17 μg/mL while its concentration was elevated by 53, 54, 90, 107 and 418 % when coadministered with KPN (4 mg/kg, IM) to 5.05, 5.53, 6.10, 5.59 and 0.88 μg/mL in the chickens, respectively. CFX pharmacokinetic parameters, such as the area under the curve (AUC), the area under the moment curve (AUMC), mean residence time (MRT), half-life (t1/2β), Tmax, and Cmax increased when KPN was coadministered with CFX by 129, 289, 70, 49, 100 and 69 %, whereas the elimination rate constant (Kel), the volume of distribution at steady state (Vss) and clearance (Cl) decreased by 36, 34 and 58 %, respectively. It was concluded that coadministration of KPN alters the plasma concentration and the pharmacokinetic parameters of CFX, suggesting that the CFX dose can be reduced when used with KPN to achieve the desired concentration of CFX in the plasma, as an antibacterial for treatment of infected animals.
The reason for the recent study was to inspect the therapeutic efficacy of meloxicam and phenylbutazone alone with their analgesic interaction and their subsequent inhibitory interaction at the level ...of cyclooxygenase-2 in mice. Meloxicam and phenylbutazone had the analgesic-median effective doses (ED50s) of 15.57 and 119.73 mg/kg, i.p., respectively, given once to mice separately as determined by the up-and-down procedure using a hot plate method. The estimated analgesic ED50s for meloxicam and phenylbutazone combination were at 12.84 and 98.75 mg/kg, i.p., correspondingly when given together at a ratio of 1:1 of their ED50s. The isobolographic analysis reveals that the analgesic interaction between meloxicam and phenylbutazone was antagonistic, as indicated by the interaction index of 1.65. The ELISA technique was used to estimate the cyclooxygenase-2 activity, reflecting that meloxicam or phenylbutazone significantly inhibited the cyclooxygenase-2 activity by 72 and 90%, respectively, compared to the control group. The combination composed of meloxicam and phenylbutazone has a lower limit of inhibition of the cyclooxygenase-2 activity (33%) in comparison to meloxicam or phenylbutazone. Meloxicam and phenylbutazone coadministration were significantly different from the control, meloxicam, and phenylbutazone groups concerning the cyclooxygenase-2 activity in mice. The sum of the data concluded that meloxicam and phenylbutazone have an excellent analgesic efficacy when administered alone. In contrast, the mixture of these two drugs has no benefit because of the antagonistic interaction at cyclooxygenase-2 in mice.
The H
-antihistamine diphenhydramine antagonizes cholinesterase inhibitor poisoning in various animal species. One aspect of acute antidotal actions of diphenhydramine is increasing the median lethal ...doses (LD50) of toxicants. The objective of this meta-analysis was to assess the antidotal action of diphenhydramine against short-term toxicity (LD50) of cholinesterase inhibitors in experimental animals. The experimental studies selected were according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. They were conducted in laboratory animals (mice, rats, and chicks) to determine acute LD50 values of cholinesterase inhibitors (organophosphates, carbamates, and imidocarb) under the influence of diphenhydramine vs. controls. Twenty-eight records were selected from 12 studies on mice (n= 242), rats (n= 27), and young chicks (n= 128). The forest plot of randomized two-group meta-analysis assessed effect size, subgroup analysis, drapery prediction, heterogeneity, publication bias-funnel plot as well as one-group proportions meta-analysis of percent protection. Diphenhydramine significantly increased the combined effect size (i.e. increased LD50) in intoxicated experimental animals in comparison to controls (-3.71, standard error (SE) 0.36, 95%CI -4.46, -2.97). The drapery plot proposed a wide range of confidence intervals. The I
index of heterogeneity of the combined effect size was high at 81.03% (
= 142.3, p < 0.0001). Galbraith regression also indicated data heterogeneity; however, the normal quantile plot indicated no outliers. Subgroup analysis indicated significantly high heterogeneity with organophosphates (I
= 63.72%) and carbamates (I
= 76.41%), but low with imidocarb (I
= 51.48%). The funnel plot and Egger regression test (t= -13.7, p < 0.0001) revealed publication bias. The median of the diphenhydramine protection ratio was 1.655, and the related forest plot of one group proportion meta-analysis revealed a statistically high level of protection (0.594, SE 0.083, 95%CI 0.432, 0.756), with high heterogeneity (I
= 99.86). The risk of bias assessment was unclear, while the total score (16 out of 20) of each study leaned towards the side of the low risk of bias. In conclusion, the meta-analysis of LD50 values indicated that diphenhydramine unequivocally protected experimental animals from the acute toxicity of cholinesterase inhibitors. The drug could be an additional antidote against acute poisoning induced by cholinesterase inhibitors, but a word of caution: it is not to be considered as a replacement for the standard antidote atropine sulfate. Further studies are needed to examine the action of diphenhydramine on adverse chronic effects of cholinesterase inhibitors.
To explore the benefits of Hydroxychloroquine (HCQ), (which is an antimalarial agent that has shown effective pharmacological properties in different malarial conditions and immunological disorders, ...particularity in chloroquine-sensitive malaria), in the treatment and prevention of Corona Virus Disease-2019 (COVID-19) pandemic because HCQ was recently advocated to minimize the pathogenicity of COVID-19. The aim of this review is to shed the light on a possible mechanism by which HCQ can defeat the COVID-19, a disease characterized by the WHO as a pandemic. Literatures from Web of Science, Scopus, PubMed, Science Direct and Google Scholar were cast-off to search the literature data. The keywords used are antimalarial agent, COVID-19, Hydroxychloroquine, SARS-CoV-2 and Zinc sulfate.The review summarizes the benefits of using HCQ against COVID-19 through exploiting the ability of this antimalarial agent in ameliorating the body immunity, inhibiting and/or delaying the viral glycosylation by increasing the pH inside the host cell and also via suppressing the viral transcription and replication through the formation of a complex structure after binding with zinc. We concluded thatthese interfering properties of HCQ support human immunity to fight against the progression of COVID-19. We hypothesize that the therapeutic efficiency of HCQ against the COVID-19 can be enhanced by the concurrent administration of zinc sulfate.
The present study was undertaken to examine the acute toxicity (LD50) and neurobehavioral manifestations in the open-field activity and tonic immobility tests in 7-14 day-old chicks treated with the ...H1-receptor antagonist diphenhydramine. Plasma and whole brain cholinesterase activities were also determined in the chicks. The LD50 of diphenhydramine in chicks was 49.3mg/kg, intramuscularly (i.m.). The signs of diphenhydramine toxicosis in the chicks which appeared within one hour after injection included excitation, jumping, whole body tremor, ataxia, gasping, frequent defecation, paralysis and recumbency. Fifteen minutes after i.m. injection, diphenhydramine at 2.5 and 5 mg/kg decreased the general locomotor activity of the chicks in the 5-min open-field activity test, as seen by a significant increase in the latency to move from the center of the open-field arena and decreases in the numbers of lines crossed and escape jumps in comparison with control values. Diphenhydramine significantly decreased the frequencies of pecking and defecation only at 5mg/kg when compared with respective control values. Diphenhydramine treatments at 2.5and 5mg/kg also significantly increased the durations of tonic immobility of the chicks and decreased their whole brain cholinesterase activity by 33 and 30%, respectively, in comparison with the control values. In conclusion, the data suggest that diphenhydramine induces central nervous system depression in chicks at doses below the LD50 value of the drug which is reported here for the first time.
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