Paracetamol Group Research Articles

Paracetamol prior to catheter balloon insertion for labor induction - A randomized controlled trial: paracetamol prior to catheter-balloon insertion for labor induction.

Assessing maternal pain and satisfaction following administration of paracetamol vs. placebo prior to catheter balloon placement. Primiparous women at term admitted for medically-indicated labor induction were randomized to receive intravenous paracetamol 1 gram in 100cc normal saline (N=71) or placebo of 100cc normal saline (N=70) prior to catheter balloon insertion. The women were blinded to the intervention allocation. Primary outcomes were visual analog scale (VAS) scores and maternal satisfaction, assessed via questionnaire. Pre-induction maternal pain did not differ between the paracetamol and placebo groups. Median VAS scores at 2, 30, and 60 minutes after catheter insertion were comparable between the groups: 6.46±2.77 vs. 6.66±2.78, p=0.68; 5.53±3.20 vs. 5.93±3.01, p=0.46; and 5.83±3.25 vs. 6.49±2.88, p=0.26, respectively. For the paracetamol vs. placebo group, the mean sum of VAS scores was lower (4.39 vs. 5.37, p=0.045) and the proportion with a mean VAS score <5 was higher (65.2% vs. 44.1%, p=0.016). This difference persisted in a multivariate logistic regression analysis adjusted for maternal age (OR=2.2, 95% CI 1.1-4.5, p=0.036). After balloon insertion, relatively fewer women in the paracetamol vs. placebo group showed immobility (33.8% vs 50.0%, p=0.037) and needed analgesics (31.3% vs. 66.1%, p<0.001). Maternal satisfaction score was similar between the groups (P=0.877). Cervical ripening, duration from catheter insertion to delivery, and labor and neonatal outcomes did not differ significantly between the groups. The administration of paracetamol compared with placebo prior to catheter balloon insertion was associated with lower VAS score and less analgesic use and maternal immobility.

Hepatoprotective efficacy of Argemone mexicana L. root in paracetamol-induced hepatotoxicity in a rat model.

Argemone mexicana L. (Papaveraceae), a weed that thrives in the tropical and subtropical areas of South and Central America, Mexico, Caribbean Islands and India. In India, it has been used traditionally to treat vesicular calculus, inflammatory conditions, and hepatobiliary disorders. The present study was aimed to investigate the hepatoprotective efficacy of A. Mexicana roots in paracetamol (PCM)-induced toxicity rat. The methanol extract of A. mexicana (MEAM) root was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) analysis to identify its compounds. Molecular docking analysis of the compounds was conducted against TGF-β and PPAR-α. The hepatoprotective activity of MEAM (200, 400mg/kg) was evaluated in PCM (3000mg/kg) intoxicated rats by measuring serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin (TB), total protein (TP), albumin (ALB), globulin (GLB), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Silymarin (100mg/kg) was used as reference drug. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and lipid peroxidation (LPO) were investigated using liver homogenate. Additionally, the levels of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) were studied. The results of the study were supported by histopathological examination. GC-MS analysis revealed 163 compounds, from which eleven compounds were selected based on their docking scores against TGF-β and PPAR-α. MEAM (400mg/kg) demonstrated a remarkable reduction in ALT, AST, ALP, GGT, and LDH in contrast to the PCM intoxicated group. A remarkable decline in TB and GLB, along with an increase in TP and ALB, was observed in the MEAM (400mg/kg) group compared to the untreated PCM group. Rats receiving MEAM (400mg/kg) exhibited a noticeable decrease in TC, TG, and LDL-C, along with an increase in HDL-C levels compared to PCM-induced untreated rats. The higher dose of MEAM also resulted in a significant decrease in TNF-α, IL-1β, and IL-6, and an increase in IL-4 and IL-10. Similarly, a notable elevation in SOD, CAT, and GSH, along with a decrease in MDA content, was observed in the group receiving MEAM (400mg/kg). The histopathological result showed reduction of sinusoidal space and vesicular nuclei, with improvement of hepatocytes at the dose of MEAM (400mg/kg). In molecular docking study, Eupatilin exhibited the highest docking scores of -10.4kcal/mol and -9.1kcal/mol against TGF-β and PPAR-α, respectively. MEAM root at dose of 400mg/kg exhibited hepatoprotective effect against PCM-induced toxicity rat. Eupatilin might be considered as a potential candidate for the hepatoprotective effect of A. mexicana root.

Effect of dapagliflozin on paracetamol-induced hepatotoxicity and nephrotoxicity in type 2 diabetic albino rats

Introduction: paracetamol (PARA) is a worldwide antipyretic and analgesic medication. It has been extensively utilized during the last few years. PARA abuse would lead to liver and kidney injury. Dapagliflozin (DAPA)a sodium/glucose cotransporter 2 (SGLT2) inhibitor that wasapproved for treating patients with type 2 DM. In addition to its antidiabetic purpose, it has many pharmacological and biological actions, including antioxidant (radical scavenging), anti-inflammatory, and cardioprotective effects.Therefore, weaim to assess and evaluate the effect of dapagliflozin on paracetamol-induced hepatotoxicity and nephrotoxicity in rats with type 2 diabetic albino rats.Materials and Methods: eighty Wistar male rats were grouped randomly into 8 equal groups (10 rats each). Oral distilled water was given to the control group, the paracetamol group received paracetamol 0.5 g/kg dissolved in purified water orally for 4 weeks, the dapagliflozin group received dapagliflozin 1 mg/Kg daily dissolved in distilled water for 4 weeks, the paracetamol + dapagliflozin groupreceivedparacetamol and were treated with dapagliflozin.Type 2 DM was induced in rats using by intraperitoneal Streptozotocin (STZ) single injection “50mg /kg”.Rats were further subdivided into 4 groups.The control group with diabetes was given distilled water, the diabetic paracetamol group, the diabetic dapagliflozin group, and thediabetic paracetamol + dapagliflozin all received the same doses as mentioned. At the end of the experimental period, FBG, insulin, C peptide, lipid profile, liver function, fructosamine, CK-MB, TNF alpha, and IL4 were measured. Also, oxidative stress biomarkers were assessed in both kidney and liver tissues.Results: Treatment of PARA-administered rats with Dapagliflozin significantly improved FBG, insulin, C peptide, lipid profile, liver function, fructosamine, CK-MB, TNF alpha, IL4, andOxidative stress biomarkers.Conclusion: dapagliflozin has a protective effect against paracetamol-induced hepatotoxicity and nephrotoxicity.

Effects of Paracetamol, Amoxicillin, and their Combination on Male Rabbit Body and Organs Weight

The administration of pharmaceuticals such as paracetamol (PAR) and amoxicillin (AMO) has been linked to physiological changes in animals. While these drugs are widely utilized for their therapeutic benefits, their potential effects on body and organ weights are not fully understood. Male rabbits were divided into four groups a control group, a group treated with PAR, a group treated with AMO, and a group receiving both drugs PAR+AMO. Body weight changes were monitored weekly, and organ weights (liver, lungs, heart, kidneys, testes, and brain) were measured at the end of the trial. Data were statistically analyzed, with significance set at p &lt; 0.05. Body weight changes were observed across all treatment groups. In the control group, there were gradual weight increase from 1839±136.20g to 1975±89.94g, remaining consistent throughout the trial. While in the PAR group, we observed initial weight loss from 1667±43.83g to 1584±31.69g in week one, followed by recovery and reaching 1860±26.48g by week five. In the AMO group, there were a minor initial weight loss, followed by steady gains peaking at 2028±12.02g in week four, slightly decreasing to 2007±4.97g in week five. In the PAR+AMO group, we reported fluctuations in weight, starting at 1857±52.43g, peaking in week one (2001±94.50g), and ending at 1900±92.61g in week five. Organ weight analysis revealed significant changes. Liver and Lungs were notable increases in the PAR (73.214±5.006g liver; 8.356±0.663g lungs) and AMO groups (76.250±0.364g liver; 6.650±0.030g lungs). Combination therapy moderated these effects. Other Organs such as kidney, heart, brain, and testes weights showed no significant alterations (p &gt; 0.05) across the groups. In conclusion, this study highlights the differential impact of PAR and AMO, individually and in combination, on body and organ weights in male rabbits. While PAR and AMO caused notable changes in liver and lung weights, combination therapy appeared to moderate these effects. Body weight fluctuations were observed across all groups, emphasizing the need for further investigation into the mechanisms underlying these physiological responses to pharmaceutical interventions.

A Pharmacokinetic Study of the Interaction Between Regorafenib and Paracetamol in Male Rats.

Background: In clinical practice, the prevalent problem of polypharmacy could result in increased risks of drug-drug interactions. Regorafenib (REG) is commonly co-administered with paracetamol (PA) as a treatment protocol in cancer patients with pain therapy. Purpose: This study aimed to demonstrate the effect of paracetamol on the pharmacokinetic parameters of regorafenib and its metabolites following a single administration of both substances in rats. Additionally, the influence of REG and its metabolites on the pharmacokinetics of paracetamol was also determined. Methods: Twenty-four rats were divided randomly into three groups: REG group (IIREG, regorafenib 20 mg/kg, n = 8), PA group (IIIPA, paracetamol 100 mg/kg, n = 8), and REG+PA co-administration group (IREG+PA, REG 20 mg/kg and PA 100 mg/kg, n = 8). The concentrations of regorafenib, regorafenib-N-oxide (M-2), and N-desmethyl-regorafenib-N-oxide (M-5) were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The plasma concentrations of PA and its glucuronide (GPA) and sulfate (SPA) metabolites were measured using the validated high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters were calculated using a non-compartmental model. The statistical evaluation was performed in the SAS program. Results: After the administration of PA, the Cmax and AUC0-∞ of REG increased by 890% and 1140%, respectively; for M-2, they increased by 220% and 170%, and for M-5, by 2130% and 1730% (Cmax and AUC0-∞, respectively). A difference in the ratio of M-2/REG for AUC0-∞ and Cmax between the groups was observed, but not for M-5/REG. The AUC0-∞ for PA and GPA decreased by 20.7% and 51.1%, respectively, when PA was co-administered with REG. But the AUC0-∞ for SPA increased by 91.35% in the IREG+PA group. A difference in the ratio of GPA/PA for Cmax and for SPA/PA for AUC0-t and AUC0-∞ between the groups was observed. Conclusions: Paracetamol increased the plasma exposure of regorafenib, M-2, and M-5, which may exacerbate the drug's side effects. In contrast, REG reduced paracetamol exposure and contributed to its faster elimination, which may reduce the analgesic and antipyretic effects of paracetamol. These findings suggest clinical relevance for oncology patients requiring analgesic treatment.

Effect of celecoxib and paracetamol on the functional state of the central nervous system, pain sensitivity, and physical endurance of rats with acute heat injury

Acute heat injury (AHI) is a serious condition caused by an excessive increase in body temperature, usually due to prolonged exposure to high environmental temperatures or intense physical activity in the heat. Without timely treatment, heat stroke can lead to severe damage to the central nervous system with cerebral edema, profound disturbances in the water-salt balance and internal organs, coma and death. Since the effectiveness of drugs for the treatment of thermal injuries has not been proven, the search for new thermoprotective agents with different mechanisms of action, in particular inhibitors of the arachidonic acid cascade, is urgent. In a preliminary screening study on the AHI model in rats, it was found that among cyclooxygenase (COX) inhibitors, the highly selective COX-2 inhibitor celecoxib and the analgesic-antipyretic para­cetamol are the most effective in preventing hyperthermia and improving the course of the recovery period. The purpose of this study was to determine the impact of the specified screening leaders on the functional state of the central nervous system, pain sensitivity and physical endurance in the recovery period of heat injury. The AHI model was reproduced on adult white male rats according to the previously proposed and validated method by means of a 30-minute exposure at +55°C. Animals were divided into 4 groups with 8 rats in each group: intact control, control pathology, paracetamol group and celecoxib group. Based on the results of the study, it was established that celecoxib exhibits a pronounced thermoprotective effect, probably improves the state of the central nervous system in terms of behavioral reactions and physical endurance of animals in the recovery period after acute heat injury. At the same time, paracetamol after acute heat injury does not have a distinct positive effect on the functional state of the central nervous system, moderately improves the physical endurance of rats and is inferior to celecoxib in all the studied parameters. These results open new opportunities for the development of approaches to the treatment of AHI and confirm the different effectiveness of the use of celecoxib and paracetamol in thermal injuries.

Hepatocellular Changes on Paracetamol Induced Liver Damage in Long Evans Male Rats upon Green Tea Administration

Background: The liver is a vital organ that serves a number of purposes in our body. It may be harmed by pollutants, substances with toxic effects, and long-term, unchecked drug use. Green tea is a well-liked beverage that has gained popularity recently and may have hepatoprotective properties. Objective: To observe the effect of green tea (Camellia sinensis) on paracetamol induced liver damage in Long Evans male rats. Methods: From July 1st, 2018, to June 30th, 2019, this study was conducted in the Department of Physiology at Sir Salimullah Medical College (SSMC), Dhaka. For the purpose of the study, thirty (30) male Long Evans rats, weighing between 150 and 200 grams and 90 to 120 days old, appeared to be in good health. They were split into two groups after 14 days of acclimatization: Group A, which served as the control group, and Group B, which served as the experimental group (green tea pretreatment and paracetamol treated). Group A1 (baseline control group) and group A2 (paracetamol treated control group) comprised the subdivided control group. There were ten rats in each of these groups. For 28 days, the rats were all fed a baseline diet. The baseline control group was given normal saline (20 ml/kg/day) orally every day for 28 days in addition to their basal diet. For the final three days of the study—the 26th and 28th—the paracetamol-treated control group was given oral paracetamol at a dose of 1.5 g/kg/day. During the final three days of the study period (the 26th and 28th days), the experimental group was given oral paracetamol (1.5g/kg/day) and an ethanolic extract of green tea (500 mg/kg/day) for a total of 28 days. On day 29, every rat was sacrificed. Following the sacrifice, liver samples were taken. Hepatic contents of malondialdehyde (MDA) were measured by using standard laboratory method. Histopathology of liver was also done by using standard laboratory procedure in the department of pathology, SSMC. Version 22 of the Statistical Package of Social Science (SPSS) for Windows was used to do the statistical analysis. The data were displayed as mean±SD. To compare the results, one-way ANOVA, post hoc Bonferroni, and Chi-square tests were used, where appropriate. A p value of less than 0.05 was regarded as significant. Result: When compared to the baseline control group, the mean malondialdehyde concentration in the liver was significantly (p) greater in the green tea pretreatment, paracetamol treated, and control groups who received paracetamol treatment. Once more, the groups treated with green tea and paracetamol had mean malondialdehyde concentrations in their livers that were significantly (p) lower than those of the paracetamol group. Additionally, 0% of the rats in the baseline control group, 100% of the rats in the paracetamol-treated group, and 30% of the rats in the green tea-pretreated and paracetamol-treated group had abnormal histological findings of the liver. Conclusion: This study revealed that green tea has hepatoprotective effect against paracetamol induced liver damage in Long Evans male rats. Bangladesh Crit Care J September 2024; 12 (2): 145-152

Piroxicam and paracetamol in the prevention of early recurrent pain and emergency department readmission after renal colic: Randomized placebo-controlled trial.

Renal colic (RC) is a common urologic emergency often leading to significant pain and recurrent hospital visits. This study aimed to compare the efficacy and safety of piroxicam versus paracetamol in preventing pain recurrence and hospital readmission in patients treated for RC and discharged from the emergency department (ED). A prospective, randomized, single-blind trial was conducted in four EDs. Eligible adults with RC were randomized to receive oral piroxicam, paracetamol, or placebo for 5 days post-ED discharge. Primary outcomes included pain recurrence and ED readmission within 7 days. Secondary outcomes included time to recurrence and treatment-related side effects. Of 1383 enrolled patients, no significant differences were observed among the groups regarding baseline characteristics. Pain recurrence rates within 7 days were 29% (95% confidence interval [CI] 24.9%-33.2%) for piroxicam, 30.3% (95% CI 26.1%-34.5%) for paracetamol, and 30.8% (95% CI 26.6%-35.0%) for placebo, with no significant between-group differences (p = 0.84). Among patients experiencing recurrence, the majority encounter it within the initial 2 days following their discharge (86% in the piroxicam group, 84.1% in the paracetamol group, and 86% in the placebo group, respectively). ED readmission rates were similar across groups: 20.8% (95% CI 17.1%-24.5%) in the piroxicam group, 23.8% (95% CI 19.9%-27.7%) in the paracetamol group, and 22.9% (95% CI 19.1%-26.8%) in the placebo group (p = 0.52). The piroxicam group reported significantly higher adverse effects compared to others. Piroxicam and paracetamol did not demonstrate efficacy in preventing pain recurrence or ED readmission within the first week following RC treatment.

Comparison of the Magnesium Sulphate With Paracetamol Combination vs the Fentanyl With Lignocaine Combination in Attenuating the Hemodynamic Response During Laryngoscopy and Intubation: A Prospective, Double-Blinded Randomized Controlled Study.

Background and aims Laryngoscopy and intubation cause an increased sympatho-adrenergic pressor response, which can be detrimental to patients with coronary artery disease, hypertension, etc. Various drugs and manoeuvres have been triedto reduce the pressor response with acceptable results but the quest for the ideal drug still continues. Hence, we planned to compare the effects of magnesium sulfate with paracetamol and fentanyl with lignocaine on attenuating the hemodynamic responses due to direct laryngoscopy and intubation and to note the complications of these drugs. Methods We studied 60 adult patients of the American Society of Anaesthesiologists (ASA) physical status I and II of either sex, scheduled for elective surgery under general anaesthesia. The patients were randomly divided into two groups. Group A received 25 mg/kg magnesium sulphate mixed with paracetamol 1 gram IV (100 ml) given over 10 minutes before induction and Group B received 2 mcg/kg fentanyl and 1.5 mg/kg lignocaine, 3 minutes before intubation. All patients were uniformly pre-medicated, induced, and intubated as per standard protocol. Heart rate (HR) and systemic arterial pressures were recorded at baseline, after study drug infusion, after induction, and 1, 3, 5, 10, and 15 mins after intubation. Hemodynamic parameters were compared using repeated measures analysis of variance (ANOVA). In the post-hoc tests, p value < 0.05 was considered statistically significant. Results We observed the mean pre-op HR (p = 0.161) and mean HR one-minute post-induction (p = 0.144). The percentage change from baseline at one-minute post-induction was 9.7 in Group A and 15.2 in Group B. We observed the mean pre-op mean arterial pressure (MAP) (p = 0.119) and mean MAP one minute post-induction (p = 0.585). The percentage change from baseline at one-minute post-induction was 3.3 in Group A and 2.8 in Group B. The percentage change from baseline was found to be within 15%, for HR in Group A and for systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP in Group B. However, there was no statistically significant difference (p > 0.05) between the mean HR, SBP, DBP, and MAP between the time points. Conclusion In our study, both the combinations of drugs, magnesium sulphate with paracetamol (Group A drugs) and fentanyl with lignocaine (Group B drugs) were found to be equally effective (i.e. neither group was superior to the other) in attenuating the hemodynamic response to laryngoscopy and intubation.

The Antiulcer and Hepatoprotective Effects of Euphorbia hirta Petroleum Ether, Chloroform and Ethanolic Extracts on Paracetamol-induced Ulcerated Wistar Rats

Background: Hepatic and gastric diseases are two of the most common ailments in people. Numerous researches have been conducted to evaluate the effectiveness of herbal remedies in the treatment of hepatitis and stomach ulcers. Objective: The study aimed to determine the antiulcer and hepatoprotective activities of Euphorbia hirta petroleum ether, chloroform and ethanolic extracts on paracetamol-induced ulcerated Wistar rats. Materials and Methods: Euphorbia hirta was collected from the area of Salem, Tamil Nadu, India. The air-dried whole plant was crushed, and 500 g of the powder and petroleum ether, chloroform and ethanol were used for continuous extraction by the Soxhlet device. Phytochemical analysis of the extract was done by conventional and GC-MS analysis. Nine sets of six male Wistar rats, each weighing between 150 and 200 g, were used in this study. The standard control group, Group I, received only 1% v/v tween 80. Group II, negative control, received saline (1 ml/kg p.o.). Group III animals were given silymarin (200 mg/kg p.o.) and paracetamol (2 g/kg), which served as the standard of care. Animals in groups IV, V, VI, VII, VIII, and IX received two separate doses (200 and 400 mg/kg) of petroleum ether, chloroform, and ethanolic extracts of Euphorbia hirta L. Liver tissue was taken for histological investigation and placed in a 10% formalin solution. The liquid supernatant of liver cells was used to measure antioxidant parameters, such as catalase, superoxide dismutase, and LPO. Results: Phytochemical and GC-MS examination confirmed Euphorbia hirta extracts to have different biologically active phytoconstituents, like alkaloids, carbohydrates, glycosides, phenolic, flavonoids, tannin, sterols and alkaloids. Euphorbia hirta has been found to significantly protect against paracetamolinduced ulcer and hepatotoxicity compared to the negative control. A significant (p &lt; 0.001) reduction in SGPT, SGOT, ALP, DB and TB levels in the EEEH 400 mg/kg extract-treated group was observed compared to the paracetamol group. The PEEH extract exhibited no significant decrease in all biochemical parameters compared to the negative control. However, the standard drug showed a significant (p &lt; 0.001) decrease when compared to the negative control. SGPT, ALP, and DB levels demonstrated a significant (p &lt; 0.01) reduction with EEEH 200 mg/kg. The PEEH extract induced no significant decrease in all biochemical parameters compared to the negative control, and the chloroform extract of 200 mg/kg showed a less significant (p &lt; 0.05 &amp; p &lt; 0.01) difference compared to the negative control. The histopathology study confirmed EEEH 200 mg/kg to show good hepatoprotective activity. Conclusion: The findings have demonstrated Euphorbia hirta ethanolic extract to have effective antiulcer capabilities, and a decrease in LPO activity along with an increase in SOD, CAT, and LPO content have been observed, thereby leading to reduced oxidative stress. The antioxidant activity of Euphorbia hirta extract as a free radical scavenger and the hepatoprotective effect of the ethanolic extract have been indicated by the results of liver enzymes, DB and TB, and histology of liver tissue. More research is needed to recommend Euphorbia hirta as an effective supplement to treat paracetamol-induced ulcers and hepatotoxicity.

Comparative Efficacy of Seed Extract of Tamarindus indica and Vitamin E on the Liver Weight of Long Evan’s Rats Intoxicated with Paracetamol

Background: Tamarindus indica is an antioxidant rich plant. It has therapeutic interest in drugs and xenobiotics induced liver damage. Objective: This study was aimed to explore the effectiveness of ethanolic extract of seed of Tamarindus indica on liver weight when liver is intoxicated with paracetamol and to compare it with the effects of Vitamin E, a known hepatoprotectant. Materials and method: A total of twenty four Long Evan’s rats were collected and divided into four groups. Each group having sixrats (n=6). Control group received normal diet ad libitum, only paracetamol group received paracetamol (1500 mg/kg) for 12 days and rest two groups received paracetamol (1500 mg/kg) along with ethanolic extract of seed of Tamarindus indica (1250 mg/kg) and vitamin E (500 mg/kg) for 12 days respectively. On 13th day, all rats were sacrificed. Then livers were collected and weighed by an electronic balance. Results: In this study, the mean (±SD) liver weight was 4.08±0.23 in control group, 6.27±0.68 in only paracetamol treated group, 5.22±0.72 and 4.57±0.86 in paracetamol along with seed extract of Tamarindus indica and vitamin E treated group respectively. Conclusion: The present study showed that mean (±SD) weight of liver increased with paracetamol and decreased with seed extract of Tamarindus indica which is similar to the effects of vitamin E. Delta Med Col J. Jan 2021;9(2): 80-83

Grape seeds waste activated carbon as an adsorber of paracetamol drug residue: Experimental and theoretical approaches

Activated carbon (AC) derived from grape seeds wastes and chemically activated with phosphoric acid was employed to remove paracetamol (PCT); from an aqueous solution; as a pharmaceutical compound model. The AC was characterized using several techniques, and a series of batch adsorption experiments were conducted. Additionally, a theoretical study investigated the interactions of PCT with various functional groups present on the AC surface. The results demonstrated that the developed AC possessed a well-developed pore structure and a high specific surface area (SBET = 543 m2/g). The AC also exhibited an acidic surface and a low pHpzc (2.5). Adsorption experiments revealed that the pseudo-second-order (PSO) and Freundlich models provided the best fits for experimental kinetic and equilibrium data, respectively. The maximum adsorption capacity of AC for PCT was found to be 17.3 mg/g. Thermodynamic analysis suggested endothermic, favorable, and spontaneous adsorption; with low enthalpy values (ΔH° = 8.099 kJ/mol), supporting physisorption. The DLPNO-CCDT(T)/6-311G(d,p) calculation method yielded the most reliable adsorption energy (Eads) and Gibbs free energy (ΔGads) values between PCT and functional groups on the carbon surface, indicating strong interactions between the acid phosphate group of AC and the acetamide fragment of PCT (ΔGads = −7.60 kcal/mol), and strong interactions between the ketone groups and lactone cycles with the hydroxyl (ΔGads = −3.40 kcal/mol), and acetamide (ΔGads = −1.91 kcal/mol) groups of PCT, respectively. The obtained results indicated, first, that the use of activated carbon from waste is an effective alternative adsorbent for the treatment of wastewater containing pharmaceutical compounds. Second, the application of theoretical computational methods in quantum chemistry provides a thorough understanding of the mechanism of the absorption of PCT at the carbon surface.

The ameliorative effect of methanol extract of Ricinodendron heudelotii (Baill.) leaves on paracetamol-induced hepatotoxicity in Wistar rats

Plants are a rich source of antioxidants that are produced naturally. Therefore, this study was aimed to evaluate the effect of the plant Ricinodendron heudelotii (Baill.) in the attenuation of paracetamol (PCM) hepatotoxicity in Wistar rats. Twenty-four male albino Wistar rats weighing between 200 and 250 g were divided into four groups, with six rats each. Group 1 served as the control group, receiving just distilled water. Groups 2 and 3 received orally 250 mg/kg bwt/day PCM and 300 mg/kg bwt/day methanol extract of Ricinodendron heudelotii (Baill.) leaves for two weeks, respectively. For group 4, the Ricinodendron heudelotii (Baill.) leaf extract was pre-administered for 1 week before receiving 300 mg/kg bwt/day Ricinodendron heudelotii (Baill.) leaves extract and 250 mg/kg bwt/day PCM for 2 weeks. As a marker of liver damage, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue reduced glutathione (GSH) concentration, superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase activities were utilized to determine antioxidant state, while malondialdehyde (MDA) concentration was employed as a lipid peroxidation indicator. When compared to the control group, the activities of serum AST, ALT, SOD, and MDA levels were considerably (p < 0.05) higher in the PCM group, although GSH level and GST and catalase activities were significantly lower. In comparison to the PCM group, co-administration of PCM with Ricinodendron heudelotii (Baill.) extract decreased serum AST and ALT activities. This study shows that the leaf extracts of Ricinodendron heudelotii (Baill.) protects Wistar rats’ livers from PCM-induced oxidative stress by increasing antioxidant enzymes.

Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial

BackgroundTo determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0–3 years after cardiac surgery with cardiopulmonary bypass.MethodsMulti-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016–July 2020. Children aged 0–3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%.ResultsIn total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0–432.5) mcg/kg vs 692.6 (IQR, 532.7–856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion − 3.1% (95% CI − 16.6–10.3%).ConclusionsIn children aged 0–3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic.Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

The effect of fluoride varnish application on colour change due to paediatric drug usage in polyacid-modified composite resin: an in vitro study.

Colour stability is important in the long-term aesthetic success of restorative materials and is affected by both internal and external factors. Internal discolourations are due to the properties of the restorative materials. External discolourations can be associated with frequent consumption of food and beverages and the use of suspensions or syrups containing colourants/additives. Fluoride varnish application has an important place in preventive dentistry. The purpose of the research was to examine the protective effect of fluoride varnish application on the colour change on polyacid-modified composite resin restorative materials caused by the use of various paediatric drugs. Two hundred ten discs were prepared from polyacid-modified composite resin material and divided into two groups: flouride varnish was applied to one group and flouride varnish was not applied to the other group. The groups were further divided into seven subgroups and the samples were kept in artificial saliva, amoxicillin + clavulanic acid, cefuroxime axetil, clarithromycin, paracetamol, ibuprofen, and iron supplement drug solutions. The colour change values of the discs were measured using a spectrophotometer device before immersion in the drug solutions and on the 7th, 14th, 21st, and 28th days after the immersion. The obtained data were calculated and statistically evaluated using IBM SPSS V23 software. It was found that the application of fluoride varnish in the iron supplement drug group prevented the colour change of the polyacid-modified composite resins for 28 days. In the amoxicillin + clavulanic acid, cefuroxime axetil, and paracetamol groups, the fluoride varnish did not prevent colour change in the polyacid-modified composite resin restorative materials at the end of the 14th day. It is thought that fluoride varnish application may be beneficial as a preservative in the colour change of polyacid-modified composite resins due to the use of various paediatric drugs, and this protective feature may be effective for a specific period of time.

Comparison of First Analgesic Demand in Post-Operative Period Among Diclofenac Group Versus Paracetamol Group

Background: Pain after major surgery causes delays in patients' postoperative recovery, extended hospitalization periods, excessive use of analgesics, and is extremely stressful for both surgery and anesthesia. Preemptive analgesia is a treatment that begins before surgery to prevent the development of central sensitization caused by incisional and inflammatory damage that occur during surgery and in the early postoperative period. Opioids and nonsteroidal anti-inflammatory medications (NSAIDs) are commonly used for this purpose. Diclofenac sodium is a typical, inexpensive NSAIDS. Preemptive analgesia can reduce the severity and duration of pain while also delaying it. Objectives: The aim of the study was to evaluate the Comparison of first analgesic demand in post-operative period among Diclofenac group versus Paracetamol group. Methods: This randomized controlled trial study was carried out in the Department of Anaesthesiology &amp; ICU Bangladesh Medical College Hospital Dhaka, Bangladesh during 18th January 2020 to 17th July 2020. A total of 50 patients were participated in the study. Sample was selected by random sampling in two groups distributed as- group A (Oral diclofenac sodium), group B (Oral paracetamol). Statistical analyses of the results were be obtained by using window-based Microsoft Excel and Statistical Packages for Social Sciences (SPSS-24). Results: The majority of patients (63.0%) were between 40 and 59 years old, with a mean age of 48.3 ± 11.2 years. In groups A (58%) and B (56%), nearly two-thirds of the patients had an ASA grade of one. There was no statistically significant difference between the two groups (p&gt;0.05). At baseline, no significant change in heart rate, SBP, or DBP was seen across groups. The postoperative heart rate and other haemodynamic state were assessed at two, six-, and twelve-hours following surgery. Conclusion: Preemptive oral Diclofenac sodium had significant effect on reducing postoperative pain and postoperative .......

Protective effects of jervine purified from Veratrum album on paracetamol-induced liver toxicity in rats

Purpose: Since paracetamol toxicity is a very common type of poisoning, we planned to investigate whether Jervine has an effect on paracetamol toxicity by utilizing its anti-inflammatory effect.&#x0D; Materials and Methods: In our study, 42 Sprague Dawley rats of 8 weeks of age were used. Seven groups were formed with 6 animals in each group. At the 24th hour of the study, all groups underwent laparotomy under anesthesia, and liver dissection was performed. Hematoxylin and Eosin (H&amp;E) staining was performed to evaluate liver histopathology. SOD, CAT, GSH, and MDA levels were analyzed biochemically.&#x0D; Results: Histopathological, while liver tissues were normal in the control group, we observed degeneration areas, inflammation, and hemorrhage in the paracetamol group. Jervine reduced the severity of paracetamol toxicity and prevented liver damage. Jervine significantly increased SOD levels. Paracetamol administration significantly decreased CAT levels. Paracetamol significantly decreased GSH levels compared to the control group. &#x0D; Conclusion: Jervine reduced the adverse effects of paracetamol toxicity on liver tissue, such as degeneration, inflammation, and hemorrhage. Jervine increased antioxidant activity and reduced the harmful effects of NAPQI, the toxic metabolite of paracetamol, on liver tissue.

COMPARATIVE STUDY OF INTRAVENOUS PARACETAMOL AND INTRAVENOUS DICLOFENAC ANALGESIA WITH RESPECT TO EFFECT ON RENAL FUNCTION, BLEEDING TIME, AND CLOTTING TIME IN POST-OPERATIVE CASES UNDERGOING LSCS UNDER SPINAL ANESTHESIA

Objectives: The aims and objectives of the study are to compare paracetamol and diclofenac for post-operative analgesia, efficacy, and safety profiles in patients undergoing LSCS under spinal anesthesia. Methods: Fifty-eight patients undergoing LSCS under spinal anesthesia were included in this study. Out of these 58 patients, 30 patients received paracetamol (Group P) and the remaining 28 patients received diclofenac (Group D). Post-operative pain was assessed using the Visual Analog Scale. Rescue analgesic used was buprenorphine intravenous at a dose of 1 mg/kg. Injection buprenorphine was given to the patient with a VAS score of more than three in addition to the routine dose of the study drug. Pre-operative and post-operative values of blood urea, serum creatinine, bleeding time, and clotting time were compared in both groups. p&lt;0.05 were taken as statistically significant. Results: The mean age of patients in both groups was found to be comparable with no statistically significant difference (p=0.3849). In post-operative period at 150, 180 min, and 210 min, Group P reported significantly higher pain scores as compared to Group D with p-values indicating statistical significance (p&lt;0.05). The analysis of pre- and post-operative renal function tests, bleeding time, and clotting time showed that there was no significant difference in the pre- and post-operative renal function tests, bleeding time, and clotting time of the patients in Group P and Group D. Conclusion: Intravenous diclofenac is found to have a superior analgesic effect as compared to intravenous paracetamol. Both paracetamol and diclofenac were found to have no significant side effects on renal functions, bleeding time, or clotting time.

Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial

Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12-38) in the paracetamol plus ibuprofen group, 20 mg (12-32) in the paracetamol plus dexamethasone group, 16 mg (10-30) in the ibuprofen plus dexamethasone group, and 15 mg (8-26) in the paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.

Comparison of Pre-emptive Analgesic Effect of Paracetamol, Ibuprofen, and Placebo in Reducing Post-operative Pain in Intra-alveolar Tooth Extraction at The University of Benin Teaching Hospital, Benin City. A Randomised Trial.

Objective: Pain is one of the most common postoperative complications of extraction. Thus, this study is aimed at determining the pre-emptive effectiveness of paracetamol and ibuprofen in the management of post extraction pain.&#x0D; Methods: A randomized, placebo‐controlled, single‐blinded comparative study of patients who needed intra-alveolar extraction of posterior teeth. Sixty‐nine patients aged 18 years and above were randomly assigned to one of three groups: (A) paracetamol 1g; (B) ibuprofen 400mg; and (C) placebo (calcium lactate) 300mg. Each of the three tablets was given 30 minutes before administration of the local anesthetic agent. The pain level was assessed using the visual analogue scale®. Chi-square (X²) test, one-way analysis of variance (ANOVA) with an appropriate post-hoc test was used. Level of significance was set at 95% (p-value &lt; 0.05).&#x0D; Results: Ibuprofen and paracetamol groups showed lower pain scores compared to placebo. Although, there was no significant difference between the VAS scores at the post-operative period (P= 0.080). There was a significant difference in time taken for use of rescue medication among the three groups (p = 0.022), with those in placebo group 8 times more likely to use rescue medication relative to the analgesics.&#x0D; Conclusion: The use of preemptive analgesics showed lower pain scores compared to placebo, and also significantly increased the time for use of rescue medication postoperatively.