Efficacy and safety of paracetamol, phenylephrine, chlorpheniramine maleate and sodium citrate in Indian paediatric patients with common cold: an active post-marketing surveillance study

Background: The common cold, mainly caused by viruses, brings discomfort to children with symptoms like sneezing, congestion, runny nose, and sore throat. As no specific antiviral treatments are available to relieve common cold symptoms, it is typically managed using decongestants, antihistamines, and antipyretics. This study aims to assess the safety and efficacy of a fixed-dose combination (FDC) of paracetamol, phenylephrine, chlorpheniramine maleate and sodium citrate in children aged 2 to 12 years with common cold. Methods: This non-randomized, open-label, non-comparative, active post-marketing surveillance (PMS) study was conducted across multiple centres in India, involving 417 patients. The study assessed efficacy using the total symptom score (TSS) scale over 5 days with visits on days 1, 3, and 5. Safety was evaluated based on adverse events reported by patients on days 3 and 5 of the trial. Results: Initially, 417 patients were enrolled in the active PMS, of which 309 completed the study. The mean TSS showed a notable decrease from 8.95 at visit 1 to 0.19 at visit 3, depicting a significant reduction i.e., 97.90% as compared to baseline. At visit 1, most patients (95.79%) exhibited severe symptoms, whereas by visit 3, 83.82% were symptom-free, with only 16.18% experiencing mild symptoms. Conclusions: This active PMS study examined the safety and efficacy of an FDC of paracetamol, phenylephrine, chlorpheniramine maleate and sodium citrate in treating common cold in children in India. The findings indicate a significant reduction in symptoms, with many patients becoming symptom-free by the third visit, demonstrating its efficacy and safety.

Safety and efficacy of a fixed dose combination of oral drops of paracetamol, phenylephrine hydrochloride, and chlorpheniramine maleate in the symptomatic treatment of common cold in children: an active post-marketing surveillance study

Background: Common cold often accompanied by mild fever and systemic symptoms in children, poses a significant social burden. Scientific evidence suggests that the pathogenesis of colds involves the activation of multiple inflammatory pathways, rendering single-molecule treatment ineffective against the symptoms. This active post-marketing surveillance study evaluated the safety and efficacy of a fixed-dose combination containing paracetamol, phenylephrine hydrochloride, and chlorpheniramine malate in treating common cold in children aged 2 to 5 years.Methods: In this clinical study, 200 children with common cold symptoms were enrolled. Maxtra� P oral drops, a fixed-dose combination containing paracetamol (125 mg), phenylephrine hydrochloride (2.5 mg), and chlorpheniramine maleate (1 mg) per ml drops, were administered as 1 ml every 4 to 6 hours for 5 days. Safety was assessed using the global tolerability assessment based on responses from parents and investigators. Efficacy was evaluated based on symptom severity scores categorised as absent, mild, moderate, severe, or very severe.Results: Complete remission from common cold symptoms was achieved in 82% (164 patients) of 200 patients. Statistically significant reductions (p<0.001) in symptom severity scores were observed for all common cold symptoms from day 1 to day 5. No adverse events were observed. Maxtra� P oral drops were regarded as good to excellent for treating common cold symptoms by 92.5% of parents and 97.5% of investigators.Conclusions: The observations of study indicate that Maxtra� P oral drops are efficacious and well- tolerated for treating common cold in children aged 2 to 5 years.

ACETAMINOPHEN-INDUCED TOXIC EPIDERMAL NECROLYSIS IN PEDIATRIC PATIENTS-A CASE SERIES

Acetaminophen is the most widely used over-the-counter medication for treating fever and pain. While adverse reactions to this drug are infrequent, they can occasionally result in severe and potentially fatal events, such as Toxic Epidermal Necrolysis (TEN). Due to the rarity of such reactions, there is a limited amount of information available about toxic epidermal necrolysis caused by acetaminophen. This case series will contribute to the existing knowledge in this area. In our cases, acetaminophen is the most suspected drug for the development of toxic epidermal necrolysis in patients. Causality assessment in all of these adverse drug reaction in context with World Health Organization (WHO) causality assessment scale suggests “Possible.” This case series concludes that severe hypersensitivity reactions like TEN caused by acetaminophen use and which can be potentially life-threatening which needs additional treatment.

Assessing the Impact of Annona muricata Aqueous Extract on Liver Enzymes in Wister Rats Exposed to Paracetamol Over Dose

Aims: This study examines the effect of the aqueous leaf extract of Annona Muricata on liver enzymes in wister rats using the spectrophotometric method. Methodology: 20 Wister rats were divided into groups A, B, C, and D, of 5 rats each, housed, fed, and the experimental groups administered treatments orally in distilled water (10 ml/kg) by means of orogastric cannula for 14 days. 500g of the plant powder was submerged for 72 hours 1500ml of distilled water. The sample was taken with a rotating evaporator, an electrical evaporator extraction apparatus. With water heated to 45癈, the solvent was removed. Before use, a paste-like sample was made and kept in a refrigerator at 4 degrees Celsius. The animals in group A were used as the control. The animals in group B were given feeds + 20mg of paracetamol, and the animals in group C were administered 100mg of paracetamol + silymarin. In comparison, the ones in group D were given 150mg of paracetamol + Annona muricata extracts. The animals were then sacrificed 48 hours following the final dose. A blood sample was collected, allowed to coagulate, and then the serum was separated, while the liver was excised and utilized for biochemical analyses.Results: The alanine aminotransferase activities (ul) recorded 9.0�71, 14.67�5, 13.50�58, 15.75�50 for animals in groups A, B, C, and D respectively with corresponding activities of aspartate aminotransferase (ul) of 7.25�50, 27.33�04, 20.00�71, 17.25�71. Results revealed a significant difference (p<0.05) in the activities of ALT and AST of all the treated groups. Thus, the aqueous leaf extract of Annona muricata could be hepato-protective. The silymarin could also be hepatoprotective, but it is less effective than Annona muricata. The untreated group, B, showed elevated levels of alanine aminotransferase and aspartate aminotransferase, confirming paracetamol's hepatotoxic activity. Conclusion: The ethanol leaf extract of Annona muricata decreased the activities of liver enzymes in male wister rats, suggesting its hepato-protective tendency. It also does not encourage body weight loss.

Comparative study of diclofenac, paracetamol infusion, or a combination in post-caesarean patients for pain management

Background: The World Health Organization (WHO) has released fresh information showing that the number of caesarean sections performed worldwide has increased and now accounts for more than one in five (21%) deliveries. 89.8% of women experienced significant post-operative discomfort following a caesarean section and 84.2% reported to have moderate to severe pain. This study aimed to compare diclofenac, paracetamol infusion, and a combination of both in patients of post-caesarean for pain management.Methods: The study was a cross-sectional study carried out in the department of obstetrics and gynaecology at a tertiary care hospital in a rural area of Panipat, Haryana. A total number of 102 women who underwent caesarean section were taken for the study. They were divided into 3 groups each having 34 women. The first group was given diclofenac, the second was given paracetamol infusion and the third was given a combination of both for pain management.Results: In our study we have done visual analog score (VAS) scoring at 0, 1, 6, 12, 18 and 24 hours and we found that the mean VAS score in group 3 was highest when compared to other two groups. We also found that on comparing data of VAS score between the three groups the p value came out to significant that is p?0.001.Conclusions: We found that combination therapy had good results in comparison to individual therapy and had fewer side effects.

Role of Bougainvillea glabra Stem Extract on Paracetamol and Alcohol-Induced Hepatotoxicity in Rats

The current study investigates the in-vivo hepatoprotective effectiveness of Bougainvillea glabra stem extract against alcohol and paracetamol-induced hepatotoxicity in animal models. The alterations in liver enzymes including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), and total bilirubin are studied in rats given B. glabra extract with paracetamol or alcohol to produce hepatotoxicity. The levels of glutathione and lipid peroxidation were also examined, and the outcomes were contrasted with silymarin as the reference. The acute toxicity studies presented the plant extract under category 5 of GHS system, which further motivated the studies for hepatoprotective activity. The induction of hepatotoxicity was confirmed with the elevated levels of serum and tissue biochemical by the administration of paracetamol and alcohol. Under paracetamol as a hepatotoxin, the animals with 200 and 400 mg/kg p.o demonstrated near figures for SGPT and SGOT of the group treated with silymarin with significance. The results were still more appreciative under alcohol as a hepatotoxin. In both cases, the group with 400 mg/kg p.o gave a promising result with the reduced inflammatory cells under histopathological studies.

Efficacy and safety of intravenous paracetamol versus intravenous tramadol for labour analgesia

Background: An effective labour analgesia improves maternal and perinatal outcome and improves the course of labour.Methods: This was a prospective, randomised study done to compare effectiveness and safety of intravenous infusion of paracetamol with tramadol when used for labour analgesia. Group A (25 parturients) received paracetamol 1000 mg and group B (25 parturients) received tramadol 1mg/Kg at 4 to 6 cm cervical dilatation. Visual analogue score for pain was assessed at the baseline, 1 hour and 3 hours of drug administration and was compared between the two groups along with various maternal and fetal outcomes.Results: The difference in mean Visual Analogue Score (VAS) just before the drug administration was not statistically significant. However, at 1 hour of drug administration, mean VAS was significantly lower in the Group A (4.60) in comparison to Group B (5.82). The mean VAS at 3 hours was slightly lower in group A (6.35) in comparison to group B (6.65), though statistically there was no significant difference. Nausea, vomiting and sedation were found to be more in the tramadol group as compared to paracetamol group. The mean 1 and 5 minute apgar scores were found to be comparable in both the groups.Conclusions: So, it can be concluded from our study that intravenous paracetamol may be preferred over intravenous tramadol as it is associated with better analgesic efficacy and less maternal side effects. Although both the drugs were found to have good neonatal outcome.

Intoxicación por paracetamol en adolescentes. Reporte de una serie de casos / Paracetamol poisoning in adolescents. Report of a series of cases / Intoxicação por paracetamol em adolescentes. Relato de uma série de casos

Introducción: la intoxicación por paracetamol puede producir falla hepática aguda. El pronóstico depende del diagnóstico precoz e inicio oportuno de las medidas terapéuticas. Objetivo: sensibilizar acerca del adecuado abordaje diagnóstico-terapéutico de la intoxicación aguda por paracetamol. Casos clínicos: se trata de 10 adolescentes de sexo femenino, mediana de edad 13,5 años, con intoxicación aguda intencional. Presentaban psicopatología 9; intentos de autoeliminación (IAE) previos 5, y seguimiento por equipo de salud mental 7. Cuatro recibían tratamiento con psicofármacos. Mediana de dosis de paracetamol 10 g (5 - 40). Se realizó carbón activado en ocho, asociado a lavado gástrico en seis pacientes. Mediana de tiempo entre ingesta y rescate 2,5 horas (1 - 3,5). Presentaron síntomas digestivos seis, fueron asintomáticas tres. Se dosificó el paracetamol luego de las 4 horas y en las primeras 24 horas de la ingesta en siete, siendo indetectable en una paciente. En las restantes, el riesgo de toxicidad hepática fue: posible en dos, probable en tres y sin riesgo en una. Se administró dosis carga de n-acetil cisteína a siete pacientes y tratamiento completo de mantenimiento a seis. Nueve ingresadas a cuidados moderados y una paciente a cuidados intensivos. No hubo complicaciones, ni fallecimientos. Se abordaron junto al toxicólogo. Conclusiones: la intoxicación aguda por paracetamol en adolescentes es habitualmente secundaria a IAE. La prevalencia de los problemas de salud mental y de IAE en esta población constituye una alerta para los profesionales de la salud que deben conocer el perfil de los fármacos utilizados y el abordaje diagnóstico-terapéutico de las posibles intoxicaciones. Dado el riesgo de hepatotoxicidad severa es necesario actuar rápidamente considerando dosis ingerida, tiempo desde la ingesta y factores de riesgo de hepatotoxicidad.

Introduction: Paracetamol poisoning can produce acute liver failure. Its prognosis depends on early diagnosis and timely initiation of specific therapeutic measures. Objective: To make health professionals aware of the appropriate diagnostic-therapeutic approach to acute paracetamol poisoning. Clinical cases: These are ten female adolescents, median age 13.5 years, with acute and intentional poisoning. 9 presented psychopathology, 5 previous self-elimination attempts (AEIs), and 7 were monitored by a mental health team. 4 received treatment with psychoactive drugs. Median dose of paracetamol 10 g (5-40 g). Drug rescue was performed with activated charcoal in 8, associated with gastric lavage in 6. The median time between intake and rescue was 2.5 hours (1-3.5 hours). They presented digestive symptoms 6 and were asymptomatic 3. Paracetamol was dosed after 4 hours and in the first 24 hours of ingestion in 7, being undetectable in 1. In the remainder, the risk of liver toxicity was classified as: possible 2, probable 3 and 1 without risk. A loading dose of n-acetyl cysteine was administered to 7 and full maintenance treatment to 6. 9 were admitted to moderate care and 1 to intensive care. There were no complications or deaths. Discussion/Conclusions: Acute paracetamol poisoning in adolescents is usually secondary to AEI. The prevalence of mental health problems and AEI in this population constitutes an alert for health professionals who must know the profile of the drugs used and the diagnostic-therapeutic approach to possible poisoning. Given the risk of severe hepatotoxicity, it is necessary to act quickly considering the dose ingested, time since ingestion, and risk factors for hepatotoxicity.

Introdução: O envenenamento por paracetamol pode levar à insuficiência hepática aguda. O prognóstico depende do diagnóstico precoce e do início oportuno das medidas terapêuticas. Objetivo: Aumentar a conscientização sobre a abordagem diagnóstica e terapêutica adequada para a intoxicação aguda por paracetamol. Casos clínicos: Dez adolescentes do sexo feminino, com idade média de 13,5 anos, com intoxicação agudada intencional. Nove apresentavam psicopatologia, 5 haviam feito tentativas anteriores de automutilação (SAI) e 7 tinham acompanhamento pela equipe de saúde mental, 44 recebiam tratamento com drogas psicotrópicas. Dose média de paracetamol 10 g (5 - 40 g). O carvão ativado foi usado em 8, associado à lavagem gástrica em 6. O tempo médio entre a ingestão e o resgate foi de 2,5 horas (1 a 3,5 horas). O paracetamol foi dosado após 4 horas e dentro de 24 horas da ingestão em 7, sendo indetectável em 1 caso. Nas demais pacientes, o risco de toxicidade hepática foi: possível em 2, provável em 3 e sem risco em 1. Uma dose de ataque de n-acetilcisteína foi administrada a 7 e o tratamento de manutenção completo a 6. Nove foram admitidas em cuidados moderados e 1 em cuidados intensivos. Esses dados foram discutidos com o toxicologista. Discussão/Conclusões: A intoxicação aguda por paracetamol em adolescentes geralmente é secundária a tentativa de autoextermínio (TAE). A prevalência de problemas de saúde mental e TAE nessa população é um alerta para os profissionais de saúde, que devem estar cientes do perfil dos medicamentos utilizados e da abordagem diagnóstica-terapêutica de possíveis intoxicações. Dado o risco de hepatotoxicidade grave, é necessário agir rapidamente, considerando a dose ingerida, o tempo decorrido desde a ingestão e os fatores de risco para hepatotoxicidade.

Study to determine feto maternal outcomes of programmed labor in a tertiary care hospital of Jharkhand

Background: Programmed labor aims to minimize duration and inconvenience of labor both for patient and obstetrician. The present study attempts to provide labor analgesia by using infusion paracetamol in place of conventional ketamine and tramadol.Methods: This study was conducted in the labor room of department of obstetrics and gynecology, RIMS, Ranchi from March 2019 to February 2020. 50 primigravida and 50 multigravidas were studied, with singleton pregnancy, cephalic presentation presenting with spontaneous onset of labor with Gestational age of 37-41 week.Results: 30% of patients were greater than 40 weeks gestation.65% of primigravida experienced severe pain, but only 20% of multigravidas had severe pain.60%primigravidas and 60% multigravidas (of 20% who had severe pain) experienced adequate pain relief with labor analgesia. 60 % primigravida presented with <4 cm cervical dilatation, whereas 40% multigravidas had <4 cm dilatation. 60% primigravida had shortened active phase (3.5 hrs), 60% multigravidas (2.5 hrs) which is suggestive of benefit of obstetrical analgesia in programmed labor. 90% patients had third stage labor less than 3 minutes. Only one multigravida landed in postpartum hemorrhage. All neonates had Apgar score greater than 8. There was no perinatal mortality. Only one primigravida landed in caesarean section due to arrest in second stage. 2 multigravidas had instrumental delivery. Maternal side effects like tachycardia, nausea, cervical and vaginal tears were more in primigravida.Conclusions: Participants with good response to obstetrical analgesia fared better than rest. Response was more satisfactory in primigravida in terms of labor progress.

Genotoxic and cytotoxic effects of thiomersal and paracetamol combination

Background: Thiomersal is used as a preservative of some vaccines or as a trace from the pathogen inactivation process in vaccine production. Prophylactic use of paracetamol upon vaccination is still common, even though paracetamol decreases immune response on some vaccines. Considering the cytotoxic and genotoxic potential of thiomersal and paracetamol and possible interaction in vivo, in vitro study was performed. Methods: The genotoxic and cytotoxic effects of thiomersal and paracetamol combination were examined on human lymphocyte cultures by using two methods: analysis of chromosomal aberrations and cytokinesis-block micronucleus cytome assay. Blood samples of three healthy donors were analyzed with the following concentrations of tested substances: thiomersal 1 µg/ml and 0.5 µg/ml, paracetamol 20 µg/ml, thiomersal 0.5 µg/ml with paracetamol 20 µg/ml and thiomersal 1.0 µg/ml with paracetamol 20 µg/ml. Results: The analysis of structural chromosomal aberrations was significantly increased in all treated cultures. In cells treated with the combination of thiomersal 1 µg/ml and 20 µg/ml of paracetamol, the number of aberrations was significantly decreased. Cytokinesis-block micronucleus cytome assay analyses showed significantly increased micronucleus frequency in lymphocytes cultivated with thiomersal 1 µg/ml compared to lymphocytes cultures exposed to thiomersal 0.5 µg/ml. Conclusions: Induction of structural chromosome aberrations and micronucleus is shown as a sign of genotoxicity for the examined concentrations of thiomersal and paracetamol. The suppressing effect of paracetamol on thiomersal genotoxicity in lymphocytes culture treated with thiomersal was shown to be indicative of further examination of paracetamol use in the prevention of genotoxicity.

Self-Medication Among Medical Students During the COVID19 Pandemic

Introduction: During the different wave of pandemic, due to various reasons self-medication practices among the public increased. Medical students are prone to such practices due to relevant background knowledge, and access to drugs. This study assessed the self-medication practice among the medial students during the different waves of pandemic of south Gujarat. Material and Methods: This descriptive study was conducted during May to June 2022 through self-administered form among medical students of south Gujarat, India. Study questionnaire included general de-mography; most frequently practice of self-medication. drug and the reason behind it. Result: Out of total 512 respondents, 381 (74.4%) did self-medication during the pandemic. 358 individuals (94.0%) did self-medication at least one drug since the start of pandemic. The most commonly utilizing medi-cines as prophylactic was Ayurvedic preparation, Multivitamins, Zinc and Vitamin C. For treatment of symp-toms during the pandemic paracetamol (650 mg) was frequently used specially for body ache and fever. The main source of information of self-medication was internet. Conclusion: This study depicted common self-medication practices among medical students during the pan-demic. It is a significant health issue especially during the pandemic times, with high consumption reported as a prevention or treating symptoms of COVID-19.

A new horizon in the prescription pattern of drugs for osteoarthritis in a tertiary care hospital: A prospective observational study

Background: Osteoarthritis (OA) is a significant contributor to chronic pain, mainly affecting lower extremity joints like the knee and hip, and causing considerable impairment in elderly individuals. OA treatment focuses on easing discomfort and enhancing mobility. Despite their adverse unfavorable effects, non-steroidal anti-inflammatory medications (NSAIDs) are frequently used for symptom alleviation. However, there is still a need for secure and efficient alternative therapies that could provide OA patients with both symptomatic relief and disease-modifying benefits. Despite the indisputable fact that the disease has a substantial socioeconomic impact on patients, there is not much research available to reflect on the medicine prescription pattern in OA. Aim and Objectives: The objectives of this study were to assess the prescription pattern and their rationality in patients with OA in a tertiary care hospital. Materials and Methods: A cross-sectional, prospective, and observational study conducted in the orthopedics department for all newly diagnosed and old treated patients with OA. Around 350 patients were taken into the study and their prescriptions were scrutinized. Descriptive statistics were used to analyze the data and present it as percentages. Results: Over 61.7% of females were affected compared to 38.3% of males with OA. The knee joint (76.2%) followed by the hip joint (13.7%) were the most common joints involved. Aceclofenac and diclofenac were the most common NSAIDs used in the patients, whereas piroxicam was the least prescribed drug. Gastroprotective agents, calcium supplements, and SYSDOA were the commonest adjuvants used in the treatment of OA patients. Conclusions: Even though NSAIDs are favored, SYSDOA and non-pharmacological treatments such as lifestyle changes, and frequent mild exercise have changed the treatment plan for OA

A Review on Methods Developed for Estimation of Paracetamol in Combination with Other Drugs

In this ever-growing world, it is crucial to improve upon the formulations in terms of potency, patient acceptability, fewer side effects, and quicker relief. Due to these requirements, the market is flooded with various combination dosage forms, with a constant increase in number. Paracetamol is a commonly used non-steroidal anti-inflammatory drug (NSAID) that has antipyretic and analgesic action. This drug is available in a wide range of combinations. It acts by inhibiting the production of prostaglandins, which combat pain and inflammation. A simultaneous multicomponent analysis is used to determine the estimation of medicines that are available in combination. Different analytical techniques are available for their determination, one of which includes the use of UV spectrophotometric methods. This review focuses on a variety of paracetamol combinations with drugs like Domperidone, Aceclofenac, Diclofenac Sodium, Etodolac, Ibuprofen, Piroxicam, Caffeine, Aspirin, and their simultaneous estimation by different UV methods viz. Simultaneous equation method, Absorbance ratio (Q-Analysis), Difference spectrophotometry, Derivative spectroscopy method, and a few other chemometric methods. This manuscript would provide the platform to have exhaustive literature on methods used for the estimation of paracetamol with different drugs using a spectrophotometer. It would help the researchers and scholars who are working in the area.

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Sobredosis de acetaminofén y comportamientos relacionados con suicidio / Acetaminophen overdose and suicide-related behaviors / Overdose de paracetamol e comportamentos suicidas

Objetivo: este trabajo busca caracterizar el comportamiento relacionado con el suicidio en la población admitida al Hospital San Vicente Fundación, Rionegro, con sobredosis de acetaminofén entre enero 2019 y diciembre 2020 y detectar factores asociados con la dosis tóxica. Metodología: análisis descriptivo con información obtenida de historias clínicas. Resultados: 63 individuos presentaron ingestión aguda de dosis tóxica de acetaminofén como comportamiento relacionado con suicidio. Cuarenta y tres eran mujeres, 60% tenía antecedente de enfermedad psiquiátrica, 35% reportó al menos un intento suicida previo y 22% consumieron 25g o más. La lesión hepática aguda se asoció con una dosis tóxica. Conclusiones: evidenciamos una alta prevalencia de antecedente de enfermedad psi­quiátrica y comportamiento relacionado con suicidio y casi un tercio de los pacientes ingirió dosis mayores al umbral de riesgo para falla hepática. Además, la impulsividad e ingesta en casa sugiere que políticas públicas restrictivas pueden no impactar en la reducción de estos eventos en la población.

Objective: this work seeks to characterize the behavior related to suicide in the po­pulation admitted to the Hospital San Vicente Fundación, Rionegro, with an overdose of acetaminophen between January 2019 and December 2020, and to identify factors associated with the toxic dose. Methodology: descriptive analysis with information obtained from medical records. Results: 63 individuals presented acute ingestion of a toxic dose of acetaminophen as behavior related to suicide. Forty-three were women, 60% had a history of psychiatric illness, 35% reported at least one previous suicide attempt, and 22% consumed 25g or more. Acute liver injury was associated with a toxic dose. Conclusions: we evidenced a high prevalence of a history of psychiatric illness and beha­vior related to suicide; almost a third of the patients ingested doses greater than the risk threshold for liver failure. In addition, impulsiveness and eating at home suggests that res­trictive public policies may not have an impact on reducing these events in the population.

Objetivo: Este trabalho busca caracterizar o comportamento relacionado ao suicídio na população internada no Hospital San Vicente Fundación, Rionegro, com overdose de acetaminofeno entre janeiro de 2019 e dezembro de 2020 e detectar fatores associados à dose tóxica. Metodologia: análise descritiva com informações obtidas dos prontuários. Resultados: 63 indivíduos apresentaram ingestão aguda de dose tóxica de paracetamol como comportamento relacionado ao suicídio. Quarenta e três eram mulheres, 60% tinham histórico de doença psiquiátrica, 35% relataram pelo menos uma tentativa de suicídio anterior e 22% consumiram 25g ou mais. A lesão hepática aguda foi associada a uma dose tóxica. Conclusões: evidenciamos alta prevalência de história de doença psiquiátrica e com-portamento relacionado ao suicídio e quase um terço dos pacientes ingeriu doses superiores ao limiar de risco para insuficiência hepática. Além disso, a impulsividade e a alimentação em casa sugerem que políticas públicas restritivas podem não ter impacto na redução desses eventos na população.

Investigation of antioxidant activity of ethanolic extract of the bark of Caesalpinia ferrea in Swiss mice exposed to paracetamol / Investigação da atividade antioxidante do extrato etanólico da casca de Caesalpinia ferrea em camundongos Swiss expostos ao paracetamol

Aims: it was evaluated the antioxidant effect of the ethanolic extract of Caesal-pinia ferrea bark in a model of oxidative stress induced by paracetamol (PCM). Methods: male Swiss mice were subdivided into four groups (control; PCM; PCM+extract; extract; n=8) in which a dose of paracetamol (250 mg.kg-1) was administered and after 3 hours the treatment with the extract (100 mg.kg-1/day) was administered for seven days, via gavage. Oxidative stress biomarkers were determined, such as catalase, glutathione-S-transferase, reduced gluta-thione, ascorbic acid, thiobarbituric acid reactive substances and carbonylated proteins of liver, kidneys and brain and plasma parameters through the dosage of glucose, cholesterol, triglycerides, aspartate aminotransferase and alanine aminotransferase. Results: the Caesalpinia ferrea extract was able to reverse the lipid and protein damage caused by the drug in the liver tissue and caused the same effect in the renal and brain tissues in the carbonylated proteins. The extract alone decreased liver glutathione-S-transferase and increased catalase and brain glutathione-S-transferase activity, in addition to lowering glucose and cholesterol, but without altering the triglycerides. Conclusions: it was possible to conclude that the ethanolic extract of the bark of Caesalpinia ferrea has a good antioxidant activity, probably due to dose of paracetamol in the samples investigated. However, more studies are needed for a better understanding of the effects of this extract compared to the effects found in this research

Objetivos: foi avaliado o efeito antioxidante do extrato etanólico da casca de Caesalpinia ferrea em modelo de estresse oxidativo induzido por paracetamol (acetaminofeno, PCM). Métodos: camundongos Swiss machos foram subdivididos em quatro grupos (controle; PCM; PCM+extrato; extrato; n=8) nos quais foi administrada uma dose de paracetamol (250 mg.kg-1) e após três horas foi administrado o tratamento com o extrato (100 mg.kg-1/ dia) por sete dias, via gavagem. Foram determinados biomarcadores de estresse oxidativo, como catalase, glutationa-S-transferase, glutationa reduzida, ácido ascórbico, substâncias reativas ao ácido tiobarbitúrico e proteínas carboniladas do fígado, rins e cérebro, além de parâmetros plasmáticos através da dosagem de glicose, colesterol, triglicerídeos, aspartato aminotransferase e alanina aminotransferase. Resultados: o extrato de Caesalpinia ferrea foi capaz de reverter os danos lipídicos e proteicos causados pela droga no tecido hepático, e também causou o mesmo efeito nos tecidos renal e cerebral nas proteínas carboniladas. O extrato sozinho diminuiu a atividade da glutationa-S-transferase hepática e aumentou a da catalase e glutationa-S-transferase cerebral, além de diminuir a glicose e o colesterol, mas sem alterar os triglicerídeos. Conclusões: foi possível concluir que o extrato etanólico da casca de Caesalpinia ferrea apresenta uma boa atividade antioxidante, provavelmente devido à presença de taninos, tendo em vista os danos causados pela alta dose de paracetamol nas amostras investigadas. Entretanto, mais estudos são necessários para um melhor entendimento dos efeitos deste extrato frente aos efeitos encontrados nesta pesquisa

Management and outcome of different drug overdose cases in a tertiary care hospital – A prospective observational study

Background: Overdose is defined as any substance that is exposed excessively, which is intended for consumption. There are many drugs which are used therapeutically, but sometimes self-harm can be done with medications such as analgesics, antiepileptics, and sedatives. The high mortality and morbidity associated with drug overdose could be due to various factors such as easy availability, improper regulations for dispensing drugs, lack of control for over the counter drugs. Aim and Objective: The purpose of this study is to document the incidence of drug overdose cases, sociodemographic characteristics, and its management in a tertiary care hospital. Materials and Methods: A prospective, observational study was conducted from January 2014 to December 2014 at Casualty and Medicine Department in a tertiary care hospital. Results: A total of 61 cases were included in the study. Drug overdose cases were seen in the age group of 21–30 years (67.2%). Intentional drug overdose is seen in 58 (95.08%) cases. In this study, 34.4% of patients presented to the hospital within 6 h of event. Paracetamol was the most common (32.7%). In most of the paracetamol overdose, cases were treated with N-acetyl cysteine, phenobarbitone overdose with forced alkaline diuresis, benzodiazepines overdose with flumazenil, and opioids overdose with naloxone. This study shows that 93.3% of patients had an uncomplicated course of stay in hospital. Conclusion: Drug overdose is a major public health concern in the society. The most vulnerable population in the society is the younger age group. Prevention strategies should be dealt in this high risk group.

Indicación de N-acetilcisteína en distintas formas de toxicidad por paracetamol / Indication of n-acetylcysteine in differents forms of paracetamol toxicity

Introducción: la hepatotoxicidad por paracetamol está relacionada con la formación del metabolito N-acetil-parabenzoquinoneimina (NAPQI) y su falta de detoxificación a través del glutatión, cuyas reservas se deplecionan en el contexto de una sobredosis. La administración de N-acetilcisteína (NAC) como sustancia dadora de grupos tioles (-SH) contribuye a la prevención del daño hepático que puede desarrollarse con dosis terapéuticas o tóxicas. Métodos: se comentan 5 casos de exposición a paracetamol en los cuales se administró NAC por alteración de la función hepática. La gravedad de los cuadros varió en función de las dosis y del tiempo de latencia hasta la consulta. Resultados: cuatro pacientes ingirieron una única dosis tóxica y una paciente recibió la dosis diaria máxima de paracetamol de 4000 mg/día durante 5 días. La paciente que consultó dentro de las 4 horas posteriores a la ingesta no presentó elevación de transaminasas. Todas las pacientes recibieron NAC y sus valores de enzimas hepáticas se normalizaron al momento del alta. Conclusión: la administración temprana de NAC puede ser útil para prevenir daño hepático tanto en ingestas de dosis tóxicas, como en casos de utilización de dosis terapéuticas máximas durante varios días. (AU)

Introduction: paracetamol hepatotoxicity is related to the formation of the metabolite N-acetyl-parabenzoquinoneimine (NAPQI) and its lack of detoxification through glutathione, whose reserves are depleted in paracetamol overdose. The administration of N-acetylcysteine (NAC) as a donor of sulfhydryl groups (-SH) can prevent liver damage that could even occur with therapeutic or toxic doses. Methods: 5 cases of exposure to paracetamol are discussed, in which NAC was administered due to impaired liver function. These manifestations presented different severity depending on the drug doses and the time until medical consultation. Results: four patients ingested single toxic doses and one patient received the maximum daily dose of paracetamol of 4000 mg/day for 5 days. The patient who consulted within 4 hours after ingestion did not present elevation of transaminases. All patients received NAC, with normal liver enzymes at discharge. Conclusion: the early administration of NAC may be useful to prevent liver damage both in toxic dose intakes and in cases of use of maximum therapeutic doses for several days. (AU)

Safety and Efficacy of Nimesulide/Paracetamol Fixed-dose Combination in Acute Pain (SAFE Study)

Background: Nimesulide shows preferential inhibition for the cyclooxygenase-2 (COX-2) enzyme, which blocks the formation of prostaglandins critical in pain and inflammatory pathways. Few studies in the past have reported rare and unpredictable hepatic effects with nimesulide. The present study aimed to evaluate the efficacy and safety of nimesulide/paracetamol (100 mg + 325 mg) fixed-dose combination twice a day for 2 weeks in the management of acute pain in Indian population. Materials and methods: This was a multicenter study, performed on 500 patients, by 24 experienced physicians across India. The primary outcome assessed clinical safety at 2 weeks for mild/serious adverse effects (AEs), change in liver function tests (LFTs), serum bilirubin and alkaline phosphatase levels. The secondary outcomes assessed the clinical effectiveness in reduction of pain at rest and at movement. Results: Analysis of LFT at 2 weeks showed a slight increase (mean change) in the aspartate transaminase {-0.73 [95% confidence interval (CI) -1.54, 0.09; p = 0.081]}, alanine transaminase [-1.73 (95% CI -2.82, -0.64; p = 0.002)], serum bilirubin [-0.02 (95% CI -0.04, -0.001; p = 0.018)] and alkaline phosphatase levels [-1.92 (95% CI -5.84, 2; p = 0.336), not exceeding the normal range. Only one in 500 patients reported AEs. The numerical rating scale (NRS) scores for intensity of pain at rest and at movement at 2 weeks, ?7 days and >7 days were 68.38%, 68.44% and 68.39%; and 65.43%, 64.60% and 66.02%, respectively. An improvement of 96.6% was observed in patient global assessment scale (GAS) and 97.2% in physician GAS. Conclusion: Nimesulide/paracetamol combination was safe, effective and well-tolerated in acute pain conditions and did not lead to clinically significant changes in liver parameters indicating hepatic safety.

Safety and Efficacy of Paracetamol + Lignocaine Injection in Patients with High-grade Fever:A Prospective Analysis

Paracetamol is frequently used as an analgesic and antipyretic across the world. However, there is no data on Indian patients regarding the safety and efficacy of paracetamol + lignocaine injection in patients with high-grade fever. Hence, a prospective analysis was conducted to assess the safety and efficacy of paracetamol and lignocaine injection in patients with high-grade fever and mild-to-moderate body pain. The study is a real-world prospective study. The results showed that following intervention with paracetamol and lignocaine injection, 98% patients showed resolution of fever and 58% patients showed improvement in pain symptoms. The authors suggest that clinicians should consider paracetamol and lignocaine injection in patients with high-grade fever and associated pain and discomfort.