In recent years, there has been increasing interest in the role of intravenous lipid formulations as potential antidotes in patients with severe cardiotoxicity caused by drug toxicity. The aim of this study was to conduct a comprehensive bibliometric analysis of all human and animal studies featuring lipid emulsion as an antidote for the treatment of acute poisoning. The Scopus database search was performed on 5 February 2016 to analyse the research output related to intravenous lipid emulsion as an antidote for the treatment of acute poisoning. Research indicators used for analysis included total number of articles, date (year) of publication, total citations, value of the h-index, document types, countries of publication, journal names, collaboration patterns and institutions. A total of 594 articles were retrieved from Scopus database for the period of 1955-2015. The percentage share of global intravenous lipid emulsion research output showed that research output was 85.86% in 2006-2015 with yearly average growth in this field of 51 articles per year. The USA, United Kingdom (UK), France, Canada, New Zealand, Germany, Australia, China, Turkey and Japan accounted for 449 (75.6%) of all the publications. The total number of citations for all documents was 9,333, with an average of 15.7 citations per document. The h-index of the retrieved documents for lipid emulsion research as antidote for the treatment of acute poisoning was 49. The USA and the UK achieved the highest h-indices, 34 and 14, respectively. New Zealand produced the greatest number of documents with international collaboration (51.9%) followed by Australia (50%) and Canada (41.4%) out of the total number of publications for each country. In summary, we found an increase in the number of publications in the field of lipid emulsion after 2006. The results of this study demonstrate that the majority of publications in the field of lipid emulsion were published by high-income countries. Researchers from institutions in the USA led scientific production on lipid emulsion research. There is an obvious need to promote a deeper engagement through international collaborative research projects and funding mechanisms.
To investigate the relationship between different types of adverse drug reaction (ADR) and late time to N-acetylcysteine (NAC) infusion in patients presenting to the hospital with acetaminophen overdose.
Snake bite has been regarded as an important health problem in Myanmar since early 1960's. In the recent years, there has been growing interest in alternative therapies and therapeutic use of natural products, especially those derive from plants. In Myanmar and Indian traditional medicine, various plants have used as a remedy for treating snake bite. The present study was carried out to evaluate the effects of alcohol extract of Tamarind (Tamarindus indica Linn.) seed on some biologic properties of Russell's viper (Daboia russelli siamensis) venom (RVV). The Phospholipase A2 (PLA2) enzyme, coagulase enzyme and caseinolytic enzyme activities of Russell's viper venom (RVV) were reduced when mixed and incubated with the extract. When the RVV and the different amount of extracts were preincubated and injected intramuscularly into mice, all of them survived, but all the mice in the control group died. On the other hand, when RVV were injected first followed by the extract into mice, all of them died. If the extract was injected near the site where Russell's viper venom was injected, all the mice survived for more than 24 hours and the survival time prolonged but they all died within 96 hours. In conclusion, according to the results obtained, the extract neutralizes some biologic properties of the Russell's viper venom and prolonged the survival time if the extract was injected near the site where the Russell's viper venom was injected.
Matched MeSH terms: Antidotes/isolation & purification; Antidotes/pharmacology*; Antidotes/therapeutic use
The current study has been designed to examine the effect of multifunctional drug therapy on carbofuran induced acute (2.187 mg/kg, s.c.) and sub-acute (0.2187 mg/kg, s.c.) neurotoxicity in male wistar rats. Drug treatment which includes nimodipine (Ca(2+) channel blocker), diazepam, ropinirole (dopamine agonist) and GSPE (antioxidant) was started 2h after carbofuran administration. Morris water maze was employed for aiming spatial memory. Narrow beam walk and rotarod were employed for testing motor functions. Brain acetylcholinesterase activity, thiobarbituric acid reactive species, nitrite, reduced glutathione, catalase levels, and mitochondrial complexes were also estimated. Carbofuran treatment resulted in significant development of cognitive and motor functions manifested as impairment in learning and memory along with increased thiobarbituric acid reactive species, nitrite levels and decreased acetylcholinesterase activity, reduced glutathione, catalase levels, and mitochondrial complexes. The standard antidote therapy (atropine) was not able to provide neuroprotection but was able to provide symptomatic relief. The multifunctional drug therapy attenuated carbofuran induced cognitive and motor dysfunction, acetylcholinesterase activity and other biochemical parameters. The triple combination in sub-acute study may be avoided in future as two drug combinations provide adequate neuroprotection. Thus it can be concluded that standard antidotal therapy may not provide neuroprotection while the multifunctional drug therapy offers neuroprotection against carbofuran and may dramatically increase survival and life quality.
Intravenous N-acetylcysteine is usually regarded as a safe antidote. However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N-acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p < 0.001), rash (p < 0.001) and pruritus (p < 0.001). However, there were no significant differences in serum acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N-acetylcysteine-induced cutaneous ADR.
Matched MeSH terms: Antidotes/adverse effects*; Antidotes/therapeutic use
Intravenous N-acetylcysteine (IV-NAC) is usually regarded as a safe antidote to acetaminophen overdose. However, during infusion of the loading dose, adverse drug reactions such as a headache may occur. The objectives of this study were to investigate the prevalence of headache in patients presenting to hospital after acetaminophen overdose and to determine which clinical findings are most predictive of headache among these patients. This is a retrospective cohort study of hospital admissions for acute acetaminophen overdose that was conducted over a period of 4 years from January 1, 2005 to December 31, 2008. Demographic data, clinical characteristics, and predictors of headache were analyzed. spss 15 was used for data analysis. Two-hundred and fifty-five patients were studied; their mean age was 23.1 ± 1.6; 83.9% of them were women and 14.9% had a headache during hospitalization. Headache among patients was significantly associated with IV-NAC administration (P = 0.001), intentional ingestion of drug (P = 0.04), acetaminophen concentration above 'possible toxicity' treatment line (P = 0.04), a high acetaminophen concentration (P = 0.04), and a long hospital stay (P = 0.03). Multiple logistic regression showed a significant risk factor for headache in patients administered IV-NAC (P = 0.04). We recorded a high frequency of headache in patients with acute acetaminophen overdose in our geographical area. This study suggests that among those patients, the use of IV-NAC is associated with an increased risk of headache.
Intravenous N-acetylcysteine (IV-NAC) is widely recognized as the antidote of choice for acetaminophen overdose. However, its use is not without adverse drug reactions (ADR) that might affect therapeutic outcome or lead to treatment delay.
The influence of copper (Cu) overload on hepatic lipid peroxidation and antioxidation defense capacity was studied by overloading rats with copper sulphate orally (500 mg Cu/kg bw) 5 d/w for 8 w. Malondialdehyde (MDA), Cu-Zn superoxide dismutase (SOD), and Se-glutathione peroxidase (GSH-Px) were measured in serum and liver homogenate at 2, 4 and 8 w of dosing. Liver Cu concentration and alanine aminotransferase (ALT) activity were also determined. As Cu loading progressed, there were multiparameter changes with significant ALT elevation, increased MDA concentrations in serum and liver homogenate, and dramatic declines of SOD and GSH-Px activities in erythrocytes and whole blood respectively, along with marked elevation of hepatic Cu in the Cu-dosed group. Excessive Cu accumulation in the liver depressed SOD and GSH-Px activities and resulted in high MDA in serum and liver homogenate due to the lipid peroxidation induced by the Cu overload.
This study examines histometrical changes induced by sodium arsenite (SA), as an environmental pollutant, and investigates the protective effect of α-tocopherol on ovaries of SA-treated rats during the prenatal stage until sexual maturity. Rats were classified into groups: control, SA (8 ppm/day), α-tocopherol (100 ppm/day), and SA+α-tocopherol. Treatment was performed from pregnancy until maturation when the rats and ovaries were weighed. The Cavalieri method was used to estimate volume of the ovaries, cortex, medulla, and corpus luteum. The mean diameter of oocytes, granulosa cells, and nuclei were measured and volume was estimated using the Nucleator method. The number of oocytes and thickness of the zona pellucida (ZP) were determined using an optical dissector and orthogonal intercept method, respectively. SA reduced the body and ovary weight, the number of secondary, antral and Graafian oocytes, volume of the ovaries, cortex, medulla and corpus luteum, mean diameter and volume of oocytes in primordial and primary follicles, mean diameter and volume of oocyte nuclei in all types of follicles, and mean thickness of the ZP in secondary and antral follicles. Also, the mean diameter and volume of granulosa cells and their nuclei in antral and Graafian follicles decreased significantly. Vacuolization and vascular congestion in the corpus luteum and an increase in the number of atretic oocytes were seen in the SA group. Most of these parameters were unchanged from the control level in the SA+α-tocopherol group. It was concluded that α-tocopherol supplementation reduced the toxic effects of SA exposure on ovarian tissue in rats.
The availability of antidotes may be considered essential and lifesaving in the management of certain poisonings. Surveys carried out in a number of countries have demonstrated inadequate availability of a variety of poisoning antidotes.
On the battlefields of Syria, many innocent civilians have been killed or injured by sarin poisoning. In Malaysia in February 2017, a North Korean man was assassinated with VX at Kuala Lumpur International Airport. In the face of such threats, a more effective antidote against organophosphonate acetylcholinesterase (AChE) inhibitors is needed, one that can freely penetrate into the central nervous system (CNS) through the blood-brain barrier (BBB). In the 1995 Tokyo subway sarin attack, which produced more than 6,000 victims, 2-pyridinealdoxime methiodide was the most commonly used antidote in hospitals, but it was unable to prevent CNS damage and no other oximes have been approved for use in Japan. Ultimately, 12 people died, and many victims had severe neurological injuries or sequelae. Although more than 25 years have passed since the incident, progress has been slow in the development of a new antidote that can penetrate the BBB, restore AChE activity in the CNS, and definitely prevent brain injury. From the perspectives of countering terrorism and protecting innocent people from nerve agent attacks, the search for nerve agent antidotes should be accelerated with the goals of improving both survival and quality of life. This review gives an overview of a series of our studies on the development of a new antidote since the Tokyo subway sarin attack and emphasizes that there is unfortunately still no promising antidote for saving the CNS in Japan.
Acetaminophen is one of the most commonly encountered medications in self-poisoning, with a high rate of morbidity. The prevalence and characteristics of acetaminophen intoxication associated with long hospital stay in patients are not well defined.
Matched MeSH terms: Antidotes/administration & dosage; Antidotes/therapeutic use
The protective effect of the ethanol extract of the rhizome of Zingiber officinale Roscoe on acute hepatotoxicity induced by paracetamol (1000 mg/kg) was studied in plasma and hepatic tissue samples obtained from male Sprague-Dawley rats. The ethanol extract was given in oral doses of 200 mg/kg and 300 mg/kg to the rats at 0, 4 and 8 hrs after paracetamol was given orally. The plasma and liver of the rats were subjected to biochemical analysis 24 hrs after hepatotoxicity was induced to determine the levels of superoxide dismutase(SOD), malonaldehyde (MDA) and aspartate transaminase (AST). The results were compared to the rats which were given the antidote N-acetylcysteine (NAC) (500 mg/kg) at 0, 4 and 8 hrs after the paracetamol dose. The results showed that at 200 mg/kg the extract reduced the plasma levels of SOD significantly (p < 0.05) while at a higher dose of 300 mg/kg it reduced plasma SOD, hepatic MDA, serum AST and increased the levels of plasma proteins significantly (p < 0.05). In conclusion, the ethanol extract of Z. officinale showed protective effect against paracetamol induced hepatotoxicity at both dose levels and the protective effect was better at the higher dose.
Orogastric lavage has been performed since 200 years ago for intoxicated patients. Due to the risk that outweighs benefits it has fallen out of favour for the last decade. A teenage girl presented to Emergency Department with history of ingestion of a bottle of pesticide within the time frame before gastric emptying. The girl was resuscitated, intubated and orogastric lavage was performed. Fifty cc of the toxic substance was siphoned and antidote of the toxin was administered. She was admitted to the Intensive Care Unit, subsequently recovered and discharge five days later. Definitive airway management, proper technique, correct selection of patients and adequate monitoring are paramount to the success of orogastric lavage.
A 16-month-old child developed a brief generalised tonic-clonic fitting episode and vomiting at home, after accidental ingestion of traditional massage oil. As the patient presented with clinical features of salicylate toxicity, appropriate management was instituted. He was admitted to the intensive care unit for multiorgan support. The child was discharged well 1 week after the incident. Methyl-salicylate is a common component of massage oils which are used for topical treatment of joint and muscular pains. However, these massage oils may be toxic when taken orally. Early recognition of the salicylate toxicity is very important in producing a good patient outcome.
Previous studies showed that venoms of the monocled cobra, Naja kaouthia from Thailand and Malaysia are substantially different in their median lethal doses. The intraspecific venom variations of N. kaouthia, however, have not been fully elucidated. Here we investigated the venom proteomes of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V) through reverse-phase HPLC, SDS-PAGE and tandem mass spectrometry. The venom proteins comprise 13 toxin families, with three-finger toxins being the most abundant (63-77%) and the most varied (11-18 isoforms) among the three populations. NK-T has the highest content of neurotoxins (50%, predominantly long neurotoxins), followed by NK-V (29%, predominantly weak neurotoxins and some short neurotoxins), while NK-M has the least (18%, some weak neurotoxins but less short and long neurotoxins). On the other hand, cytotoxins constitute the main bulk of toxins in NK-M and NK-V venoms (up to 45% each), but less in NK-T venom (27%). The three venoms show different lethal potencies that generally reflect the proteomic findings. Despite the proteomic variations, the use of Thai monovalent and Neuro polyvalent antivenoms for N. kaouthia envenomation in the three regions is appropriate as the different venoms were neutralized by the antivenoms albeit at different degrees of effectiveness.
From 1970 to 1984, 100 patients suffering from organophosphate poisoning were treated in the Intensive Care Unit at the University Hospital. These patients developed signs and symptoms of cholinergic over-activity and were treated with continuous intravenous atropine. Many of the patients also developed acute respiratory failure, which necessitated ventilatory support in the form of intermittent positive pressure ventilation. Other measures included the use of inotropes and nutritional support. Daily estimation of serum cholinesterase levels were useful in assessing degree of recovery of the patients from the effects of the organophosphates.
N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.