Antidote Drug Research Articles

A RARE CASES OF METHEMOGLOBINEMIA IN CANCER PATIENTS: CLINICAL CASES

Relevance: Methemoglobinemia is a serious disease characterized by impaired oxygen binding to iron in hemoglobin, followed by impaired oxygen delivery to body tissues. Various drugs, including antacids containing benzocaine, can cause acquired methemoglobinemia. The presented clinical cases describe methemoglobinemia that arose in connection with the use of the antacid Almagel A in a 32-year-old woman who underwent surgery on the laryngopharynx, suffering from T3NxM0 St III hypopharyngeal cancer and in a 45-year-old woman diagnosed with cancer of the left kidney St I. Condition after resection of the left kidneys.
 The study aimed to describe clinical cases of acquired methemoglobinemia induced by Almagel A (antacid), widely used in post-antitumor therapy treatment of cancer patients with digestive system diseases.
 Methods: We present clinical cases of methemoglobinemia in patients (32 and 45 years old) hospitalized at JSC “Kazakh Research Institute of Oncology and Radiology.” Complaints, anamnesis of the disease, clinical picture, and clinical, laboratory, and instrumental test results were analyzed retrospectively.
 Results: This article reports on the clinical picture of our patients, discusses the causes and mechanisms of possible poisoning, and reviews the latest recommendations for the treatment of methemoglobinemia. Treatment with intravenous methylene blue led to a rapid improvement in the patient’s respiratory status.
 Conclusion: Acquired methemoglobinemia is an acute condition that most often results from poisoning with certain drugs and compounds, which can be fatal. These clinical cases demonstrate the difficulties of diagnosing methemoglobinemia, highlight the value of taking anamnestic data, studying the acid-base state and blood gases, and the effectiveness of using methylene blue as an antidote drug in treatment.

In vitro activity of methylene blue on Mycobacterium tuberculosis complex isolates.

Methylene blue is used for bacterial staining in microbiology and as an antidote drug in medicine. In this study, we aimed to investigate the antimicrobial effects of methylene blue against Mycobacterium tuberculosis complex clinical isolates. Seventeen stored M. tuberculosis complex clinical isolates were included in the study. The isolates were inoculated into Mycobacteria Growth Indicator Tubes and incubated in Automated Mycobacterial Detection System. Mycobacteria Growth Indicator tubes containing methylene blue at critical concentrations of 0.2, 2, 20, 1000 µg ml-1 and control tube were prepared. Antimicrobial susceptibility testing was performed using Automated Mycobacterial Detection System which is gold standard for second line anti-tuberculosis drug testing. At the end of the study, six clinical isolates were susceptible to methylene blue at all critical concentrations. Five isolates were susceptible to only 1000 µg ml-1 methylene blue. Three isolates were susceptible to 1000 and 20 µg ml-1 methylene blue. Susceptibility rate was found as 94% when the critical proportion was accepted 400 GU (1/100 of control). Significant relationship was observed between the administered methylene blue concentrations and bacterial survival rate in statistical analysis. We conclude that methylene blue may become a potential anti-tuberculosis agent due to its well-known side effects and dosing regimens.

Nanomaterial-Enabled Sensors and Therapeutic Platforms for Reactive Organophosphates.

Unintended exposure to harmful reactive organophosphates (OP), which comprise a group of nerve agents and agricultural pesticides, continues to pose a serious threat to human health and ecosystems due to their toxicity and prolonged stability. This underscores an unmet need for developing technologies that will allow sensitive OP detection, rapid decontamination and effective treatment of OP intoxication. Here, this article aims to review the status and prospect of emerging nanotechnologies and multifunctional nanomaterials that have shown considerable potential in advancing detection methods and treatment modalities. It begins with a brief introduction to OP types and their biochemical basis of toxicity followed by nanomaterial applications in two topical areas of primary interest. One topic relates to nanomaterial-based sensors which are applicable for OP detection and quantitative analysis by electrochemical, fluorescent, luminescent and spectrophotometric methods. The other topic is directed on nanotherapeutic platforms developed as OP remedies, which comprise nanocarriers for antidote drug delivery and nanoscavengers for OP inactivation and decontamination. In summary, this article addresses OP-responsive nanomaterials, their design concepts and growing impact on advancing our capability in the development of OP sensors, decontaminants and therapies.

Profil Penggunaan Obat Antidotum Di Rumah Sakit Umum Daerah Undata Provinsi Sulawesi Tengah Periode 2016-2018

Antidotes drug is indicated in intoxication or poisoning patients, in addition to the antidote drugs, it can also be used as an appropriate therapeutic indication of his own medicine. The high increasing number of the antidote drug used every year in inpatient instalation Undata hospital, for exmple atropine, N-acetylcysteine and pyridoxine (vitamin B6). Therefore, this study aims to determine the percentage of drug use of antidote category indicated as an antidote therapy in Undata hospitals Central Sulawesi Province period 2016-2018. This is a descriptive study with retrospective approach and using purposive sampling techniques.The results showed that the sample size was 75 patients, with the percentage of drug use as antidotes category in Undata Hospital Central Sulawesi province period 2016-2018, namely pyridoxine (vitamin B6) of 49.33%, N-acetylcysteine drug of 42.66% and the atropine drug of 8%. The use of antidotes drug category are indicated as an antidote to the poisoning therapy drugs obtained 0%. It can be concluded that there is no antidote drug category that used as an antidote therapy on patients with drug poisoning in inpatient instalation Undata hospital Central Sulawesi Province Period 2016-2018.

Profil Penggunaan Obat Antidotum Di Rumah Sakit Umum Daerah Undata Provinsi Sulawesi Tengah Periode 2016-2018

Antidotes drug is indicated in intoxication or poisoning patients, in addition to the antidote drugs, it can also be used as an appropriate therapeutic indication of his own medicine. The high increasing number of the antidote drug used every year in inpatient instalation Undata hospital, for exmple atropine, N-acetylcysteine and pyridoxine (vitamin B6). Therefore, this study aims to determine the percentage of drug use of antidote category indicated as an antidote therapy in Undata hospitals Central Sulawesi Province period 2016-2018. This is a descriptive study with retrospective approach and using purposive sampling techniques.The results showed that the sample size was 75 patients, with the percentage of drug use as antidotes category in Undata Hospital Central Sulawesi province period 2016-2018, namely pyridoxine (vitamin B6) of 49.33%, N-acetylcysteine drug of 42.66% and the atropine drug of 8%. The use of antidotes drug category are indicated as an antidote to the poisoning therapy drugs obtained 0%. It can be concluded that there is no antidote drug category that used as an antidote therapy on patients with drug poisoning in inpatient instalation Undata hospital Central Sulawesi Province Period 2016-2018.

In vitro activity of methylene blue and eosin methylene blue agar on colistin-resistant A. baumannii: an experimental study.

Introduction. Colistin is a last-resort antibiotic used against carbapenem-resistant Acinetobacter baumannii (AB); however, colistin resistance has been reported recently. Methylene blue (MB) is used in microbiology for staining, and in medicine as an antidote drug.Aim. We aimed to investigate the antimicrobial effects of MB and eosin methylene blue (EMB) agar against colistin-resistant AB strains.Methodology. Firstly, a standard strain and AB clinical isolate were included in the study. After determining MICs, two strains were transformed into colistin-resistant forms, using Li's method. At each step, new MICs were determined and subcultures were inoculated onto EMB and sheep blood agar (SBA). Colistin MICs of the subcultures were also determined using Mueller-Hinton agar (MHA) containing MB. Secondly, colistin-resistant clones from 31 multidrug-resistant AB clinical isolates were screened to investigate their susceptibilities to EMB agar.Results. In the first round, MICs of both strains had risen to 64 μg ml-1. Subpopulations with high colistin resistance were inhibited by MB and EMB agar, but could grow well on SBA. In MHA plates containing MB, the MICs decreased to 0.5 μg ml-1 for colistin-susceptible or moderately resistant clones. Additionally, clones with high colistin resistance showed atypical colony morphology on SBA. In the second round, 35 % of the clinical isolates, which had gained resistance to colistin, were inhibited by EMB agar.Conclusion. MB may have inhibitory effects against colistin-resistant AB. Secondly, using only EMB agar for subculturing may cause missing of colistin-resistant strains.

Favorable Outcome of Severe Poisoning by Snake Green Mamba (<i>Dendroaspis viridis</i>) Clinical Case

This clinical case of acute poisoning due to bite of snake Dendroaspis viridis seems interesting to share because of its rare incidence inRussiaand management peculiarities: the critical care was conducted without specific antidote therapy due to absence of the antidote.The prevailing clinical presentation included signs of toxic myopathy combined with paresis of skeletal and breathing muscles that led to development of acute respiratory failure and metabolic disorders. The processes described were induced by the action of snake poison dendrotoxins featuring the activities of potassium channel blockers and acetyl cholinesterase inhibitors.The proper critical care included conduct of syndrome therapy aimed at maintaining life support systems adequately to condition (replacement of the breathing and circulation functions), antibiotic therapy and desensitizing treatment and metabolic care by administration of drugs characterized by antihypoxant/antioxidant mechanism of action.The comprehensive therapy applied has resulted in a favorable outcome of acute poisoning by snake green mamba without development of possible complications even when the specific antidote drug has not been included into the treatment protocol.

A computational and spectroscopic interpretation (FT-IR, FT-Raman, UV–vis and NMR) with molecular docking studies on 3-carboxy-2-hydroxy-N, N, N-trimethyl-1-propanaminium hydroxide: A pharmaceutical drug

Abstract An Antidote drug 3-carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium hydroxide (C7H16NO3) has been used in this work to investigate the vibrational frequencies using FT-IR, FT-Raman UV–vis and NMR spectra experimentally and quantum chemical calculations of the scaled frequencies using DFT B3LYP/6-311++G(d,p)basis set compared theoretically. In order to assign vibrational wavenumbers Potential Energy Distribution (PED) has been carried out. The Natural bond orbital (NBO) analysis of this molecule has been carried out to describe the various intra molecular interactions responsible for the stabilization of the molecule. Local reactivity properties of the title molecule have been executed through molecular electrostatic potential (MEP).The HOMO and LUMO energy gap were performed using TD-DFT theory and the differences are compared with UV-absorption spectra. The statistical thermodynamical functions (Entropy, Enthalpy and Heat capacity) have been calculated for the range of 100–1000 K. The Fukui functions are evaluated to describe the activity of the sites and Molecular docking study has been executed to investigate the potential of the title molecule to bind with 1S5O receptor, an antidote protein.

Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach

Paraquat poisoning is a medical problem in many parts of Asia and the Pacific. The mortality rate is extremely high as there is no effective treatment. We analyzed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the efficacy of immunosuppressive therapy in hospitalized paraquat-intoxicated patients. The aim of this analysis was to characterize the toxicokinetics and toxicodynamics of paraquat in this population. A non-linear mixed effects approach was used to perform a toxicokinetic/toxicodynamic population analysis in a cohort of 78 patients. The paraquat plasma concentrations were best fitted by a two compartment toxicokinetic structural model with first order absorption and first order elimination. Changes in renal function were used for the assessment of paraquat toxicodynamics. The estimates of toxicokinetic parameters for the apparent clearance, the apparent volume of distribution and elimination half-life were 1.17 l h(-1) , 2.4 l kg(-1) and 87 h, respectively. Renal function, namely creatinine clearance, was the most significant covariate to explain between patient variability in paraquat clearance.This model suggested that a reduction in paraquat clearance occurred within 24 to 48 h after poison ingestion, and afterwards the clearance was constant over time. The model estimated that a paraquat concentration of 429 μg l(-1) caused 50% of maximum renal toxicity. The immunosuppressive therapy tested during this study was associated with only 8% improvement of renal function. The developed models may be useful as prognostic tools to predict patient outcome based on patient characteristics on admission and to assess drug effectiveness during antidote drug development.

Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

Crystal and Molecular Structure of Bis(1-Vinylimidazole)diacetatozinc

The crystal and molecular structure of bis(1-vinylimidazole)diacetatozinc (C14H18N4O4Zn), a highly effective antidote and antihypoxic drug, was determined [R1 0.0335 for 8902 unique reflections with I > 2σ(I) and wR2 0.0931 for all 10 752 unique reflections]. The triclinic unit cell contains two independent molecules of the complex, A and B. These molecules have short contacts O⋯H-C. The zinc atoms in molecules A and B have distorted tetrahedral coordination with the coordination sites occupied by the imidazole nitrogen atoms and acetate oxygen atoms. The lengths of the Zn-N bonds (2.019–2.050 A) and Zn-O bonds with three acetate groups (1.956–1.958 A) are typical for zinc complexes, whereas the Zn-O3 bond with one of the acetate groups in molecule A is somewhat longer, 2.009(1) A; also, there is an additional contact of the zinc atom with the carbonyl oxygen atom of this group (Zn-O4 2.498 A).

Where Is the Evidence for Treatments Used in Pesticide Poisoning? Is Clinical Toxicology Fiddling While the Developing World Burns?

Where Is the Evidence for Treatments Used in Pesticide Poisoning? Is Clinical Toxicology Fiddling While the Developing World Burns?

Stability study of a new antidote drug combination (Atropine–HI-6–Prodiazepam) for treatment of organophosphate poisoning

The main purpose of this study was to investigate the chemical stability of a new antidote combination for the treatment of organophosphate poisoning. The antidote combination was packed (enclosed) in two plastic compartments separated by a barrier film. One of them contained a powder oxime cholinesterase reactivator (HI-6-monohydrate 1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyimino)methyl]-pyridinium dichloride). The other contained an anticholinergic (Atropine) and an anticonvulsant (Prodiazepam or Avizafone ( l-lysyl-N-(2-benzoyl-4-chlorophenyl)-N-methyl-glycinamide dihydrochloride) drug in a liquid mixture. The plastic compartments were mounted in an autoinjector device to study the dissolution of HI-6 by ejection of the solution. Drug analysis was performed by high-performance liquid chromatography. The results obtained after 6 months show that this new antidote combination is stable. The amount of each antidote is unchanged during the study. Some known degradation products can be detected in small amounts. The autoinjector mechanism used, gives a complete dissolution of HI-6 powder in the liquid mixture throughout the study.