Use Of Antidotes Research Articles

Tunable cytotoxic aptamer–drug conjugates for the treatment of prostate cancer

Therapies that can eliminate both local and metastatic prostate tumor lesions while sparing normal organ tissue are desperately needed. With the goal of developing an improved drug-targeting strategy, we turned to a new class of targeted anticancer therapeutics: aptamers conjugated to highly toxic chemotherapeutics. Cell selection for aptamers with prostate cancer specificity yielded the E3 aptamer, which internalizes into prostate cancer cells without targeting normal prostate cells. Chemical conjugation of E3 to the drugs monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) yields a potent cytotoxic agent that efficiently kills prostate cancer cells in vitro but does not affect normal prostate epithelial cells. Importantly, the E3 aptamer targets tumors in vivo and treatment with the MMAF-E3 conjugate significantly inhibits prostate cancer growth in mice, demonstrating the in vivo utility of aptamer-drug conjugates. Additionally, we report the use of antidotes to block E3 aptamer-drug conjugate cytotoxicity, providing a safety switch in the unexpected event of normal cell killing in vivo.

A pilot study on the management and outcomes of self-poisoning in a rural Ugandan Emergency Centre.

IntroductionThe Global Emergency Care Collaborative and Nyakibale Hospital in Rukungiri opened the first functional emergency centre in rural Uganda. We investigated decontamination, management and outcomes of poisoned patients in the emergency centre.MethodsAn electronic database started recording charts from 24 March 2012. A search for diagnoses concerning self-poisoning was performed from 24 March 2012 to 30 December 2013 and 192 charts were found and de-identified. Data collection included: age, sex, poison and duration, intent, vital signs, physical examination, decontamination, antidote use and follow-up status.ResultsFrom 24 March 2012 to 30 December 2013 poisoning accounted for 96 patient encounters. Of these, 33 were associated with alpha-2 agonists and 16 were associated with organophosphorous or carbamate pesticides. The post-decontamination fatality rate was 5.7%. The fatality rate of those without decontamination was 8.3%. Of those who were given atropine, 38.8% had no known indication. Of the 96 patient encounters, there were seven deaths; six were due to pesticides.DiscussionIn resource-limited settings where antidotes and resuscitative capabilities are scarce, decontamination needs to be studied further. Repeat atropine use without indication may lead to depletion of an essential antidote. Future directions include a public health education programme and an algorithm to help guide clinical decisions.

A system-wide solution to antidote stocking in emergency departments: the Nova Scotia antidote program.

Inadequate stocking of essential antidotes in hospitals is an internationally documented problem. A concrete and sustainable system-wide solution for easy access to antidotes in emergency departments (EDs) was developed and implemented in Nova Scotia, Canada. Antidote stocking guidelines and a systemwide antidote management strategy were established. A standardized collection of antidotes housed in highly visible containers in provincial EDs was implemented for timely access. Antidote-specific online administration guidelines were developed. Using the poison centre for surveillance, the antidote program maintained a database of antidote utilization patterns; 11 years of data were available for analysis. 2/2 (100%) tertiary care, 9/9 (100%) regional EDs, and 21/25 (84%) community EDs in Nova Scotia stock antidote kits, for an overall compliance rate of 32/36 (89%). A total of 678 antidotes (excluding N-acetylcysteine) were used for 520 patients. The distribution of antidote use by hospital type was 99/678 (14.6%) at community hospitals, 379/678 (55.9%) at regional hospitals, and 200/678 (29.5%) at tertiary care hospitals. The five most commonly used antidotes were: naloxone 143/678 (21.1%), fomepizole 111/678 (16.4%), glucagon 94/678 (13.9%), calcium 70/678 (10.3%), and sodium bicarbonate 67/678 (9.9%). Of the 520 patients in whom antidotes were used, death occurred in 3% (15/520), major outcomes in 35% (183/520), and moderate outcomes in 39% (205/520). The Nova Scotia Antidote Program demonstrates that a solution to inadequate antidote stocking is achievable and requires a system-wide approach with ongoing maintenance and surveillance. The frequency and distribution of antidote usage documented in this program supports the need for enhancement of emergency preparedness. The poison centre and hospital pharmacies are crucial to surveillance and maintenance of this program.

Cyanide poisoning in Thailand before and after establishment of the National Antidote Project

Context: Antidote shortage is a global problem. In Thailand, the National Antidote Project (NAP) has operated since November 2010 to manage the national antidote stockpile, educate the healthcare providers on appropriate antidote use, and evaluate antidote usage.Objective: To evaluate the effect of NAP implementation on mortality rate and antidote use in cyanide poisoning cases arising from ingestion of cyanide or cyanogenic glycoside.Methods: This is a retrospective cohort of poisoning cases involving cyanide or cyanogenic glycoside ingestion reported to Ramathibodi Poison Center from 1 January 2007 to 31 December 2015. Mortality rate, antidote use, and appropriateness of antidote use (defined as correct indication, proper dosing regimen, and administration within 90 min) before and after NAP implementation were compared. Association between parameters and fatal outcomes was analyzed.Results: A total of 343 cases involving cyanide or cyanogenic glycoside ingestion were reported to Ramathibodi Poison Center. There were 213 cases (62.1%) during NAP (Project group) and 130 cases (37.9%) pre-NAP implementation (Before group). Implementation of NAP led to increased antidote use (39.9% in Project group versus 24.6% in Before group) and a higher rate of appropriate antidote use (74.1% in Project group versus 50.0% in Before group). All 30 deaths were presented with initial severe symptoms. Cyanide chemical source and self-harm intent were associated with death (OR: 12.919, 95% CI: 4.863–39.761 and OR: 10.747, 95% CI: 3.884–28.514, respectively). No difference in overall mortality rate (13 [10.0%] deaths before versus 17 [8.0%] deaths after NAP) was found. In subgroup analysis of 80 cases with initial severe symptoms, NAP and appropriate antidote use reduced mortality (OR: 0.327, 95% CI: 0.106–0.997 and OR: 0.024, 95% CI: 0.004–0.122, respectively). In the multivariate analysis of the cases with initial severe symptoms, presence of the NAP and appropriate antidote use independently reduced the risk of death (OR: 0.122, 95% CI: 0.023–0.633 and OR: 0.034, 95% CI: 0.007–0.167, respectively), adjusted for intent of exposure, cyanide source, age, and sex.Conclusions: After NAP implementation, both antidote use and appropriate antidote use increased. In cases presenting with severe symptoms, presence of the NAP and appropriate antidote use independently reduced the risk of mortality.

A Complicated Opioid Overdose: A Simulation for Emergency Medicine Residents.

Opioid abuse is a growing problem in the United States. As a result, emergency medicine physicians often use naloxone to reverse opioid overdoses. While normally a safe drug, one potential complication of the antidote's use is flash pulmonary edema. This simulation was created after a patient followed the clinical course described after an opioid overdose. This simulation utilized a high-fidelity simulator to expose resident emergency medicine physicians to flash pulmonary edema secondary to naloxone administration. The simulation involved a 31-year-old male patient presenting with agonal respirations following an opioid overdose. The residents managed the patient appropriately with naloxone. However, he developed progressive dyspnea. The residents soon discovered that the patient was in flash pulmonary edema. They managed his airway, provided mechanical ventilation, and considered extracorporeal membrane oxygenation. When this simulation was run for emergency medicine residents at SUNY Upstate Medical University, the learners felt that it was highly useful, and that it expanded their knowledge in this field. Out of 17 learners, the average rating to the question of: "[This simulation] added to my understanding of key concepts and helped the session meet the objectives" was 4.6 on a 1-5 Likert scale. This simulation is a practical method by which many institutions can help to further physician knowledge on opioid overdose complications. It is relatively straightforward to run, and the educational yield is high.

Saline irrigation for the management of skin extravasation injury in neonates.

Extravasation injury, a complication commonly seen in the neonatal intensive care unit, can result in scarring with cosmetic and functional sequelae. A wide variety of treatments are available, including subcutaneous irrigation with saline (with or without hyaluronidase), liposuction, use of specific antidotes, topical applications, and normal wound care with dry or wet dressings. All such treatments aim to prevent or reduce the severity of complications. Primary objective To compare the efficacy and safety of saline irrigation or saline irrigation with prior hyaluronidase infiltration versus no intervention or normal wound care for tissue healing in neonates with extravasation injury. Secondary objectives To evaluate by subgroup analysis of controlled trials the influence of type of extravasate, timing of irrigation following extravasation, and postmenstrual age (PMA) of the neonate at the time of injury on outcomes and adverse effects.Specifically, we planned to perform subgroup analysis for the primary outcome, if appropriate, by examining:1. time to irrigation from identified extravasation injury (< 1 hour or ≥ 1 hour);2. type of extravasate (parenteral nutrition fluid or other fluids or medications);3. amount of saline used (< 500 mL or ≥ 500 mL); and4. PMA at injury (< 37 completed weeks or ≥ 37 completed weeks). We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 2 February 2017), Embase (1980 to 2 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 2 February 2017). We also searched clinical trial databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We used the Google Scholar search tool for reverse citations of relevant articles. Randomised controlled trials (RCTs) and quasi-randomised controlled trials comparing saline irrigation with or without hyaluronidase infiltration versus no intervention or normal wound care for the management of extravasation injury in neonates. Three review authors independently reviewed and identified articles for possible inclusion in this review. We used the GRADE approach to assess the quality of evidence. We found no eligible studies. Our search revealed 10 case reports or case series describing successful outcomes with different interventions for this condition. To date, no RCTs have examined the effects of saline irrigation with or without prior hyaluronidase infiltration for management of extravasation injury in neonates. Saline irrigation is frequently reported in the literature as an intervention for management of extravasation injury in neonates. Research should focus first on evaluating the efficacy and safety of this intervention through RCTs. It will also be important for investigators to determine effect size by examining the timing of the intervention, the nature of the infusate, and severity of injury at the time of intervention.

Antidotes: Familiar Friends and New Approaches for the Treatment of Select Pediatric Toxicological Exposures

Drug overdoses and therapeutic misadventures, whether intentional or inadvertent, are a common cause of presentation to pediatric emergency departments. Timely administration of antidotes is often an important component of treatment for these patients, and in many cases, this can be life-saving. Because randomized control trials are very difficult to perform in the realm of medical toxicology, there is often a paucity of information regarding efficacy and best use of antidotes, and it is important to continually examine the literature for new data and evidence. We review the current evidence and indications for some newer antidotes and therapies for selected common pediatric poisonings, as well as recent data regarding use of a well-known and commonly used antidote.

Suicide attempt with acetonitrile ingestion in a nursing mother

Context: Acetonitrile (ACN) is a solvent rapidly absorbed through lungs and intestinal tract, and is slowly metabolized to cyanide (CN) by enzymatic processes mediated by CYP2E1.Objective: To describe the clinical and laboratory evolution, ACN elimination half-life, and its presence in breast milk in a nursing mother who attempted suicide.Case details: A 25-year-old 2-month nursing mother ingested an estimated dose of 2.1 g/kg of ACN. Blood and urine samples were collected 24 h later for ACN, CN and thiocyanate analysis, and 12.5 g sodium thiosulfate i.v. in 1-h infusion was started and repeated every 24 h for 4 days. ACN results showed 200 mg/L in blood and 235 mg/L in urine. ACN analysis in the breast milk at Day 6 showed level of 21 mg/L compared to 27 mg/L in blood collected at the same time, suggesting a possible relationship of 1.3:1.0 ratio. An elimination half-life of 40.4 h was calculated, compared to 32 and 36 h showed in other studies.Discussion: The clinical management must involve the use of CN antidotes for more than 24 h depending on the symptoms and blood levels of ACN. Furthermore, our data showed the possible existence of a close relationship between plasma and breast milk levels.

Rising cost of antidotes in the U.S.: cost comparison from 2010 to 2015

Context: Our poison control center observed a large increase in the cost of many antidotes over the past several years. The high cost of antidotes has previously been cited as a factor leading to inadequate antidote supply at some hospitals. Continued increases in the cost of antidotes may lead to further reductions in antidote supply and represent serious concerns. This research aims to quantify recent trends in the costs of antidotes in the U.S.Methods: Antidotes and minimum stocking recommendations were retrieved from published guidelines. RED BOOK Online® was used to identify the U.S. average wholesale price (AWP) of each antidote in 2010 and 2015. The AWP in 2010 was adjusted using the U.S. Consumer Price Index to adjust for inflation. The cost of minimum stocking levels for each antidote was calculated and compared between the year 2010 and 2015.Results: The cost of stocking many antidotes demonstrated a large increase in AWP from 2010 to 2015. Of the antidotes evaluated, 15 out of 33 had greater than 50% increase in AWP and 8 out of 33 had greater than $1000 increase in AWP. Only four antidotes demonstrated decreases in AWP greater than 10% and only one antidote had its cost of stocking decrease in AWP by more than $1000.Discussion: The price increase over the last 5 years may further hinder the willingness of hospitals to stock recommended antidotes at adequate quantities. This may impede timely treatment of patients, and negatively impact poisoning outcomes.Conclusions: The price of many antidotes substantially increased in the United States from 2010 to 2015. Strategies should be investigated to help decrease the cost associated with stocking and use of antidotes, including dose rounding, consignment, and regional sharing.

Methanol Poisoning with Fatality- Case Series in Dhaka Medical College Hospital in Bangladesh

Background: Adulterated methanol is highly toxic and leads to severe metabolic acidosis and blindness and mortality is very high if not treated with specific antidote. The time of ingestion and severity of illness is very short and comprehensive quick assessment and care is crucial for survival of patient. The selective antidote Fomepizole is not available in Bangladesh and pure intravenous ethanol is also out of reach in health care facility. The oral ethanol has its legislative regulation. Occasional clusters of severe methanol poisoning leading to fatality has been observed in recent years in Bangladesh. Here is a case series of 8 cases of adulterated methanol poisoning in a tertiary care hospital with lethality. Results and discussion: From November 2012 to January, 2013, in sphere of 3 months medicine units of Dhaka Medical College Hospital (DMCH) experienced 8 cases of methanol poisoning with fatality. Six patient presented in unconscious states within 3 to 7 h of consuming methanol while two patient presented within 48 h. All of them had gastrointestinal toxicity with variable episodes of vomiting. Three patients presented with visual impairment while only two out of eight had normal ophthalmoscopy. Respiratory distress was uniformly found in all patients before unstable profound shock. Blood ethanol level was not performed in any patient due to lack of available facility. Seven patients received only supportive measures ranging from steroids to sodium bi carbonate while one patient presented in severe toxicity and died quickly before any supportive measures. Antidote was not prescribed in any patient in the form of fomepizole or intravenous or oral ethanol. Conclusion: The judicious use of antidote even in the form of oral ethanol and folinic acid can save the precious life. A national guideline should be uniformly practiced by the physicians to combat the catastrophic methanol poisoning in Bangladesh.

To further understand and make good use of the antidote is an issue for concern

To further understand and make good use of the antidote is an issue for concern

Reversal of Anticoagulation and Management of Bleeding in Patients on Anticoagulants.

Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4.5 to 10 in patients with other risk factors for bleeding. Fresh frozen plasma or prothrombin complex concentrate (PCC) may be necessary in major bleeding related to warfarin. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors. The PCC may reverse the effect of rivaroxaban to some extent, but no data are available regarding reversal of apixaban and edoxaban. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.

Wait a minute: Not all cases of paracetamol overdose need N-acetylcysteine, quality improvement project in Hamad General Hospital Emergency Department

Background: Management of serious paracetamol overdose with N-acetylcysteine (NAC) is an effective strategy. Early treatment with NAC prevents the formation of a toxic metabolite that leads to hepatic injury. However, inappropriate treatment with NAC and overtreatment with NAC can lead to potential adverse side effects and unnecessary hospital admission. The aim of the study was to assess the administration of NAC in the setting of paracetamol overdose and determine whether the institutional use of this antidote is consistent with the international standards. We hypothesize that some patients receive antidotal NAC unnecessarily after paracetamol exposure, and that a simple quality improvement intervention in educational activity may improve the administration of this antidote. Methods: A retrospective quality improvement chart review evaluated charts of patients who were treated with NAC for paracetamol exposure over a 2-month period in the Emergency Department of Hamad General Hospital. The quality improvement intervention consisted of establishing a paracetamol clinical practice guideline, providing access to a treatment nomogram for NAC use, enhancing educational activities to improve the clinician's understanding of appropriate NAC use, and establishing a clinical toxicology service for all paracetamol exposures. Results: NAC administration to 67% of the cases after paracetamol exposure were found to be medically unnecessary according to the established international guidelines for management of paracetamol overdose. Post-intervention measurement showed significant improvement by decreasing unnecessary NAC administration to only 33%. Conclusion: In our institution, NAC treatment after paracetamol exposure is usually administered unnecessarily. Inappropriate administration of this antidote results in a significant waste of resources and unnecessarily prolonged hospital stay. Adherence to the clinical practice guidelines may lead to a significant improvement in this antidote use after paracetamol exposure. Given that this antidote is used inappropriately despite widespread knowledge that guidelines for paracetamol exposure exist, we believe that continuous education on the topic, chart audits and feedback, and use of a clinical toxicology service may improve the knowledge and appropriate use of this antidote and will improve patient care.

TOLERANCE OF COMMON BEAN PLANTS TO ETHOXYSULFURON HERBICIDE AND THE MECHANISM INVOLVED IN THE PROCESS

ABSTRACT The objectives of this study were to determine the effect of herbicide ethoxysulfuron on the development of commom bean (Phaseolus vulgaris), to evaluate the impact of the herbicide on the crop grain yield and to determine the mechanism of tolerance of common bean to ethoxysulfuron. Field experiments were carried out with several doses of ethoxysulfuron to determine its effect on the grain yield of two varieties of common bean ("IPR Andorinha", "IPR Tangará"). The mechanism of plant tolerance was evaluated through several methods, including the analysis of the ALS enzyme sensitivity to herbicide and the use of P450 inhibitors (the insecticides malathion + chlorpyrifos) and the use of antidote (mefenpyr-diethyl). When the rate of ethoxysulfuron was 83.2 g ha-1, the grain yield loss reached 25% (IPR Tangará) and 35% (IPR Andorinha). The ALS enzyme activity was severely reduced even at low concentrations ethoxysulfuron (1 μM), indicating that the mechanism of tolerance is not the insensitivity of the herbicide target enzyme. The inhibitors of herbicide detoxification increased the sensitivity of the bean plants to ethoxysulfuron, and the antidote (stimulator of herbicide degradation) mitigated the herbicidal effect. These results strongly support the hypothesis that the mechanism of tolerance of common bean plants to ethoxysulfuron is enhanced herbicide detoxification.

Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6

Organophosphorus nerve agents interfere with cholinergic signaling by covalently binding to the active site of the enzyme acetylcholinesterase (AChE). This inhibition causes an accumulation of the neurotransmitter acetylcholine, potentially leading to overstimulation of the nervous system and death. Current treatments include the use of antidotes that promote the release of functional AChE by an unknown reactivation mechanism. We have used diffusion trap cryocrystallography and density functional theory (DFT) calculations to determine and analyze prereaction conformers of the nerve agent antidote HI-6 in complex with Mus musculus AChE covalently inhibited by the nerve agent sarin. These analyses reveal previously unknown conformations of the system and suggest that the cleavage of the covalent enzyme-sarin bond is preceded by a conformational change in the sarin adduct itself. Together with data from the reactivation kinetics, this alternate conformation suggests a key interaction between Glu202 and the O-isopropyl moiety of sarin. Moreover, solvent kinetic isotope effect experiments using deuterium oxide reveal that the reactivation mechanism features an isotope-sensitive step. These findings provide insights into the reactivation mechanism and provide a starting point for the development of improved antidotes. The work also illustrates how DFT calculations can guide the interpretation, analysis, and validation of crystallographic data for challenging reactive systems with complex conformational dynamics.

Who gets antidotes? choosing the chosen few.

An understanding of mechanisms, potential benefits and risks of antidotes is essential for clinicians who manage poisoned patients. Of the dozens of antidotes currently available, only a few are regularly used. These include activated charcoal, acetylcysteine, naloxone, sodium bicarbonate, atropine, flumazenil, therapeutic antibodies and various vitamins. Even then, most are used in a minority of poisonings. There is little randomized trial evidence to support the use of most antidotes. Consequently, decisions about when to use them are often based on a mechanistic understanding of the poisoning and the expected influence of the antidote on the patient's clinical course. For some antidotes, such as atropine and insulin, the doses employed can be orders of magnitude higher than standard dosing. Importantly, most poisoned patients who reach hospital can recover with supportive care alone. In low risk patients, the routine use of even low risk antidotes such as activated charcoal is unwarranted. In more serious poisonings, decisions regarding antidote use are generally guided by a risk/benefit assessment based on low quality evidence.

SPECIFIC ANTIDOTES TO NEW ORAL ANTICOAGULANTS

Safety profiles of the novel oral anticoagulants (NOAC) (rivaroxaban, apixaban, edoxaban, dabigatran) are better than that of warfarin. However, the risk (including lifethreatening) of bleeding is no less than 2.3–3.1% per year. Three specific antidotes to NOAC are currently in different phases of clinical trial and implementation. Idarucizumab is a monoclonal antibody which immediately and completely reverses the anticoagulation effect of dabigatran. Andexanet alfa is a recombinant, modified factor Xa molecule that binds and inhibits the effects of oral and parenteral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, fondaparinux, heparins). Andexanet is already in 3b Phase, and at the end of 2016 — beginning of 2017 it is expected to be approved for clinical use. Ciraparantag is a small molecule, non-covalently binding to factor Xa inhibitors, and dabigatran (i.e., a universal antidote). Recently, promising results of phase 1 trials involving aripazin were published. The article tells about the practical aspects of the use of antidotes, treatment approaches for life-threatening bleeding during treatment with NOAC.

Management of poisoning with ethylene glycol and methanol in the UK: a prospective study conducted by the National Poisons Information Service (NPIS)

Background: Poisoning with methanol and ethylene glycol can cause serious morbidity and mortality. Specific treatment involves the use of antidotes (fomepizole or ethanol) with or without extracorporeal elimination techniques. Methods: A prospective audit of patients with methanol or ethylene glycol poisoning reported by telephone to the National Poisons Information Service (NPIS) in the UK was conducted during the 2010 calendar year and repeated during the 2012 calendar year. The study was conducted to determine the frequency of clinically significant systemic toxicity and requirement for antidote use and to compare outcomes and rates of adverse reaction and other problems in use between ethanol and fomepizole. Results: The NPIS received 1315 enquiries involving methanol or ethylene glycol, relating to 1070 individual exposures over the 2-year period. Of the 548 enquiries originating from hospitals, 329 involved systemic exposures (enteral or parenteral as opposed to topical exposure), of which 216 (66%) received an antidote (204 for ethylene glycol and 12 for methanol), and 90 (27%) extracorporeal treatment (86 for ethylene glycol and 4 for methanol). Comparing ethanol with fomepizole, adverse reactions (16/131 vs. 2/125, p < 0.001) and administration errors, lack of monitoring, or inappropriate use (45/131 vs. 6/125, p < 0.0001) were reported more commonly, whereas non-availability and inadequate stocks were reported less commonly (6/125 vs. 33/131, p < 0.0001). Eight fatalities and complications or sequelae occurred in 21 patients. Poor outcome (death, complications, or sequelae) was significantly associated with older age, higher poisoning severity scores, and lower pH on admission (p < 0.001). Conclusions: Systemic poisoning with ethylene glycol or methanol results in hospitalisation at least 2–3 times per week on average in the UK. No difference in outcome was detected between ethanol and fomepizole-treated patients, but ethanol was associated with more frequent adverse reactions.

Intoxicaciones agudas por alcohol, otras drogas y fármacos psicoactivos

Initial management begins with the conventional system ABC (airway, breathing and circulation) and neurological assessment and management of complications (seizures, arrhythmias and electrolyte disorders). Subsequently, more specific to reduce the absorption, promote disposal and use of antidotes (if any) measures. The clinical manifestations of acute ethanol intoxication, relate directly with blood alcohol levels. Clinical management is based on general measures, thiamine must be used as prophylaxis for Wernicke encephalopathy. Several studies have shown that Metadoxine may be useful in treating acute alcohol intoxication. The clinical manifestations related to drug abuse are a common target, the condition of the central nervous system and hemodynamic instability. The handling is very similar, despite the variety of illicit substances: hydration, use of naloxone / flumazenil, checking vital signs. Psychotropic drugs are a very heterogeneous group, have a wide margin of safety (with exceptions). The use of activated charcoal should be performed at multiple doses, due to the long half life of this group, being ineffective measures to accelerate the elimination of the drug. Lithium is the drug within the group, sequels and organ damage can cause poisoning last once. The handling is related in case of serious poisoning, existing as only specific antidote flumazenil for benzodiazepine poisoning.

Reversal Strategies for NOACs: State of Development, Possible Clinical Applications and Future Perspectives.

The non-vitamin K antagonist oral anticoagulants (NOACs) are used for thromboembolic prophylaxis of patients with atrial fibrillation and in the treatment as well as secondary prophylaxis of patients with venous thromboembolism. Even though NOACs have a better safety profile than vitamin K antagonists (VKAs), there will still be bleeding complications on NOAC treatment. In some cases, stopping the NOAC and non-drug-related management such as manual compression and interventional endoscopy will be sufficient to stop the bleeding. In more serious bleeding events and before acute surgery, coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants including NOACs is currently undergoing phase II trials. For use of these specific antidotes, it is desirable that measurements for coagulation activity with a short response delay are widely available for the different NOACs and further research in this field is needed. Furthermore, guidelines for antidote use, including general measures for the treatment of NOAC-related bleeding, should be available.