[Therapy for poisonings--antidotes. 1. The ABC of poisoning treatment, antidotes (indications, dosage)].
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Antidotes↗
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[Therapy of poisoning--antidotes 6: The antidote dexamethasone spray, polyethyleneglycol 400].
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Aerosols↗
[Therapy in poisonings--antidote 7: The antidotes physostigmine salicylate, toluidin blue].
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Antidotes↗
[Availability of antidotes in hospital pharmacies in the Czech Republic].
Availability of antidotes in the Czech Republic (CR) is insufficient. Many antidotes are not approved in CR, so their obtaining is problematic. The purpose of this study is to examine the real availability of antidotes in Czech hospital pharmacies and to assess the influence of hospital size, hospital localisation, antidote cost, and the fact of antidote approval in CR on antidote availability. Finally, some proposals for the solution of the situation are mentioned. A structured questionnaire was constructed and mailed to 85 hospital pharmacies. A total of 46 hospital pharmacies sent back completely answered questionnaires and they were statistically assessed. The questionnaire included a summary of poisonings and usable antidotes. The recommended quantity of each antidote was included. Availability of antidotes (D) and sufficient availability of antidotes (DD) were calculated for each answering hospital pharmacy as a ratio of poisonings for which the antidote was available or available in a sufficient quantity, to all poisonings mentioned in the questionnaire. The other calculated parameter was the availability of an individual antidote (d) and the sufficient availability of an individual antidote (dd)--they were calculated as a ratio of pharmacies stocking the antidote, or stocking the antidote in a sufficient quantity, to evaluated pharmacies. Availability of 23 different antidotes for 20 poisonings was assessed. Antidotes for roughly one half of assessed poisonings are available (D 55.69 +/- 12.42%) and for about one third of poisonings the antidotes are available in a sufficient quantity (DD--37.23 +/- 14.10%). The D and DD have been dependent on hospital size (measured as the number of beds). D and DD have not been dependent on the localisation of the hospital (measured as a period of transport time to the hospital of higher type of care), d and dd ranged between 0-100% and were dependent on the antidote cost. There were significant differences between d and dd of antidotes approved (R) and unapproved (NR) in CR (d(R)--70.51 +/- 33.26%, d(NR)--10.19 +/- 9.26%, p < 0.001; dd(R)--47.55 +/- 29.94%, dd(NR)--6.93 +/- 7.76%, p < 0.001). The results of the study confirm a very unsatisfactory situation in antidote availability in Czech hospital pharmacies. Hospital stocks of many antidotes are inadequate. Often, the antidotes are available, but their quantity is insufficient. The worst situation is in small hospitals, in the very costly antidotes, and in the antidotes not registered in CR.
Antidotes↗
Inadequate stocking of antidotes in Taiwan: is it a serious problem?
OBJECTIVE: Insufficient hospital stock of a variety of poisoning antidotes is a worldwide problem. In an attempt to establish an antidote storage and distribution system for the response of the various poisoning accidents, we conducted a nationwide survey to characterize the current availability of selected antidotes and their anticipated need in Taiwan. MATERIALS AND METHODS: A questionnaire was mailed to 834 hospitals to gather information on the availability, anticipated need, and preferred purchase policy of 20 selected antidotes. A survey on the availability of cyanide antidote in 523 cyanide-handling facilities and their neighboring hospitals was also conducted. RESULTS: Hospitals of different size and service levels had a statistically significant difference in response rates. Except for pyridoxine, the availability and anticipated need for antidotes also varied significantly among different hospital groups. We found that physostigmine, cyanide antidote kit, BAL, EDTA, methylene blue, Vipera Russell formosensis antivenin, and botulism antitoxin were not available in most (>90%) hospitals. Interestingly, these antidotes are also among the most needed antidotes. Most hospitals preferred a government-ordered purchase of antidotes. In the survey of cyanide-processing facilities, a response rate of 24.1% was obtained and only 9.3% of these 107 facilities that both replied to the questionnaire and continued handling cyanide products had stocked cyanide antidote. It is noteworthy that cyanide antidote was also frequently lacking in the neighboring hospitals. CONCLUSIONS: The appropriate storage of antidotes in hospitals or workplaces in rural areas is instrumental in the timely treatment of certain poisonings, while nationwide unavailability is the critical problem. Raising awareness of the importance of antidotes by education, regular review of antidote storage, distribution plans, and appropriate legislation might provide solutions.
Antidotes↗
The relative efficacy of antidotes: the IPCS evaluation series. International Programme on Chemical Safety.
Antidotes may play an important role in the treatment of poisoning. For many physicians and toxicologists an antidote is an antidote. According to the IPCS definition, an antidote is a therapeutic substance used to counteract the toxic action(s) of a specified xenobiotic. Given this wide definition, the efficacy of an antidote may vary considerably depending on which toxic action(s) is/are being counteracted and on the level of counteracting power: An almost 100% efficacy is seen using specific antagonists, such as naloxone in opiate poisoning or flumazenil in benzodiazepine poisoning, e.g. resulting in complete reversal of opiate toxicity unless complications, such as anoxic brain damage, have developed. At the other end of the efficacy scale, we may place chelating agents for heavy metal poisoning and diazepam for organophosphorus insecticide poisoning. Therefore, in the IPCS/EC evaluation series of antidotes, some chelating agents are considered only to be an adjunct to supportive care which is the cornerstone of treatment. When teaching clinical toxicology or recommending the use of antidotes in poisoned patients, the expected efficacy level of the antidote in question should be stressed. This may be particularly important in severe poisonings when the antidote may only be considered as an adjunct to supportive care, e.g. deferoxamine in acute iron poisoning. Unless this is stressed, the unexperienced physician may rely too much on the antidote and may not pay sufficient attention to the supportive care. In this presentation, the varying efficacy levels of antidotes are discussed as based on the presently ongoing IPCS/EC evaluation programme on antidotes.
Antidotes↗
Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States.
STUDY OBJECTIVE: To develop guidelines for the stocking of antidotes at hospitals that accept emergency admissions using combined evidence-based and consensus methods. METHODS: Study participants were 12 medical care providers from disciplines that are affected by insufficient stocking of emergency antidotes (clinical pharmacology, critical care, clinical pharmacy, emergency medicine, hospital pharmacy, internal medicine, managed care pharmacy, clinical toxicology, pediatrics, poison control centers, pulmonary medicine, regulatory medicine). Selection of individuals for the study panel was based on evidence of previous antidote research or perspective regarding the purchase and use of antidotes. The literature regarding each antidote was systematically amassed using pre-1966 literature files, current MEDLINE searches, the reference lists of major medical textbooks, and citations solicited from the consensus panel. Articles relevant to 4 defined core questions were included. These articles formed the basis of an evidence-based analysis performed by the principal investigator. After literature analysis, a literature summary and proposed guidelines for antidote stocking were submitted to the panel. Consensus was formed by electronic iterative presentation of alternatives to each panel member using a modified Delphi method. All panel members participated in 5 rounds of guideline analysis of 20 antidotes. RESULTS: Of the 20 antidotes, 16 antidotes were ultimately recommended for stocking (N -acetylcysteine, atropine, Crotalid snake antivenin, calcium gluconate and chloride, cyanide antidote kit, deferoxamine, digoxin immune Fab, dimercaprol, ethanol, fomepizole, glucagon, methylene blue, naloxone, pralidoxime, physostigmine, sodium bicarbonate), 2 were not recommended for stocking (black widow antivenin, ethylenediamine tetraacetic acid), and consensus could not be reached for 2 antidotes (flumazenil, physostigmine). CONCLUSION: These guidelines provide a tool to be used in revising or creating policies and procedures with regard to the stocking of antidotes in hospitals that accept emergency patients.
Antidotes↗
[Availability of antidotes in French emergency medical aid units].
OBJECTIVE: To study the availability of antidotes in French emergency medical aid units (SAMU). METHODS: The physicians or nurses responsible for antidotes in French emergency medical aid units (SAMU) were interviewed by phone. The study involved 102 SAMU in metropolitan France. Four answers on availability of 37 antidotes were possible: the antidote was available in the emergency vehicle used for interventions; the antidote was available in the hospital-located SAMU; the antidote was available in the referral hospital (emergency unit, intensive care unit, operating room, pharmacy); the antidote was not available or not known to be available. RESULTS: Adrenaline and atropine were available in all the intervention vehicles. Nine other antidotes were available in more than two-thirds of the vehicles: 30% glucose (101/102), isoprenaline (100/102), dobutamine (98/112), sodium bicarbonate (97/102), naloxone (95/102), calcium chloride or bicarbonate (89/102), flumazénil (83/102), sodium lactate (77/102), and magnesium sulfate (66/102). Among the other antidotes, hydroxocobalamine and propranolol were available in 24/102 intervention vehicles and activated charcoal in 22/102. Antidigitalic antibodies and 4-methylpyrazole were not available in any vehicle, and were available in less than 25% of the hospitals. CONCLUSION: There is a great disparity of antidote availability. Certain essential antidotes, for which there is no alternative, are not available in emergency intervention vehicles and even in the hospital. The SAMU should develop an economically acceptable departmental management scheme for exceptional-use antidotes.
Ambulances↗
Availability of antidotes at acute care hospitals in Ontario.
BACKGROUND: Acutely poisoned patients sometimes require immediate treatment with an antidote, and delays in treatment can be fatal. We sought to determine the availability of 10 antidotes at acute care hospitals in Ontario. METHODS: Mailed questionnaire with repeated reminders to pharmacy directors at all acute care hospitals in Ontario. RESULTS: Responses were obtained from 179 (97%) of 184 hospitals. Only 9% of the hospitals stocked an adequate supply of digoxin immune Fab antibody fragments, a life-saving antidote for patients with severe digoxin toxicity, whereas most of the hospitals stocked sufficient supplies of ipecac syrup (88%) and flumazenil (92%), arguably the least crucial antidotes in the survey. Only 1 hospital stocked adequate amounts of all 10 antidotes. Certain hospital characteristics were associated with adequate antidote stocking (increased annual emergency department volume, teaching hospital status and designation as a trauma centre). Conversely, antidote supplies were particularly deficient at small hospitals and, paradoxically, geographically isolated facilities (those most reliant on their own inventory). The cost of antidotes correlated only weakly with stocking rates, and many examples of excessive antidote stocking were identified. INTERPRETATION: Most acute care hospitals in Ontario do not stock even minimally adequate amounts of several emergency antidotes, possibly jeopardizing the survival of an acutely poisoned patient. Much of this problem could be rectified at no additional cost by reducing excessive stock of expensive antidotes and redistributing the resources to acquire deficient antidotes.
Antidotes↗
Evaluation of antidotes: activities of the International Programme on Chemical Safety.
Important developments concerning the role of antidotes in managing poisoning cases have taken place in recent decades due to new toxicodynamic and toxicokinetic studies and to growing international concern regarding the effectiveness of antidotes. A number of activities are carried out by the International Programme on Chemical Safety which aim to: (1) evaluate their effectiveness in clinical practice, (2) disseminate evaluated information, and (3) promote the availability of useful antidotes. The International Programme on Chemical Safety has undertaken the preparation of Antidote Monographs that summarize and assess the clinical use, mode of action, effectiveness, and other evaluated information, and a consolidated International Programme on Chemical Safety List of Antidotes that classifies antidotes and related drugs by their clinical effectiveness and urgency of need. A chart of Antidote Dosages, with information concerning the recommended antidotes and their indications, is being prepared, and the Availability of Antidotes in different countries is being surveyed. Further International Programme on Chemical Safety initiatives are also being undertaken in the area of antidotes and clinical toxicology in order to examine particular issues. The International Programme on Chemical Safety INTOX Project and related activities provide powerful tools for multicenter studies, but such research faces continuing financial and regulatory difficulties. Twinning arrangements between scientists from different parts of the world are being promoted to enhance the capabilities of evaluating treatment procedures and to compare clinical data. International organizations have important aims: to promote adequate and appropriate regulations and increase antidote availability, to establish international consensus and to increase interest in co-operative research. Cooperation with scientific bodies is essential in supporting these aims.
Animals↗
Antidote availability in Quebec hospital pharmacies: impact of N-acetylcysteine and naloxone consumption.
OBJECTIVES: To study the availability of 13 specific antidotes in hospitals and correlate the availability of those antidotes to the number of poisonings seen in hospitals using N-acetylcysteine and naloxone consumption as a surrogate. METHODS: Pharmacy directors of hospitals with an emergency department were surveyed for number of adequately stocked antidotes (N-acetylcysteine, ethanol, cyanide antidote kit or hydroxycobalamine, deferoxamine, digoxin-immune FAB, dimercaprol, flumazenil, glucagon, methylene blue, naloxone, physostigmine, pralidoxime and pyridoxine). RESULTS: Data were obtained from 96 of 112 (86%) of the pharmacies surveyed. Number of adequately stocked antidotes per hospital ranged from zero to nine of 13. There was a correlation between all hospital characteristics evaluated and the number of adequately stocked antidotes (P<0.05). Correlations between the number of adequately stocked antidotes and the amount of N-acetylcysteine and naloxone consumed were significant (rs=0.58, P<0.001; r(s)=0.53, P<0.001). The amount of N-acetylcysteine consumed, the number of annual visits to the emergency department and the number of hours of pharmacy coverage on weekends independently predicted the presence of adequately stocked antidotes. CONCLUSIONS: Larger hospitals are more likely to have adequate stocks of antidotes. Adequate stocking of antidotes is significantly correlated with the amount of N-acetyl- cysteine and naloxone consumed. This suggests that hospitals more likely to see serious acetaminophen and opiate poisonings are more likely to maintain adequate stocks of antidotes.
Acetylcysteine↗
Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women?
OBJECTIVE: We reviewed evidence suggesting teratogenic risk associated with the use of antidotes in the acute management of poisoned pregnant women. METHODS: Medline, Toxline, and DART/ETIC searches; references of retrieved articles, pertinent databases and textbooks were also searched. RESULTS: There are case reports or case series of women who received antidotes for poisoning during (*) or after (+) the period of organogenesis who showed no fetal adverse effects. Some antidotes, however, have no teratogenic risk: atropine (cohort/surveillance studies)+, calcium (oral supplement: cohort study)+ and pyridoxine (Bendectin studies). Also, ethanol+, methylene blue (intra-amniotic injection but not oral) and penicillamine* can be considered teratogens but their risks in the treatment of poisonings are unknown. There is no epidemiologic study evaluating the risk of the following antidotes during pregnancy: N-acetylcysteine(*+), BAL (dimercaprol)+, black widow spider antivenin+, calcium EDTA+, crotalidae antivenin, crotalidae polyvalent immune FAB, cyanide antidote kit (amyl and sodium nitrate, sodium thiosulfate), deferoxamine(*+), digoxin immune FAB+, DMSA+, flumazenil+, fomepizole, methylene blue (IV), naloxone, physostigmine, pralidoxime+, protamine+; and parenteral pharmacologic doses of calcium+, folinic acid*, glucagon+, hydroxycobalamin, phytonadione (vitamin K), and pyridoxine. CONCLUSIONS: Despite the limited evidence supporting the risk of antidote use during pregnancy, antidotes should be used when there is a clear maternal indication to decrease the morbidity or mortality associated with poisoning. The only exception may be penicillamine, which is a teratogen. Better antidotes exist for most poisonings that penicillamine could potentially treat. At this time, there is no known fetal indication for all antidotes. Reporting the use of an antidote during pregnancy should be encouraged, especially if used during the critical period of organogenesis.
Abnormalities, Drug-Induced↗
Off-label and unlicensed use of antidotes in paediatric patients.
OBJECTIVE: To determine the extent of unlicensed and off-label antidotes among medicines recommended by the International Programme on Chemical Safety (IPCS) for children. MATERIALS AND METHODS: We considered 77 antidotes from the "IPCS List of antidotes and other useful agents in the treatment of human poisoning" (1996 version). Primary reference sources used were the Physicians' Desk Reference (PDR) and package inserts. Antidotes were assessed for off-label (outside of the term of product license) and unlicensed use in children. RESULTS: Our data show that only 31 (40.3%) of 77 recommended antidotes correspond to the demands of licensing systems for use in children. The rest (46 or 59.7%) are either off-label (32 or 41.5%) or unlicensed (14 or 18.2%). Five antidotes are off-label for two reasons; thus the total number of off-label use (37) is greater than the number of such drugs (32). Inappropriate age is the main reason for use outside the stipulations of the product license (24 of 77 antidotes or 31.2%), whereas different indication and route occur in 11 (14.3%) and 2 (2.6%) antidotes, respectively. The 14 unlicensed antidotes have been used only in animal experiments or in a small number of patients in certain poison centres. CONCLUSIONS: Sixty percent of antidotes and other useful agents in the poison treatment of children do not correspond to the demands of licensing systems. Drugs used in the treatment of poisoned children, as well as adults, must be evaluated scientifically.
Adolescent↗
Clinical applications of commonly used contemporary antidotes. A US perspective.
Poisonings are a common problem. In 1995, over 2 million exposures were reported to American poison information centres alone. The majority of poisoning exposures can be treated without major therapeutic intervention. If therapy is indicated, it is usually in the form of gastrointestinal decontamination with activated charcoal, to prevent absorption of the toxin and the subsequent toxicity that may occur. In a limited number of cases, more aggressive life-support measures may be necessary to treat the adverse effects of poisons. Occasionally, that intervention may include the use of pharmacological antagonists, more commonly referred to as antidotes. According to the American Association of Poison Control Centers, the most commonly used antidotes are acetylcysteine, naloxone, atropine, deferoxamine (desferrioxamine) and antivenins. Overall, 17 antidotes account for 99% of all antidote use and those agents are reviewed in this article. With the exception of naloxone, most antidotes have pharmacological effects that are independent of their inherent antidotal properties. Therefore, antidotes should be used judiciously because their pharmacological properties may exacerbate pre-existing toxicity and only in rare circumstances are they used prophylactically. Some antidotes, such as digoxin-specific antigen binding fragments (digoxin immune Fab), are very expensive, and both the risk: benefit ratio and the associated cost should be considered before the antidote is administered. The principle aims are to "treat the patient, not the poison' and to do no harm to the patient. Antidotes should be used only when they are indicated and may help a patient.
Acetylcysteine↗
[Effect of diazepam on antidote therapy of lethal toxic effects of soman in rats].
Experiments on male rats examined the effect of a basic antidotal therapy consisting of various types of anticholinergic substances and reactivators of acetylcholinesterase on the lethal effects of the highly toxic organophosphorous compound soman by means of determination of the medium lethal dose of soman in 24-hour survival of experimental animals. The efficacy of the basic antidotal therapy of acute intoxications by soman evaluated in this way was compared with the effect of an antidotal therapy enriched with diazepam, a drug with anticonvulsive action. The obtained results show that addition of diazepam to the basic antidotal therapy increases the ability of the antidotal therapy to eliminate acute lethal effects of soman if it includes atropine as an anticholinergic agent regardless of the employed type of acetylcholinesterase reactivator. In the case of employment of anticholinergic agents with prevailing central effects, such as benactyzine, biperiden, or scopolamine, the addition of diazepam will not significantly influence the therapeutic efficacy of the antidotal therapy regardless of the selected aetylcholinesterase reactivator. At the same time, the addition of diazepam to the antidotal therapy does not change the difference in the efficacy of the antidotal therapy in dependence on the selected anticholinergic agent or acetylcholinesterase reactivator. At present the most common combination of antidotes against soman, consisting of obidoxime and atropine, as well as a prospective combination containing oxime HI-6 and atropine should be supplemented with diazepam not only to prevent centrally induced seizures and tonic-clonic convulsions but also to increase the ability of such antidotal therapy to eliminate acute lethal toxicity of soman.
Animals↗
Insufficient stocking of poisoning antidotes in hospital pharmacies.
OBJECTIVE: To determine whether antidotes for poisoning and overdose are available in hospitals that provide emergency department care. DESIGN: Written survey of hospital pharmacy directors, each of whom reported the amount currently in stock of 8 different antidotes: antivenin (Crotalidae) polyvalent, cyanide kit, deferoxamine mesylate, digoxin immune Fab, ethanol, naloxone hydrochloride, pralidoxime chloride, and pyridoxine hydrochloride. PARTICIPANTS: Pharmacy directors of all hospitals with emergency departments in Colorado, Montana, and Nevada. MAIN OUTCOME MEASURES: Proportions of hospitals with insufficient stocking of each antidote, defined as complete lack of the antidote or an amount inadequate to initiate treatment of 1 seriously poisoned 70-kg patient. RESULTS: Questionnaires were mailed to 137 hospital pharmacy directors and 108 (79%) responded. Only 1 (0.9%) of the 108 hospitals stocked all 8 antidotes in adequate amounts. The rate of insufficient stocking for individual antidotes ranged from 2% (for naloxone) to 98% (for digoxin immune Fab). In a multiple regression analysis, smaller hospital size and lack of a formal review of antidote stocking were independent predictors of the number of antidotes stocked insufficiently. CONCLUSIONS: Insufficient stocking of antidotes is a widespread problem in Colorado, Montana, and Nevada. Although these states are served by a certified regional poison center, potentially lifesaving antidotes are frequently not available when and where they might be needed to treat a single poisoned patient.
Analysis of Variance↗
[Availability, use and cost of antidotes in Catalonia].
BACKGROUND: To know the availability of antidotes in hospital and extra-hospital emergency services in Catalonia (Spain), their real use, and the cost. PATIENTS AND METHODS: Availability was studied by means of a transversal questionnaire carried out in 24 hospitals and 3 extra-hospital emergency services in Catalonia; the real use of antidotes was investigated using a prospective study carried out for one year in the same 24 hospitals, and the cost was determined using the data obtained over 12 months in one large hospital. RESULTS: Average availability was 35 antidotes in hospital and 13 in extra-hospital emergency services. In no service did the availability coincide exactly with that of another service, nor with the recommendations made by international institutions (World Health Organization and International Programme for Chemical Safety) or the Government of Catalonia. The low incidence of availability of antidotes to cyanide was notable. Antidotes were used in 12.9% of acute intoxications. In 167 cases treated with these drugs, only 9 different antidotes were used. The consumption of these antidotes represents 0.1% of the budget of a pharmacy service in one large hospital. CONCLUSIONS: The availability of antidotes in Catalonia is heterogeneous and some services lack antidotes whose use is considered essential. Antidotes are scarcely used in acute intoxications and their economic cost is low.
Antidotes↗
The use of specific antidotes as a response to bleeding complications during anticoagulant therapy for venous thromboembolism.
When a bleeding complication occurs during therapy with heparin or vitamin K antagonists, there is an option to give a specific antidote. Several new anticoagulants have been developed that are likely to have some risk of bleeding complications, for which no specific antidotes are available. Interestingly, it is unknown how often the use of an antidote is necessary in clinical practice. We investigated 1877 patients treated for venous thromboembolism included in three large clinical trials, of which 181 (9.6%) had a total of 225 adjudicated bleeding episodes; 46 hemorrhages being designated as major. Some form of antidote was given to 26 (14.4%) patients with a hemorrhage. Of the patients with at least one major hemorrhage, 19 (41.3%) received an antidote. Vitamin K was given to 23 (1.2%) patients, one (0.05%) patient received protamin sulfate and seven (0.4%) patients received fresh frozen plasma. The use of antidotes was comparable for initial and long-term treatment. Antidotes were statistically significantly more frequently given in Canada as compared to other participating countries. Vitamin K was more frequently given in case of a higher international normalized ratio value. Although antidotes against anticoagulant treatment are widely available, our analysis shows that in only a very small number of patients a direct, or slow-acting antidote to reverse the anticoagulant effect was used.
Aged↗