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PubMed2002

Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents.

The cholinesterase-inhibiting organophosphorus compounds referred to as nerve agents (soman, sarin, tabun, GF agent, and VX) are particularly toxic and are considered to be among the most dangerous chemical warfare agents. Included in antidotal medical countermeasures are oximes to reactivate the inhibited cholinesterase. Much experimental work has been done to better understand the properties of the oxime antidotal candidates including the currently available pralidoxime and obidoxime, the H oximes HI-6 and Hlö-7, and methoxime. There is no single, broad-spectrum oxime suitablefor the antidotal treatment of poisoning with all organophosphorus agents. If more than one oxime is available, the choice depends primarily on the identity of the responsible organophosphorus compound. The H oximes appear to be very promising antidotes against nerve agents because they are able to protect experimental animals from toxic effects and improve survival of animals poisoned with supralethal doses. They appear more effective against nerve agent poisoning than the currently used oximes pralidoxime and obidoxime, especially in the case of soman poisoning. On the other hand, pralidoxime and especially obidoxime seem sufficiently effective to treat poisonings with organophosphorus insecticides that have relatively less toxicity than nerve agents.

Animals↗
PubMed1999

Toxicology cart for stocking sufficient supplies of poisoning antidotes.

Within a three-month period, the University of New Mexico Health Sciences Center (UNMHSC) encountered three toxicological emergencies in which antidotes were either unavailable or inadequately stocked. Patient A was a patient with ethylene glycol intoxication. The emergency department (ED) physician ordered a 10% ethanol infusion. The pharmacy staff was unable to locate the commercially available solution and had to compound the infusion, resulting in a delay in administration of the antidote. Patient B was a patient at an outside hospital with organophosphate exposure whose transfer to our ED was requested by the other hospital. The pharmacy staff was unable to locate the pralidoxime needed to treat this patient; therefore; the patient was not transferred. It was later discovered that the pralidoxime had been stored in a location inconsistent with the storage policy for this medication. Patient C was a patient with severe rattlesnake envenomation. The pharmacy staff could locate only half of the antivenin needed to treat this patient. In each of these three cases, it was necessary to compound the required medication or to obtain it from other local facilities. These cases underscore the need for pharmacies to stock adequate amounts of poisoning antidotes in one immediately accessible location. A similar problem with understocking of poisoning antidotes exists throughout the United States.

Antidotes↗
PubMed2006

New and novel antidotes in pediatrics.

Antidotal therapy can be lifesaving in the management of poisoned children. Although supportive care is sufficient in many cases, a specific antidote can significantly reduce morbidity and mortality in a number of poisoning scenarios, and so the pediatric emergency medicine practitioner must be familiar with its indications for use, dosage and administration, and contraindications. A number of new antidotes have emerged in recent years. This review discusses the pediatric uses and limitations of intravenous N-acetylcysteine, octreotide, crotaline Fab antivenom, fomepizole, atropine and pralidoxime autoinjectors and provides some brief discussion on newer antidotes for which data is only starting to emerge.

Acetylcysteine↗
PubMed2006

Antidotal efficacy of pyridinium chloride derivatives against soman poisoning.

Acetylcholinesterase (AChE; EC 3.1.1.7.) is an extremely active enzyme necessary for terminating the action of acetylcholine in cholinergic synapses. The aim of this study was to evaluate the efficacy of four mono-pyridinium compounds 1-phenacylpyridinium chloride (I), 1-phenacyl-2-methylpyiridinium chloride (II), 1-benzoylethylpyridinium chloride (III), and 1-benzoylethylpyridinium-4-aldoxime chloride (IV) in the therapy of soman poisoning. Their effect was compared with HI-6 and TMB-4 oximes. The inhibitory potency (IC50) of compounds as well as reactivating (%R) and protective potency (P50) with respect to soman-inhibited AChE were determined for each of the compounds. Their acute intraperitoneal toxicity (LD50 with 95% confidence limits) was tested in mice and observed for 24 hr. The therapeutic effect was expressed as the protective index and as the therapeutic dose. The tested compounds were found to be reversible inhibitors of AChE. In vivo results show that the tested compounds are relatively toxic (their LD50 was from 74.9 to 210.0 mg/kg body weight). The best antidotal efficacy was obtained with compound II, which had the highest affinity for AChE (IC50 was 1.9 x 10(-5) mol l(-1)) and seems to be an adequate antidote in soman poisoning (its protective index and therapeutic dose were 2.8 and 2, respectively). Our results indicate that its antidotal effect is related to the reactivation or protection of AChE. The type of the substituent in the pyridinium ring generally has a significant influence on toxicity in vitro and in vivo, and on the antidotal efficacy of all new tested compounds.

Acetylcholine↗
PubMedDate not supplied

Antidote use in the critically ill poisoned patient.

The proper use of antidotes in the intensive care setting when combined with appropriate general supportive care may reduce the morbidity and mortality associated with severe poisonings. The more commonly used antidotes that may be encountered in the intensive care unit (N-acetylcysteine, ethanol, fomepizole, physostigmine, naloxone, flumazenil, sodium bicarbonate, octreotide, pyridoxine, cyanide antidote kit, pralidoxime, atropine, digoxin immune Fab, glucagon, calcium gluconate and chloride, deferoxamine, phytonadione, botulism antitoxin, methylene blue, and Crotaline snake antivenom) are reviewed. Proper indications for their use and knowledge of the possible adverse effects accompanying antidotal therapy will allow the physician to appropriately manage the severely poisoned patient.

Antidotes↗
PubMed1997

Are we ready to replace dimercaprol (BAL) as an arsenic antidote?

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulphonate sodium (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour. 2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication-especially with lipophilic organoarsenicals-may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular availability. 3 This article focuses on aspects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue-bound arsenic in various experimental models, such as monolayers of MDCK (= Madin-Darby canine kidney) cells from dog kidney, isolated perfused liver from guinea-pigs, and perfused jejunal segments from rat small intestine. 4 The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins, DMPS and DMSA may advantageously replace BAL whenever intervention time is not critical. With severe intoxication by organic arsenicals, when the point-of-no-return is a limiting factor, BAL may still have a place as an arsenic antidote.

Animals↗
PubMed1982

Evaluation of activated charcoal-sorbitol suspension as an antidote.

Studies in rats were performed to evaluate the effect of sorbitol on the antidotal efficacy of activated charcoal against four test drugs and to investigate the influence of storage upon the antidotal effect of activated charcoal-sorbitol suspension. The antidotal potency of activated charcoal was not diminished by sorbitol solution 70% w/v. In fact, it was enhanced by the sorbitol solution, as indicated by greater decrease in peak tissue drug concentration, compared to the effect produced by activated charcoal in aqueous suspension. Furthermore, storage of activated charcoal in sorbitol for as long as 1 year did not reduce the antidotal-efficiency of the absorbent.

Animals↗
PubMedDate not supplied

Stroma-free methemoglobin solution as an antidote for cyanide poisoning: a preliminary study.

Effective treatment of cyanide poisoning requires rapid diagnosis, good supportive treatment and the use of a specific antidote. The currently available antidotes offer demonstrated efficacy along with significant potential adverse side effects. We have investigated an alternate approach to antidote therapy for cyanide poisoning by using Stroma-Free Methemoglobin Solution ( SFMS ). Rats injected with an LD100 intravenous dose of cyanide were treated with SFMS equal to 1.5% of their total body hemoglobin. There was a highly significant increase in the survival rate of the treated group compared to saline controls. The potential advantages of SFMS over current antidotes include an immediate onset of action, rapid elimination of cyanide from the body and a mode of action that doesn't compromise any of the patients' oxygen carrying capacity. SFMS shows promise as a significant adjunct in the treatment of cyanide poisoning.

Animals↗
PubMed1999

[An epidemiological study of acute intoxications and provision of medical-cabinet antidotes].

OBJECTIVES: The aims of this work is to know first, the characteristics of the cases of acute intoxication seen in the emergency room of he "Hospital Clínico de Salamanca", Spain; and second, the existence of first-aid antidote kits, their location within the hospital, and their supplies in relation of the level of assistance being provided in hospitals in the region of "Castilla-León". METHODS: All cases of acute intoxication attended in the Emergency Room in he "Hospital Clínico de Salamanca" during one year (from June 1993 through May 1994) were studied prospectively. A descriptive analysis of several variables was performed including age, sex, monthly distribution, causes, toxic substances involved, route of exposure, clinical manifestations, treatment, department in witch patients were admitted and clinical evolution. Additionally, a questionnaire was sent to physicians in charge of emergency services of hospital in "Castilla-León" regarding the existence, location an equipment of first-aid antidote units. RESULTS: A total of 425 cases of acute intoxication were attended, representing 0.69% of all cases seen in the emergency room, during the mentioned period. The age range with the highest incidence was 20-30 years, representing 28.94% of the cases of acute intoxication. 51.3% of cases corresponded to male individuals, although in the 20-30 year range 63.11% were females. February was the month with the highest incidence. With regard to etiology, accidental exposure was the most common, representing 60.47% of cases, while among females 49.28% of cases of intoxication were self inflicted. The toxic substances most frequently involved were alcoholic drinks (23%) and benzodiazepines (17.16%). Recreation and opiate drugs represented 16.23% of the cases. The route of exposure was oral ingestion in 81% of cases and the most common clinical manifestation were of neurologic type which were present in 48% of patients attended. 25% of patients were admitted, representing 0.80% of admissions from the Emergency Room, with the intensive care unit and the Department of Psychiatry (32% of cases in each one) being the areas in which the highest number of patients were hospitalized. The number of patients that died was 2, which represents 0.47% of intoxicated patients attended. In 40% of hospital of the region there is a specific location within the Emergency Room for the first aid antidote drug kit. There is a good correlation between the levels of assistance of hospitals of Castilla-León and the supplies of the first aid antidote kit in the Emergency Room as well as in the Pharmacy Unit.

Acute Disease↗
PubMed1999

Neuroprotective effects of antidotes in soman-poisoned rats.

1. The neuroprotective effects of antidotes (atropine, obidoxime/atropine mixture, HI-6/atropine mixture) on rats poisoned with soman at a sublethal dose (48 micrograms/kg i.m.; 60% of LD50 value) were studied. The neurotoxicity was monitored using a functional observational battery (FOB) and an automatic measurement of motor activity. The neurotoxicity of soman was monitored at 24 h and 7 d following soman poisoning. 2. The results indicate that atropine alone and the oxime HI-6 in combination with atropine seem to be effective antidotal treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings. 3. On the other hand, the combination of obidoxime with atropine appears to be practically ineffective in diminishing neurotoxic soman-induced symptoms. 4. Dealing with neuroprotective effects of antidotes, the oxime HI-6 in combination with atropine seems to be more suitable antidotal mixture than obidoxime in combination with atropine even in the case of sublethal poisoning with nerve agents.

Animals↗
PubMed2002

[Antidotal effects of vitamin B(6) and sodium dimercaptopropane sulfonate on acute poisoning with tetramethylene disulphotetramine in animals].

OBJECTIVE: The study was designed to examine the antidotal effects of vitamin B(6) (Vit B(6)) with sodium dimercaptopropane sulfonate (Na-DMPS) on acute poisoning with tetramethylene disulphotetramine (TETS) in animals. METHODS: Through the acute toxicity experiments, the antidotal effects of Vit B(6) with Na-DMPS on mice immediately and 10 minutes after poisoning were observed. RESULTS: Used of Vit B(6) with Na-DMPS in early stage showed excellent inhibition of tetanic convulsion in acute poisoning with TETS in mice and can reduce very significantly the death rate (P < 0.001). Vit B(6) with Na-DMPS used 10 minutes after poisoning also significantly elongate the death time (68.8 +/- 15.2) and reduce significantly the death rate (60%) then control group's death time (31.6 +/- 7.8) and the death rate (100%) on acute poisoning in mice (P < 0.01). CONCLUSION: Antidotal effects of Vit B(6) with Na-DMPS were significant on acute TETS poisoning in animals. Vit B(6) with Na-DMPS is an excellent antidote for acute TETS poisoning. It is suggested that Vit B(6) with Na-DMPS may be clinically used to rescue patients poisoned by TETS.

Acute Disease↗
PubMed2000

[Poisons and antidotes according to Gunyetü'l Muhassilin and an 18th century Ottoman pamphlet].

This study deals with the chapter on poisons (Sümum) of Gunyetü'l-Muhassilin, a translation, and a pamphlet on antidotes called Panzehir, by Ahmed Sani, one of the most prominent figures of the Ottoman physicians. As a foreword, the terminology related with the subject; and an introduction to the Islamic medical theory, the basis of the subject, is discussed. The main topics on poisons are; protection against and treatment of poisons; being poisoned by the sting of insects, snakes etc. and diseases such as rabies, as a result of bites of animals and their treatment; treatment of poisoned suppuration; insecticide drugs and measures; and common drugs against all kinds of poisons. Immunization and nutrition with respect to being poisoned; and preventive measures against insects; and mineral and organic antidotes are also discussed. The classification of diseases and treatment ase evaluated on the humoral theory basis. The treatment of insect poisoning is viewed from the perspective of its symptoms. The pamphlet named Panzehir is about a special antidote, the bezoar stone. This antidote is divided into two, of the mineral and the animal origin and the uses of the bezoar are discussed. A vocabulary is added to help readers to understand the terminology.

Antidotes↗
PubMed2000

[Poisons and antidotes according to Gunyetü'l Muhassilin and an 18th century Ottoman pamphlet].

This study deals with the chapter on poisons (Sümum) of Gunyetü'l-Muhassilin, a translation, and a pamphlet on antidotes called Panzehir, by Ahmed Sani,one of the most prominent figures of the Ottoman physicians. As a foreword, the terminology related with the subject; and an introduction to the Islamic medical theory, the basis of the subject, is discussed. The main topics on poison are; protection against and treatment of poisons; being poisoned by the sting of insects, snakes etc. and diseases such as rabies, as a result of bites of animals and their treatment; treatment of poisoned suppuration; insecticide drugs and measures; and common drugs against all kinds of poisons. Immunization and nutrition with respect to being poisoned; and preventive measures against insects; and mineral and organic antidotes are also discussed. The classification of diseases and treatment are evaluated on the humoral theory basis. The treatment of insect poisoning is viewed from the perspective of its symptoms. The pamphlet named Panzehir is about a special antidote, the bezoar stone. This antidote is divided into two, of the mineral and the animal origin; and the uses of the bezoar are discussed.A vocabulary is added to help readers to understand the terminology.

Antidotes↗
PubMed1992

The poison center as a reservoir for antidotes for veterinary poisoning emergencies.

Animal poisonings account for a significant number of the cases responded to by poison centers. The majority of consultations involve small animals and do not necessitate the use of large amounts of pharmacologic antagonists, such as atropine to treat anticholinesterase pesticide poisonings. However, large animals such as cattle present unique management problems, since phenomenal amounts of antidotes may be needed to treat a herd of cattle, creating a significant economic impact. The most challenging dilemma is providing 24-h availability and a means of acquisition of sufficient quantities of antidotes to reduce the economic impact of large-animal poisonings. In conjunction with a state veterinary medical association, a RPIC serves as a depot for the storage and distribution of emergency veterinary antidotes. Sufficient quantities of atropine, methylene blue, calcium EDTA, sodium nitrite and thiosulfate, and activated charcoal are available via the RPIC to treat a herd of 200 cattle. The antidotes are available only for emergency treatment and with a veterinary prescription. The 24-h nature of the poison center makes it an ideal location to serve the needs of veterinarians.

Animals↗
PubMed2004

Anticholinergic drugs--functional antidotes for the treatment of tabun intoxication.

1. To study the influence of antidotes on tabun-induced neurotoxicity, the rats were injected intramuscularly with organophosphate tabun (LD50). The efficacy of choice antidotal treatment consisting of acetylcholinesterase reactivator obidoxime and one of four anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) was compared. 2. Testing of tabun-induced neurotoxicity progress was carried out using the method Functional observational battery. The experimental animals as well as controls were observed at 24 hours and 7 days following tabun or saline administration. 3. The results were compared to the condition of animals without anticholinergic drug (oxime alone) and control rats that received physiological solution instead of tabun and treatment. Antidotal treatment involving centrally acting anticholinergic drugs (benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine.

Animals↗
PubMed2004

[Gastric lavage, hemodialysis and specific antidotes in acutely poisoned patients treated at the Specialist Hospital in Biała Podlaska (1993, 2001 and 2002)].

Gut decontamination, the methods of extracorporeal elimination of poisons and antidote use are the specific measures in clinical toxicology. Statistically they are not often used in intoxicated patients. It is not known, in how many cases of poisoning treated outside toxicological units are they applied. Approximately 110 poisoned patients were hospitalised each year in the Specialist Hospital in Biała Podlaska in years 1993, 2001 and 2002. Gastric lavage was performed in about 50 percent of those cases, especially often in children up till third year of life and in the cases of poisoning with medical drugs. The Gut Decontamination Position Statement of AACT and EAPCCT, published in 1997, had no significant impact on use of decontamination procedures in our hospital. Haemodialyses were performed in 3-5% of poisoned patients. All those patients were poisoned with ethylene glycol or methanol. Only 4 specific antidotes were used in years 1993, 2001 and 2002. The most commonly used antidote was ethanol, despite its level is not measured in our laboratory. Recommendations for gut decontamination should be widely popularised. The use of activated charcoal may be in many cases more suitable as a gastric lavage. Safe and effective use of ethanol as an antidote in a hospital requires its measuring in own laboratory.

Acute Disease↗
PubMedDate not supplied

Antidotes to lethal cocaine toxicity in the rat.

Cocaine, like catecholamines or angiotensin II, may induce lethal cardiac or cerebral damage. Restrained rats were fitted with a caudal arterial catheter for on-line cardiovascular monitoring and antidote administration. They were given 60 mg/kg of cocaine i.p., a dose which produces behavioral and cardiovascular effects, convulsions and death in an average time of 10 min. Selected antidotes were administered 5 min after the lethal dose of cocaine. Incidence of lethality was not changed by propranolol, prazosin, labetalol, diazepam or enalaprilat, a converting enzyme inhibitor. Animals treated with any one of the following agents, alpha- or beta-blockers, diazepam or competitive inhibitors of angiotensin II [Sar-1-ile-8] and [Sar-1-thr-8] angiotensin II, presented myocardial infarction. All animals treated with calcium channel antagonists or enalaprilat, whether they survived or not, did not present myocardial infarction. Treatment with nitrendipine, flunarizine or diltiazem, resulted in survival of the animals with no observable aftereffects. Similar results were observed when enalaprilat was administered, with diazepam as an antidote, to a lethal dose of cocaine. Antagonists to the sympatho-adrenal system and to the renin angiotensin system appear to be effective antidotes to cocaine toxicity in the present experimental model.

Adrenergic alpha-Antagonists↗
PubMed1990

Evaluation of potential antidotes for sodium fluoroacetate in mice.

Pathogenesis in fluoroacetate poisoning is multifactorial. Biochemically it is characterized by lethal synthesis of fluorocitrate, causing hypocalcemia, and energy deficiency through blockade of the TCA cycle. Calcium gluconate (CaG) was chosen to antagonize hypocalcemia, while sodium alpha kelogluterate (NaKG) and sodium succinate (NaSuc) were selected as potential antidotes to revive the TCA cycle. Effectiveness of each of these antidotes individually and in certain combinations was tested in mice exposed to lethal doses (15 mg/kg ip) of sodium fluoroacetate (NaFAC). Antidotal treatments were administered at 15 min, 4 h, 10 h, 24 h, and 36 h after NaFAC. All 3 of the antidotes alone, as well as a combination of CaG with NaKG, were ineffective in reducing mortality in mice after NaFAC. On the other hand, a combination of CaG (130 mg/kg) with NaSuc (240 mg/kg) was effective if the 2 solutions were either injected at separate sites or mixed in the same syringe just prior to injection. Similar solutions, if mixed for 24 h or longer before administrations, were ineffective. Increasing the dose of NaSuc to 360 or 480 mg/kg with CaG (130 mg/kg) was unrewarding. These results indicate that CaG in combination with 240 mg NaSuc/kg offer a promising therapy modality in NaFAC intoxication. Additional studies involving biochemical parameters and other species are needed to confirm the efficacy and mechanism(s) of action of this combination.

Animals↗