Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Antidotes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2006

[Antidotes availability in health services of Catalonia, Spain].

BACKGROUND AND OBJECTIVE: Acute poisoning can be treated in different hospital and extrahospital health services. Thus, availability of antidotes in hospital pharmacies, emergency departments and health centres play an important role in poisoning treatment. MATERIAL AND METHOD: This is a descriptive and transversal study of antidotes availability in different health services of Catalonia (Spain). From April to May 2005, a proper questionnaire was sent to 50 different health centres: 28 basic health centres (including medical ambulances) and 22 hospitals with a distinct medical complexity level, to assess the qualitative (QLA) and quantitative availability (QTA) of antidotes. RESULTS: QLA resulted to be 82% in extrahospital health centres and 50% in medical ambulances. QTA was 94% for ambulances, whereas, in health centres, differences were observed between rural (55%) and urban (33%) areas. Regarding basic general hospitals (level 1), reference hospitals (level II) and high technology hospitals (level III) the QLA showed values of 39, 54 and 55%, respectively, and the QTA came about 70, 54 y 54.5%, in that order. Furthermore, lack of adequate stocking was observed for compounded formulations, such as albumin, starch, ipecacuanha syrup or IV ethanol, and for essential antidotes as snake antivenin, digoxin immune Fab or hydroxocobalamine. CONCLUSIONS: There is understocking of poisoning antidotes throughout the health services of Catalonia. Heterogeneity was observed between services with a medical complexity level. The main deficiencies are found in antidotes that, to date, are available as compounded formulations or imported from other countries.

Acute Disease↗
PubMed2001

Clinical and institutional aspects of antidote therapy in Russia.

The problem of antidote application for treatment of acute poisoning is related to epidemiology and characterization of poisoning cases, and possibilities for supplying antidotes to health care institutions. To investigate the situation in Russia we have analyzed reports by poisoning treatment centers for 1997-1999, comparison of medical aid standards for poisoning treatment in Russia with WHO recommendations. Acute poisoning pattern varies in different regions. Particularly, poisoning pattern in large cities in European Russia and the Urals is dominated by pharmaceuticals (up to 63.1%). Pesticide and insecticide poisoning cases do not exceed 1 to 2%, metal compounds and methemoglobin forming poisons (below 1% in each group). Antidotes are used in Russia in line with the recommendations adopted in international toxicological practice. The most actual are antagonists of opiates and benzodiazepines, physostigmine, atropine, pyridoxine, antagonists of beta-adrenergic blockers, activated charcoal. Such antidotes as DMPS (Unithiol), N-acetylcysteine, methylene blue, amyl nitrite (or sodium nitrite), complex formers of EDTA group are also included in the list of specific agents. The main problem is that some important antidotes are currently not produced in Russia. The Ministry of Health of the Russian Federation is taking efforts to launch production of some previously known and also newly developed important antidotes.

Alcoholism↗
PubMed2002

The impairment of spatial memory following low-level sarin inhalation exposure and antidotal treatment in rats.

1. To study the influence of antidotes on low-level sarin-induced impairment of cognitive functions, the rats were exposed to three various low concentrations of sarin (LEVEL 1-3) for 60 minutes in the inhalation chamber. In addition, one group of rats was exposed to LEVEL 2 of sarin repeatedly. 2. Testing of cognitive functions was carried out using the Y-maze evaluating learning and spatial memory. The correct averse behavior of sarin-exposed rats in the Y-maze was tested several times within four weeks following sarin inhalation exposure and antidotal treatment to look for any cognitive impairments. 3. The results were compared to the Y-maze performance of sarin-exposed rats without antidotal treatment and control rats exposed to pure air instead of sarin with or without antidotal treatment. While antidotal treatment was able to eliminate a short-term deficiency in the Y-maze performance in rats exposed to the LEVEL 1 of sarin, a significant decrease in the Y-maze performance in rats exposed to sarin at the LEVEL 2 and 3 was only shortened. Sarin-induced spatial memory impairments in rats exposed repeatedly to sarin at the LEVEL 2 was also shortened when rats were treated following each sarin inhalation exposure. 4. The findings confirm that antidotes currently used for nerve agent poisonings are beneficial for the treatment of rats singly or repeatedly exposed to non-convulsive symptomatic or even clinically asymptomatic concentrations of sarin.

Administration, Inhalation↗
PubMed2003

A comparison of the neuroprotective efficacy of pharmacological pretreatment and antidotal treatment in soman-poisoned rats.

1. To study the influence of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6 plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned with a lethal dose of soman (54 (g/kg i.m.; 100% of LD50 value) and observed at 24 hours and 7 days following soman challenge. The neurotoxicity of soman was evaluated using a Functional observational battery and an automatic measurement of motor activity. 2. Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning. The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone. To compare both pharmacological pretreatments, the combination of pyridostigmine with biperiden seems to be more efficacious to eliminate soman-induced signs of neurotoxicity than PANPAL. 3. At 7 days following soman poisoning, the combination of pharmacological pretreatment involving pyridostigmine and biperiden with antidotal treatment was only able to completely eliminate soman-induced neurotoxic signs. 4. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is able not only to protect the experimental animals from the lethal effects of soman but also to eliminate most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL.

Animals↗
PubMedDate not supplied

[The effect of sodium cyanide and its antidotes on the isolated perfused rat heart].

The experiments were performed to investigate the effects of cyanide and several antidotes (sodium nitrite, DMAP, sodium thiosulfate and phentolamine) on isolated perfused rat heart to further elucidate the mechanism of action of cyanide and its antidotes. Sodium cyanide (40, 50 and 60 mg/ml) produced maximum effects on amplitude, heart rate and coronary flow, after 3 min, regardless of the event recorded. Some dose-dependence was noted, especially on the heart rate, somewhat less on amplitude and almost none on the coronary flow up to 15 min, but notable afterwards. Some spontaneous recovery occurred in each event, the most significant being that of the heart rate. Antidotes per se did not differ significantly in their action on isolated rat heart. All values, with some variations, were maintained within 10-20% of control. Antidotes, injected 1 min after sodium cyanide produced the most evident effects on amplitude and heart rate -- all antidotes practically and almost instantly neutralized the depressant effect of cyanide. Nitrite and particularly DMAP, were the most effective on coronary flow while other antidotes, although effective up to 3 min, did not much differ from cyanide alone throughout the rest of observation.

Aminophenols↗
PubMed1990

Induction of glutathione s-transferase isozymes in sorghum by herbicide antidotes.

Certain chemicals referred to as herbicide antidotes protect sorghum from injury by chloroacetanilide herbicides such as metolachlor. The effect of herbicide antidotes on the glutathione S-transferase isozyme complement of etiolated sorghum (Sorghum bicolor [L.] Moench) shoots was examined. Elution profiles of glutathione S-transferase isozymes from untreated and antidote-treated seedlings were generated by fast protein liquid chromatography utilizing an anion exchange (Mono Q) column. In untreated seedlings, there were two glutathione S-transferase isozymes, a major isozyme which exhibited activity toward 1-chloro-2,4-dinitrobenzene and a minor isozyme which exhibited activity toward metolachlor. Treating sorghum seedlings with various antidotes (flurazole, oxabetrinil, CGA-133205, naphthalic anhydride, dichlormid) resulted in the appearance of four to five additional glutathione S-transferase isozymes (de-pending on the particular antidote) which exhibited activity toward metolachlor as a substrate and little or no activity with 1-chloro-2,4-dinitrobenzene. Treating etiolated sorghum shoots with metolachlor was also found to induce at least four isozymes which exhibited activity toward the herbicide. An increase in glutathione S-transferase activity, measured with metolachlor as substrate, was detected within 4 h after treatment with 30 micromolar oxabetrinil, but 36 hours were required for maximum expression of activity. Addition of either the transcription inhibitor cordycepin or the translation inhibitor cycloheximide inhibited the appearance of glutathione S-transferase activity measured with metolachlor as substrate. The results are consistent with the hypothesis that antidotes confer protection against metolachlor injury in sorghum by inducing the de novo synthesis of glutathione S-transferase isozymes which catalyze the detoxification of the herbicide.

Journal Article↗
PubMed1989

Attenuation of soman-induced lesions of skeletal muscle by acetylcholinesterase reactivating and non-reactivating antidotes.

It has been reported recently that some oximes reactivating acetylcholinesterase (AChE) exhibit concomitant ganglion-blocking effects which presumably could contribute independently to their powerful antidotal action in organophosphate inhibitor (OPI) poisoning, thus mimicking some unrelated substances which are effective antidotes without reactivating AChE. This raises the question whether OPI-induced muscle lesions, like some other symptoms could also be attenuated by oximes and other antidotes in the absence of AChE reactivation. To test this possibility, the oxime HI-6 was applied at increasing time intervals after the injection of soman until and beyond the point when soman-AChE complex becomes completely "aged" and not capable of reactivation. As the examples of OPI antidotes which do not reactivate AChE, the muscarinic antagonist atropine and the ganglion-blocking agent hexamethonium were also tested on possible attenuation of muscle lesions. The proportions of fibers with lesions, AChE inhibition and muscle fasciculations in experimental groups relative to the controls treated with soman only were evaluated. The results show that HI-6 can attenuate lesions only if AChE is partially reactivated and muscle fasciculations are permanently eliminated. However, atropine does not affect either AChE inhibition or muscle fasciculations and is also ineffective in counteracting the lesions in spite of its potency as an effective general antidote. Hexamethonium also does not affect AChE inhibition, but abolishes fasciculations and effectively attenuates muscle lesions. The latter findings reveal the existence of lesion-protecting mechanisms unrelated to AChE reactivation, which if further elucidated might become potentially relevant for additional treatment in OPI poisoning.

Acetylcholinesterase↗
PubMed1983

Brain neuronal RNA metabolism during acute soman toxication: effects of antidotal pretreatments.

Effects of various antidotal treatments on neuronal RNA contents and on soman induced RNA and acetylcholinesterase (AChE) depletion were monitored using quantitative cytochemical techniques. In rats only with antidotes, atropine depressed whereas pralidoxime (2-PAM) elevated RNA contents of both caudate and cerebrocortical (Layer V) neurons. Soman produced a virtually complete inhibition of AChE activity and a moderate decline in neuronal RNA contents. Atropine pretreatment partially restored neuronal RNA levels. Atropine + 2-PAM prophylaxis eventuated in a complete restoration of RNA levels but no reactivation of AChE. Addition of physostigmine to the atropine + 2-PAM treatment regimen resulted in appreciable AChE reactivation but reduced RNA levels. The overall data indicate that: (1) soman-induced neuronal RNA depletion can be completely reversed by antidotal pretreatments; (2) no precise relationship exists between the extents of antidote-induced restoration of RNA and AChE levels; and (3) 2-PAM exerts marked effects on the brain neuronal network which are unrelated to AChE reactivation. It is postulated that effects of soman and antidotes on neuronal RNA metabolism may signify alterations in acetylcholine (ACh) sensitivity and that pharmacologic manipulation of ACh responsiveness during organophosphate cholinesterase poisoning may be a mechanism for additional therapeutic intervention.

Acetylcholinesterase↗
PubMed1982

A hypothesis for the selection of chelate antidotes for toxic metals.

The problem of finding antidotes for toxic metal species for which antidotes have not been previously reported can be approached via a consideration of the metal-ion preferences of chelating agents already in clinical use. The metal ion preferences of six types of chelating agents together with information on antidotes used for other elements in the same family in the periodic table can be used to obtain a preliminary notion of which of these six structural types might furnish efficacious antidotes. The results of animal tests on a few of these chelate types can then serve as a guide in the selection of further compounds for testing. The data from the literature on antidotes for 20 toxic metal ions is summarized to assist the selection process.

Animals↗
PubMed2005

Excessive methaemoglobinaemia and multi-organ failure following 4-DMAP antidote therapy.

This report describes the clinical history of a patient intoxicated with methyl isocyanate (MIC), a toxic agent first receiving attention in 1984 after a mass accident in a pesticide plant in Bhopal, India, and treated with the cyanide-specific antidote 4-DMAP. The numerous clinical conditions requiring 39-day intensive care treatment included ARDS, renal and hepatic failure, haemolysis, bone marrow depression, septic encephalopathy and critical illness polyneuropathy. The most outstanding condition, however, was a methaemoglobinemia of 86.7%, which was predominantly related to the use of 4-DMAP, although uptake of MIC may have been a significant contributing factor. Since significant cyanide intoxication could be excluded clinically and by laboratory testing in the initial phase of emergency treatment, most of the clinical effects were due to the side-effects of the antidote therapy. Due to intensive therapy, the patient survived without any neurological or organ deficit. This case shows that antidotes should be used cautiously in cases where uncertainties about the nature of the underlying toxic agent exist. This may prevent severe side-effects associated with antidote therapy, e.g. 4-DMAP, if there is-as in our case-a mismatch between the toxic agent and the antidote.

Adult↗
PubMed2006

The dilemma of approving antidotes.

Clinical trials with antidotes are difficult to perform for a variety of practical, ethical, and financial reasons. As acute poisoning is a rare event, the commercial interest in basic and clinical research is low. Poisoned patients are usually not available for normal clinical trial procedures and, if they are, they cannot give informed consent. This situation results in a dilemma: antidotes are essential drugs. A resolution of the Council of Europe requests to guarantee the optimal availability of antidotes and the improvement of their use. As comprehensive data on the efficacy of antidotes are often missing, a marketing authorisation under exceptional circumstances according to Article 14(8) of Regulation (EC) No. 276/2004, will often be the only way to get an approval, as: (1) the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence ("orphan drug"), (2) in the present state of scientific knowledge, comprehensive information cannot be provided, or (3) it would be contrary to generally accepted principles of medical ethics to collect such data. Typically, data on antidotes are obtained from a patchwork of studies with animals, human tissue and a few observations from human poisoning corroborated with data from clinical observations and biochemistry. Generalisations from chemical and mechanistic similarities between groups of poisons are usual, but often lack scientific evidence. Current standards of good clinical practice can rarely be observed. Therefore, public funding and other financial support are necessary incentives to initiate trials in this important area.

Antidotes↗
PubMed2000

Neuroprotective effects of currently used antidotes in soman-poisoned rats.

The neuroprotective effects of antidotes (atropine, obidoxime, obidoxime/atropine mixture) on rats poisoned with soman at a sublethal dose (54 microg/kg, im, 80% of LD(50) value) were studied. The soman-induced 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 days following soman challenge. The results indicate that obidoxime alone is not able to protect the rats from the lethal effects of soman. Three soman-poisoned rats treated with obidoxime alone died within 24 h. On the other hand, atropine alone or combined with obidoxime allows all soman-poisoned rats to survive within 7 days following soman challenge. Atropine alone and combined with obidoxime seems to be relatively effective antidotal treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings, although the antidotal mixture is significantly less effective than atropine alone because obidoxime can counteract the beneficial effects of atropine. Obidoxime appears to be practically ineffective to diminish soman-induced neurotoxicity. The neuroprotective effects of antidotal mixture consisting of atropine and obidoxime depend on the antimuscarinic effects of atropine only. Thus, the replacement of obidoxime by more effective acetylcholinesterase (AChE) reactivators is necessary to increase the neuroprotective efficacy of antidotal treatment in the case of soman poisonings.

Animals↗
PubMed2003

Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition.

A structure of the Escherichia coli chromosomal MazE/MazF addiction module has been determined at 1.7 A resolution. Addiction modules consist of stable toxin and unstable antidote proteins that govern bacterial cell death. MazE (antidote) and MazF (toxin) form a linear heterohexamer composed of alternating toxin and antidote homodimers (MazF(2)-MazE(2)-MazF(2)). The MazE homodimer contains a beta barrel from which two extended C termini project, making interactions with flanking MazF homodimers that resemble the plasmid-encoded toxins CcdB and Kid. The MazE/MazF heterohexamer structure documents that the mechanism of antidote-toxin recognition is common to both chromosomal and plasmid-borne addiction modules, and provides general molecular insights into toxin function, antidote degradation in the absence of toxin, and promoter DNA binding by antidote/toxin complexes.

Antidotes↗
PubMed2004

Antidote-mediated control of an anticoagulant aptamer in vivo.

Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.

Animals↗
PubMed1997

The poison-antidote stability system of the broad-host-range Thiobacillus ferrooxidans plasmid pTF-FC2.

In plasmid pTF-FC2, three small open reading frames (ORFs) are situated between the repB (primase) gene and the repA (helicase) gene of its IncQ-type replicon. Disruption of each of the three ORFs followed by tests for plasmid stability and host cell growth indicated that the ORFs encoded a poison-antidote plasmid stability system. The three genes were named pasA, pasB and pasC (plasmid addiction system), in which PasA is the antidote, PasB the toxin and PasC a protein that appears to enhance the ability of the antidote to neutralize the toxin. Disruption of the pasA gene resulted in two different spontaneous deletions, which inactivated the stability system but did not alter the host range or plasmid copy number. This indicated that the three small ORFs were not involved in plasmid replication. When placed behind a tac promoter, induction of pasB was found to be highly lethal to host cells, which suggests that the Pas system acts by killing plasmid-free host cells rather than by retarding the growth of plasmid-free segregants, as occurs in the ParD system of R1. In spite of this, the presence of the Pas poison-antidote system resulted in a relatively modest threefold stabilization of the pTF-FC2 host replicon and a similar increase in the stabilization of an unstable heterologous R1 plasmid replicon. The Pas system is a poison-antidote plasmid stability module, which appears to have become integrated within the pTF-FC2 replicon module.

Amino Acid Sequence↗
PubMedDate not supplied

Chelate antidotes for sodium vanadate and vanadyl sulfate intoxication in mice.

Eighteen different chelating agents, including all of those previously shown to have a protective action in vanadium intoxication, have been compared as antidotes for acute vanadium intoxication using mice. Of these compounds, those found to be effective antidotes for both vanadate (VO3(-3)) and vanadyl (VO2+) include ascorbic acid, deferoxamine, D-penicillamine, sodium calcium diethylenetriaminepentaacetic acid (Na3CaDTPA), Na2CaEDTA, glutathione, Tiron, and ethylenediaminetetra(methylene phosphonate). Of the compounds examined, ascorbic acid appeared to be the most promising for human use. When administered at the levels used in this study, it is an effective antidote for intoxication due to either the vanadate or the vanadyl ion. Certain compounds are able to act as antidotes for vanadate solely by virtue of their action as a reducing agent; when these compounds are unable to form complexes with the reduction product (vanadyl ion), they are effective antidotes for the higher oxidation state only when the concentration of vanadyl produced is less than the level that results in toxic effects.

Animals↗
PubMed1985

The antidotal action of thiosulfate following acute nitroprusside infusion in dogs.

The authors previously demonstrated in dogs that a bolus dose of sodium thiosulfate maintained enhanced cyanide metabolism throughout a 1-h infusion of sodium nitroprusside (SNP). To further test this antidotal action, a bolus dose of thiosulfate (150 mg . kg-1) was given to eight dogs at the end of a 60-min near-lethal infusion of nitroprusside (3 mg . kg-1). Within 2 min of the antidote, mean plasma thiocyanate levels (70.3 mumol . l-1) were significantly higher than those of seven control dogs given nitroprusside only (45.9 mumol . l-1, P = 0.002) and plateaued at 153.8 mumol . l-1 within 60 min, while the control values only reached 79.1 mumol . l-1 (P less than 0.001). Although differences between plasma cyanide levels in the two groups only attained significance 1 h after administering the antidote (0.8 vs. 2.74 mumol . l-1, P = 0.03), red blood cell cyanide concentrations were significantly lower in the antidote group within 5 min (166 vs. 225 mumol . l-1, P = 0.004) and remained so throughout the 2-h observation period. Compared with the controls, there was an impressive reduction in mean half-lives of plasma cyanide (25.1 vs. 74.1 min) and red blood cell cyanide (22.4 vs. 203.6 min). Similarly, peak cyanide levels occurred much sooner following the antidote (mean times: plasma cyanide 2.9 vs. 5.9 min; red blood cell cyanide 0.25 vs. 11 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Imbalance↗
PubMed1997

Effect of Panpal pretreatment and antidotal treatment (HI-6 plus benactyzine) on respiratory and circulatory function in soman-poisoned rats.

1 The effect of pharmacological pretreatment (pyridostigmine, benactyzine and trihexyphenidyle), designated Panpal, and antidotal treatment (the oxime HI-6 plus benactyzine) in soman poisoning was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activity in diaphragm and various brain parts. 3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acetylcholinesterase activity in all brain parts studied. 4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreatment or antidotal treatment alone. 5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman-poisoned rats without significant reactivation of brain acetylcholinesterase.

Acetylcholinesterase↗