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At least 19 recordsLinked to original sources

PubMed2006

Adequacy of antidote stocking in British Columbia hospitals: the 2005 Antidote Stocking Study.

BACKGROUND: Inadequate hospital stocking and the unavailability of essential antidotes is a worldwide problem with potentially disastrous repercussions for poisoned patients. Research indicates minimal progress has been made in the resolution of this issue in both urban and rural hospitals. In response to this issue the British Columbia Drug and Poison Information Centre developed provincial antidote stocking guidelines in 2003. We sought to determine the compliance with antidote stocking in BC hospitals and any factors associated with inadequate supply. METHODS: A 2-part survey, consisting of hospital demographics and antidote stocking information, was distributed in 2005 to all acute care hospital pharmacy directors in BC. The 32 antidotes examined (21 deemed essential) and the definitions of adequacy were based on the 2003 BC guidelines. Availability was reported as number of antidotes stocked per hospital and proportion of hospitals stocking each antidote. For secondary purposes, we assessed factors potentially associated with inadequate stocking. RESULTS: Surveys were completed for all 79 (100%) hospitals. A mean of 15.6+/-4.9 antidotes were adequately stocked per hospital. Over 90% of hospitals had adequate stocks of N-acetylcysteine, activated charcoal, naloxone, calcium salts, flumazenil and vitamin K; 71%-90% had adequate dextrose 50% in water (D50W), ethyl alcohol or fomepizole, polyethylene glycol electrolyte solution, protamine sulfate, and cyanide antidotes; 51%-70% had adequate folic acid, glucagon, methylene blue, atropine, pralidoxime, leucovorin, pyridoxine, and deferoxamine; and <50% had adequate isoproterenol and digoxin immune Fab. Only 7 (8.9%) hospitals sufficiently stocked all 21 essential antidotes. Factors predicting poor stocking included small hospital size (p < 0.0001), isolation (p = 0.01) and rural location (p < 0.0001). CONCLUSION: Although antidote stocking has improved since the implementation of the 2003 guidelines, essential antidotes are absent in many BC hospitals. Future research should focus on determining the reasons for this situation and the effects of corrective interventions.

Antidotes↗

PubMed2006

[Antidotes availability in Emergency Departments of the Italian National Health System and development of a national data-bank on antidotes].

The availability of antidotes in Italian hospitals has been evaluated through the answers to a specific questionnaire sent to all Italian Emergency Departments, Intensive Care Units, 118 emergency response system, and Poison Centres. Five Poison Centres and, approximately, the 30% of the Emergency Departments and Intensive Care Units of all Italian emergency hospitals answered to the questionnaire. The results point out an insufficient availability of antidotes in the Italian emergency hospitals, with an almost total absence of those necessary for the treatment of less frequent and less known poisonings (e.g. digoxin, industrial agents), also when the antidote is a lifesaving drug. To improve the antidotes availability for the toxicological emergencies and to facilitate its supplying, a "national antidotes data-base" (BaNdA) has been realized, freely available to the hospital services which register themselves and make their antidotes stockpile available.

Antidotes↗

PubMed2006

First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity.

BACKGROUND: Selectivity, titratability, rapidity of onset, and active reversibility are desirable pharmacological properties of anticoagulant therapy administered for acute indications and collectively represent an attractive platform to maximize patient safety. A novel anticoagulation system (REG1, Regado Biosciences), developed using a protein-binding oligonucleotide to factor IXa (drug, RB006) and its complementary oligonucleotide antidote (RB007), was evaluated in healthy volunteers. The primary objective was to determine the safety profile and to characterize the pharmacodynamic responses in this first-in-human study. METHODS AND RESULTS: Regado 1a was a subject-blinded, dose-escalation, placebo-controlled study that randomized 85 healthy volunteers to receive a bolus of drug or placebo followed 3 hours later by a bolus of antidote or placebo. Pharmacodynamic samples were collected serially. Subject characteristics were the following: median age, 32 years (interquartile range, 23 to 39 years); female gender, 35%; and median weight, 79 kg (interquartile range, 70 to 87 kg). No significant differences were found in median hemoglobin, platelet, creatinine, or liver function studies. There were no significant bleeding signals associated with RB006, and overall, both drug and antidote were well tolerated. One serious adverse event, an episode of transient encephalopathy, occurred in a subject receiving the low intermediate dose of RB006. The subject's symptoms resolved rapidly, and no further sequelae occurred. A predictable dose-pharmacodynamic response, reflected in activated partial thromboplastin time measurements, was seen after administration of the bolus of drug, with a clear correlation between the peak posttreatment activated partial thromboplastin time and post hoc weight-adjusted dose of drug (correlation coefficient, 0.725; P<0.001). In subjects treated with drug, antidote administration reversed the pharmacological activity of the drug, with a rapid (mean time, 1 to 5 minutes across all dose levels) and sustained return of activated partial thromboplastin time to within the normal range. The activated clotting time followed a similar anticoagulant response and reversal pattern. As anticipated, prothrombin time remained unchanged compared with baseline. CONCLUSIONS: These observations represent a first-in-human experience of an RNA aptamer and its complementary oligonucleotide antidote used as an anticoagulant system. The findings contribute to an emerging platform of selective, actively reversible anticoagulant drugs for use among patients with thrombotic disorders of the venous and arterial circulations.

Adult↗

PubMed1998

Efficiency of the pTF-FC2 pas poison-antidote stability system in Escherichia coli is affected by the host strain, and antidote degradation requires the lon protease.

The stabilization of a test plasmid by the proteic, poison-antidote plasmid addiction system (pas) of plasmid pTF-FC2 was host strain dependent, with a 100-fold increase in stability in Escherichia coli CSH50, a 2.5-fold increase in E. coli JM105, and no detectable stabilization in E. coli strains JM107 and JM109. The lethality of the PasB toxin was far higher in the E. coli strains in which the pas was most effective. Models for the way in which poison-antidote systems stabilize plasmids require that the antidote have a much higher rate of turnover than that of the toxin. A decrease in host cell death following plasmid loss from an E. coli lon mutant and a decrease in plasmid stability suggested that the Lon protease plays a role in the rate of turnover of PasA antidote.

ATP-Dependent Proteases↗

PubMed1988

Thermodynamic evaluation of activated charcoal as a poison antidote by high-performance liquid chromatography. II: In vitro method for the evaluation of activated charcoal as a poison antidote.

A previous report detailed the derivation and validation of an equation for calculating the Gibbs free energy of liquid-solid adsorption via high-performance liquid chromatography (HPLC). This study utilizes an improved form of that equation in conjunction with an in vitro model of solute adsorption to give an ordered listing of the antidotal activity of activated charcoal towards different drugs and other chemicals. The in vitro model consists of an activated charcoal column with a nominal particle diameter of 15 micron and a surface area of 447 x 10(4) cm2/g, together with a series of acetonitrile:water mobile phases at pH 3. A simple and efficient procedure was developed for ranking the solutes. First, each compound was run in an acetonitrile(ACN):water mobile phase chosen to give a convenient retention time and ideal chromatographic response. The capacity factor for this mobile phase was extrapolated to give a predicted capacity factor for a 35:65 (v/v) ACN:water mobile phase using an empirical equation developed from the exhaustive chromatography of four standard compounds (phenobarbital, strychnine, cyclohexanone, methyl ethyl ketone) in a variety of ACN:water mobile phases. In addition to the standards, 12 other compounds (glutethimide, chlordiazepoxide, quinine, brucine, d-propoxyphene, pentobarbital, methyprylon, methadone, meperidine, codeine, antipyrine, morphine) were evaluated. Based on these data, the Gibbs free energies of liquid-solid adsorption for these compounds were calculated and used to evaluate activated charcoal as a poison antidote for them. The results indicate that a rapid and accurate estimation of the utility of activated charcoal as an antidote for drugs and toxic substances can be obtained from a single chromatographic run of the test compound.

Adsorption↗

PubMed1997