BackgroundLaboratory tests for routine drug of abuse and toxicology (DOA/Tox) screening, often used in emergency medicine, generally utilize antibody-based tests (immunoassays) to detect classes of drugs such as amphetamines, barbiturates, benzodiazepines, opiates, and tricyclic antidepressants, or individual drugs such as cocaine, methadone, and phencyclidine. A key factor in assay sensitivity and specificity is the drugs or drug metabolites that were used as antigenic targets to generate the assay antibodies. All DOA/Tox screening immunoassays can be limited by false positives caused by cross-reactivity from structurally related compounds. For immunoassays targeted at a particular class of drugs, there can also be false negatives if there is failure to detect some drugs or their metabolites within that class.MethodsMolecular similarity analysis, a computational method commonly used in drug discovery, was used to calculate structural similarity of a wide range of clinically relevant compounds (prescription and over-the-counter medications, illicit drugs, and clinically significant metabolites) to the target ('antigenic') molecules of DOA/Tox screening tests. These results were compared with cross-reactivity data in the package inserts of immunoassays marketed for clinical testing. The causes for false positives for phencyclidine and tricyclic antidepressant screening immunoassays were investigated at the authors' medical center using gas chromatography/mass spectrometry as a confirmatory method.ResultsThe results illustrate three major challenges for routine DOA/Tox screening immunoassays used in emergency medicine. First, for some classes of drugs, the structural diversity of common drugs within each class has been increasing, thereby making it difficult for a single assay to detect all compounds without compromising specificity. Second, for some screening assays, common 'out-of-class' drugs may be structurally similar to the target compound so that they account for a high frequency of false positives. Illustrating this point, at the authors' medical center, the majority of positive screening results for phencyclidine and tricyclic antidepressants assays were explained by out-of-class drugs. Third, different manufacturers have adopted varying approaches to marketed immunoassays, leading to substantial inter-assay variability.ConclusionThe expanding structural diversity of drugs presents a difficult challenge for routine DOA/Tox screening that limit the clinical utility of these tests in the emergency medicine setting.

BACKGROUND:Immunoassays used for routine drug of abuse (DOA) and toxicology screening may be limited by cross-reacting compounds able to bind to the antibodies in a manner similar to the target molecule(s). To date, there has been little systematic investigation using computational tools to predict cross-reactive compounds.

Background. Acute poisoning represents one of the most common medical emergencies in childhood. In view of paucity of literature on accidental poisoning among children in Egypt, this study was designed to describe the pattern of childhood poisoning in Zagazig University Hospitals. Patients and Methods. This retrospective study included 300 children up to 12 years with acute poisoning admitted to the Pediatric Department and Poisoning Treatment Unit, Zagazig University Hospitals, from January 2011 to August 2012. Complete epidemiological and clinical data were recorded and analyzed. Results. Three hundred of poisoned children were enrolled in this study. Children from 1 to 6 years were more liable to poisoning (81%). More boys than girls were poisoned at all age groups. The majority of all cases (99%) were due to accidental poisoning. Overall, 32% of the poisoned cases were living in Zagazig city while 68% were living in the rural areas. The presenting symptoms were classic in 60% of the cases. Pesticides, therapeutic drugs, and cleaning and disinfectant agents were the most frequent poisoning agents (28.7%, 22.7%, and 17.0%, resp.). In 86.0% of cases, observation with or without supportive measures together with decontamination and specific antidote therapy whenever needed was sufficient. Conclusion. Most of the poisonings were due to accidental ingestions by infants and young children. Pesticides and medications were the most commonly involved agents.

Immunoassays are used for therapeutic drug monitoring (TDM) yet may suffer from cross-reacting compounds able to bind the assay antibodies in a manner similar to the target molecule. To our knowledge, there has been no investigation using computational tools to predict cross-reactivity with TDM immunoassays. The authors used molecular similarity methods to enable calculation of structural similarity for a wide range of compounds (prescription and over-the-counter medications, illicit drugs, and clinically significant metabolites) to the target molecules of TDM immunoassays. Utilizing different molecular descriptors (MDL public keys, functional class fingerprints, and pharmacophore fingerprints) and the Tanimoto similarity coefficient, the authors compared crossreactivity data in the package inserts of immunoassays marketed for in vitro diagnostic use. Using MDL public keys and the Tanimoto similarity coefficient showed a strong and statistically significant separation between cross-reactive and non-cross-reactive compounds. Thus, two-dimensional shape similarity of cross-reacting molecules and the target molecules of TDM immunoassays provides a fast chemoinformatics methods for a priori prediction of potential of cross-reactivity that might be otherwise undetected. These methods could be used to reliably focus cross-reactivity testing on compounds with high similarity to the target molecule and limit testing of compounds with low similarity and ultimately with a very low probability of cross-reacting with the assay in vitro.

Background Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. Case Report A 37 yo woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 hours on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6mcg/ml(5–20). Discussion Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life which has not been studied after overdose was 15.79 hours. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Conclusion Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.