Incapacitating agents review: 20 years after Nord Ost Siege.

Incapacitating agents are chemical weapons that produce a temporary disabling condition that persists for hours or days after exposure. Their main site of action is the central nervous system and includes substances that are considered depressants or stimulants. While not intended to cause death, can produce significant morbidity in affected patients. The objective of this narrative review is to update the toxicokinetics, toxicodynamics, diagnosis, and treatment of these chemicals, considering that 20 years have passed since the Nord Ost Siege, where a fentanyl derivative was used by Russian forces to neutralize a group of Chechen dissidents. A bibliographic search was carried out in PubMed, SciELO, and Cochrane Library databases as well as nonindexed scientific literature.

Carfentanilo: una doble amenaza para la salud pública / Carfentanil: a double threat to public health

El carfentanilo es un opioide sintético con una potencia 10.000 veces superior a la de la morfina. Esta y otras características posicionan al carfentanilo como una sustancia de interés dual, pues ha sido empleada como agente incapacitante y como droga de abuso. Entre las características toxicocinéticas del carfentanilo destacan su elevada liposolubilidad y la posibilidad de que siga una cinética de eliminación no lineal. En 2002 este compuesto fue empleado por las Fuerzas de Seguridad Rusas para intentar resolver la crisis de rehenes del teatro Dubrovka de Moscú, causando la muerte de al menos 123 rehenes. Por otro lado, el carfentanilo, se ha empleado como droga de abuso y como adulterante en otras drogas. En caso de intoxicación por carfentanilo puede ser necesaria la administración de dosis repetidas de antídoto. Los antecedentes expuestos en este trabajo justifican la necesidad de desarrollar y validar un método analítico para la detección del carfentanilo y su metabolito norcarfentanilo en muestras biológicas. (AU)

Carfentanil is a synthetic opioid with a potency 10,000 times greater than that of morphine. For this and other reasons carfentanil is a substance with dual interest, since it has been used as an incapacitating agent and as an abuse drug. Among the toxicokinetic characteristics of carfentanil, its high lipid solubility stands out. In addition, there is the possibility that carfentanil follows a non-linear elimination kinetics. In 2002 this compound was used by the Russian Security Forces to try to resolve the hostage crisis at the Dubrovka theater in Moscow, causing the death of at least 123 hostages. On the other hand, carfentanil has been used as a drug of abuse and as an adulterant in other drugs. In case of carfentanil overdose, the administration of repeated doses of antidote may be necessary. The content of this review justifies the need to develop and validate an analytical method for the detection of carfentanil and its metabolite norcarfentanil in biological samples. (AU)

Carfentanilo: una doble amenaza para la salud pública / Carfentanil: a double threat to public health

El carfentanilo es un opioide sintético con una potencia 10.000 veces superior a la de la morfina. Esta y otras características posicionan al carfentanilo como una sustancia de interés dual, pues ha sido empleada como agente incapacitante y como droga de abuso. Entre las características toxicocinéticas del carfentanilo destacan su elevada liposolubilidad y la posibilidad de que siga una cinética de eliminación no lineal. En 2002 este compuesto fue empleado por las Fuerzas de Seguridad Rusas para intentar resolver la crisis de rehenes del teatro Dubrovka de Moscú, causando la muerte de al menos 123 rehenes. Por otro lado, el carfentanilo, se ha empleado como droga de abuso y como adulterante en otras drogas. En caso de intoxicación por carfentanilo puede ser necesaria la administración de dosis repetidas de antídoto. Los antecedentes expuestos en este trabajo justifican la necesidad de desarrollar y validar un método analítico para la detección del carfentanilo y su metabolito norcarfentanilo en muestras biológicas. (AU)

Carfentanil is a synthetic opioid with a potency 10,000 times greater than that of morphine. For this and other reasons carfentanil is a substance with dual interest, since it has been used as an incapacitating agent and as an abuse drug. Among the toxicokinetic characteristics of carfentanil, its high lipid solubility stands out. In addition, there is the possibility that carfentanil follows a non-linear elimination kinetics. In 2002 this compound was used by the Russian Security Forces to try to resolve the hostage crisis at the Dubrovka theater in Moscow, causing the death of at least 123 hostages. On the other hand, carfentanil has been used as a drug of abuse and as an adulterant in other drugs. In case of carfentanil overdose, the administration of repeated doses of antidote may be necessary. The content of this review justifies the need to develop and validate an analytical method for the detection of carfentanil and its metabolite norcarfentanil in biological samples. (AU)

Combating Fentanyl: National Guard Physician Assistants on the Front Lines of America's War Against Synthetic Opioids.

There is a significant threat to global health security due to synthetic opioids, illicitly manufactured fentanyl (IMF), and nefarious uses of pharmaceutical based agents (PBA). Since 2014, increased distribution of synthetic opioids including IMF into the US through China, India, and Mexico has resulted in devastating consequences to the average street drug user. Additionally, clandestine lab operations for pill manufacturing and distribution have increased, along with unintentional drug overdoses due to drugs being laced with fentanyl or some other synthetic opioid derivative. Naloxone has been shown to be an effective and useful tool for reversing signs and symptoms of synthetic opioid overdose, though additional doses may be required depending on the analog. In addition to the risk of overdose in US civilians, other state actors have utilized fentanyl and its analogs as incapacitants resulting in significant numbers of casualties. The National Guard Weapons of Mass Destruction-Civil Support Teams (WMD-CST) have been on the front lines supporting federal law enforcement agencies with hazard identification and assessment. Physician Assistants (PA) are assigned to these units and provide the necessary skills and expertise to keep on scene personnel safe. This article aims to dispel some of the rumors and myths surrounding fentanyl in an effort to educate first receivers, first responders, and hospital providers. Lastly, this article provides a review of synthetic opioid production, overdose, hazards, treatment/countermeasures, decontamination for responders, and the potential use of synthetic opioids as WMDs.

Chemical Agents Encountered in Protests.

The most common chemicals used in riot control agents are chlorobenzylidene malononitrile, chloroacetophenone, dibenz[b,f]-[1,4]-oxazepine, and oleoresin capsicum. They cause ocular, respiratory, and dermal effects usually within seconds to minutes of exposure, but delayed effects have been reported. In addition, the canisters containing these chemicals can cause traumatic injuries when launched as projectiles. Although most effects are mild, some may be serious, especially in those with preexisting respiratory disease. Treatment consists of removing the patient from the source of exposure, removing contaminated clothes, and copiously irrigating the affected areas with water.

3-Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats.

3-Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non-lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC-MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half-life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t1/2 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.