3-Quinuclidinyl Benzilate Poisoning: Background, Pathophysiology, Epidemiology (original) (raw)

Overview

Background

The chemical warfare agent 3-quinuclidinyl benzilate (QNB, BZ) is an anticholinergic agent that affects both the peripheral and central nervous systems (CNS). QNB is classified as an incapacitating agent and is listed in Schedule 2 by the Organization for the Prohibition of Chemical Weapons (OPCW). [1] It is one of the most potent anticholinergic psychomimetics known, with only small doses necessary to produce incapacitation. [2] It is classified as a hallucinogenic chemical warfare agent.

QNB usually is disseminated as an aerosol and the primary route of absorption is through the respiratory system. Absorption also can occur through the skin or gastrointestinal tract. It is odorless. QNB's pharmacologic activity is similar to other anticholinergic drugs (eg, atropine) but with a longer duration of action. The median effective dose (ED50) of QNB under field conditions is approximately 60 mg/min/m3 for a man of 75 kg body weight with a volume of respiration of 15 L/min. [2]

Also, see the article Chemical Warfare Agents.

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Pathophysiology

QNB acts by competitively inhibiting muscarinic receptors. QNB binds to all subtypes of muscarinic receptors (M1-M5). [2] Muscarinic receptors primarily are associated with the parasympathetic nervous system, which innervates numerous organ systems, including the eye, heart, respiratory system, skin, gastrointestinal tract, and bladder. Sweat glands, innervated by the sympathetic nervous system, also are modulated by muscarinic receptors. QNB readily crosses the blood-brain barrier. [2]

Effects of QNB by any route of exposure are slow in onset and long in duration. The onset of action is approximately 1 hour, with peak effects occurring 8 hours postexposure. Symptoms gradually subside over 2-4 days. Most of the QNB that enters the body is excreted by the kidneys, making urine the choice for detection.

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Epidemiology

Frequency

United States

Use of QNB against the United States has never been reported. Currently, the US Federal Government conducts chemical defense programs including research and development, training, and stockpiling of supplies and antidotes to prepare the nation for potential chemical terrorist attacks against citizens and the military; however, initial responses are dependent on local emergency response agencies.

International

Use of QNB has been suggested, but not confirmed, in two past international conflicts.

On January 16, 1992, Mozambican government forces (approximately 400 soldiers) attacked one of the largest strongholds of the RENAMO resistance group in southern Mozambique, close to the South African border. As they approached the camp on foot, an unidentified light aircraft was seen flying above the area. They came under limited small arms fire and took cover when an explosion occurred above their heads, releasing a dense cloud of black smoke, which then dissipated. The wind was blowing towards the rear of the formation.

Fifteen minutes later, the first complaints occurred: “It became very hot. Some of us were going crazy.” They felt severe chest pains, were tired and thirsty, and when they drank water the next morning some of them vomited. Others said they had difficulty seeing. As a consequence, the troops became disorganized.

The United Nation’s report on this incident concluded that the effect on the troops was consistent with the use of a chemical warfare agent such as QNB, but that in the absence of analytical data, they could not conclude that a chemical warfare agent was used in the attack because a considerable delay occurred between the attack (January 1992) and the formal investigation (March 1992).

On July 11 of 1995, approximately 15,000 people assembled in the village of Jaglici, situated in the Rebublika Srpska of Bosnia and Herzegovina. This group had fled from Srebrenica (15 km away) after Bosnian Serb forces began to shell the town. In order to flee the Bosnian Serbs, the assembled column started to leave Jaglici on July 12 at 12:30 am, with the last members of the column leaving 12 hours later. The reported progress of the column was slow because of concern for minefields. Individuals were required to walk in single file holding hands to avoid getting lost in the forest at dark and enabling them to walk in each other’s footsteps to avoid landmines. Only a fraction of the members of the column eventually reached safe territory on July 16, after coming under fire from Bosnian Serb forces on a number of occasions.

According to eyewitness accounts, the Bosnian Serbs used different shells, some exploded and others gave out a "strange smoke" that did not rise in the air but rather spread toward the column at the height of a man. Reportedly, a large number of those exposed suffered from hallucinations during the course of the 5-day march. It was subsequently suspected that the Bosnian Serb forces had used a chemical warfare agent to disorient the marchers, prompting Human Rights Watch to visit the location in March of 1996.

During the course of the investigation, marchers were interviewed. Subsequent testimony suggested that unusual munitions may have been used by the Bosnian Serbs, and that those interviewed had experienced themselves or witnessed others with marked hallucinations. The agent suspected to have caused these effects was QNB.

Mortality/Morbidity

The LD50 (lethal dose to 50% of an exposed population) for QNB is estimated to be similar to that of atropine, which is approximately 100 mg; however, QNB causes incapacitation at much lower levels. Other factors, such as the exposed patient's preexisting health status and the time from exposure to medical care, are also important.

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Author

Christopher P Holstege, MD Professor of Emergency Medicine and Pediatrics, University of Virginia School of Medicine; Chief, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, UVAHS Blue Ridge Poison Center; Executive Director, Department of Student Health and Wellness, University of Virginia

Christopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College Health Association, American College of Emergency Physicians, American College of Medical Toxicology, European Association of Poisons Centres and Clinical Toxicologists, Medical Society of Virginia, Society for Academic Emergency Medicine, Society of Toxicology, Wilderness Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Aaron S Frey, DO Attending Physician, Department of Emergency Medicine, UVA University Hospital and Richmond Emergency Physicians, Inc

Aaron S Frey, DO is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Thomas M Stewart University of Virginia

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: University of Virginia.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Duane C Caneva, MD, MSc Senior Medical Advisor to Customs and Border Protection, Department of Homeland Security (DHS) Office of Health Affairs; Federal Co-Chair, Health, Medical, Responder Safety Subgroup, Interagency Board (IAB)

Disclosure: Nothing to disclose.

Additional Contributors

Suzanne White, MD Medical Director, Regional Poison Control Center at Children's Hospital, Program Director of Medical Toxicology, Associate Professor, Departments of Emergency Medicine and Pediatrics, Wayne State University School of Medicine

Suzanne White, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Clinical Toxicology, American College of Epidemiology, American College of Medical Toxicology, American Medical Association, Michigan State Medical Society

Disclosure: Nothing to disclose.