Weapons of Mass Destruction (WMD)

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Incapacitating Agents

Fentanyl (FEN-ta-nil) belongs to the group of medicines called narcotic analgesics (nar-KOT-ik an-al-GEE-ziks). Narcotic analgesics are used to relieve pain. The transmucosal form of fentanyl is used to treat breakthrough cancer pain. Breakthrough episodes of cancer pain are the flares of pain which "breakthrough" the medication used to control the persistent pain. Transmucosal fentanyl is only used in patients who are already taking narcotic analgesics. Fentanyl acts in the central nervous system (CNS) to relieve pain. Some of its side effects are also caused by actions in the CNS.

An overdose can cause severe breathing problems (breathing may even stop), unconsciousness, and death. Serious signs of an overdose include very slow breathing (fewer than 8 breaths a minute) and drowsiness that is so severe that you are not able to answer when spoken to or, if asleep, cannot be awakened. Other signs of an overdose may include cold, clammy skin; low blood pressure; pinpoint pupils of eyes; and slow heartbeat.

First synthesized in Belgium in the late 1950s, fentanyl, with an analgesic potency of about 80 times that of morphine, was introduced into medical practice in the 1960s as an intravenous anesthetic under the trade name of Sublimaze®. Thereafter; two other fentanyl analogues were introduced; alfentanil (Alfenta®), an ultra-short (5-10 minutes) acting analgesic, and sufentanil (Sufenta®), an exceptionally potent analgesic (5 to 10 times more potent than fentanyl) for use in heart surgery.

Today, fentanyls are extensively used for anesthesia and analgesia. Duragesic®, for example, is a fentanyl transdermal patch used in chronic pain management, and Actiq® is a solid formulation of fentanyl citrate on a stick that dissolves slowly in the mouth for transmucosal absorption. Actiq® is intended for opiate-tolerant individuals and is effective in treating breakthrough pain in cancer patients. Carfentanil (Wildnil®) is an analogue of fentanyl with an analgesic potency 10,000 times that of morphine and is used in veterinary practice to immobilize certain large animals.

Illicit use of pharmaceutical fentanyls first appeared in the mid-1970s in the medical community and continues to be a problem in the United States. To date, over 12 different analogues of fentanyl have been produced clandestinely and identified in the U.S. drug traffic. The biological effects of the fentanyls are indistinguishable from those of heroin, with the exception that the fentanyls may be hundreds of times more potent. Fentanyls are most commonly used by intravenous administration, but like heroin, they may also be smoked or snorted.

Fentanyl has an extremely low therapeutic index. Narrow therapeutic index drugs are those pharmaceuticals having a narrowly defined range between risk and benefit. Such drugs have less than a twofold difference in the minimum toxic concentration and minimum effective concentration in the blood or are those drug product formulations that exhibit limited or erratic absorption, formulation-dependent bioavailability, and wide intrapatient pharmacokinetic variability that requires blood-level monitoring.

Narrow therapeutic Index is a term of art which has come into current use, but the term more correctly, is narrow therapeutic ratio. Narrow therapeutic ratio is defined in the regulations at 21 CFR 320.33(c). This subsection deals with criteria and evidence to assess actual or potential bioequivalence problems. Under Section 320.33(c) of Code of Federal Register 21, the US FDA defines a drug product as having a narrow therapeutic ratio as follows: there is less than a 2-fold difference in median lethal dose and median Effective dose values, or there is less than 2-fold difference in the minimum toxic concentrations and minimum effective concentrations in the blood.

More than 100 hostages died from the effects of the incapacitating fentanyl gas used by Russian troops in an October 2002 rescue operation. The captives died after Russian security forces used a gas to incapacitate Chechen gunmen during a raid on the theater where the hostages were being held. Nearly 48-hours after being freed, most of the hostages remained hospitalized from the effects of the gas, about a quarter of them were placed in intensive care. Russian officials initially did not specify what type of gas they used during the raid on 26 October 2002. Gunmen demanding an end to the war in Chechnya took hundreds of people hostage on 23 Octobre 2002 after storming a Moscow theatre. The gunmen rigged explosives throughout the building and threatened to shoot hostages or blow up the theater if Russian forces raided the building. All hostages treated at their hospital were given naloxone, and none failed to respond.

The gas used to subdue the terrorists and their hostages was most likely an aerosol form of carfentanil, an extremely potent narcotic normally used to used to sedate big game animals. The gas may have also contained halothane, an inhalational anesthetic. Carfentanil, about 8,000 times as powerful as morphine and 100 times more potent than fentanyl, is a fentanyl derivative sold under the trade name Wildnil. Carfentanil has an unusually wide safety margin, which is why it's the immobilizing agent of choice when delivery is by the unpredictable route of a rifle-fired hypodermic dart. The therapeutic index of carfentanil in rats is 10,000, meaning that a lethal dose is about 10,000 times more than the dose required to relieve pain. Halothane, in contrast, has a therapeutic index of about 3, meaning that a lethal dose is only 3 times that required to put someone to sleep.

On 09 April 1989, troops from the Soviet Ministries of Defense and Interior used gas against a peaceful protest by 8,000 to 10,000 people in Tbilisi, Soviet Georgia. At least 20 people were killed, and hundreds of people were injured and admitted to hospitals. The Soviet authorities initially denied that toxic gas had been used, though a week after the event they acknowledged that CN tear gas had been used. The nonlethal gas became sadly notorious as "cheryomukha" (bird cherry, also a name of a flavored vodka).

On 17 May 1989, a team of three Physicians for Human Rights (PHR) physicians from the United States arrived in Tbilisi. The Physicians for Human Rights team concluded that the Soviet troops most probably used a toxic agent called chloropicrin, in addition to the use of one or two tear gases (CN and CS). This gas was identified on the basis of mass spectroscopy in a canister allegedly recovered on the scene.

Chemical agents which attack lung tissue, primarily causing pulmonary oedema, are classed as lung damaging agents. To this group belong phosgene (CG), diphosgene (DP), chlorine (Cl) and chloropicrin (PS). Chloropicrin is known for its unpredictable toxicities in crowd use, and can cause skin and mucosal blisters, bronchoconstriction, and pulmonary edema. All these symptoms were reported among the casualties of the April 9 demonstration.

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