With all the uncertainties we face daily from rampant infectious diseases, a lack of control over who is entering the U.S. through open borders, criminal acts of terrorism becoming more common, and the increase in drug shortages, pharmacists and other healthcare professionals must be prepared for possible domestic disasters/attacks involving biological, chemical, or nuclear weapons. Federal, state, and local agencies must have the knowledge, intelligence, training, and supplies to counter these threats. Pharmacists have a unique role to perform in providing needed pharmaceuticals (e.g., beta-lactam antibiotics) and information to their communities, and they should be involved in a community's planning for response to bioterrorist or terrorist attacks.

Preparedness
An effective response to bioterrorism will require prepared, well-trained local responders who can interact with state and federal agencies. Training for responders should cover the characteristics of biological and nonbiological agents that can be used in destruction. Pharmacists should be trained in their duties as responders, and they should be protected in the event of an attack so they can perform those duties. Security of the pharmacy may be a top concern because break-ins to obtain medications may occur.

Although the threat of terrorist attacks has grown in recent years, natural disasters such as floods, hurricanes, and tornadoes are a recurring cause of mass destruction. For these situations, too, pharmacists should be involved in local disaster planning.

Even small communities must be prepared to handle a mass-casualty incident until state and federal assistance arrives. In such circumstances, healthcare providers must manage many patients who require urgent care, and pharmacists are likely to be pressed into action to deliver the medications needed to save lives; relieve pain; and limit potential damage from exposure to caustic, infectious, or other harmful agents. Pharmacists may be involved in treating not only patients suffering from exposure to nerve gas, biological weapons, or trauma, but also victims of a bombing.

Pharmacies’ maintenance of just-in-time inventory works against an adequate response to disasters and terrorism. Competition for limited resources could challenge the ability to maintain civic order. Pharmacists involved in an emergency situation may find that providing information is relatively simple but providing pharmaceuticals is more difficult because pharmacies routinely stock commercially available products in limited quantities only. Many pharmacists can compound some preparations to help fill the need until commercial stocks are replenished. Compounding pharmacists can provide various dosage forms to all types of patients.

Causative Agents
Terrorists may use chemical agents, including blistering agents (e.g., lewisite, mustard gas, phosgene oxime), choking agents, nerve agents (e.g., mustard gas, sarin gas, soman, tabun, VX), and cyanide. Biological agents used as weapons may include bacteria (e.g., those causing anthrax, brucellosis, plague, Q fever, and tularemia), toxins (e.g., botulinum toxin, ricin, and staphylococcal enterotoxin B), and viruses (e.g., those causing smallpox, Lassa fever, Rift Valley fever, Venezuelan equine encephalomyelitis).

Genetic engineering is expanding the list of potential agents for use in terrorism. Novel forms of agents, including multidrug-resistant organisms, may be made available in vast quantities.

Biological agents may be disseminated through the use of conventional explosives or aerosol generators (e.g., aircraft, cruise missiles, mail) or through contamination of the food or water supply. Exposure may occur by the pulmonary (e.g., plague, Q fever, staphylococcal enterotoxin B) or systemic (e.g., botulinum toxin, viruses) route or through person-to-person (e.g., smallpox, pneumonic plague) or vector (e.g., plague, Rift Valley fever) contact.

Chemical Agents
The availability, extreme toxicity, and rapid onset of action of many chemical agents have made them desirable to terrorists. Agents of chemical warfare are commonly classified as blood agents (cyanogen chloride, hydrogen cyanide), nerve agents (sarin, soman, tabun), lung agents (diphosgene, phosgene), or blister agents (lewisite, mustard).

Blood Agents
Blood agents produce their effects by interfering with oxygen use at the cellular level. Certain types of cyanide are referred to as blood agents. Nitrite is the common ingredient used to displace cyanide from the oxygen that carries hemoglobin after contact with a blood agent has occurred. Other pharmaceuticals that serve as adjunctive therapy for cyanide poisoning are injectable sodium bicarbonate, which can correct metabolic acidosis, and benzodiazepines (e.g., diazepam or lorazepam), which are used as anticonvulsants. Formulations that counteract the effects of blood agents include: (1) sodium nitrite 3% injection, (2) sodium thiosulfate 25% injection, (3) sodium bicarbonate 8.4% injection, (4) diazepam 5-mg/mL injection, and (5) lorazepam 2-mg sublingual tablets.

Nerve Agents
Nerve agents are organophosphorus cholinesterase inhibitors. They inhibit the enzyme acetylcholinesterase. Chemotherapeutic intervention consists of the use of three antidotal agents: atropine sulfate, which blocks muscarinic receptor sites; pralidoxime chloride, which regenerates cholinesterase activity; and diazepam or lorazepam, both of which are used as anticonvulsants. Topical ophthalmic homatropine or atropine can be used to relieve dim vision, pain, and possible nausea. Formulations to counteract the effects of nerve agents include: (1) pralidoxime chloride injection (1-g vial), (2) atropine sulfate 1-mg/mL injection, and (3) diazepam 5-mg/mL injection.

Lung Agents
Chemical agents that attack lung tissue are also referred to as pulmonary agents or choking agents. They inflict injury on the respiratory tract, including the nose, throat, and especially the lungs. Victims typically inhale these agents, which can all lead to pulmonary edema and respiratory failure. These agents include chlorine and phosgene, deadly and unpredictable gases that were used in World War I. Because they have many industrial applications, pulmonary agents are readily available to terrorists in large quantities. No specific antidotes exist for these lung and eye irritants, but supportive care may include the use of bronchodilators such as nebulized albuterol sulfate or sodium bicarbonate. Methylprednisolone acetate injection also has been used as supportive therapy to counteract the effects of these agents. Formulations that counteract the effects of pulmonary agents include (1) albuterol sulfate 0.5% inhalation solution, (2) sodium bicarbonate 3.75% inhalation solution, and (3) methylprednisolone acetate 40-mg/mL injection.

Blister Agents
Blister agents, or vesicants, are potent alkylating agents that produce scarring blisters, eye damage, and airway damage. They include lewisite, nitrogen mustard, and phosgene oxime. Treatment may include the application of topical silver sulfadiazine or topical mafenide acetate. Only one blister agent, lewisite, has an antidotal compound (dimercaprol), which acts as a chelating agent for arsenicals and other heavy metals. Dimercaprol skin and eye ointment applied to victims after decontamination may reduce the severity of lesions. Dimercaptosuccinic acid has been used successfully in animals for the treatment of lewisite exposure and lead ingestion. Available in 100-mg capsules, dimercaptosuccinic acid can be administered orally to treat multiple exposures to blister agents. Formulations that counteract the effects of blister agents include: (1) silver sulfadiazine cream, (2) mafenide acetate cream, (3) dimercaprol injection, (4) dimercaprol ointment, and (5) dimercaptosuccinic acid 100-mg capsules.

Biological Agents
Biological terrorism could involve sophisticated or unsophisticated techniques (i.e., use of dried anthrax spores, botulinum toxins, the use of Salmonella, or other common bacteria, respectively). Unlike chemical nerve agents, which can cause immediate death or severe injury at the site of attack, biological agents cause delayed signs and symptoms because of their incubation periods. If used against unsuspecting, nonimmune civilian populations, biological weapons could enable terrorists to cause a large number of casualties and create international panic.

In the event of an attack, frontline clinicians and primary-care practitioners will need to identify and manage exposed patients. Pharmacists will need to be knowledgeable about diseases caused by biological agents and about patient management, vaccines, and potential chemotherapeutic agents, so that they can educate the public and other healthcare practitioners.

Many oral and injectable medications, in extraordinarily large amounts, may be needed to treat an outbreak of illness caused by a biological weapon. Pharmaceutical needs will depend on the duration of illness, the virulence of an outbreak of disease, and the number of patients affected. Uncommonly used vaccines and antitoxins should be prepositioned with the assistance of federal government storage and distribution programs.

Nuclear Agents
Dirty bombs, conventional explosives used to spread hazardous radioactive material, might be involved in a terrorist attack. Radioactive materials can emit three types of harmful radiation: α (alpha), β (beta), and γ (gamma). Inhalation or ingestion of α or β particles poses the greatest hazard. The most harmful type overall, γ rays, can penetrate most sheltering material in a wide area.

Exposure to a harmful radiological agent may require treatment with a chelator or a radionuclide blocker. Some general radionuclide chelating agents are penicillamine (Cuprimine), edetate calcium disodium (Calcium Disodium Versenate), dimercaprol (British anti-Lewisite, or BAL), succimer (Chemet), and deferoxamine (Desferal). (Colony-stimulating factors may be considered in patients experiencing significant bone-marrow suppression.) Information about this specialized class of drugs can be obtained 24 hours a day from the Radiation Emergency Assistance Center/Training Site (http://orise.orau.gov/reacts/) telephone 865-576-3131, or 865-576-1005 for emergencies.

A variation of radionuclide chelation to entrap and remove the radioactive agent is the use of radionuclide-blocking agents. These agents saturate tissues with a nonradioactive element that reduces the uptake of radioactive iodine. The most commonly known radionuclide-blocking agents are potassium iodide tablets and Lugol’s solution, both of which reduce the uptake of radioactive iodine by thyroid tissue.

Next Week: “Pharmacists’ Involvement During An Emergency�

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

Articles and complete issues on the topics of terrorism and natural disasters have been published in the International Journal of Pharmaceutical Compounding. To see a list, including some available for free, go to:
https://ijpc.com/​Products/​Search​ByKeyword.cfm​?searchstr​=terrorism%20disaster.