Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical Warfareanimals. 75 Like PCP, its mode of action is complex.Also like LSD, both ketamine and PCP are attractedto 5-HT 2Aserotonin receptors, but they also possessaffinity for a number of other receptors. PCP acts as aninverse agonist at the glutamate receptor, which hasbeen called “the PCP receptor.” 76 PCP’s multiplicity ofreceptor affinities produces a complex clinical picture,with psychedelic, delirium-producing, energizing, andanalgesic elements.Treatment for PCP, unlike for LSD, is difficult. Benzodiazepinesare generally used. Physostigmine mightimprove cognitive functions, and antipsychotics areoften given to minimize irrational behavior, but thesealone do not reverse all effects. Keeping the patientin dark, quiet surroundings tends to minimize agitationand assaults. Temporary hospitalization may benecessary. 77,78TranquilizersDiazepam (Valium, Hoffmann-La Roche Inc, Nutley,NJ), successor to the popular drug meprobamate(Equanil, Wyeth-Ayerst Laboratories, Madison, NJ)was initially hailed as a wonder drug when it wasintroduced in 1959. Psychiatrists considered it to be a“minor tranquilizer,” in contrast to “major” tranquilizerssuch as chlorpromazine or haloperidol (Haldol,Ortho-McNeil Pharmaceutical, Raritan, NJ). Over thenext two decades, a bevy of benzodiazepines structurallyrelated to diazepam appeared on the market. 79The major tranquilizers were meanwhile renamed“antipsychotics,” and the minor tranquilizers became“anxiolytics.” In addition to their antianxiety andtranquilizing effects, benzodiazepines have musclerelaxant, anticonvulsant, amnestic, and sedativehypnoticeffects. All of these contribute to performanceimpairment.Flumazenil, a benzodiazepine antagonist, is aninverse agonist at the γ-aminobutyric acid receptorwith the side effect of severe anxiety 80 (which wouldobviously affect performance adversely, making it incapacitatingin its own right). Many benzodiazepinesnow exist, ranging in duration of action from extremelyshort to very long. Some of the more recently introducedmembers of the family are also highly potent.Alprazolam (Xanax, Pfizer US Pharmaceuticals, NewYork, NY) and triazolam (Halcion, Pfizer US Pharmaceuticals,New York, NY ) require small oral doses toproduce sedation or tranquilization. 81Antipsychotic DrugsThe more potent antipsychotic drugs were previouslycalled major tranquilizers or “neuroleptics.”These drugs are valued not only for their sedativeeffects, but also for their ability to reduce psychotichyperactivity. They tend to produce extrapyramidalsymptoms similar to parkinsonism, which is causedby the loss of dopamine-producing neurons in themidbrain’s substantia nigra. Because they block dopaminereceptors, most antipsychotic drugs causethe same problems: rigidity, tremor, and reducedactivity, which results in considerable impairment ofmovement. The potency of some antipsychotic drugs,although impressive, generally would not satisfylogistical constraints. 82 Performance decrements onthe usual cognitive measures were only slightly doserelated, with a shallow dose-response slope, meaningthat the effects would be difficult to predict, and considerablyhigher doses would be required to ensurecomplete incapacitation.The lethal dose of an antipsychotic drug is manytimes the therapeutic dose, but precise values areunavailable. Very high doses of haloperidol, forexample, can be tolerated; paradoxically, such highdoses may actually produce fewer parkinsonian sideeffects. Some clinicians, perhaps frustrated with thelack of response to ordinary doses of haloperidol, triedgiving larger doses to psychotic patients. No greatertherapeutic response occurred, but because haloperidolhas significant anticholinergic effects at highdoses, it prevented the parkinsonian side effects thatare common after lower doses (working like the drugbenztropine [Cogentin, Merck & Co Inc, WhitehouseStation, NJ]). 83 Malignant hyperthermia, a potentiallylethal complication, occasionally occurs after repeatedingestion of much lower doses.Parkinsonian symptoms, particularly in the form ofpainful spasms of neck muscles, occurred in many ofthe volunteers. These did not usually appear until 8to 12 hours after ingestion, and invariably respondedpromptly to an injection of benztropine or diphenhydramine(Benadryl, Pfizer Consumer Healthcare,New York, NY). Delayed spasms could therefore beprevented in the field if prompt medical custody ofthe affected individuals were assured.Neuropeptides and NeuromodulatorsThe newest potential incapacitating agents are thosethat operate on the central nervous system, either assurrogate neurotransmitters with unwanted effects, oras natural neuropeptide transmitters applied in waysthat were unintended by nature. Military considerationof such substances was spurred by a review submittedin 2000 by the University of Pennsylvania under a governmentcontract. 84 In 2003, three analysts from the USDefense Intelligence Agency authored a paper called420