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

Medical Aspects of Chemical WarfareFig. 5-7. An infusion of 25 mg/kg of 2-pyridine aldoximemethyl chloride (2-PAM Cl) over about 25 minutes producesmarked hypertension, which is rapidly but transiently reversedby phentolamine (5 mg). The mean blood pressureis the diastolic plus one third of the difference between thesystolic and the diastolic.Reproduced with permission from: Sidell FR. Clinical considerationsin nerve agent intoxication. In: Somani SM, ed.Chemical Warfare Agents. New York, NY: Academic Press;1992: 181.dose is excreted in 3 hours, 198 probably by an activetubular excretory mechanism (its renal clearance isclose to that of p-aminohippurate 199 ), with a half-timeof about 90 minutes. 144 Both clearance and amountexcreted are decreased by heat, exercise, or both. 200Thiamine also decreases excretion (presumably byblocking tubular excretion), prolongs the plasma halflife,and increases the plasma concentration for theduration of thiamine activity. 198–202 Some 203 questionthe therapeutic benefit of thiamine.An early clinical report 204 on the use of 2-PAM Cl ininsecticide-poisoned people indicated that the oximereversed the CNS effects of the poison (eg, patientsregained consciousness and stopped convulsingshortly after the oxime was given). However, otherearly investigators found no oxime in the brains ofanimals 205,206 or the cerebrospinal fluid of humans 207after experimental administration of 2-PAM Cl. Otherinvestigators 74,208 found small amounts of 2-PAM Cl orreversal of the brain ChE inhibition in brains of animalspoisoned with organophosphorus compounds.AdministrationAn oxime should be initially administered withatropine. In cases of severe exposure, the contents ofthree Mark I kits or ATNAA should be administered;if these are not available, then oxime 1 to 1.5 g shouldbe administered intravenously over a period of 20 to30 minutes or longer. Additional atropine should begiven to minimize secretions and to reduce ventilatoryproblems, thereby relieving the casualty ’ s distress anddiscomfort.Since an improvement in the skeletal muscle effectsof the agent (ie, an increase or decrease in muscle toneand reduced fasciculations) may be seen after oximeadministration, medical personnel may be tempted torepeat the oxime along with atropine. Because of sideeffects, however, no more than 2.5 g of oxime shouldbe given within 1 to 1.5 hours. If the oxime is effective,it can be repeated once or twice at intervals of 60 to90 minutes.2-PAM Cl can be administered intravenously, intramuscularly,and orally. Soon after it became commerciallyavailable, 2-PAM Cl was administered orallyboth as therapy and as a pretreatment for those inconstant contact with organophosphorus compounds(eg, crop dusters). At one time, the United Kingdomprovided its military personnel with a supply of oximetablets for pretreatment use, but it no longer does so.Enthusiasm for this practice waned for a number ofreasons:• erratic absorption of the drug from the gastrointestinaltract, leading to large differences(both between individuals and in the sameperson at different times) in plasma concentration;• the large dose required (5 g to produce anaverage plasma concentration of 4 µg/mL);• the unpopularity of the large, bitter 0.5-g or1.0-g tablets; and• the relatively slow absorption compared withthat for administration by other routes.In addition, the frequent administration (every 4–6h) required by at-risk workers caused gastrointestinalirritation, including diarrhea. It is no longer commonpractice for crop workers to be given 2-PAM Cl as apretreatment either, the rationale being that crop workerswho take the medication might have a false senseof security and therefore might tend to be careless withsafety measures.Despite these drawbacks, 2-PAM Cl tablets may bethe best alternative in certain cases, such as that of adepot worker exposed to a nerve agent who shows noeffects except for an inhibition of RBC-ChE activity. Anoxime might be given to restore the worker ’ s RBC-ChEactivity to 80% of the baseline value, which is necessaryfor return to work. (See Blood Cholinesterases section,above, for discussion of monitoring RBC-ChE activity.)188