Pralidoxime chloride (2-PAM) is the only oxime currently approved for use in the United States. Oximes differ in their effectiveness against specific agents, recommended doses, and side-effect profiles. Oximes commonly used in other countries include obidoxime, trimedoxime, and HI-6.
Oximes are more effective when given before AChE has been bound irreversibly (“aged”) by the organophosphate. The rate of aging varies considerably with each OP compound. For dimethylphosporylated AChE (eg, from dichlorvos or malathion poisoning), the aging half-life is approximately 3.7 hours, whereas for diethylphosphorylated AChE (eg, from diazinon or parathion poisoning), the aging half-life is approximately 33 hours. For some chemical warfare agents, aging may occur in several minutes (eg, with soman, the phosphorylated AChE aging half-life is about 2–6 minutes). However, late therapy with 2-PAM is appropriate (even several days after exposure), especially in patients poisoned with diethyl compounds and with fat-soluble compounds (eg, fenthion, demeton) that can be released from tissue stores over days, causing continuous or recurrent intoxication.
“Nerve” agents prepared as chemical warfare weapons, such as sarin, soman, tabun, and VX, are mechanistically similar to AChE-inhibiting insecticides. However, they are far more potent and responsive only to certain oximes. Pralidoxime is not effective against tabun, for example, but HI-6 has been found to be effective. Current oxime research seeking agents with broader activity against nerve agents is evaluating oximes HI-6, K027, K048, K074, and K075.
Inadequate dosing of 2-PAM may be a contributing cause of “intermediate” syndrome, which is characterized by prolonged muscle weakness.
Peak plasma concentrations are reached within 5–15 minutes after intravenous 2-PAM administration. Pralidoxime is eliminated by renal excretion and hepatic metabolism, with a half-life of 0.8–2.7 hours.