Oximes work by reactivating AChE. They bind to the organophosphate-inactivated AChE and displace and hydrolyze the organophosphate. They must be administered rapidly to be effective, due to a process called "aging," which refers to the organophosphoryl moiety and the amino acids of the active site becoming covalent and changing their structure. Once this has happened, the enzyme cannot be reactivated. The aging times depend on the nerve agent: GD has the fastest aging time, with a half-time of 2 minutes [106] . GB ages in 3 to 4 h, others take longer; VX ages very little. The oximes affect nicotinic sites; there is no clinical effect at muscarinic sites, and available oximes do not cross the blood brain barrier. Pralidoxime is the compound most frequently used in a dosing of 1 to 2 mg in 100 cc normal saline for 15 to 30 minutes, followed by a second dose after an hour if paralysis persists [102] . In critically ill patients, a pralidoxime infusion at 7.5 mg/kg/h is safe [107] . Very rapid administration of pralidoxime, on the other hand, can worsen motor weakness. Oximes are mostly given in conjunction with atropine and benzodiazepines.