Obidoxime with atropine

The oxime HI-6 with atropine is reasonably effective against soman regardless of the choice of experimental animals while currently used oximes (pralidoxime and obidoxime) seem to be practically uneffective to protect mammals poisoned with supralethal dose of soman (Table 4). Presented data confirm that soman appears to be one of the most resistant nerve agent to the antidotal treatment because of the rapid aging of soman-phosphonylated AChE and the existence of a soman depot in the poisoned organisms (31, 54, 55). The soman-AChE complexes age very quickly and this fact prevents the oxime-induced reac-... 

In three studies reviewed by FAO/WHO (1994) on phosalone and 2-PAM methylsulfate in mice, P2S in rats, and obidoxime in mice, all appeared effective, although various aspects of the design of the. studies were not optimal. Oximes (PAM or obidoxime) in combination with atropine were successful in rats experimentally poisoned with pyrazophos, and there was some indication that repeated dosing was required for optimal antidotal efficacy (FAO/WHO, 1993). In a rat study of experimental terbufos poisoning, little benefit was observed from PAM and atropine (FAO/WHO, 1991). In rat studies on triazophos, combinations of atropine. sulfate and 2-PAMI or atropine sulfate and obidoxime were successful as experimental therapies (FAO/WHO, 1994). The effects of oximes in profenofas-poisoned chicks and mice were reported to be limited, as expected, although atropine was effective (FAO/WHO, 1991). 

In a case report, continuous PAM infusion (with atropine sulfate) was successful in treating chlorpyrifos poisoning, and the nicotinic signs and symptoms were controlled (Tush and Anstead, 1997). In a case series, Tbiermann ef al. (1997) reported that in parathion poisoning, obidoxime... 

Obidoxime can be given with atropine in the treatment of OP poisoning in a usual initial dose of 250 mg (4mg/kg) by slow intravenous injection. This may be followed by intravenous infusion of 750 mg over 24 h, continued until the concentration of OP is below critical levels alternatively, repeated doses of 4-8mg/kg may be given at intervals of 2-4 h. It has also been given by intramuscular injection (Obidoxime Chloride, 2009). 

F. Vetterlein and W. Haase, Regional blood flow determinations in the rat during paraoxon-poisoning and treatment with atropine and obidoxime. Toxicology, 1979,12,173-181. 

The standard treatment of nerve agent-induced muscle toxicity calls for (1) reactivation of the phosphorylated AChE with an oxime, and (2) blockage of the nicotinic ACh receptor sites from the stimulating action of ACh with fii-tubocurarine. Oximes such as obidoxime, pralidoxime (2-pyridine aldoxime methochloride, 2-PAM) and a few others have been found very effective when given in combination with other drugs such as atropine, pretreatment with oximes varies with the ehemieal structures of the nerve agents and depends on the time after exposure. For example, it has been... 

However, there are publications demonstrating that some oximes are not considered to reach a plasma concentration of > 4 pg/ml to counteract the toxic effects of OPC. Shiloff and Clement reported that a plasma concentration of HI-6 of only 0.72 pg/ml and plasma concentration of pralidoxime of only 2.56 pg/ml were required to protect 50% of rats against a subsequent dose of three times the LD50 of sarin when followed immediately by atropine. On the other hand, obidoxime has to reach the plasma concentration of 9.05 pg/ml to protect 50% of rats poisoned with sarin at a dose of 3xLD50 (18). 

Urbanski, R., Evaluation of the therapeutic effectiveness of optimal doses of atropine sulphate, obidoxime and diazepam in acute poisoning with soman, sarin and VX, Lek. Wojsk., 64,486-490, 1988. 

In another case series, Thiermann et al. (1999) reported that in parathion poisoning, reactivation was possible 7 days after poisoning, whereas with oxydemeton methyl, response was only seen when obidoxime therapy was instituted soon after poisoning. Similarly, Zilker et al. (1997) reported that obidoxime (750 mg/day by infusion) drastically reduced the need for atropine in parathion poisoning, but that demeton-5-methyl poisoning only responded to obidoxime if therapy was instituted soon after intoxication. 

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