Antidotes atropine/oxime

Fig. 6 Concentration-time profile of antidotal atropine and its enantiomers S- and / -hyoscyamine in plasma of an in vivo swine study. Swine were topically exposed to the nerve agent VR (302 pg/ kg, t0) followed by administration of atropine sulphate (30 pg/kg) and the reactivating oxime HI 6 (12.8 mg/kg) via three i.m. injections into the rear leg at 30 (I), 180 (II) and 330 min (III). Blood samples were collected at distinct time points to generate EDTA plasma. Maximum concentrations were found 4 min after drug administration each. No differences of S- and R-Hyo concentrations were evident underlining similar elimination kinetics for both enantiomers. Data are mean and SD from duplicate measurement using the enantioselective LC-MS/MS approach of John et al. [47,49]. Black circles, total hyo grey circles, S-hyo grey triangles, R-hyo...

Paddle, B.M. Dowling, M.H. Simple high-performance liquid chromatographic method for assessing the deterioration of atropine-oxime mixtures employed as antidotes in the treatment of nerve agent poisoning. J.Chromatogr, 1993, 648, 373-380... 

Pyridostigmine Bromide An antidote enhancer that blocks acetylcholinesterase, protecting it from nerve agents. When taken in advance of nerve agent exposure, pyridostigmine bromide increases survival provided that atropine and oxime and other measures are taken. 

Treatment — Patients should be decontaminated immediately prior to treatment using the decontamination method presented in Section 7.3.2. Ventilate the patient because of a possible increase in airway resistance due to constriction and the presence of secretions. If breathing is difficult, administer oxygen. Administer antidotes as soon as possible. The antidote for this agent is atropine alone or in combination with pralidoxime chloride (2-PAMC1) or another oxime. Diazepam may be required to control severe convulsions. 

Tables 2 and 3 show the standard protocol for treatment of nerve agent casualties which includes administration of atropine as the gold standard antidote for nerve agent therapy and oxime as a complementary treatment which has a significant role in treatment of patients with nerve agent intoxication, as well as diazepam.

In the field hospital the patients were treated with antidotal therapy (Atropine sulfate), oxime therapy (HI-6 or Pralidoxim), anticonvulsive therapy (Diazepam) and other supportive treatment such as ventilatory support. Victim with serious symptoms like unconsciousness, fasciculation, miosis, uncontrolled urination and defecation, severe dyspnea, convulsions and flaccid paralysis were immediately lifted in Zadar hospital. 

Gender differences are observed in the antidotic-and-therapeutic action of oximes. The single administration of an oxime concurrently with atropine protects males from 4.2 DL50 of soman and 2.5 DL50 of tabun, with respective values for females being 10.5 and 4.3 DL50 [79],... 

The therapeutic efficacy of oximes is usually focused on the evaluation of the protective ratio (PR), which is the ratio of the LD50 value of nerve agents for therapeutically protected animals to the LD50 value of nerve agents for unprotected animals. The authors usually publish data obtained from experiments where a combination of atropine and an oxime is used as an antidotal treatment because this possibility is much more relevant to anticipated military use than atropine or oxime alone. The results of published experiments are listed in Table 4(10, 32-47). 

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-... 

Casualties receiving antidotes should be moved to hospital as soon as possible. Casualties who do not develop the features of systemic toxicity, notably rhinorrhoea and bronchorrhoea, should be triaged but not given atropine or oxime. 

Pyridostigmine pre-treatment increased the antidotal efficacy of oxime-atropine combinations in various studies, especially in soman-poisoned animals (Gordon et al, 1978 Dimhuber et al., 1979 Inns and Leadbeater, 1983 Leadbeater et al., 1985), but some reports indicate that pyridostigmine reduced the antidotal effect in sarin, VX and VR poisoning (Anderson et al, 1992 Koplovitz and Stewart, 1992 Maxwell et al, 1997). 

The efficacy of orally administered pyridostigmine syrup, when used as a pretreatment for rhesus monkeys exposed to sarin and treated with antidotes such as atropine sulfate, the oxime TMB-4 and the anticholinergic agent benactyzine hydrochloride, was evaluated. The authors showed that oral PB treatment followed... 

Current antidotal therapy for organophosphate exposure resulting from warfare or terrorism includes parenteral atropine, an oxime (2-PAM or HI-6), and a benzodiazepine as an anticonvulsant. Oximes and their metabolites are readily eliminated by the kidney. 

The plant should have access to a full- or pan-lime occupational health physician supported by an occupational health nurse. They. should be responsible for the conduct and recording of pre- and periodic medical surveillance and be available for any emergency overexposures and poi.soning, Equipment and antidotes should be readily available in the event trf an accidental poisoning (c,g., aiisvays, oxygen, mask with manual inflator, and atropine and oxime). 

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