Explore chapters and articles related to this topic
Military Chemical Casualty Treatment
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Timothy J. Byrne, Raymond Vazquez, Dan Boehm, Laukton Rimpel, Charles. G. Hurst
Pralidoxime chloride is an oxime. Oximes attach to the nerve agent that is inhibiting the cholinesterase and break the agent–enzyme bond to restore the normal activity of the enzyme. Clinically, this is most noticeable in those organs with nicotinic cholinergic receptors. Abnormal activity in skeletal muscle decreases, and normal strength returns. The effects of an oxime are not as apparent in organs with muscarinic cholinergic receptors; for example, a decrease in secretions and bronchospasm. This is because the muscarinic receptors have already been saturated by the use of atropine, a muscarinic cholinergic-blocking drug. Oximes are not useful after aging occurs. Aging is a chemical process that renders oximes ineffective at reactivating cholinesterase. You can think of aging metaphorically as a nerve agent becoming glued into the acetylcholinesterase. Aging is usually only important with soman, which has an aging half-life of 2 minutes. Other classic nerve agents age after 4–48 hours depending on the agent; however, lethal exposure to nerve agent must be treated in minutes, not hours. When possible, the use of IV injectable antidotes is always more effective. IV and IM dosage ranges are very similar.
Novichok: a murderous nerve agent attack in the UK
Published in Clinical Toxicology, 2018
J. Allister Vale, Timothy C. Marrs, Robert L. Maynard
Pralidoxime salts are the most widely used oximes in treating patients poisoned with organophosphorus compounds, though other oximes, including obidoxime (Toxogonin) and the H (Hagedorn) series, for example, HI-6 and HLö-7, have also been employed. With the possible exception of the treatment of cyclosarin and soman poisoning, when HI-6 might be preferred, there are no clinically important differences between pralidoxime, obidoxime and HI-6 in the treatment of nerve agent poisoning [23]. Oxime regimens are also based on those in use for organophosphorus insecticide poisoning. Pralidoxime chloride 30 mg/kg by intravenous injection should also be administered as soon as possible and repeated at 4–6 h intervals; alternatively an intravenous infusion of 8–10 mg/kg/h may be employed [24]. Obidoxime 250 mg intravenously, followed by a continuous infusion at a dose of 750 mg/day, is an alternative [25]. Combined oxime therapy has been proposed [26].
Comparative evaluation of antidotal efficacy of 2-PAM and HNK-102 oximes during inhalation of sarin vapor in Swiss albino mice
Published in Inhalation Toxicology, 2018
Devyani Swami, Ruchi Yadav, A.S.B. Bhaskar, A. Soni, D.P. Nagar, J. Acharya, H.N. Karade, K.P. Singh, Pravin Kumar
Pralidoxime chloride (2-PAM), a mono-pyridinium oxime, has been used as antidote against some nerve agents poisoning such as sarin and VX (Koplovitz & Stewart, 1994). As reported elsewhere, when the anticonvulsant drug diazepam, atropine and 2-PAM given prior to sarin aerosol, protection against sarin induced lung lesions were observed in albino rats (Pant et al. 1993). Hence, the challenge of protecting the unprotected individuals from vapors/aerosols of nerve agent is matter of concern to many researchers. In search of a broad spectrum and more efficacious antidote against nerve agent’s intoxication, some new bis-pyridinium acetamide derivatives (HNK oximes) were synthesized in our establishment (Karade et al., 2014). Having established the efficacy of HNK oximes over 2-PAM against poisoning of some of the representative organophosphorus (OP) compounds, e.g., DFP (Kumar et al., 2014), DDVP (Kumar et al., 2016) and nerve agents, e.g., sarin (Swami et al., 2017), tabun and soman (Kumar et al., 2017), the present study deals with evaluation of protection efficacy of HNK-102 oxime during inhalation exposure to sarin vapor in Swiss albino mice.
Anticonvulsant effectiveness of scopolamine against soman-induced seizures in African green monkeys
Published in Drug and Chemical Toxicology, 2022
John H. McDonough, Joseph D. McMonagle, Benedict R. Capacio
Treatment of nerve agent poisoning is focused along several lines. Prevention or reduction of the toxic signs is accomplished primarily via the (a) administration of anticholinergic drugs, atropine sulfate being almost universally used for this purpose; (b) reactivation of agent-inhibited enzyme with oxime reactivators such as pralidoxime chloride (2-PAM Cl) or obidoxime (Toxigonin); and when indicated in cases of severe poisoning (c) treatment of convulsions/seizures with benzodiazepine drugs such as diazepam or midazolam (Departments of the Army, Navy, Air Force, and Commandant Marine Corps 1995, Chemical Casualty Care Division 2014).