Highlights
 

Received: July 2, 2008; Revised: July 9, 2008; Accepted: July 9, 2008

Terrorist Attacks or Poisoning by Organophosphate Pesticides - Is There Any Defence?

Huba Kalász1,* and Kornélia Tekes2

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; e-mail: huba.kalasz@gmail.com
2: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary; e-mail: drtekes@gmail.com

Keywords: Organophosphates, poisoning, antidotes, K-27, K-48, K-203

*Address of correspondence to this author at the Department of Pharmacology and Pharmacotherapy, 1089 Budapest, Nagyvárad tér 4, Hungary

 
 

Organophosphate poisoning in agriculture (millions of cases) and the threat of further chemical terrorist attacks [1] require intensive research on antidotes such as pyridinium aldoximes. Acute poisoning shows a range of signs and symptoms characteristic of anticholinesterase compounds (Table 1).

The toxicological effects of organophosphates are due to the overabundance of acetylcholine in the central nervous system, the parasympathetic nerve endings, the somatic nerves and the ganglionic synapses of autonomic ganglia.

Post exposure antidote treatment of victims is possible, the therapy is known by the acronym A FLOP (atropine, fluid, oxygen and pralidoxime) [4]. Obidoxime and HI-6 are the other commonly recommended pyridinium aldoximes (PYAs) for medicinal use [5]. Preliminary/preventive treatment for rescue personnel is also advisable.

Pyridinium aldoximes conjugate with organophosphates [5], either after or before cholinesterase inhibition takes place. Clinical experiments, however, have been disappointing with any one of the presently available aldoximes [3,4,6,7]. Fast and effective disposition and excretion of the conjugates (phosphoryloximes, POXs) may have vital importance as POXs play an

 

essential part of anticholinestrase activity, and POXs may be hydrolyzed with endogenous enzymes to give the original organophosphates [8].

Cabal et al. [9] and Musilek et al. [10,11] synthesized a series of very effective bis-pyridinium aldoximes marked with the letter K- and a serial number [9-11]. Recent publications gave evidence of their superiority compared to the generally used PYAs.

The therapy of people poisoned with insecticides, pesticides (e.g. paraoxon) and gases used by terrorists (e.g. tabun, sarin) may require different drugs. Petroianu et al. found K-27 and K-48 to be more effective in pesticide poisoning than other drugs [5]; relative risk of death of rats related to untreated animals was compared for treatment with several pyridinium aldoximes. The efficiency of treatment decreases in the following order: K-27, K-48, methoxime, BI-6, pralidoxime.

Musilek et al. showed the superiority of K-203 for the regeneration of tabun inhibited cholinesterases [10-12]. The ability of several aldoximes to reactivate tabun-inhibited acetylcholinesterase was evaluated in the case of pralidoxime, HI-6,

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