VZL 2004, 73(3):107-115

Pharmacological Prophylaxis and Antidotal Treatment of Acute Tabun Poisoning

Jiří Kassa ORCID..., Gabriela Kunešová, Josef Vachek, Kamil Kuča ORCID..., Jiří Cabal
Katedra toxikologie Vojenské lékařské akademie J. E. Purkyně, Hradec Králové

Na samcích myší kmene NMRI byl testován vliv perorálně podaného profylaktického prostředku PANPAL na akutní toxické účinky tabunu a srovnávána jeho účinnost s běžně používaným pyridostigminem cestou stanovení indexu účinnosti. Stejným způsobem byl srovnáván účinek antidotní terapie akutní otravy tabunem v závislosti na výběru anticholinergika či přidání látky s antikonvulzivním účinkem. Dále byla na samcích laboratorního potkana kmene Wistar testována reaktivační účinnost vybraných oximů cestou stanovení procenta reaktivace tabunem inhibované acetylcholinesterázy v krvi, bránici a mozku otrávených potkanů 30 minut po otravě a následné terapii. Na potkanech byl též testován vliv farmakologické profylaxe a výběru vhodného reaktivátoru na tabunem vyvolané příznaky neurotoxicity pomocí Funkční pozorovací baterie.
Získané výsledky potvrdily, že ze současných reaktivátorů acetylcholinesterázy se jako nejvhodnější jeví obidoxim, zatímco oxim HI-6, tak účinný proti somanu, je vůči tabunu téměř neúčinný. Jako perspektivní reaktivátor acetylcholinesterázy se pro terapii akutních otrav tabunem nabízí též trimedoxim. Pro dosažení dostatečné úrovně antidotní terapie akutní otravy tabunem je navíc vhodné nahradit běžně používané anticholinergikum atropin za cholinolytikum s prohloubenou centrální účinností (biperiden, benaktyzin či skopolamin). Pokud je k antidotní terapii akutní otravy tabunem použit atropin, je žádoucí přidat k takovéto terapii látku s antikonvulzivním účinkem (např. diazepam). Použijeme-li v případě hrozby expozice živé síly tabunem český originální profylaktický prostředek PANPAL, dosáhneme nejen zvýšení odolnosti exponovaného organismu vůči letálním účinkům tabunu, ale také zvýšíme účinnost následné antidotní terapie otravy. Na rozdíl od PANPALu je efekt samotného pyridostigminu vůči akutní toxicitě tabunu jen minimální.

Keywords: Tabun; PANPAL; Pyridostigmin; Anticholinergika; Reaktivátory acetylcholinesterázy; Funkční pozorovací baterie; Myš; Potkan

Male NMRI mice were used to test the influence of orally administered prophylactic mean PANPAL on acute toxic effects of tabun and to compare its efficacy with the commonly used pyridostigmine by means of protective ratio evaluation. The effect of antidotal treatment of acute tabun poisoning which depends on the choice of anticholinergic drug or the addition of anticonvulsive drug was compared in the same way. Then the reactivating efficacy of selected oximes was tested on Wistar rats using evaluation of the percentage of tabun-inhibited acetylchollinesterase reactivation in blood, the diaphragm and in the brain of poisoned rats 30 minutes after poisoning and antidotal treatment. We also used the rats to test the influence of pharmacological prophylaxis and the choice of a suitable reactivator for tabun-induced neurotoxic symptoms with the help of functional observatory battery.The results confirm that obidoxime seems to be the most suitable acetylcholinesterase reactivator while the oxime HI-6, which is very effective against soman, is practically ineffective against tabun. Trimedoxim also appears to be a prospective acetylcholinesterase reactivator for the antidotal treatment of tabun poisoning. In order to achieve the sufficient effectiveness of antidotal treatment of acute tabun poisonings, the commonly used anticholinergic drug atropine should be replaced by a cholinolytic drug with pronounced central effects (biperiden, benactyzine, scopolamine). If atropine is used for the antidotal treatment of tabun poisoning, the addition of an anticonvulsive drug such as diazepam is suitable. If PANPAL is administered in case of tabun exposure threat, the resistance of the exposed organism as well as the efficacy of postexposure antidotal treatment are significantly increased. Unlike PANPAL, pyridostigmine is not practically effective against acute toxic effects of tabun.

Keywords: Tabun; PANPAL; Pyridostigmine; Anticholinergic drugs; Acetylcholinesterase reactivators; Functional observatory battery; Mouse; Rat

Received: March 3, 2004; Published: September 1, 2004  Show citation

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Kassa, J., Kunešová, G., Vachek, J., Kuča, K., & Cabal, J. (2004). Pharmacological Prophylaxis and Antidotal Treatment of Acute Tabun Poisoning. Vojenské Zdravotnické Listy, 73(3), 107-115
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