CBRNE - Nerve Agents, G-series - Tabun, Sarin, Soman Medication

Reversal of nerve agent toxicity depends on the prompt parenteral administration of the 2 antidotes, atropine and pralidoxime.

Although IV administration of these antidotes is preferred, this may not be practical in combat situations or civilian mass casualty incidents. The US military Mark 1 kit contains 2 IM autoinjectors, one with atropine 2 mg and the other with pralidoxime 600 mg, to be administered simultaneously in the event of nerve gas exposure. The recommended number of Mark 1 kits to be administered varies from 1-3 and depends on the route of exposure, severity of clinical effects, and elapsed time after exposure.

Deployed US military personnel typically carry 3 Mark 1 kits per person. The Antidote Treatment-Nerve Agent Auto-Injector (ATNAA) contains 2.1 mg of atropine and 600 mg of pralidoxime chloride in a single injector. A pediatric dosage atropine autoinjector (AtroPen) is commercially available.^[10] This product contains atropine and does not include pralidoxime. A Pediatric Expert Advisory Panel recommends the use of the Mark 1 kit in children 3 years and older.^[10]

While seizures complicating nerve agent exposure often respond to IV atropine and pralidoxime, they also may require IV benzodiazepines titrated to effect. The convulsant antidote for nerve agent (CANA) autoinjector consists of diazepam and is recommended after 3 Mark 1 kits have been administered. Midazolam has been considered as a replacement to diazepam. Midazolam is twice as potent and acts more rapidly than diazepam in nonhuman primates with nerve agent–induced seizures.^[11]

Another common complication of vapor nerve agent exposure is ocular pain, which may be treated effectively with a mild, mydriatic-cycloplegic ophthalmic solution (eg, 0.5% tropicamide). Atropine or homatropine ophthalmic solution also can be used to treat ocular pain, but these agents tend to exacerbate visual impairment.

Pretreatment with pyridostigmine before exposure to GA, GD, and GF may improve survival.^[12] No evidence supports the chemoprophylactic use of pyridostigmine against GB or VX.

A number of other novel treatments currently are under investigation. Newer H-series oximes and dioximes (HI-6, HLo7) have greater ability to reactivate phosphorylated AChE. These agents demonstrate greater efficacy against all nerve agents (particularly GD) in animal studies and have direct antimuscarinic and antinicotinic actions to antagonize the effects of nerve agents. Other promising treatments currently under investigation include exogenous cholinesterase and the use of human monoclonal antibodies against nerve agents, both of which scavenge nerve agents and prevent them from binding to tissue AChE.

Class Summary

Act directly on smooth muscles and secretory glands innervated by cholinergic nerves to block muscarinic effects of excess ACh.

Atropine IV/IM (Isopto, Atropair, Atropisol)

Initial DOC for symptomatic victims of nerve agent exposure; acts via muscarinic receptors to reverse bronchoconstriction, bronchorrhea, abdominal pain, nausea, vomiting, and bradycardia; appears to be involved in stopping seizure activity. Because atropine does not act on nicotinic receptors, has no effect on muscle weakness or paralysis. The most important therapeutic endpoints are drying of respiratory secretions, reversal of bronchoconstriction, and reversal of bradycardia; pupillary response and tachycardia are not useful measures of adequate atropinization; >20 mg rarely is needed in first 24 h, unlike in organophosphate insecticide poisoning where up to 200 mg may be required; atropine almost never is required beyond 24 h postexposure.

Class Summary

Reactivate AChEs, which have been inactivated from phosphorylation by nerve agents (or other compounds, such as organophosphate pesticides).

Pralidoxime chloride (2-PAM Cl, Protopam)

Reverses skeletal muscle weakness by reactivating AChE; acts by disrupting covalent bond between nerve agent and AChE before it becomes permanent. Bonds between different nerve agents and AChE have various aging periods. The half-time of the aging reaction for GD is approximately 2 min, for GB it is 5 h, and for GA it is 13 h. Accordingly, administer pralidoxime IV as early as possible (ideally concurrently with atropine). Excreted rapidly and almost completely unchanged by the kidneys.

Administration over 30-40 min minimizes adverse effects (eg, hypertension, headache, blurred vision, epigastric pain, nausea, vomiting).

Class Summary

Believed to exert antiseizure effect by enhancing binding of the major CNS inhibitory neurotransmitter, GABA, to A-type GABA receptors in the CNS, reducing depolarization of neurons and preventing generation and spread of seizures.

Diazepam (Valium, Diazemuls, Diastat)

Indicated for treatment of seizures associated with nerve agent toxicity. Depresses all levels of CNS function by increasing activity of the inhibitory neurotransmitter GABA.

Class Summary

Dilate iris and relax ciliary muscle, reversing ocular pain and miosis of nerve agent toxicity.

Tropicamide (Mydriacyl, Tropicacyl)

Anticholinergic compound that reverses miosis and relieves ocular pain in nerve agent toxicity. Acts by blocking cholinergic stimulation of sphincter muscle of iris and ciliary muscle. When applied as weaker preparation (0.5%), causes pupillary dilation (mydriasis); when applied as stronger preparation (1%), results in loss of accommodation (cycloplegia). Acts rapidly; effect is relatively short lasting.

Class Summary

Temporarily bind and inhibit AChE, thus blocking subsequent binding of certain nerve agents to AChE. Although usually used to treat myasthenia gravis or reverse nondepolarizing neuromuscular blockade, also may be useful as chemoprophylactic agents when administered before exposure to certain nerve agents.

Pyridostigmine (Mestinon, Regonol)

Orally available cholinesterase inhibitor, which may be useful as chemoprophylactic agent when administered prior to exposure to GA, GD, and GF. This recommendation is based on animal studies; little information is available regarding the efficacy of pyridostigmine chemoprophylaxis in humans. Only effective in preventing peripheral (non-CNS) effects of nerve agents; since it exists in an ionized form (quaternary amine), does not readily pass into CNS and thus cannot prevent nerve agent–induced CNS injury; no evidence demonstrates that pretreatment before exposure to GB or VX is effective.