Organophosphate (OP) and carbamate poisonings can lead to significant morbidity and mortality when recognition is delayed. These cholinesterase inhibitors work by inhibiting the normal breakdown of the neurotransmitter acetylcholine, leading to an excess amount of acetylcholine at skeletal neuromuscular junctions and synapses. Thousands of structurally similar substances have been developed since their discovery.

Common pesticides used in agriculture are parathion, Malathion, Diazinon, Chlorpyrofos, and Dichlorvos. The use is primarily to protect livestock, crops, and communities from insects, but these compounds also pose a threat. Each year an estimated 500,000 deaths occur in rural Asia due to suicide, and an estimated 200,000 of these are due to intentional organophosphate poisoning [1].

Nerve agents are extremely potent organophosphates developed for chemical warfare and used in acts of terror. They were developed initially by German military scientists in the 1930s. The G-type nerve agents, [i.e., Tabun (GA), Sarin (GB), Soman (GD), and Cyclosarin (GF)] are clear, colorless, and tasteless liquids. The most recognizable use of Sarin (GB) in a terrorist attack was in the Tokyo Subway Attack in 1995 where 5500 civilians sought medical care [1–4]. The attack left 12 dead, 50 critically injured, and 1000 suffering temporary vision problems. More recently, Sarin was used as a weapon of mass destruction when it was deployed in Syria.

The next group developed by the British in the 1950’s was the V-series, many times more powerful than the G-type nerve agents. VX is an amber-colored, oily liquid with low volatility until exposed to high temperatures. The adult VX LD₅₀ is only 3 mg [2, 4–6]. VX was used in the assassination of the Kim Jong Nam December 2017. Beyond the V-series, the development of the Novichok series, Russian for “newcomer,” were developed by the Soviets and had not been used in known attacks until the Sergei and Yulia Kripal were poisoned in the UK in March 2018. These newer agents are several times more potent than VX.

Acetylcholine is a neurotransmitter that triggers stimulation of postsynaptic nerves, muscles, and exocrine glands. Acetylcholinesterase (AChE) breaks down acetylcholine, so there is no overstimulation. Organophosphates and carbamates are anticholinesterase inhibitors; blockade of AChE leads to the accumulation of excessive amounts of acetylcholine at muscarinic receptors and nicotinic receptors and in the CNS.

Maturation of the bond between AChE and AChE inhibitor is called “aging.” Blockade of AChE may be reversible for a period, but once the bond ages, then the blockade becomes irreversible. For some agents, like Soman “aging” is only 2 minutes, whereas for Sarin “aging” takes 8.5 hours, and for Malathion, it is approximately 72 hours.

Carbamate poisoning has similar acute effects as OP poisoning, but toxicity is not as severe. Unlike OP, carbamates do not “age” the AChE enzyme; the bond between carbamate and AChE will spontaneously lyse, resulting in recovery of enzyme activity within several hours [3]. CNS effects are also less prominent, since they do not cross the blood-brain barrier as easily [3].

Onset of toxicity depends on the mode of delivery and the agent involved. The term “nerve gas” is a misnomer as these agents are liquids under temperate conditions. Depending how they are dispersed, they may present as a vapor, aerosol, or liquid. The tendency of vapor is to sink to the ground, as these agents are heavier than air. Dermal agents frequently have local fasciculations at the site of exposure before weakness. Inhalation can lead to death under a minute, with massive exposure. Very high doses of nerve agents can act quickly, even if dermal. Certain chemical compounds lead to more rapid onset.