Pharmacological Characteristics and Mechanism of Action of Emetics

Vomiting — is a reflex expulsion of stomach contents through the mouth. Evolutionarily, vomiting emerged as a protective mechanism serving to remove toxic or irritating substances from the body.

Interestingly, the stomach plays almost no role in the act of vomiting; on the contrary, the muscles of the stomach floor and the esophageal sphincter relax. The expulsion of stomach contents occurs due to the reflex contraction of the abdominal wall muscles and diaphragm. During vomiting, the epiglottis blocks the airways, protecting them from the entry of vomit, while the soft palate rises and closes the nasal cavity. Vomiting is accompanied by nausea, increased salivation, pallor of the skin, and general weakness.

Neurochemical Mechanisms of Vomiting

The physiological and neurochemical mechanisms of vomiting are not fully understood. It is believed that the vomiting reflex occurs when stimulating the so-called "vomiting center," which includes the nucleus tractus solitarius (nucleus tractus solitarius, NTS) in the medulla oblongata and the chemoreceptor-rich "trigger zone" located in the area postrema.

Pathophysiology of chemo induced-nausea and vomiting (Negusu D., 2015)[3]

The NTS region contains histamine (H₁) and muscarinic receptors, while serotonin (5-HT₃), dopamine (D₂, D₃), and opioid receptors are found in the "trigger zone." In recent decades, data has been obtained confirming the involvement of neurokinin (NK₁) and cannabinoid (CB₁) receptors in the pathological vomiting reflex[1]. Several publications mention the strong emetic effect discovered in a new group of medications — type 4 phosphodiesterase inhibitors (PDE₄)[2].

The mechanism of vomiting induced by chemical warfare agents and incapacitating substances varies.

Vomiting agents (DA, DC, and adamsite) used during World War I cause vomiting by stimulating vagus nerve receptors in the lower part of the pharynx and larynx, as well as through the toxic effects of arsenic.

Apomorphine and aminotetralin derivatives have a central stimulating effect on D₂-dopamine chemoreceptors in the trigger zone.

Vomiting caused by malodorants with strong repulsive odors has a central origin and is triggered by the activation of corticobulbar afferent neurons.

"Labyrinth poisons" from the thebaine derivatives group, like all similar opioids, cause nausea and vomiting through stimulation of NTS opioid receptors.

The search for vomiting chemical agents began in the early 20th century and led to the discovery of Substance PG for military use and malodorants for controlling civil unrest. In the early 1970s, Substance PG was banned as it was classified as a biological weapon. Malodorants, however, continue to see limited use in some countries today, primarily as a safer alternative to "riot control agents." For both agents, the emetic effect is not the primary mechanism of action, and when inhaled, vomiting occurs in only a small number of affected individuals.

Vomiting chemical agents from other groups have not been adopted for various reasons: arsenic derivatives due to pronounced toxicity, apomorphines and aminotetralins due to severe side effects on the cardiovascular system. However, the primary drawback of emetic incapacitating agents is the high risk of aspiration of vomit, which can lead to the development of a life-threatening complication—aspiration pneumonia.