The clinical pharmacology of emesis and anti-emetics is dictated by the neurochemistry of the vomiting (emetic) center as well as the various afferent (input) and efferent (outflow) pathways involved in the act of emesis.
The clinical pharmacology of emesis and anti-emetics is dictated by the neurochemistry of the vomiting (emetic) center as well as the various afferent (input) and efferent (outflow) pathways involved in the act of emesis. Figure 1 summarizes our current understanding of the neural pathways and receptors that mediate this process, and Table 1 further describes the receptors and neurotransmitters involved.
It is the combination of the cause of the emesis, the neural input that transmits that causation to the Vomiting Center, and the transmitters/receptors that mediate that neural communication that dictate the anti-emetic most likely to be effective (Table 2), bearing in mind that sometimes the best strategy to prevent movement of the GI contents in the wrong direction is to encourage it to flow in the correct direction (i.e. promotility agents).
For example, many chemotherapeutic agents are thought to stimulate the release of large amounts of serotonin in the GI tract, causing nausea and vomiting. Hence, it is common practice to treat those pets receiving chemotherapy with a 5-HT3 antagonist such as Ondansetron prior to the administration of the chemotherapeutic drug. The neurochemistry of emesis may also help to explain why certain anti-emetics appear more powerful than others regardless of the underlying cause, as drugs such as Maropitant can act at both the Chemoreceptor Trigger Zone and the Vomiting center. Differences in these neural pathways between species will help account for differences in efficacy when the same drug is used in cats compared to dogs. Histamine receptors appear to play only a minor role in the vomiting reflex in cats, hence diphenhydramine is not a recommended anti-emetic in this species, despite being a reasonably effective anti-emetic for certain causes of vomiting in the dog. Dopamine receptors are an important input in the CRTZ of the dog, whereas they may not be present in the CRTZ of the cat. This explains why apomorphine is such an effective emetic agent in the dog, but likely to do very little except cause extrapyramidal side-effects (craziness) in the cat. The converse of this is that metoclopramide (a D2-dopaminergic antagonist) is much less effective as an anti-emetic in the cat than the dog. In contrast to this, α2-adrenergic and 5-HT3-serotonergic receptors appear to be more important in the CRTZ in the cat compared to the dog, and a side-effect of xylazine (an α2-adrenergic agonist) administration in a cat is vomiting. In some cases both species respond to the same anti-emetic, but for different reasons (i.e. the 5-HT3-serotonergic antagonists ondansetron and dolasetron help prevent vomiting in the cat by acting at the CRTZ, whereas it is their action on peripheral receptors that make them effective anti-emetics in the dog.)