Physiology of vomiting
Whilst treating the offending cause of vomiting, antiemetic agents are employed to minimise clinical signs of disease. These antiemetic agents address the neurological target of vomiting, located within the central nervous system of the dog.
The vomiting reflex has a number of areas within the brain that are involved within the reticular formation. Firstly, emetic agents (toxins, medications, azotemia, etc) reach the chemoreceptor trigger zone (CRTZ) located within the area postrema on the floor of the fourth ventricle.
Vomiting shares many physiologic characteristics with coughing due to both being vagally-mediated, peripherally triggered by noxious stimuli, preceded by an urge, threshold regulation, and motor patterns of varying duration and intensity depending upon the stimulus.
- The humoral pathway
The CRTZ is located external to the blood-brain barrier and therefore can sense stimuli through the humoral pathway. Triggering of neurones in the area postrema leads to secondary activation of the vomiting center and initiation of the vomiting reflex.
- The neuronal pathway
The second pathway for activation of vomiting is via specific receptors located within the abdomen of the dog, specifically the gastrointestinal tract. When these receptors are activated, the stimulus ascends the vagal and sympathetic afferent nerves directly to the vomiting center in the brain. Neuronal pathways are also located in the vestibular apparatus and in cerebrocortical neurons of the forebrain.
The mechanisms involved in eliciting vomiting in dogs therefore determines the efficacy of antiemetic agents. Specific receptors involved in eliciting vomiting in dogs include:
- dopamine (D2-dopaminergic receptors)- e.g. metoclopramide,
- Norepinephrine (α2-adrenergic receptors)
- 5-hydroxytryptamine (5-HT-serotonergic receptors) - e.g. ondansetron, dolasetron, cisapride
- Acetylcholine (M1-cholinergic receptors) - e.g. cisapride (dual action)
- Histaminergic antagonists (H1- and H2-histaminergic receptors) - e.g. famotidine, ranitidine
- Enkephalins (enkμ- and enkδ-enkephalinergic receptors)
- Neurokinin antagonists (Neurokinin1-receptors) - e.g. maropitant
- Motilin receptor agonists
- Proton pumps - e.g. omeprazole, lansoprazole
- Cytoprotectants - e.g. sucralfate
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