Chemoreceptor trigger zone, opioids

Opioids depress respiration via the ji2-receptor at the level of the medulla and thereby increase PCO2. Opioids reduce respiration, an effect that is fatal in the case of overdose, by a dual action. The opioids decrease both the sensitivity of the medulla to carbon dioxide concentrations and the respiratory rate. Cardiovascular function and the response to hypoxia are not compromised. By contrast, tolerance to the respiratory depressant effects of the opioids does not appear to occur, while tolerance to the emetic effects of the opioids occurs upon repeated administration. The area postrema chemoreceptor trigger zone of the medulla mediates opioid-induced vomiting. 

The opioid analgesics can activate the brainstem chemoreceptor trigger zone to produce nausea and vomiting. There may also be a vestibular component in this effect because ambulation seems to increase the incidence of nausea and vomiting. 

The "chemoreceptor trigger zone" or area postrema is located at the caudal end of the fourth ventricle. This is outside the blood-brain barrier but is accessible to emetogenic stimuli in the blood or cerebrospinal fluid. The chemoreceptor trigger zone is rich in dopamine D2 receptors and opioid receptors, and possibly serotonin5-HT3 receptors and NKi receptors. 

Opioids cause nausea and vomiting by stimulating the chemoreceptor trigger zone in the medulla, although tolerance to this effect usually develops within a few days (30). 

Nausea and emesis are common unpleasant side-effects of opioids (Campora et al., 1991 Aparasu et al., 1999). They are most intensively experienced at the beginning of the treatment. During chronic administration, tolerance may occur, which reduces the emetic sequelae. Nausea and emesis are induced via activation of chemoreceptors which are located in the trigger zone of the area postema of the formatio reticularis. The receptors are at the tissue surface and in contact with the circulating blood. Thus the emetic effect of opioids is not mediated centrally, i.e. after penetration of the blood-brain barrier, but rather peripherally via the amount of the compound, which is distributed in the circulating blood. 

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