Common side effects
Opioid receptorsStimulation of opioid receptors is responsible for some of the commonly-observed side effects of opioids. Nausea, for instance, occurs when opioids circulating in the bloodstream activate opioid receptors in the chemoreceptor trigger zone (CTZ). When this reaches a certain threshold neurotransmitters that activate the vomiting centre pathways are released. These include dopamine, which is why the dopamine antagonists haloperidol and metoclopramide are recommended for opioid-induced nausea.This is only one cause nausea and vomiting related to opioids. A full assessment is required to exclude other causes such as constipation, gastric stasis and vestibular disturbance. Even unpalatable preparations – such as liquids and solutions – can be an issue.
Individual variationDue to genetic variations in the expression of receptors, side effects of opioids can vary considerably between individuals. The exception to this is constipation, which occurs in virtually all patients (except those with short bowels, for instance following surgery).
Development of toleranceSome side effects disappear as the patient develops tolerance to them. Tolerance develops due to changes at the cellular level involving the activated G-protein subunit. Opioid receptors in the enteric nervous system have different cellular properties to those elsewhere with regards to the development of tolerance. In addition, opioids are universally constipating, suggesting there is little individual genetic variation in this subset of opioid receptors.
Switching opioidsThere are two different rationale for switching opioids in order to manage their side effects. Firstly, the drug’s pharmacokinetics may be causing toxicity and conversion to another opioid may be safer for the patient. For example, the accumulation of toxic metabolites of morphine in severe renal failure is best managed by conversion to an opioid whose metabolites are inactive. Secondly, the receptor-subtype profile differs between opioids.Although the latter may, in theory, prevent the development of certain side effects, it is not generally recommended. Outcomes are unpredictable due to genetic variation in individual receptor expression and a lack of research evidence in humans. Nevertheless, it is not uncommon to see an opioid being switched to manage side efects in practice. We will discuss this further at the end of this week.
Opioid analgesics: Treating Pain in People with Cancer
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