HPE Chronic pain – part two - Page 7

TREATMENT Chronic pain: Atypical vs typical opioids Over the last 30 years, a number of analgesics have been identified with similar analgesic efficacy to typical/conventional opioids but the effects of which are not exclusively mediated by the mu receptor – these are the atypical opioids Stephan Schug MD FANZCA FFPMANZCA EDPM Emeritus Professor and Honorary Senior Research Fellow, Anaesthesiology and Pain Medicine, University of Western Australia and Royal Perth Hospital, Perth, Australia Opioids are most likely the medicines that have been used for the longest time; the pain-relieving effects of extracts of the poppy seed have been known for over 6000 years. 1 Only much later was morphine chemically defined as the active ingredient and, subsequently, the pharmaceutical industry synthesised a large number of compounds with similar effects. It took until 1973 for the mechanism of action of opioids to be elucidated as activation of the mu-opioid receptor, 2 a binding site for endogenous ‘opioids’ such as endorphins and enkephalins. 3 Opioids in their various preparations are essential components for relief of certain moderate to severe pain conditions (including cancer- and non-cancer pain). However, the activation of the mu-opioid receptor does not only mediate analgesia, but also results in adverse effects such as potentially life-threatening respiratory depression (opioid-induced ventilatory impairment (OIVI)’) 4 or other known adverse reactions such as nausea, vomiting, constipation, urinary retention, sedation and confusion or agitation. 1 In addition, long-term use of strong mu-receptor agonists can lead to opioid-induced hyperalgesia (OIH), 5 opioid-induced androgen deficiency (OPIAD) resulting in hypogonadotropic hypogonadism with very low testosterone levels, 6 effects on bone health, and suppressed immune function. 7,8 Furthermore, their induction of euphoria and rewarding effects, mediated by the mu-receptor and activation of the dopaminergic system, have resulted in the abuse of opioids, even when used for pain control. 9 Most opioids currently available differ in potency, pharmacokinetics and metabolism, but rely primarily on their agonist activity on the mu-opioid receptor for their analgesic efficacy; thereby their use is intrinsically linked to the adverse effects linked to mu-opioid receptor activation. 1 Atypical opioids Tramadol, an opioid analgesic developed in the 1970s, was initially thought to be a partial mu-opioid receptor agonist similar to many other newly GETTY hospitalpharmacyeurope.com | 2020 | 7