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
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