Home' Australian Pharmacist : Australian Pharmacist September 2014 Contents Australian Pharmacist September 2014 I © Pharmaceutical Society of Australia Ltd.
CONTINUING PROFESSIONAL DEVELOPMENT
The analgesic effect of commercially
available opioids is most notably
achieved through activation of the μ
In some opioids such
as oxycodone, the activation of the ĸ
opioid receptor also appears important
for analgesic properties6; while the
analgesic effects of some opioids such
as methadone, are also related to effects
at non-opioid receptors, e.g. antagonist
effects at the N-methyl-D -aspartate
The opioid dose used, and circumstances
around its use (e.g. acute vs chronic
use) will affect the type and severity of
the adverse effects.
Some side effects
such as constipation and sedation are
well documented, but the full spectrum
of potential problems and adverse
effects has not been fully elucidated.
Many of the adverse effects are
associated with activation of the opioid
receptor (Table 2); e.g. opioid-induced
bowel dysfunction (i.e. constipation,
nausea, and biliary dyskinesia), and
dose-related respiratory depression.
Other troublesome adverse effects
include opioid-induced hyperalgesia
(where opioids sensitise the nervous
system and paradoxically cause pain),
tolerance, physical dependence,
psychological dependence, and
addiction.2,9 Side effects may also be
mediated via non-opioid receptors; for
instance, opioid-induced histamine
release can cause urticaria, and pruritus.
While tolerance can develop to some
side effects, others can be dose-limiting.
Management includes reducing the dose
of the opioid and adding an non-opioid
or adjuvant analgesic, controlling the
symptoms, or opioid rotation.
In relation to receptor binding,
the number of symbols is an indication of
binding affinity; the plus sign represents
an agonist effect, a minus sign indicates
an antagonist effect, while plus signs
in brackets represent partial agonist
activity. In relation to histamine release,
the number of plus signs represents
relative histamine release, and n/a
denotes not applicable.
Selecting an opioid –
When selecting an opioid for a patient,
consideration must be given to the
patient’s clinical situation and condition,
drug interactions, previous analgesic
requirements and response. People with
a history of opioid misuse, or those on
chronic opioid treatments, may require
higher doses than opioid-naïve patients
before adequate analgesia is achieved.2
When considering opioids for chronic
non-cancer pain, it is recommended
that they be trialled for 4–6 weeks,
starting with low doses, and titrating
slowly according to response. It is
also important to agree on goals of
therapy, have an agreed endpoint/finite
duration for the opioid use, regular
assessments if long-term use is deemed
appropriate and necessary, and a clear
The properties of individual opioids also
need to be considered. These include,
but are not limited to, the potency,
efficacy, route of administration, and
duration of action.2,6
General patient considerations
Age: The opioid dose required generally
decreases with increasing age. When
opioids are used in the elderly, there
is an increased risk of side effects such
as cognitive impairment, sedation,
respiratory depression, and falls.
Some opioids are contraindicated
in the elderly for this reason (e.g.
dextropropoxyphene, pethidine, and
tramadol).2 Use of opioids in children is
usually under the advice of specialists.
When using opioids in children and the
elderly, the general advice is to start at a
low dose and titrate slowly to effect.2
Genetic polymorphisms and ethnicity:
Codeine is a pro-drug and requires the
cytochrome P450 (CYP) 2D6 isoenzyme
to metabolise it into its active form.
Genetic polymorphism means 6–10%
of Caucasians, and 1–2% of Asians
would not benefit from codeine as they
lack the enzyme. Conversely, 10% of
Caucasians and up to 30% of North
Africans are ultrarapid metabolisers,
putting them at risk of morphine
Tramadol is also converted
into an active metabolite by CYP2D6,
so people lacking the enzyme would
experience a reduced analgesic effect.
Hepatic impairment: Most opioids
may require a dose adjustment when
used in people with compromised
liver function, and some opioids
may be contraindicated in cases of
severe hepatic impairment (Table 4).
The general advice is to start at a low
dose, and to titrate the doses carefully
according to response and side effects.
Renal impairment: The general concern
is the accumulation of active or toxic
metabolites, so those with inactive or
Table 1. Opioid receptor agonists – actions of opioids at the opioid receptors, and relative
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