Opioids commonly used in pain management

buprenorphine

USE:

severe, acute nociceptive pain (specialist only)

chronic pain, when indicated

PHARMACOKINETICS:

mu-receptor agonist, with some activity at kappa and delta opioid receptors [NB2]

dose adjustment is not required in patients with renal impairment

long half-life (approximately 24 hours), and slow onset and offset of effect—rapid dose titration is impossible. Dose intervals typically used for administration of other opioids may not be suitable

OTHER COMMENTS:

despite buprenorphine’s high affinity for mu-receptors, it does not block the effects of other opioids if administered concomitantly—do not withhold buprenorphine if additional opioids are required for analgesia

although opioid-induced ventilatory impairment can occur at any dose, buprenorphine appears to have a ceiling effect for opioid-induced ventilatory impairment, but not analgesia—analgesia will increase with increasing doses, but risk of opioid-induced ventilatory impairment may not increase

epidemiological studies suggest that when opioid misuse occurs, fewer fatalities result from buprenorphine patches compared to other opioids (excluding tapentadol and tramadol)

opioid-induced hyperalgesia is less common due to buprenorphine’s antihyperalgesic effects

fentanyl

USE:

moderate to severe, acute nociceptive pain [NB3]

chronic pain, only under specialist advice [NB4]

PHARMACOKINETICS:

full mu-receptor agonist

no active metabolites—suitable for use in patients with severe renal impairment

poorly absorbed orally, but well absorbed across mucous membranes (eg nasal mucosa)

fastest onset of effect compared to other commonly used opioids when administered intravenously or intranasally

OTHER COMMENTS:

fentanyl’s fast onset of effect may increase its likeability among drug users

to reduce the risk of inadvertent overdose with intravenous fentanyl, use lower than calculated equianalgesic doses

morphine

USE:

moderate to severe, acute nociceptive pain

chronic pain, when indicated

PHARMACOKINETICS:

full mu-receptor agonist

two main metabolites—one contributes significantly to morphine’s analgesic effect; the other has no analgesic effect, but may be responsible for some of the neurotoxic adverse effects sometimes seen with long-term, high-dose morphine treatment

active metabolites are renally excreted—avoid or reduce doses in patients with moderate or severe renal impairment

OTHER COMMENTS:

caution is required if morphine liquid is prescribed because dose inaccuracies are common

oxycodone

USE:

moderate to severe, acute nociceptive pain

chronic pain, when indicated

PHARMACOKINETICS:

full mu-receptor agonist

metabolised in the liver—cytochrome P450 polymorphism does not affect analgesic effect or toxicity

reduce initial doses in patients with severe renal impairment

OTHER COMMENTS:

oxycodone abuse rates are similar to that of other opioids

an oral combination formulation of controlled-release oxycodone+naloxone may be less constipating compared with controlled-release oxycodone alone, but evidence is weak

caution is required if oxycodone liquid is prescribed because dose inaccuracies are common

tapentadol

USE:

moderate acute nociceptive pain—unlikely to provide sufficient analgesia for severe acute pain

chronic pain, when indicated

PHARMACOKINETICS:

analgesic effect results from a synergistic combination of mu-receptor agonism and noradrenaline reuptake inhibition; it has no relevant effect on serotonin reuptake

more potent opioid effect than tramadol

OTHER COMMENTS:

epidemiological studies suggest that when opioid misuse occurs, fewer fatalities result from tapentadol compared to other opioids (excluding buprenorphine patches and tramadol)

at the time of writing, immediate-release tapentadol tablets are not available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of acute pain. See the PBS website for current information

tramadol

USE:

moderate acute nociceptive pain—unlikely to provide sufficient analgesia for severe acute pain

chronic pain, when indicated

PHARMACOKINETICS:

analgesic effect results from weak mu-receptor activity (mediated primarily by active metabolite), and inhibition of serotonin and noradrenaline reuptake

converted to an active metabolite (via cytochrome P450 2D6 isoenzyme) that is a more potent mu-receptor agonist—rapid metabolisers are at increased risk of mu-receptor-mediated adverse effects (especially opioid-induced ventilatory impairment) if excessive doses are administered, or the patient has risk factors for opioid-induced ventilatory impairment; poor metabolisers may experience inadequate analgesia and increased serotonergic toxicity

metabolite is renally excreted—dose adjustments required in severe renal impairment

OTHER COMMENTS:

concurrent use of tramadol with other serotonergic drugs increases the risk of serotonin toxicity (see Drugs most commonly associated with serotonergic toxidrome for drugs that associated with serotonin toxicity) [NB5]

rapid intravenous administration is associated with an increased incidence of nausea and vomiting compared with oral administration because peak blood concentrations are reached more quickly

epidemiological studies suggest that when opioid misuse occurs, fewer fatalities result from tramadol compared to other opioids (excluding buprenorphine patches, and tapentadol)

although reported anecdotally, there is inconclusive evidence that tramadol increases the risk of confusion in older patients compared to other opioids when doses are appropriately adjusted for age and comorbidities