Page 103 Acute Pain Management

4. SYSTEMICALLY ADMINISTERED

ANALGESIC DRUGS

4.1 OPIOIDS

Opioids remain the mainstay of systemic analgesia for the treatment of moderate to severe
acute pain.
4.1.1 Choice of opioid

All full opioid agonists given in appropriate doses produce the same analgesic effect and
therapeutic index (McQuay, 1991), although accurate determination of equianalgesic doses is
difficult due to interindividual variabilities in kinetics and dynamics (Gammaitoni et al, 2003).
Equianalgesic conversion dose tables are often used to assist in the change from one opioid to
another. However, such tables should be used as a guide only as they are based largely on
single‐dose studies in opioid‐naive subjects and may not be as relevant when conversions are
made after repeated doses of an opioid have been given (either in the acute pain or chronic
pain setting) and do not take into account incomplete cross‐tolerance (Weschules & Bain, 2008).
In general there is little evidence, on a population basis, to suggest that there are any major
differences in efficacy or the incidence of side effects between any of the pure agonist opioids, CHAPTER 4
although the results of individual studies are inconsistent. However, for pharmacokinetic and
other reasons, some opioids may be better in some patients (Woodhouse et al, 1999 Level II).
Comparisons of the different opioids are commonly done in patients using patient‐controlled
analgesia (PCA) (see Section 7.1.2 for these comparisons).
While the data to support the concept of opioid rotation originate from cancer pain (Quigley,
2004 Level I), it may be a useful strategy in the management of acute pain in patients with
intolerable opioid‐related side effects that are unresponsive to treatment, and in opioid‐
tolerant patients (see Section 11.7).

4.1.2 Specific opioids
The efficacy of various opioids administered by the different routes used in the management
of acute pain is discussed in detail in Sections 6 and 7.1. The following section describes other
relevant aspects of selected opioid agents including tramadol.
Buprenorphine
Buprenorphine is a semi‐synthetic derivative of thebaine, an alkaloid of opium, and a partial
mu‐opioid receptor agonist and kappa‐opioid receptor antagonist with high receptor affinity
and slow dissociation from the mu‐receptor (Johnson et al, 2005). Mean terminal half‐lives are
24 hours following sublingual administration and 2 to 3 hours after parenteral injection; two‐
thirds of the drug is excreted unchanged, mainly in faeces, while the remaining one‐third is
metabolised predominantly in the liver and gut wall via glucuronidation to an inactive
metabolite, buprenorphine‐3‐glucuronide, and via CYP3A4 to norbuprenorphine, which has
40 times less analgesic effect than buprenorphine (Kress, 2009). Maximum onset of effect is
slower than for other opioids making acute titration difficult. In a study using experimental
pain stimuli, the time to maximal peak effect after administration of an IV bolus dose of
buprenorphine was between 70 and 100 minutes (Yassen et al, 2006 Level III‐3).

Acute pain management: scientific evidence 55