• Principal alkaloid in opium, although most morphine is now synthetic (therefore opioid, not opiate).

  • Powerful mu agonist, with effects on areas rich in mu receptors: brain stem, posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, certain cortical areas, and the lungs.

  • Mu receptors also common in spinal cord/gastrointestinal tract.

  • Some analgesic activity from metabolites of morphine (M3G, M6G).

  • Adverse effects mediated through other receptors, e.g. kappa and delta.

  • Strong analgesic: not recommended for long-term use in non-malignant pain after recent misuse and high levels of opioid addiction primarily related to oxycodone (see box 7).

  • Available in immediate-release and modified-release forms.

  • Undergoes significant first-pass metabolism, hence variation in level after same dose in different people.

  • Most common adverse effects need active management (e.g. treatment of nausea and vomiting or constipation) or reduction in dose and then slow titration upwards again (e.g. sedation) [62–64].

  • Adverse effects of opioids may be limiting factor in patients accepting treatment, hence initiate low dose and increase slowly (wait at least 7 days before dose titration).

  • Modified-release form should not be used in those with significant renal/hepatic impairment (e.g. estimated glomerular filtration rate <25 mL·min−1) due to accumulation risk from active metabolites; care should also be taken in elderly/frail/cachectic patients for the same reason.

  • The principle (as in other prescribing) is to use minimum effective dose for shortest time.

Licensed preparation (Therapeutic Goods Administration, Australia)
  • Sustained-release morphine (10 mg/24 h; 20 mg/24 h capsules) as Kapanol# now has an extension to its licensed indication to include chronic breathlessness.

  • Should only be used in the palliative care of patients with “distressing breathlessness due to severe COPD, cardiac failure, malignancy or other cause, after treatments for the underlying cause(s) of the breathlessness have been optimised and non-pharmacological treatments are not effective”.

  • Dose: start at 10 mg·day−1, and limit to maximum of 30 mg·day−1.

  • Must be initiated by a specialist knowledgeable in its use.

#: although many countries do not have access to Kapanol, most have access to modified/sustained-release preparations that allow similar steady-state blood levels; total initial daily starting dose can be 10 mg in 24 h on Kapanol.