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9 Analgesicsvolume Morphine is anti-tussive. It may precipitate histamine release and bron-
chospasm.
Nausea and vomiting – the chemoreceptor trigger zone is stimulated via 5-HT 3
and dopamine receptors. The cells within the vomiting centre are depressed by
morphine and do not stimulate vomiting.
Central nervous system – sedation, euphoria and dysphoria occur with increasing
doses.
Circulatory – morphine may induce a mild bradycardia and hypotension secondary
to histamine release and a reduction in sympathetic tone. It has no direct myocar-
dial depressant effects.
Gut–morphine constricts the sphincters of the gut. Constipation results from a
state of spastic immobility of the bowel. Whilst the sphincter of Oddi is contracted
bymorphine thereby raising the pressure within the biliary tree the clinical signif-
icance of this is unknown.
Histamine release – reducing the rate of administration will help to
limit histamine-induced bronchospasm and hypotension. Histamine release
may result in a rash and pruritus but this may be reversed by naloxone.
Pruritus – most marked following intrathecal or epidural use. However, this does
not appear to be due to histamine release and is generally not associated with a rash.
Paradoxically, antihistamines may be effective treatment for pruritus, possibly as
aresult of their sedative effects.
Muscle rigidity – occasionally, morphine (and other opioids) can precipitate chest
wall rigidity, which is thought to be due to opioid receptor interaction with
dopaminergic and GABA pathways in the substantia nigra and striatum.
Meiosis – due to stimulation of the Edinger–Westphal nucleus, which can be
reversed by atropine.
Endocrine – morphine inhibits the release of adrenocorticotrophic hormone
(ACTH), prolactin and gonadotrophic hormones. Antidiuretic hormone (ADH)
secretion is increased and may cause impaired water excretion and hyponatraemia.
Urinary – the tone of the bladder detrusor and vesical sphincter is increased and
may precipitate urinary retention. Ureteric tone is also increased.Kinetics
When given orally morphine is ionized in the acidic gastric environment (because
it is a weak base, pKa=8.0) so that absorption is delayed until it reaches the rela-
tively alkaline environment of the small bowel where it becomes unionized. Its oral
bioavailability of 30% is due to hepatic first pass metabolism. Its peak effects fol-
lowing intravenous or intramuscular injection are reached after 10 and 30 minutes,
respectively, and it has a duration of action of 3–4 hours. It has been given by the
epidural (2–4 mg) and intrathecal (0.2–1.0 mg) routes but this has been associated
with delayed respiratory depression.