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Section IICoredrugs in anaesthetic practiceMorphine concentration in the brain falls slowly due to its low lipid solubility, and
consequently plasma concentrations do not correlate with its effects.
Morphine metabolism occurs mainly in the liver but also in the kidneys. Up to 70%
is metabolized to morphine 3-glucuronide which appears to have effects on arousal
and is possibly aμ-receptor antagonist. The other major metabolite is morphine 6-
glucuronide, which is 13 times more potent than morphine and has a similar duration
of action. They are both excreted in urine and accumulate in renal failure. Morphine
is also N-demethylated. Neonates are more sensitive than adults to morphine due
to reduced hepatic conjugating capacity, and in the elderly peak plasma levels are
higher due to a reduced volume of distribution.Diamorphine
Diamorphine is a diacetylated morphine derivative with no affinity for opioid recep-
tors. It is a prodrug whose active metabolites are responsible for its effects. It is said
to be approximately two times as potent as morphine.Presentation and uses
Diamorphine is available as 10 mg tablets and as a white powder for injection con-
taining 5, 10, 30, 100 or 500 mg diamorphine hydrochloride, which is readily dis-
solved before administration. It is used parenterally for the relief of severe pain and
dyspnoea associated with pulmonary oedema at 2.5–10 mg. It is used intrathecally
(0.1–0.4 mg) and via the epidural route (1–3 mg) for analgesia where, due to a higher
lipid solubility, it is theoretically less likely to cause delayed respiratory depression
when compared with morphine.Kinetics
Owing to its high lipid solubility it is well absorbed from the gut but has a low oral
bioavailability due to an extensive first-pass metabolism. Its high lipid solubility
enables it to be administered effectively by the subcutaneous route. Once in the
plasma it is 40% protein bound. It has a pKa=7.6 so that 37% is in the unionized
form at pH 7.4. Metabolism occurs rapidly in the liver, plasma and central nervous
system by ester hydrolysis to 6-monoacetylmorphine and morphine, which confer its
analgesic and other effects. The plasma half-life of diamorphine itself is aproximately
five minutes.
Itproduces the greatest degree of euphoria of the opioids and subsequently has
become a drug of abuse.Papaveretum
Papaveretum is a semi-synthetic mixture of the anhydrous hydrochlorides of the
alkaloids of opium. It contains morphine, codeine and papaverine. Noscapine was
removed from its formulation after it had been shown to be teratogenic in animal
studies resulting in a standard dose of 15.4 mg, which is approximately equivalent