Pharmacology for Anaesthesia and Intensive Care

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9 Analgesics

Table 9.4.Summary of actions of some partial agonists at

various opioid receptors.

Agonist action at: Antagonist action at:

Nalorphine κμ

Pentazocine κ(partial)

δ(partial)

μ

Buprenorphine μ(partial)

NOP (partial)

Nalbuphine κ(partial) μ(partial)

produce hyperalgesia at low doses but analgesia at high doses. NOP-receptor antag-

onists produce long-lasting analgesia and prevent morphine tolerance, and may be

useful in the future.

Morphine

Morphine is a naturally occurring phenanthrene derivative. It has a complex struc-

ture (Figure 9.2) and is the reference opioid with which all others are compared. It is

aμ-receptor agonist.

Presentation and uses

Morphine is formulated as tablets, suspensions and suppositories, and as slow-

release capsules and granules in a wide range of strengths. The oral dose of morphine

is 5–20 mg 4 hourly. The parenteral preparation contains 10–30 mg.ml−^1 and may be

given intravenously or intramuscularly. The intramuscular dose is 0.1–0.2 mg.kg−^1

4 hourly. Intravenous morphine should be titrated to effect, but the total dose is

similar. It should be noted that these doses are only guidelines and the frequency of

administration and/or the dose may have to be increased. The subcutaneous route is

usually avoided due to its relatively low lipid solubility and therefore slow absorption.

Delayed respiratory depression following intrathecal or epidural administration may

occur and is again due to its relatively low lipid solubility.

Effects


Analgesia – particularly effective for visceral pain while less effective for sharp or

superficial pain. Occasionally increased doses may be required but this is usually

due to a change in pathophysiology rather than dependence.


Respiratory depression – the sensitivity of the brain stem to carbon dioxide is

reduced following morphine while its response to hypoxia is less affected. How-

ever if the hypoxic stimulus is removed by supplementary oxygen then respira-

tory. depression may be potentiated. The respiratory rate falls more than the tidal