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9 AnalgesicsOpioid partial agonists
This group of drugs has been used to control pain and to reverse opioid-induced
respiratory depression with variable success. They are not widely used.
Nalorphinewas the first partial agonist to be introduced as a morphine antagonist
but was subsequently found to have analgesic effects of its own. It produced a high
incidence of psychomimetic effects at analgesic doses and is no longer available in
the UK.
Pentazocineproduces analgesia with little respiratory depression. However, side
effects including nausea, vomiting, hallucinations and dysphoria have meant that it
is rarely used.
Buprenorphineis structurally similar to and more potent than morphine with a
duration of up to 10 hours due to receptor binding. Due to its receptor-binding profile
it produces analgesia at low concentrations (μ-receptor) but with increasing doses
the NOP effects take over to produce anti-analgesic effects. Nausea and vomiting are
severe and prolonged.
Nalbuphineis equipotent to morphine but appears to have a ceiling effect with
respect to its respiratory depression. Unfortunately it also appears to have a ceiling
effect with respect to its analgesic actions. Its actions may be reversed with naloxone.Non-steroidal anti-inflammatory drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs are used widely to treat mild to moderate
pain and also to reduce opioid consumption in the peri-operative period.
The route of administration is usually oral or rectal although some agents may be
administered intravenously (tenoxicam, ketorolac, parecoxib). Absorption is rapid
through the small bowel. NSAIDs are highly protein bound in the plasma and have
low volumes of distribution. The effects of other highly protein bound drugs (e.g.
warfarin) may be potentiated as they become displaced. Characteristically these
drugs are metabolized in the liver and excreted in an inactive form in the urine and
bile.Mechanism of action
Non-steroidal anti-inflammatory drugs inhibit the enzyme cyclo-oxy-
genase thereby preventing the production of both prostaglandins (including
prostacyclin) and thromboxanes from membrane phospholipids (Figure 9.3).
Thromboxane is produced by platelets when activated by exposure to adenosine,
collagen or adrenaline, and promotes haemostasis by vasoconstriction and platelet
aggregation. Conversely, endothelial prostacyclin promotes vasodilatation and
inhibits platelet aggregation.
Low-dose aspirin prevents arterial thromboembolism by selectively inhibiting
platelet thromboxane production. Platelets have no nuclei and are therefore not
able to regenerate new cyclo-oxygenase so that aspirin’s effects last for the life span