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Section IICoredrugs in anaesthetic practicePresentation
Tramadol is available as tablets, capsules or sachets in a variety of strengths (50–
400 mg modified release) and as a solution for intravenous or intramuscular injection
containing 100 mg in 2 ml. Its analgesic potency is one-fifth to one-tenth that of
morphine.Mechanism of action
Tramadol has agonist properties at all opioid receptors but particularly atμ-receptors
but has not been classified as a controlled drug. It also inhibits the re-uptake of
noradrenaline and 5-HT, and stimulates presynaptic 5-HT release, which provides
an alternative pathway for analgesia involving the descending inhibitory pathways
within the spinal cord.Effects
Inequi-analgesic doses to morphine, tramadol produces less respiratory depression
and constipation. In other respects it has similar actions to morphine. Respiratory
depression and analgesia are reversed by naloxone.Interactions
Tramadol has the potential to interact with drugs that inhibit central 5-HT or nora-
drenaline re-uptake, that is, the tricyclic antidepressants and selective serotonin
re-uptake inhibitors, resulting in seizures. It should not be used in patients with
epilepsy.Kinetics
Tramadol is well absorbed from the gut with an oral bioavailability of 70% which
increases to more than 90% after repeated doses. It is metabolized in the liver by
demethylation and subsequent glucuronidation to a number of metabolites, only
one of which (O-desmethyltramadol) has been shown to have analgesic activity.
These products are excreted in the urine. Its volume of distribution is 4 l.kg−^1 and its
elimination half-life is 5–6 hours.Naloxone
Naloxone is a pure opioid antagonist and will reverse opioid effects atμ-,κ-and
δ-receptors, although its affinity is highest forμ-receptors. Other occasional effects
include hypertension, pulmonary oedema and cardiac arrhythmias and antanalge-
sia in opioid naive subjects.
At1–4μg.kg−^1 intravenously it is the drug of choice in opioid overdose. However, its
duration of action at 30–40 minutes is shorter than morphine and high-dose fentanyl
so that supplementary doses or an infusion of naloxone may be required.