TRAMADOL BACKGROUND

BACKGROUND





Tramadol is a centrally acting, synthetic analgesic of the aminocyclohexanol group, which has
opioid-like effects

1. It has been in clinical use in Europe since the late 1970s

2. Its mode of action is not completely understood but it appears to have a dual mechanism of
action, which involves inhibition of re-uptake of serotonin (5-HT) and/or noradrenaline as
well as weak affinity for opioid (mu) receptors

3. Since tramadol does not affect prostaglandin synthesis, it does not have antipyretic
or anti-inflammatory effects
4. In Australia, tramadol is marketed under the trade name Tramal
and is available as capsules (50mg), sustained-release tablets (100mg, 150mg, 200mg) and
ampoules (100mg/2ml). It is approved for oral, intravenous (iv) and intramuscular (im)
administration for relief of moderate to severe pain. (Government subsidy for the immediate
and sustained-release formulations is limited to use for pain where aspirin and/or
paracetamol alone are inappropriate or have failed.) In Australia it is not recommended for
use in children, although in other countries, licence for use in children over
the age of one year exists.
5 Tramadol has high oral bioavailability

6. Tramadol is extensively metabolised
the production of the only known active metabolite, M1
(mono-o-desmethyltramadol) is dependent on the CYP2D6 isoenzyme of the cytochrome P-450
enzyme system and hepatic impairment results in decreased metabolism of both the parent
compound and the active metabolite

7. Patients who metabolise drugs poorly via CYP2D6 may
obtain reduced benefit from tramadol due to reduced formation of M11. However, there is still
measurable analgesia with tramadol in these patients, in contrast to the complete lack of
analgesic efficacy with codeine in such patients (7% of Caucasians are poor metabolisers)
In such patients there may be an argument for using tramadol as an alternative to codeine

8. Tramadol causes a minor delay in colonic transit, but has no effect on upper gastrointestinal
transit or gut smooth muscle tone

9. It has no significant effect on the Sphincter of Oddi or intrabiliary
pressure and it has weak spasmolytic properties

10.The recommended dose for moderate to severe pain is 50-100mg every four to six hours (or 100-
200mg twice daily for the sustained-release formulation), to a maximum daily dosage of 400mg
for oral therapy or 600mg parenterally.