tramadol

see also:

• pain, analgesia and analgesics
• opiates and opioids
• tapentadol

• a synthetic, opioid-like, centrally acting analgesic
• it is not chemically related to opiates
• it is related to the newer analgesic, tapentadol
• believed to act on mu opioid receptors & inhibit reuptake of serotonin & NA in the pain pathways of the CNS which may play the more important part of its actions.
• affinity for mu receptor is 1/10th that of codeine, & 1/6000th less than morphine
• unlike morphine, it does not cause histamine release.
• unlike non-steroidal anti-inflammatory drugs (NSAIDs), it has no effect on PG synthesis & thus no effect on GIT bleeding, renal impairment, bronchospasm or reduced platelet activity, but it does still have some anti-inflammatory effect via direct inhibition of the formation of prostanoids.
• rapidly absorbed orally with 70-90% bioavailability & peak plasma level at 2hrs after 50mg capsule or 5hr after S-R capsules.
• peak level after IM injection is 45min.
• undergoes extensive hepatic metabolism & like codeine is metabolized by CYP2D6 which is deficient in 10% of Caucasians (thus codeine has no effect in these people as it does not get converted to morphine, while tramadol, being an active drug as well as its metabolite has little difference compared to those who are not deficient) 
• half lives are 5h & 9h for its active metabolite
• although widely used in Europe since the late 1970's, it was introduced in Australia & NZ in 1998, with a rapid increase in its use.

• nausea, vomiting, somnolence constipation
• SSRI-like effects such as headaches, dizziness, sweating, & dry mouth.
• lowered seizure threshold
• myocardial & resp. depression, serotonin syndrome, tachycardia, agitation, seizures in OD

• useful as an adjunctive analgesia, comparable to paracetamol/codeine or NSAID and perhaps better than oral morphine for chronic pancreatitis due to its less GIT effects.

• may be of limited use in Mx of the drug seeker or the chronic pain patient in the ED as not as pharmacologically addictive as are the opiates and opioids although there is the potential for tolerance, dependence, abuse & a withdrawal syndrome.

• usually 50mg capsules and given every 4-8 hours

• annotated with “SR”
• avoid in acute pain when rapid titration of doses is needed
• available as 50mg, 100mg, 150mg and 200mg tablets given twice daily

• annotated with “XR”
• available as 100mg, 200mg or 300mg and given once daily
• start at 100mg daily swallowed whole, increase to 200mg daily on day 3 if needed, and to 300mg on day 5 if pain not adequately controlled.
• manage incident pain with paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs (NSAIDs)
• similar efficacy as SR formulations
• avoid in acute pain when rapid titration of doses is needed
• Durotram XR is a biphasic formulation with outer layer releasing 25% of dose within 2hrs, while remainder is gradually released from the core over 24hrs.
• restricted benefit under PBS - 10 days course (ie. 10 tablets)
• NPS RADAR article Dec 2008