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Dihydrocodeine tartrate by Alan McLeod

Group: opioid analgesic

Indications: Moderate to severe pain

Mechanism of action: Interaction with opioid receptors – similar in action to codeine.

TRAMADOL hydrochloride by Katie Lambert

Mode of action:

Tramadol is a member of the non opiate opioid analgesic family and works to reduce or eliminate severe pain. It is synthetic analogue of codeine.

It is a centrally acting analgesic (brain and spinal cord), its mechanism of action is at the mu opioid receptors but is also thought to produce analgesia through enhancement of adrenergic and serotonergic descending pathways (as explained below).

Tramadol has been shown to have a low affinity for mu receptors, the M1 metabolite of tramadol, produced by liver O-demethylation, shows a higher affinity for opioid receptors than the parent drug. The rate of production of this M1 derivative (O-demethyl tramadol), is influenced by its metabolism by cytochrome P450.

The affinity of Tramadol for mu receptors of the CNS remains low, being 6000 times lower than that of morphine.

Moreover, and in contrast to other opioids, the analgesic action of tramadol is only partially inhibited by the opioid antagonist naloxone, which suggests the existence of another mechanism of action. This was demonstrated by the discovery of a monoaminergic activity that inhibits noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake, making a significant contribution to the analgesic action by blocking nociceptive impulses at the spinal level.

After oral administration, tramadol demonstrates 68% bioavailability, with peak serum concentrations reached within 2 hours. The elimination kinetics can be described as 2-compartmental, with a half-life of 5.1 hours for tramadol and 9 hours for the M1 derivative after a single oral dose of 100mg. This explains the approximately 2-fold accumulation of the parent drug and its M1 derivative that is observed during multiple dose treatment with tramadol.

Tramadol can be administered concomitantly with other analgesics, particularly those with peripheral action, while drugs that depress CNS function may enhance the sedative effect of tramadol.

Tramadol has pharmacodynamic and pharmacokinetic properties that are highly unlikely to lead to dependence.

Side effects:

Nausea and vomiting (particularly in initial stages).



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