Tramadol- highlights
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✔️both opioid and non-opioid modes of action. .
(1) inhibition of noradrenaline re-uptake
(2)increased release and decreased re-uptake of serotonin in the spinal cord, and
(3)a weak effect on mu opioid receptors
✔️The weak, opioid effect is mediated by an active metabolite, (+)-M1 (O-desmethyltramadol), formed via the genetically polymorphic P450 CYP2D6 iso-enzyme system. The biological activity of this system is variable, and individuals may be classified as extensive or poor metabolisers of tramadol.
✔️Tramadol’s affinity for opioid receptors is about 6000 times weaker than morphine, but the (+)-M1 metabolite has an affinity about 200 times greater than tramadol. Poulsen et al. report much higher concentrations of the (+)-M1 metabolite and greater analgesic efficacy of tramadol in extensive metabolisers compared to poor metabolisers. Also noted was a reduction of nausea, vomiting and tiredness amongst poor metabolisers
Ondansetron-highlights
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✔️Ondansetron competitively antagonises serotonin, subtype 3 (5-HT3) receptors in the CTZ and enteric neurones.
✔️ Peripheral 5-HT3 receptors are also involved in nociceptive pathways and ondansetron may alter 5-HT3 nociceptive responses at the level of dorsal horn neurones
✔️ Ondansetron can block sodium channels in a similar fashion to local anaesthetic agents, and exhibit agonist activity at mu opioid receptors, thus resulting in a peripheral anti-nociceptive effect.
Tramadol + Ondansetron
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✔️PONV due to Tramadol is often managed with a competitive serotonin antagonist, ondansetron
✔️ There is evidence that the concurrent use of these two drugs results in a mutual reduction of effect—tramadol is a less potent analgesic and ondansetron is a less effective as an antiemetic.
✔️ But the effect of ondansetron on tramadol consumption diminished with time.
✔️ De Witte et al. found a significant (50%) increase in cumulative tramadol consumption during the first post-operative hour when patients were given ondansetron along with Tramadol.
✔️ Ondansetron is, in part, metabolised by the CYP2D6 iso-enzyme system—an iso-enzyme system responsible for formation of an active tramadol metabolite that has analgesic effect . Competition for this metabolic pathway may result in a reduction in formation of the (+)-M1 metabolite of tramadol and a consequent reduction in analgesic efficacy.
DO YOU KNOW❓😳 additional points➕
✔️ There is animal and human evidence that both tramadol and ondansetron have local anaesthetic type properties.
✔️ Ondansetron was approximately fifteen times more potent than lignocaine and may well be a prototype molecule for the development of a new group of local anaesthetic agents.
✔️ These findings are further supported in a human clinical study by Memis et al.which showed that tramadol and ondansetron both significantly reduced the pain associated with the injection of the neuromuscular blocking drug, rocuronium.
(Ref: J.H. Ye, W.C. Mui, J. Ren, T.E. Hunt, W.H. Wu, V.K. Zbuzek Ondansetron exhibits the properties of a local anesthetic. Anesth. Analg., 85 (1997), pp. 1116–1121)
✔️Tropisetron and granisetron are able to reverse an acetaminophen-mediated analgesia completely.
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References:
Anaesthesia. 2015 Feb;70(2):209-18. doi: 10.1111/anae.12948. Epub 2014 Dec 10.
The effect of ondansetron on the efficacy of postoperative tramadol: a systematic review and meta-analysis of a drug interaction.
Stevens AJ1, Woodman RJ, Owen H.
Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT3 Spinal Receptor Involvement in Acute Pain in Humans
Arcioni, Roberto MD*,; della Rocca, Marco MD*,; Romanò, Sarah MD*,; Romano, Rocco MD†,; Pietropaoli, Paolo MD*, and; Gasparetto, Alessandro MD*
ScienceDirect Review
Aspects of tramadol and ondansetron interactions Bruce Hammonds, David A. Sidebotham, Brian J. Anderson,
