Note: This post was originally published on PalliMed as part of the World Series of Blogs Payback-Ed. In 2013, there were 43.8 million prescriptions for tramadol filled in the U.S. It has a slightly different method of action from many other pain medications, as tramadol is both a mu-opioid receptors agonist and a reuptake inhibitor of serotonin and norepinephrine. It is also thought that the opioid activity is due to both the parent compound and the more active O-desmethylated metabolite (which, like codeine is metabolized by CYP 2D6 and therefore gives the same big inter-individual differences in pharmacokinetics). The overall efficacy as a pain medicine is comparable to that of other weak opioids. Most people know it is associated with serotonin syndrome as well as seizures especially when used with other medications that lower seizure threshold. A new study that came out in JAMA IM reveals a pretty robust association between tramadol use and hospitalizations for hypoglycemi