Alpha 2 agonists have been shown to have opioid-sparing effects, but can cause hypotension and bradycardia and must be taken into consideration when administered. Acetaminophen is commonly used in a multimodal approach, with recent evidence lacking for the use of IV over oral formulations in patients able to take medications by mouth. Studies involving gabapentinoids have been mixed with some showing benefit; however, future large randomized controlled trials are needed. Ketamine is known to have powerful analgesic effects and, when combined with magnesium and other agents, may have a synergistic effect. Dexamethasone reduces postoperative nausea and vomiting and has been demonstrated to be an effective adjunct in multimodal analgesia. The serotonin-norepinephrine reuptake inhibitor, duloxetine, is a novel agent, but studies are limited and further evidence is needed. Overall, a multimodal analgesic approach should be used when treating postoperative pain, as it can potentially reduce side effects and provide the benefit of treating pain through different cellular pathways.

In the setting of data demonstrating an almost fourfold increase in overdose deaths from 1999 to 2008, states began restricting access to Food and Drug Agency (FDA) approved opioid medications. Another factor further exacerbating the opioid crises is that the cost of all formulations of naloxone has increased significantly over the past several years. In order to combat the opioid epidemic, stricter prescribing practices and prescription-monitoring programs have been instituted. Also, improvements in abuse-deterrent strategies for all opioid preparations can play an important role by increasing the safety of these medications and is a major focus of the FDA.

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