No abstract

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.

Summary. Recent studies suggest that nitric oxide (NO) may partly be responsible for the beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) patients. NO stimulates cyclic guanosine monophosphate (cGMP) production, which mediates vasodilatation. We investigated the association between NO, cGMP and fetal haemoglobin (HbF) levels after HU administration. Our data showed that chronic HU significantly increased NO, cGMP, and HbF levels in SCD.Recently it was shown that HbF production was stimulated by cGMP-dependent protein kinase. Our results suggest that NO stimulates cGMP production, which then activates a protein kinase and increases the production of HbF.

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.

The mechanism of action of hydroxyurea (HU) in decreasing the frequency of pain crisis in sickle cell disease (SCD) has not been fully elucidated. In vitro and in vivo studies suggest that nitric oxide (NO), a potent vasodilator, may partly be responsible for the beneficial effect of HU. This study was designed to determine the effect of oral administration of HU on plasma levels of NO metabolites (NO(x) ) in sickle cell patients (SCP). The results indicate that during steady-state plasma levels of NO(x) were significantly higher in HU-treated patients compared to non HU-treated patients or normal controls (p <.05). In five inpatients in mild pain plasma levels of NO(x) increased significantly after 2 h of HU administration (p <.05); however, in three inpatients in persistent pain with significantly lower baseline NO(x) there was a minimal NO(x) response to HU at 2 h (p <.01). These observations indicate that HU administration is associated with the production of NO in some SCP, but that further study of the pharmacodynamics of this effect is necessary.