Severe pain associated with mucositis may necessitate reductions, delays or termination of anticancer therapy and so intravenous morphine, preferably by patient-controlled analgesia (PCA) is the treatment of choice.

Methods:

Retrospective review of consecutive episodes of mucositis in children requiring intravenous opioid analgesia over a 3-year period (May 2006-April 2009).

Results:

In 24/92 (26%) of cases, morphine PCA provided insufficient

pain relief and children required adjuvant ketamine therapy. These children had rapidly increasing morphine requirements approaching 1000 mcg/kg/day by day 2 (more than double compared with children on morphine alone), were more likely to be female, and tended to be older (median [IQR] age 12 [6-12] years vs 7 [3-14] years). The addition of ketamine to the morphine PCA appears to Selleck HKI272 be associated with reduced morphine consumption, improved pain scores, causing minimal side effects and no hallucinations.

Conclusions:

Children with severe mucositis who have escalating morphine requirements may benefit from the addition

of ketamine to their morphine PCA.”
“P2Y(12) inhibitors were introduced clinically as effective inhibitors of adenosirie-5′-diphosphate (ADP) mediated platelet activation and aggregation. This class of pharmacological agents has enjoyed considerable success. Cangrelor is a recently developed P2Y(12) inhibitor that has the advantage ol.: being an active drug not requiring metabolic conversion, although it is not orally BI 2536 available. Coated-plate lets are a subclass of activated platelets generated on dual agonist activation with collagen plus thrombin; the primary hallmark of coated-platelets is their ability to Support prothrombinase

activity. Interestingly, we recently observed that the relatively weak agonist ADP potentiates the production of coated-platelets by the very strong agonists collagen plus thrombin, a previously unknown role for ADP. The authors sought in this study to determine if P2Y(12) inhibitors, Such as cangrelor, were capable of attenuating this augmentation of coated-platelet generation. Cangrelor, at physiologically relevant concentrations, was able to eliminate the ADP-dependent increase in coated-platelet production with art Proteasome inhibitor IC(50) of 1.4 nM. Cangrelor, however, had no effect on thrombin-dependent platelet activation as measured by P-selectin expression. Although this in vitro Study does not address the question of whether the effectiveness of cangrelor in vivo is partially due to an attenuation of coated-platelet production in addition to its documented antiaggregatory effects, it does reveal an unexpected action of cangrelor. Additional Studies will be required to determine if all P2Y(12) inhibitors are equally effective in attenuating coated-platelet production.