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Objective To evaluate and analyze the drug-drug interactions(DDI)of different antidiabetic drugs.Methods DDI database Lexi-InteractionTMwas used to evaluate DDI for 28 commonly used antidiabetic medications(including insulin and 27 non-insulin preparations).Results 882 DDIs were identified for 28 drugs.Category C was the top rated DDI(69.8%). Category C,D,X were accounted for 91.2% of the total DDI.28 medication combinations belonged to category X,which should be avoided to use together.Sulfonylureas had the most DDI,followed by metformin.Alpha-glucosidase inhibitors had least DDI.Conclusion Hypoglycemic drugs with less DDI,such as α-glycosidase inhibitors,glucagon-likepeptide1(GLP-1)an-alogs and sodium-dependent glucose transporters 2 inhibitor(SGLT2i)should be considered with high priority for patients tak-ing multiple antidiabetic medications,elderly patients and patients with liver-kidney dysfunction.
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Objective To investigate the effects of intrathecal injection (IT) of agonist and antagonist of N-methyl-D-aspartate receptor subunit 1 (NMDA NR1) on pain threshold and spinal levels of glutamate and glutamate transporter-1 (GLT-1) in rat model of chronic constriction injury (CCI) induced neuropathic pain.Methods Sprague-Dawley (SD) rats were randomly divided into 4 groups (Sham,CCI,NM-DA,and Humanin).The CCI model was established by right sciatic nerve constriction.The thermal and mechanical thresholds were assessed by paw withdrawal latency (PWL) to radiant heat and yon Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after CCI.The NMDA and Humanin groups were administered intrathecally for 3 days before surgery.Spinal expression of GLT-1 assessed by Weston blotting and levels of glutamate were measured by enzyme-linked immunosorbent assay (ELISA).Results Compared to Sham group,the rats in CCI group gradually appeared the symptoms of toe close together,foot valgus and repeated licking to the operative side of the hind legs after surgery,and the paw withdrawal threshold (PWT),and PWL were greatly decreased,reaching the lowest level on the 7th day.Meanwhile,the glutamate content was increased,and the GLT-1 expression was decreased in spinal cord (P ＜ 0.05).Compared to CCI group,the rats in NMDA group were observed with further decrease in PWT,PWL and GLT-1 expressions at all observed timepoints (P ＜ 0.05),but increase in glutamate content in spine cord (P ＜0.05).Compared to CCI group,the rats in Humanin group were observed with increase in PWT,PWL and GLT-1 expressions at all observed timepoint (P ＜ 0.05),but decrease in glutamate content in spine cord (P ＜ 0.05).Conclusions NMDA receptor NR1 subunit participated in regulating neuropathic pain,inhibiting NMDA receptor NR1 subunit can alleviate neuropathic pain by down-regulating of glutamate and GLT-1.
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Objective To observe the effects of intrathecal injection(IT)of agonist and antagonist of cannabinoid receptor 1 on pain threshold in rat model of sciatic nerve ligation(SNL)induced neuropathic pain,and investigate the role and mechanism of CB1 in neuropathic pain. Methods Male Sprague-Dawley rats were randomly divided into 4 groups:sham group( intrathecal normal saline,IT DMSO),SNL group(SNL+IT 30μL DMSO),AM841 group(SNL+IT 5μg AM841,dissolved in 30μL of DMSO)and AM281 group(SNL+IT 5μg AM281,dissolved in 30μL of DMSO). IT was given 3 days before surgery. Sham group only had sciatic nerve exposure but without ligation. SNL model in the other three groups were established by right sciatic nerve ligation. The thermal and mechanical thresholds were assessed by paw withdrawal latency(PWL)to radiant heat and von Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after SNL. Spinal expressions of CB1 were assessed by West-ern blotting. Results Compared with the sham group,symptoms of rats in SNL group,such as heat hyperalgesia,mechanical allodynia and poste-rior paws prone to close together,were gradually appeared in the observation time points,with lower spinal proteins expression of CB1(P<0.05). AM841 group exhibited increased proteins expression of CB1 and inhibited SNL-induced heat hyperalgesia and mechanical allodynia(P<0.05). AM281 group further decreased expression of CB1 and amplified the pain abnormality(P<0.05). Conclusion Spinal CB1 participates in the regulation of neuropathic pain,and exogenous cannabinoid CB1 agonists can alleviate the SNL-induced neuropathic pain.
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Objective:To screen clinical pharmacists’ intervention points in the medical order safety management according to the classification of irrational medical order, ranking of risk and causes analysis in order to provide ideas and reference for clinical pharma-cists. Methods:The prior interventions and post reviews were conducted on medical orders in an intensive care unit of the hospital from July to December in 2014. Results:A total of 224 medical records and 6583 medical orders were intervened, reviewed and audi-ted. Among the medical orders, 653 cases were irrational with a ratio up to 9. 92%. The 653 irrational medical orders were mainly classified with incompatibility, inappropriate dosage and irrelevant combinations, and mainly D level errors according to the risk rating. Most of the irrational medical orders were due to the lack of professional knowledge. Conclusion: Clinical pharmacists should partici-pate in medical order safety management including interfering drug compatibility, dosage and combination therapy, which can reduce or even avoid the error occurrence in medical orders and promote safe and reasonable medication through reasonable medication training and prior interventions.
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Objective To observe the effect of intrathecal injection (IT) of oxycodone hydrochloride on neuropathic pain and spinal cord level of microglial c-Jun N-terminal kinase/chemokine (C-X-C motif) ligand 1 (c-JNK/CXCL) 1signal in rat model of chronic constriction injury (CCI).Methods Male Sprague-Dawley rats were randomly divided into five groups (n =40 per group):sham group (intrathecal normal saline,IT NS),CCI group (CCI + IT NS),oxy group (CCI + IT 5 μg/30 μl oxy),mino group (CCI + IT 5 μg/30 μl Minocycline),and c-JNK inhibitor group (SP group,CCI + IT 5 μg/30 μl SP600125).The lumbar intrathecal catheters were implanted in L5-6 of rats and CCI models were established as previously described.The thermal and mechanical nociceptive thresholds were assessed by paw withdrawal latency (PWL) to radiant heat and von Frey filaments.The oxycodone,minocycline and SP600125 were administered intrathecally for 3 days before surgery.The spinal cord expression of Ⅰ ba-1,p-c-JNK and CXCL1 proteins assessed by Western blot.Immunofluorescence staining was performed to examine microglia morphology and the number of Ⅰ ba-1 positives cells in dorsal horn of injured spinal cord at 7 days post-IR.Results Compared to sham group,rats in CCI group had significantly lower mechanical and thermal pain thresholds,but higher spinal proteins expression of Ⅰ ba-1,and p-c-JNK and CXCL1 (P ＜0.05).Rats in oxy group,mino group and SP group had significantly higher mechanical and thermal pain thresholds and significantly lower proteins expression of Ⅰ ba-1,p-c-JNK and CXCL1 compared to those in CCI group (at any observed time-point after ligation,but most significantly at 7days,P ＜ 0.05).At the 7days after surgery,microglial cells in CCI group transformed from the ramified shape to amoeboid macrophage-like shape by immunofluorescence staining with the increases of Ⅰ ba-1 positive cells;while the other three groups exhibited hypertrophic morphology with less number Ⅰ ba-1 positive cells (P ＜ 0.05).There were no significant differences between these three groups at any observed time (P ＞ 0.05).Conclusions Intrathecal injection of oxycodone hydrochloride can relieve CCI-induced neuropathic pain by down-regulation microglial c-JNK/CXCL1 signal in spinal cords.Provide new therapeutic targets for clinical treatment of neuropathic pain.