质子泵抑制剂不良反应综述

概述质子泵抑制剂类药品的不良反应,为该类药品的临床合理使用提供参考。     

质子泵抑制剂在3种I类切口清洁手术患者中使用的合理性分析

目的考察质子泵抑制剂（proton pump inhibitor,PPI）在3种I类切口清洁手术（甲状腺次全切术、乳腺肿物切除术、充填式张力疝修补术）术后应用的合理性,旨在提高我院临床合理用药的水平。方法选取2010年我院3种I类切口清洁手术（甲状腺次全切术、乳腺肿物切除术、充填式无张力疝修补术）患者,分为实验组（术后使用PPI）351例和对照组（术后不使用抑酸药）366例,经统计分析实验组与对照组在预防术后应激性溃疡和吸入性肺炎的差别。结果实验组与对照组比较．其术后应急性溃疡和吸入性肺炎的发生率均无显著性差异（P〉0．05）。结论行甲状腺次全切术、乳腺肿物切除术、充填式张力疝修补术的患者术后使用PPI预防应激性溃疡和吸人性肺炎是没有必要的,是PPI过度使用的一种表现。     

我院质子泵抑制剂临床应用131例合理性分析

目的了解该院质子泵抑制剂(PPI)的临床应用情况。方法从该院2011年1～6月病区出院病历中,每个病区每月随机抽取10份病历,共计480份,其中使用PPI病历131份,对病历中PPI适应证描述、给药方案及途径进行回顾性统计与分析。结果 131份病例中用于改善消化道不适最多为58例(44.27%),防治上消化道出血24例(18.32%),预防应激性溃疡13例(9.92%),预防激素引起溃疡10例(7.63%),未明确描述26例(19.85%)。157种给药方案中,仅有9种方案采用了口服给药,分别为"奥美拉唑20mg,qd,po"2种,"奥美拉唑20mg,bid,po"4种,"奥美拉唑20mg,tid,po"3种。其余148种方案均采用注射给药,采用最多的3种方案分别为"注射用奥美拉唑60mg,qd"占35.67%,"注射用奥美拉唑40mg,qd"占19.11%,"注射用奥美拉唑60mg,bid"占13.38%。结论该院使用PPI存在不合理用药现象,临床使用应严格掌握用药指征及用法、用量,避免无适应证及超剂量使用。     

Increase in Vertebral Fracture Risk in Postmenopausal Women Using Omeprazole

Proton pump inhibitors are taken by millions of patients for prevention and treatment of gastroesophageal diseases. Case-control studies have suggested that use of omeprazole is associated with an increased risk of hip fractures. The aim of this prospective study was to assess the risk of vertebral fractures in postmenopausal women using omeprazole. We studied 1,211 postmenopausal women enrolled in the Osteoporosis and Ultrasound Study from the general population. Information on omeprazole and other risk factors for fractures including prevalent fractures and bone mineral density was obtained at baseline. Vertebral fractures were assessed on X-rays obtained at baseline and at the end of the 6-year follow-up and analyzed centrally. At baseline, 5% of this population was using omeprazole. Age-adjusted rates for vertebral fractures were 1.89 and 0.60 for 100 person-years for omeprazole users and nonusers, respectively (P = 0.009). In the multivariate analysis, omeprazole use was a significant and independent predictor of vertebral fractures (RR = 3.50, 95% CI 1.14–8.44). The other predictors were age higher than 65 years (RR = 2.34, 95% CI 1.02–5.34), prevalent vertebral fractures (RR = 3.62, 95% CI 1.63–8.08), and lumbar spine T score ≤ −2.5 (RR = 2.38, 95% CI 1.03–5.49). Omeprazole use is associated with an increased risk of vertebral fractures in postmenopausal women. Further studies are required to determine the mechanism of the association between the underlying gastric disease, omeprazole use, and risk of osteoporotic fractures.     

Distribution of neurochemical abnormalities in patients with narcolepsy with cataplexy: An in vivo brain proton MR spectroscopy study

Narcolepsy with cataplexy is characterised by excessive daytime sleepiness, sudden drops of muscle tone triggered by emotions, termed cataplexy, disrupted nocturnal sleep and other dissociated rapid eye movement (REM) sleep phenomena. Narcolepsy has been linked to a loss of hypothalamic neurons producing hypocretins, neuropeptides implicated in the regulation of the arousal system. Neuroimaging and neurometabolic studies have shown the pathophysiological involvement of other brain structures such as cerebral cortex and thalamus, but, overall with inconsistent results.We investigated, by using an advanced quantitative MR technique, proton MR spectroscopy (¹H-MRS), the distribution of brain neurochemical abnormalities in narcolepsy with cataplexy patients. Single voxel ¹H-MRS study was performed in the thalamus, hypothalamus, and parietal–occipital cortex of hypocretin deficient, narcolepsy with cataplexy patients, HLA-DQB1*0602-positive, drug free. No significant changes were detected in the thalamus and parietal–occipital cortex of the patients. On the other hand, the neuronal marker N-acetyl-aspartate was reduced in the hypothalamus of narcolepsy with cataplexy patients compared to controls.These ¹H-MRS findings further support that in narcolepsy with cataplexy patients, the hypothalamus is the primary site of neural lesions. The absence of ¹H-MRS neurodegenerative changes in the thalamus and cerebral cortex suggests that the abnormalities detected in these brain regions by other neuroimaging techniques are likely of functional nature.     

The gastric HK-ATPase: structure, function, and inhibition

The gastric H,K-ATPase, a member of the P₂-type ATPase family, is the integral membrane protein responsible for gastric acid secretion. It is an α,β-heterodimeric enzyme that exchanges cytoplasmic hydronium with extracellular potassium. The catalytic α subunit has ten transmembrane segments with a cluster of intramembranal carboxylic amino acids located in the middle of the transmembrane segments TM4, TM5,TM6, and TM8. Comparison to the known structure of the SERCA pump, mutagenesis, and molecular modeling has identified these as constituents of the ion binding domain. The β subunit has one transmembrane segment with N terminus in cytoplasmic region. The extracellular domain of the β subunit contains six or seven N-linked glycosylation sites. N-glycosylation is important for the enzyme assembly, maturation, and sorting. The enzyme pumps acid by a series of conformational changes from an E₁ (ion site in) to an E₂ (ion site out) configuration following binding of MgATP and phosphorylation. Several experimental observations support the hypothesis that expulsion of the proton at 160 mM (pH 0.8) results from movement of lysine 791 into the ion binding site in the E₂P configuration. Potassium access from the lumen depends on activation of a K and Cl conductance via a KCNQ1/KCNE2 complex and Clic6. K movement through the luminal channel in E₂P is proposed to displace the lysine along with dephosphorylation to return the enzyme to the E₁ configuration. This enzyme is inhibited by the unique proton pump inhibitor class of drug, allowing therapy of acid-related diseases.     

Proton therapy in clinical practice

Radiation dose escalation and acceleration improves local control but also increases toxicity.Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients.Compared with photon therapy,proton therapy spares more critical structures due to its unique physics.The physical properties of a proton beam make it ideal for clinical applications.By modulating the Bragg peak of protons in energy and time,a conformal radiation dose with or without intensity mo...