临床药师参与1例粪肠球菌腹腔感染患者的治疗分析

目的:探讨临床药师在参与粪肠球菌腹腔感染患者抗感染治疗中的作用。方法:通过1例粪肠球菌腹腔感染的案例,根据药敏试验给予替考拉宁治疗后,患者感染指标呈下降趋势,但患者反复、间断性发热。临床药师从利奈唑胺与替考拉宁的体内外抗菌活性、临床疗效与组织穿透性方面进行了对比,建议医师将替考拉宁替换为利奈唑胺。患者治疗2 d后,感染得到控制。结果:抗感染取得了良好的效果,患者好转出院。结论:临床药师参与患者抗感染方案制订,可为医师和患者提供更加有效的治疗方案。     

1例肝硬化合并肾功能不全患者利奈唑胺剂量调整的药学监护

报道1例利奈唑胺致肝硬化合并肾功能不全患者血小板减少的病例。患者为老年男性,以“院外治疗后腹痛、腹胀加剧”为主诉入院。临床药师结合患者实际情况,建议经验给予亚胺培南西司他丁（1 g,iv gtt,q8h）联合利奈唑胺（0.6 g,iv gtt,q12h）抗感染治疗,并对利奈唑胺进行血药浓度监测。治疗过程中患者利奈唑胺谷浓度异常偏高且出现血小板减少,考虑为利奈唑胺所致不良反应,停用利奈唑胺并对症处理后血小板回升。因临床需要,在血药浓度监测下再次启用利奈唑胺（0.2 g,iv gtt,q12h）抗感染治疗,治疗后患者感染得到了有效控制,且未再出现血小板减少。     

临床药师参与1例椎间神经鞘瘤切除术后脓肿分枝杆菌感染的药学监护

目的 为治疗脓肿分枝杆菌感染的药学监护提供思路。方法 对临床药师参与的1例椎间神经鞘瘤切除术后脓肿分枝杆菌感染患者的诊疗方案进行分析。临床药师根据创口分泌物细菌培养及药敏试验结果,及时处理治疗过程中出现的药物不良反应,针对患者服用阿米卡星（0.4 g,静脉滴注,q12 h）后引起的耳鸣,建议停用阿米卡星,改为利奈唑胺,但该患者在服用利奈唑胺后出现膝关节痛,临床药师再次建议停用利奈唑胺,继续使用阿米卡星,并将剂量调整为0.8 g,静脉滴注,q24 h;同时对患者进行用药指导并嘱患者出院后定期复查随访。结果 临床医师采纳了临床药师的建议,该患者未再出现耳鸣、膝关节痛等不适,肝肾功能也无异常。结论 临床药师及时协助临床医师调整用药方案,提高了患者用药的有效性和安全性。     

临床药师参与1例利奈唑胺个体化治疗的药学实践

目的 探讨利奈唑胺个体化给药治疗策略,为优化利奈唑胺给药方案积累经验。方法 介绍临床药师参与1例利奈唑胺治疗化脓性链球菌脓毒症合并骶髂关节感染患者的案例。临床药师通过血药浓度监测,结合利奈唑胺的药动学特点以及文献阅读结果,为临床提供超说明书增加利奈唑胺给药剂量的建议,并进行药学监护。结果 增加利奈唑胺给药剂量后,患者感染得到了有效控制,未出现药物不良反应,病情好转出院。结论 该案例为国内首例利奈唑胺超说明书剂量治疗化脓性链球菌脓毒症致多器官功能障碍合并骶髂关节感染对于部分特殊人群治疗,利奈唑胺的说明书剂量不足问题应受到关注。     

利奈唑胺与帕罗西汀合用引起 5?羟色胺综合征 1例分析

目的探讨帕罗西汀与利奈唑胺合用致 5?羟色胺综合征的临床特点及临床药师在药源性疾病的鉴别及处置方面发挥的作用。方法临床药师对一例因焦虑症长期口服帕罗西汀的病人，在使用利奈唑胺 600 mg，每 12小时 1次，静脉滴注治疗人葡萄球菌心内膜炎 2d后突发高热、瞻望、震颤及血压飙升等症状进行分析。结果 5?羟色胺再摄取抑制剂帕罗西汀与单胺氧化酶抑制剂利奈唑胺合用可导致内源性升压物质拟交感胺类破坏减少，引起 5?羟色胺综合征，与病人症状相符。后立即停用两药，同时在监护下进行镇静、降压等对症治疗，最终病人症状纠正。结论在制定临床给药方案时，临床医生应警惕利奈唑胺与 5?羟色胺再摄取抑制剂的相互作用，同时重视临床药师在保障用药安全方面发挥的积极作用。     

1例氟康唑和沙利度胺致皮肌炎合并肺部感染的药学监护

目的 探讨临床药师在皮肌炎合并肺部感染治疗中的药学监护作用。方法 临床药师参与1例皮肌炎合并肺部感染的药物治疗,分析患者出现药品不良反应的原因,并提供药学监护。结果 患者出现四肢及口唇发麻后,临床药师建议停用可疑药品沙利度胺,医师采纳;患者四肢及口唇发麻未见明显改善,临床药师再次建议停用可疑药品氟康唑,患者四肢及口唇发麻症状改善。结论 临床药师参与治疗方案的制订,提供药学服务,有助于提高患者的治疗效果,促进合理用药。同时,在药学查房过程中,密切监测使用沙利度胺的患者,一旦出现药源性周围神经炎,应立即减量或停用可疑药物。     

临床药师参与纹带棒状杆菌致肺部感染合并肾功能不全患者的药学实践

1例88岁女性患者,因“咳嗽、咳痰4 d,胸痛1 d”入院,诊断为慢性肾功能不全、重症肺炎,给予气管插管辅助通气、头孢哌酮钠舒巴坦钠联合氟康唑抗感染治疗,后因支气管肺泡灌洗液细菌培养及基因测序结果均提示纹带棒状杆菌感染,故加用利奈唑胺葡萄糖注射液(0.6 g,q 12 h,ivgtt),使用利奈唑胺第6天测谷浓度为13.21 mg·L^-1,PLT 55×10⁹·L^-1,判断为利奈唑胺血药浓度超出上限并引起骨髓抑制,临床药师建议停用利奈唑胺并换用万古霉素,临床医生采纳并给予注射用万古霉素(0.5 g,qod,ivgtt),期间监测万古霉素谷浓度为5.7 mg·L^-1,临床药师分析万古霉素谷浓度不达标的原因,并建议给药方式由静脉滴注改为24 h持续输注,临床医生采纳意见,后复测万古霉素谷浓度为19.6 mg·L^-1,19 d后患者感染得到控制,PLT恢复正常,病情稳定后患者转院治疗。     

利奈唑胺致肝损伤一例并文献分析

目的 分析利奈唑胺致药物性肝损伤的不良反应特点,为临床合理用药提供依据。方法 分析1例老年患者使用利奈唑胺致急性肝损伤的诊疗经过,并采用文献回顾性研究的方法,对利奈唑胺致肝损伤患者的临床资料进行分析。结果 患者给予利奈唑胺联合美罗培南抗感染治疗1 d后肝酶出现升高,2 d后肝酶升至丙氨酸氨基转移酶（ALT）583.6 U/L、天门冬氨酸氨基转移酶（AST）575.8 U/L,碱性磷酸酶（ALP）61 U/L,谷氨酰转肽酶（GGT）113 U/L。停用利奈唑胺,给予保肝治疗后肝酶下降明显,7 d后复查肝功能恢复正常。利奈唑胺致患者肝损伤的不良反应可能与老年女性、用药剂量有关,出现肝损伤时应评估抗感染治疗效果,必要时建议暂停药物治疗。结论 利奈唑胺可快速致药物性肝损伤的不良反应,应加强其用药监测。     

疑似利奈唑胺引发肝功能损伤患者的药学监护

目的 探讨临床药师参与1例疑似利奈唑胺引发肝功能损伤患者的药学监护。方法 针对肺部感染患者在使用利柰唑胺过程中出现肝功能损伤的具体病例,临床药师从原发疾病、肝功能变化、合并用药等因素推断利奈唑胺是肝功能损伤的可能原因,并适时提出干预建议。结果 临床药师对患者肝功能损伤的原因进行了及时和准确的分析,医师采纳了临床药师的建议,患者病情得到了控制。结论 临床药师主动参与患者用药过程,给予医师相应的建议,可以确保患者的用药安全有效。     

临床药师参与1例利奈唑胺引发的周围神经炎患者的药学实践

临床药师参与1例利奈唑胺致周围神经炎不良反应的分析和监护,以期引起临床重视,减少严重不良反应发生。临床药师根据药物引发周围神经炎的时间相关性和药物与不良反应因果关系的判断准则,建议临床停用利奈唑胺,患者周围神经炎好转。临床药师积极参与临床治疗实践,可保障患者用药安全,促进临床合理用药。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture

Arsenic at a nonlethal level in drinking water consumed over a period of time has been reported to produce chronic toxicity and various types of health problems ranging from skin cancer to disturbance in memory. Neurotoxic effects have been reported in clinical cases with chronic exposure to arsenic. Physiological detoxication of arsenic occurs partially through methylation. Arsenic and its methylated derivatives are distributed in different organs and systems. The present study examined the possible interference in the neuronal development and differentiation due to the exposure to arsenic during gestation. The experiments were carried out to examine short and long term effects of arsenic on brain explants and cells grown and maintained in tissue culture system. The effects of arsenic exposure showed changes in brain cell membrane function indicated by generation and release of reactive oxygen-nitrogen intermediates. On the morphological aspect the explants' growth was reduced, ground matrix was lost and neural networking was inhibited. Cells showed signs of apoptotic changes. Arsenic toxicity may induce damage to brain cells prior to more visible clinical conditions. The deleterious effects also pass from the maternal to fetal tissue across the transplacental barrier.     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85–100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.     

SalB stimulates neurogenesis and angiogenesis in vitro and in vivo

Aims： Previous studies suggested that Salvianolic acid B （SalB） has strong protective effect against cerebral ischemia. Recently, Sal B has been reported to enhance angiogenesis in vitro. Based on the information above, in this study we are interested in the effect of SalB on neurogenesis and angiogenesis. Methods：In vitro study, we used embryonic mouse （El6） primary cortical neural cultures. Neuron was recognized by anti-MAP2 with immunocytochemistry. Neurogenesis was tested with BrdU incorporation by ELSA method. SalB（ 10 -6 -10 -8M） or vehicle was added to the culture medium 24 hrs before BrdU addition. In vivo, middle cerebral artery occlusion （MCAO） rats were used as focal cerebral ischemia model.     

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

INTRODUCTION: There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications. AREAS COVERED: This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments. EXPERT OPINION: Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.     

Consistency in catecholamine and cortisol excretion in males and females

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.     

Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats

Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome. Send offprint requests to K. J. Netter     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85-100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.