《平喘药物的临床应用.ppt》由会员分享，可在线阅读，更多相关《平喘药物的临床应用.ppt（28页珍藏版）》请在三一办公上搜索。
1、平喘药物的临床应用,GINA平喘药物的分类,控制药物：吸入性和全身性糖皮质激素；色甘酸钠；缓释茶碱；吸入型、口服型长效2受体激动剂；白三烯受体调节剂；酮替酚等。缓解药物：短效2受体激动剂；全身性皮质激素；短效茶碱；抗胆碱能药和肾上腺素等。,Mechanisms Underlying the Definition of Asthma,Risk Factors(for development of asthma),INFLAMMATION,AirwayHyperresponsiveness,Airflow Obstruction,Risk Factors(for exacerbations),Sy
2、mptoms,平喘药物作用机制,抑制炎症过程：包括抑制炎症细胞的激活和向炎症部位的聚集；抑制炎症介质的合成和释放；拮抗炎症介质，阻断其作用；稳定感觉神经未梢。缓解气道阻塞：通过增加cAMP、降低细胞内游离钙离子和开放钾通道等舒张气道平滑肌；降低血管渗透性，减轻粘膜水肿和气道狭窄；清除粘液。气道外作用：茶碱类有解除呼吸肌（膈肌）疲劳和轻度的呼吸中枢兴奋作用。,2受体激动剂的分类,按化学结构分类儿茶酚胺类：肾上腺素；异丙肾上腺素。配基糖苷类：舒喘灵。间苯二酚类：博利康尼。水杨醇类：美喘清；沙米特罗；福摩特罗。按开发年代分类第一代（19011967）：肾上腺素；异丙肾上腺素；异丙喘宁；麻黄素。第二代
3、（19681975）：舒喘灵；叔丁喘宁。第三代（19761979）：妥布特罗等。第四代（1980今）：长效，具抗炎作用沙米特罗和福摩特罗。按对受体作用特性分类 非选择性。选择性：短效和长效。,作用机理,直接作用抑制肥大细胞和嗜碱细胞释放介质突触前膜上少量2受体抑制Ach的释放,常 用 2 受体 激 动 剂,药 物 商品名 途径 剂量（ug/次）副反应 维持t（h）沙丁胺醇 喘乐宁 吸入 100400 轻微 45 舒喘宁 口服 20004000 静滴 0.5mg,滴速28ug/min 特布他林 喘康速 吸入 100400 轻微 46 博利康尼 口服 25005000 妥布特罗 息克平 口服 50
4、0 轻微 10 普鲁特罗 美喘清 口服 2550 轻微 1012 沙美特罗 施立稳 吸入 2550 极微 12 福摩特罗 奥克斯 吸入 4.59.0 极微 12,临床对2受体激动剂的评价,在哮喘治疗中的不良反应：反常性、矛盾性支气管痉孪炎性负荷增加，诱导气道高反应性。掩盖气道炎症，增加哮喘严重度和病死率。在哮喘治疗中的地位：作用与副作用。,M胆碱能受体拮抗剂受体分布,M1受体位于气道的副交感神经节内；M2受体位于动脉壁节后纤维的突触前膜上（还有少量的受体），反馈性调节；M3受体位于气道平滑肌和粘膜下腺体中。,M胆碱能受体拮抗剂临床应用,本品与受体激动剂合用可相互增强疗效，如可必特（异丙托溴铵加
5、硫酸沙丁胺醇）。某些哮喘患者应用较大剂量2激动剂不良反应明显，可换此类药物，尤其是夜间哮喘及痰多和哮喘患者。可用MDI，每日36次，每次2575ug，或用0.025%的溶液12ml持续雾化吸入。气雾吸入后5分钟左右起效，约30分钟作用达峰值，维持46小时。,磷酸二酯酶抑制剂平喘机理,抑制磷酸二酯酶；刺激内源性儿茶酚胺的释放；拮抗腺苷作用；对Ca的调节。,磷酸二酯酶抑制剂分类,茶碱与不同盐或碱基形成复盐:氨茶碱和胆茶碱茶碱N-7位以不同基团取代的衍生物:羟丙茶碱和二羟丙茶碱(喘定)；缓释剂:葆乐辉(优喘平)和舒弗美。,影响茶碱代谢的因素,增加清除率 降低清除率 吸烟 肝硬化 年龄116岁 甲亢
6、低碳水化合物，心肾功能不全 高蛋白饮食 低氧血症，诱导酶的药物：高碳酸血症 苯巴比妥 老年人或新生儿 卡马西平 大环内酯，喹诺酮类 苯妥因钠 甲氰咪胍 异烟肼，利福平 氯霉素,临床应用,（）口服氨茶碱，控释型茶碱 用于轻中度哮喘；剂量常为610mg/kg/d；慎与2激动剂联合应用。小剂量具抗炎作用。（）静脉用药 重症24小时内未用：首剂46 mg/kg，继之以0.60.8mg/kg/h的速度静滴，有效血药浓度在515ug/ml。,.,临床应用指南,因茶碱的生物利用度与消除速率的个体差异较大,且安全范围窄,须进行血药浓度监测。了解影响茶碱消除的各种因素，及时调整用量，以免影响疗效或引起中毒。熟悉
7、茶碱的不良反应，出现中毒症状立即停药，对症处理。,肾上腺皮质激素,作用机理：抗炎；抗过敏；抗渗漏；松驰气道平滑肌；降低气道高反应性。,临床应用,按给药途径分全身和吸入两种 吸入丙酸倍氯松，丁地去炎松，氟地卡松 注意事项：提前2至4周用药；急性发作时与支气管扩张药合用；中度以上哮喘需长期吸入治疗（200600ug/d）；一定程度上可减少甚至替代口服激素。副作用：念珠菌感染；声嘶；抑制HPA轴。,临床应用,口服强的松 适应症：中度哮喘急性发作；重度哮喘发作经静脉注射控制症状需巩固治疗者；激素依赖性哮喘长期维持治疗；慢性哮喘单纯用吸入激素仍不能控制症状者。注意副作用。维持剂量最好mg/d。,临床应用
8、,静脉用药琥珀酸氢化考的松和甲基强的松龙 严重发作应尽早用药，因注射后46小时才起效；短期（35日）使用；连续用药2周以上者应先减量维持，以免复发。,白三烯受体调节剂,两大类：白三烯受体拮抗剂（安可来，顺尔宁）5-脂氧化酶抑制剂（Zileuton,齐留通）,白三烯的产生过程,花生四烯酸 环氧化酶 5-脂氧化酶 前列腺素 白三烯,Classification of Severity,CLASSIFY SEVERITYClinical Features Before Treatment,Symptoms,NocturnalSymptoms,FEV1 or PEF,STEP 4Severe Pers
9、istent,STEP 3Moderate Persistent,STEP 2Mild Persistent,STEP 1Intermittent,ContinuousLimited physical activity,DailyAttacks affect activity,1 time a week but 1 time a day,1 time a weekAsymptomatic and normal PEF between attacks,Frequent,1 time week,2 times a month,2 times a month,60%predictedVariabil
10、ity 30%,60-80%predicted Variability 30%,80%predictedVariability 20-30%,80%predictedVariability 20%,The presence of one feature of severity is sufficient to place patient in that category.,Part 4:Long-term Asthma ManagementStepwise Approach to Asthma Therapy-Adults,Reliever:,Rapid-acting inhaled 2-ag
11、onist prn,Controller:Daily inhaledcorticosteroid,Controller:Daily inhaled corticosteroid Daily long-acting inhaled 2-agonist,Controller:Daily inhaled corticosteroid Daily long acting inhaled 2-agonistplus(if needed),When asthma is controlled,reduce therapyMonitor,STEP 1:Intermittent,STEP 2:Mild Pers
12、istent,STEP 3:Moderate Persistent,STEP 4:Severe Persistent,STEP Down,Outcome:Asthma Control,Outcome:Best Possible Results,Alternative controller and reliever medications may be considered(see text).,Controller:None,-Theophylline-SR-Leukotriene-Long-acting inhaled 2-agonist-Oral corticosteroid,Stepwi
13、se Approach to Asthma Therapy:Adults Step 1:Intermittent Asthma,None required,Rapid-acting inhaled 2-agonistfor symptoms(but once a week)Rapid-acting inhaled 2-agonist,cromone,or leukotriene modifier before exercise or exposure toallergen,Continuously review medication technique,compliance and envir
14、onmental controlReview treatment every three months.Step up if control is not achieved;step down if control is sustained for at least 3 monthsPreferred treatments are in bold print,Daily Controller Medications,Reliever Medications,Inhaled glucocorticosteroid(500 g BDP or equivalent)Other options(ord
15、er by cost):sustained-release theophylline,orCromone,or leukotriene modifier,Rapid-acting inhaled 2-agonistfor symptoms(but 3-4 times/day)Other options:inhaled anticholinergic,orshort-acting oral 2-agonist,orshort-acting theophylline,Continuously review medication technique,compliance and environmen
16、tal control.Review treatment every three monthsStep up if control is not achieved;Step down if control is sustained for at least 3 monthsPreferred treatments are in bold print,Stepwise Approach to Asthma Therapy:AdultsStep 2:Mild Persistent Asthma,Daily Controller Medications,Reliever Medications,In
17、haled glucocorticosteroid,(200 1000 g BDP or equivalent)plus long-acting inhaled 2agonistOther options(order by cost):Inhaled glucocorticosteroid(500 1000 g BDP equivalent)plus sustained-release theophylline,orInhaled glucocorticosteroid(500 1000 g BDP equivalent)plus long-acting inhaled 2-agonist,o
18、rinhaled glucocorticosteroid at higher doses(1000 g BDP equivalent),orInhaled glucocorticosteroid(500 1000 g BDP equivalent)plus leukotriene modifier,Rapid-acting inhaled 2-agonist for symptoms(but 3-4 times/day)Other options:inhaled anticholinergic orshort-acting oral 2-agonist orshort-acting theop
19、hylline,Continuously review medication technique,compliance and environmental control.Review treatment every three months.Step up if control is not achieved;Step down if control is sustained for at least 3 months.Preferred treatments are in bold print.,Stepwise Approach to Asthma Therapy:AdultsStep
20、3:Moderate Persistent Asthma,Daily Controller Medications,Reliever Medications,Inhaled glucocorticosteroid,(1000 gBDP or equivalent)plus long-actinginhaled 2agonist plus one or more of the following,ifneeded(order by cost):sustained-release theophylline,orleukotriene modifier ororal glucocorticoster
21、oid,Rapid-acting inhaled 2-agonist for symptoms(but 3-4 times/day)Other options:inhaled anticholinergic orshort-acting oral 2-agonist orshort-acting theophylline,Continuously review medication technique,compliance and environmental control.Review treatment every three months.Step up if control is no
22、t achieved;Step down if control is sustained for at least 3 months.Preferred treatments are in bold print.,Stepwise Approach to Asthma Therapy:AdultsStep 4:Severe Persistent Asthma,Daily Controller Medications,Reliever Medications,Emergency Department ManagementAcute Asthma,Respiratory Failure,Admit to ICU,
