知识.镇静药.pptVIP

一般剂量无毒，偶有头晕，思想不集中，嗜睡 2.其他：偶有核黄疸，粒细胞降低，唾液、气管分泌增加，致畸（兔唇） 1. 中枢毒性：共济失调（步态不稳，定向不准，动作不协调）。反应与血药浓度有关 Untoward effects * Untoward effects and attentions 长期大剂量：耐受性、依赖性 孕妇、哺乳妇忌用 急性中毒：昏迷、呼吸抑制。 解毒药：氟马西尼 (Flumazenil)——在BDZ受体部位竞争性拮抗地西泮等的作用 * 硝西泮（nitrazepam）——中短效 特点：口服吸收好，30分起效，维持睡眠6～8小时；醒后无明显后遗效应;兼抗癫痫作用 艾司唑仑（estazolam，舒乐安定)——短效 特点：吸收快，口服后20～60分钟入睡，维持5～8小时;副作用小；兼抗癫痫、抗惊厥作用 氟西泮（flurazepam）——长效 特点：与地西泮相似，镇静催眠作用较强。代谢物有活性，作用持久 Homologous series drugs 同类药物 * * Buspirone 丁螺环酮/布司匹隆 absorbed rapidly metabolized to at least 1 active metabolite eliminated in urine and feces mechanism of action unclear May be a partial agonist of 5-HT1A receptor 用于抗焦虑和伴有焦虑的失眠、抑郁症，对恐怖症无效 §3 New type Sedative and hypnotic drugs * 镇静催眠作用较强。失眠者服用后入睡快，睡眠时间长．增加深睡眠，睡眠质量高，醒后感觉良好。无肌松作用。不影响驾驶技能。常规剂量不产生耐受性。停药后无“反跳”现象 同类药 吉吡隆（gepirone）, 依沙匹隆（ipsapirone）， 噻斯匹隆（tiaspirone）等 巴比妥类 §4 Barbiturates  药物构效关系图 * * Barbiturates Phenobarbital 苯巴比妥 Pentobarbital 戊巴比妥 Amobarbital 异戊巴比妥 Mephobarbital 甲苯比妥 Secobarbital 司可巴比妥 Aprobarbital 阿普比妥 Thiopentone 硫喷妥 “barbital” always in the name * Often classified according to their rate of onset or duration of action long acting (slow metabolism and slow renal excretion) shorter acting (more rapid metabolism) very short acting (redistribution from CNS to other tissues) - e.g. barbitone, phenobarbital (巴比妥，苯巴比妥) - e.g. pentobarbital (戊巴比妥) - e.g. thiopentone (硫喷妥) – rapid onset of action: 10 s in man (i.v.) i.v. injection of thiopentone blood other tissues - e.g. CNS well perfused, lipid rich tissues blood Barbiturates * * Pharmacokinetics of Barbiturates Rapid absorption following oral administration Rapid onset of central effects Extensively metabolized in liver, however, there are no active metabolites Phenobarbital is excreted unchanged. Its excretion can be increased by alkalinization of the urine * Pharmacokinetics of Barbiturates In the elderly and in those with limite