复旦大学附属中山医院：《内科学》课程教学资源（PPT讲稿）姚晨玲－镇静催眠药中毒 Toxicity, Sedative?Hypnotics

Toxicity, Sedative Hypnotics 中山急诊姚晨玲

Toxicity, Sedative￾Hypnotics 中山急诊 姚晨玲

Background Sedative-hypnotics are a group of drugs that cause CnS depression Benzodiazepines(bzd) the most commonly a barbiturates used agents a nonbarbiturate nonbenzodiazepine sedative hypnotics( nbnb

Background Sedative-hypnotics are a group of drugs that cause CNS depression. ◼ Benzodiazepines (BZD) ◼ barbiturates ◼ nonbarbiturate nonbenzodiazepine sedative￾hypnotics (NBNB) the most commonly used agents

Background acute sedative-hypnotics poisoning a withdrawal syndrome

Background ◼ acute sedative-hypnotics poisoning ◼ withdrawal syndrome

Etiology Benzodiazepines(BzD) Long acting(half life >30h) chlordiazepoxide(利眠宁) diazepam(地西泮、安定) flurazepam(氟安定) Short acting(half life 6-30h) alprazolam(阿普唑仑) Ultrashort acting triazolam(三唑仑)

Etiology Benzodiazepines (BZD) • Long acting (half life >30h): chlordiazepoxide (利眠宁) diazepam（地西泮、安定） flurazepam （氟安定） • Short acting (half life 6-30h): alprazolam(阿普唑仑) • Ultrashort acting : triazolam(三唑仑)

Etiology Barbiturates Ultrashort acting Methohexital Brevital甲己炔巴比妥) thiopental( Pentothal硫喷妥那) Short acting pentobarbital( Nembutal巴比妥) secobarbital( Seconal司可巴比妥 Intermediate acting Amobarbital( Amytal异戊巴比妥) butalbital( Fioricet, Fiorina|异丁巴比妥) ong acting Phenobarbital( Luminal鲁米那)

Etiology ◼ Barbiturates ◼ Ultrashort acting ◼ Methohexital (Brevital甲己炔巴比妥) ◼ thiopental (Pentothal硫喷妥那) ◼ Short acting ◼ pentobarbital (Nembutal戊巴比妥) ◼ secobarbital (Seconal司可巴比妥) ◼ Intermediate acting ◼ Amobarbital (Amytal异戊巴比妥) ◼ butalbital (Fioricet, Fiorinal异丁巴比妥) ◼ Long acting ◼ Phenobarbital (Luminal鲁米那)

Etiology Nonbarbiturate, nonbenzodiazepine sedative-hypnotics(NBNB) Chloral hydrate(水合氯醛) Ethchlorvynol(乙氯维诺) Glutethimide(导眠能) Methyprylon(甲乙哌酮) Meprobamate(眠尔通)

Nonbarbiturate, nonbenzodiazepine sedative-hypnotics (NBNB) Chloral hydrate (水合氯醛) Ethchlorvynol (乙氯维诺) Glutethimide (导眠能) Methyprylon (甲乙哌酮) Meprobamate (眠尔通) Etiology

Pathogenesis 、 Pharmacokinetics: 1 Pharmacokinetics of the bzd Most bzd are extensively metabolized by the liver Some are metabolized to products which are active and may have a much longer half life than the parent drug The major route of metabolism is N-demethylation in the elderly↓ Cimetidine↓

一、Pharmacokinetics ： 1、Pharmacokinetics of the BZD • Most BZD are extensively metabolized by the liver. • Some are metabolized to products which are active and may have a much longer half life than the parent drug. • The major route of metabolism is N-demethylation. in the elderly Cimetidine Pathogenesis

Pathogenesis 2 Pharmacokinetics of barbiturates Barbiturates with low lipid solubility are excreted in the unchanged form by the kidneys. ie phenobarbita|(苯巴比妥) Barbiturates with high lipid solubility are metabolized to more polar compounds in the liver before being excreted via the kidneys. ie thiopental(硫喷妥)

Pathogenesis 2、Pharmacokinetics of Barbiturates ◼ Barbiturates with low lipid solubility are excreted in the unchanged form by the kidneys. ie phenobarbital（苯巴比妥）. ◼ Barbiturates with high lipid solubility are metabolized to more polar compounds in the liver before being excreted via the kidneys. ie thiopental （硫喷妥）

Pathogenesis 3 Pharmacokinetics of nBNB Most nbnb are extensively metabolized by the liver

3、Pharmacokinetics of NBNB ◼ Most NBNB are extensively metabolized by the liver Pathogenesis

Pathogenesis The mechanism of action ◆BZD In the CNS, benzodiazepines exert their clinical effect by enhancing the activity of the inhibitory neurotransmitter GABa (The clinical effects of GABa release and GABA-gated chloride channels include sleep induction and excitement inhibition) ◆ Barbiturates in prolongation of the duration of opening of GABA-gated chloride channels, leading to hyperpolarization of the membrane and suppression of neurotransmission. ◆NBNB similar to the action of barbiturates

 BZD In the CNS, benzodiazepines exert their clinical effect by enhancing the activity of the inhibitory neurotransmitter GABA. (The clinical effects of GABA release and GABA-gated chloride channels include sleep induction and excitement inhibition)  Barbiturates in prolongation of the duration of opening of GABA-gated chloride channels, leading to hyperpolarization of the membrane and suppression of neurotransmission. 。 NBNB similar to the action of Barbiturates 二、 The mechanism of action Pathogenesis