姚晨玲－镇静催眠药中毒

nullToxicity, Sedative-Hypnotics 中山急诊 姚晨玲Toxicity, Sedative-Hypnotics 中山急诊 姚晨玲Background 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 BackgroundBackgroundacute sedative-hypnotics poisoning withdrawal syndromeEtiologyEtiologyBenzodiazepines (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) EtiologyEtiologyBarbiturates 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)EtiologyNonbarbiturate, 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)EtiologyPathogenesisPathogenesis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 PathogenesisPathogenesis2、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）. PathogenesisPathogenesis3、Pharmacokinetics of NBNB Most NBNB are extensively metabolized by the liver Pathogenesis 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 actionPathogenesisnullBZD GABAchloride channelCl-Cl-＋＋＋＋＋－－－－－hyperpolarizationClinicalClinicalBenzodiazepine blurred vision, dizziness, confusion, drowsiness, anxiety, agitation, and unresponsiveness or coma. BZD overdose in itself is remarkably safe. most patients with benzodiazepine overdose can be managed in the ED and released home after appropriate care. When combined with other sedatives (most frequently alcohol), patients with benzodiazepine overdose can present with profoundly depressed levels of consciousness. .  ClinicalClinicalBarbiturates Mild intoxication is characterized by ataxia, incoordination, nystagmus, slurred speech, and altered level of consciousness. Moderate poisoning leads to respiratory depression and hyporeflexia. Severe poisoning leads to flaccid areflexic coma, apnea, and hypotension. Occasionally, hyperreflexia, rigidity, clonus, and Babinski signs are present. Miosis is common, but mydriasis may be present with certain agents. Generally, 10 times the hypnotic dose produces severe toxicity.ClinicalClinicalChloral hydrate Mild intoxication is characterized by ataxia, lethargy Severe poisoning leads to stupor, coma, pinpoint pupils, hypotension, slow or rapid and shallow respiration, hypothermia, areflexia, and muscle flaccidity. Arrhythmias ClinicalGlutethimide (Doriden) Loss of brainstem reflexes Flaccidity Anticholinergic effects Delayed gastric emptying May cause hyperthermia or heatstroke Clinical ClinicalClinicalMethaqualone (Quaalude) Resembles barbiturate poisoning Has more pronounced motor problems (eg, ataxia) and is known as wallbanger because of this phenomenon. Can lead to severe muscular hypertonicity and seizures Lab Studies Lab Studies Obtain a complete blood count (CBC), arterial blood gas (ABG), glucose, chemistry, Imaging Studies: Obtain an abdominal x-ray. Chloral hydrate is radiopaque. Other Tests: Obtain an electrocardiogram (ECG); Co-ingested drugs may have direct cardiac effects (eg, tricyclic antidepressants). Lab Studies Lab Studies Quantitative serum drug concentrations are recommended for patients with serious toxicity Barbiturates: For short-acting drugs, the lethal dose is 3 g or a serum concentration higher than 3.5 mg/dL. For long-acting drugs, the lethal dose is 5-10 g or a concentration higher than 8 mg/dL. Chloral hydrate: The lethal dose is 10 g and a concentration higher than 100 mg/mL is toxic DiagnosisDiagnosisHistory Symptom and sign serum drug concentrations DifferentialsDifferentialsToxicity, Alcohols Hypoglycemia Diabetic Ketoacidosis Neoplasms, Brain TreatmentTreatmentEmergency Department Care Establish ABCs, obtain IV access, provide oxygen Ensure adequate airway and ventilation. Do endotracheal intubation if necessary. Fluid resuscitation and anti-shock Naloxone is recommended to the patients with comma. TreatmentTreatmentPrevention of absorption Gastric lavage may be performed if the patient presents obtunded within 2hour of ingestion Activated charcoal is recommended for sedative-hypnotic overdoses. Multi-dose activated charcoal (20-50 g q4h) is recommended for overdoses with barbiturates, glutethimide, and meprobamate. TreatmentTreatmentElimination enhancement Alkaline diuresis enhances elimination of phenobarbital and other long-acting barbiturates. It is recommended for all symptomatic patients with long-acting barbiturate toxicity. Consider hemodialysis or hemoperfusion in glutethimide, methyprylon, phenobarbital, meprobamate, and chloral hydrate poisoning.TreatmentTreatmentDetoxicant Flumazenil Flumazenil competitively and reversibly binds benzodiazepine receptors (ie, GABA). The use of flumazenil for suspected benzodiazepine overdoses is controversial. If used, it should be administered slowly (0.2 mg/min up to 3-5 mg) because large doses cause agitation and withdrawal. This drug is contraindicated in patients with increased intracranial pressure (ICP) or closed head injury (CHI), those with a history of epilepsy, or those known to have ingested a tricyclic antidepressant (TCA) agent Treatment of complicationTreatment of complicationPneumonia Arrhythmias Acute renal failure nullPrognosis prophylaxis