化學(xué)物品中毒現(xiàn)場(chǎng)急救

化學(xué)物品中毒現(xiàn)場(chǎng)急救第1頁/共164頁ContentsBackgroundGeneralintroductionAcuteOrganophosphatepoisoningAcutecarbonmonoxidepoisoningAcutesedatives-hypnoticspoisoningAlcoholIntoxication/Withdrawal第2頁/共164頁BackgroundThereareabout9000000kindsofchemiclaPeoplehavemanyopportunitytotouchwithpoison第3頁/共164頁BackgroundThereare1751476poisoningpt’sinUSAin1993Poisoncontrolcenter(PCC)

isestablishedinChicago1953。Majorduty:componentof

poison;4.informationDangerous5.toxicologyfirstaid6.

generalknowledgeofpreservation第4頁/共164頁第5頁/共164頁第6頁/共164頁第7頁/共164頁BackgroundCountryside>city。Countryside----pesticideintoxication。City---food-poisoning,carbonmonoxidepoisoning,Hypnoticintoxication。EstablishPCCinBeijing,Shanghai,Shenyang第8頁/共164頁Whatispoison?Apoisonisanythingsomeoneeats(ingestion),breathes(inhalation),getsintheeyes(ocularexposure),orontheskin(dermalexposure),thatcancausesicknessordeathifitgetsintobodyoronthebody.Poisoncanbefoundinfourforms:solid,liquid,sprayandgas.第9頁/共164頁Generalintroductiontoxicsubstance:drug,chemical,badfoodandsoon.Acutepoisoning：shorttime，largedoseChronicpoisoning：longtime、smalldose第10頁/共164頁Etiopathogenisis

andpathogenesyCauseofapoisoningOccupationalpoisoningLifepoisoningAccidentalpoisoning,SuicidalAbuse，addication,homicdal第11頁/共164頁P(yáng)athogenesy--Absorption

Bymouth;inhalation（Powderdust、smoke、steam）,skinmucosa,muscleorintravenousinjectionRectum、urinarycanal、femalesheath

vagina、bladder、peritoneum、eyeInsectstingsorbite第12頁/共164頁P(yáng)athogenesis--metabolismspreadalloverbodybyblood

livermetabolismPoisonousnessPoisonousnessOxidation,deoxidize,hydrolyse,bonding第13頁/共164頁P(yáng)athogenesis---Eliminatebreatheoutbyrespiratorytract（gas，volatilematter）DischargebykidneyDischargebyalimentarytractSkinMilk第14頁/共164頁1.Localeffect強(qiáng)酸、強(qiáng)堿吸收組織水分與蛋白質(zhì)脂肪結(jié)合組織細(xì)胞變性壞死第15頁/共164頁2.HypoxiaInhibitionrespiratoryfunction：ChangebloodconstituentInhibitioncellsrespiratory：cyanide，hydrogensulfideDestroyCardiovascularfunction第16頁/共164頁破壞酶蛋白質(zhì)部分的金屬或活性中心——氰化物抑制細(xì)胞色素氧化酶Fe++；一氧化碳抑制細(xì)胞色素氧化酶Fe+++從而破壞酶蛋白質(zhì)分子中的金屬，使細(xì)胞發(fā)生窒息毒物與基質(zhì)競(jìng)爭(zhēng)同一種酶而產(chǎn)生抑制作用,丙二酸結(jié)構(gòu)與琥珀酸相似，抑制三羥酸循環(huán)中琥珀酸脫氫酶3.Inhibitoryenzymeactivity第17頁/共164頁與酶的活性劑作用：——氟化物與Mg++形成復(fù)合物，使Mg++失去激活磷酸葡萄糖變?yōu)槊傅淖饔萌コo酶：——鉛中毒時(shí)，造成煙酸的消耗增多，使輔酶I和輔酶II減少，抑制了脫氫酶的作用與基質(zhì)直接作用：——氟乙酸直接與檸檬酸相結(jié)合形成氟檸檬酸，阻止三羧酸循環(huán)的繼續(xù)進(jìn)行第18頁/共164頁

Organophosphatepoisoning，可抑制體內(nèi)的膽堿酯酶，使組織中乙酰膽堿過量積蓄，引起一系列以乙酰膽堿為傳導(dǎo)介質(zhì)的神經(jīng)處于過度興奮狀態(tài)，最后則轉(zhuǎn)為抑制Carbontetrachloridepoisoning，首先作用于CNS，使之產(chǎn)生交感神經(jīng)沖動(dòng)，體內(nèi)產(chǎn)生大量單胺類物質(zhì)，使內(nèi)臟血管收縮引起供血不足，中毒數(shù)小時(shí)后可出現(xiàn)肝、腎損害4.Dromotropism

medium第19頁/共164頁

一氧化碳與氧競(jìng)爭(zhēng)血紅蛋白，而形成碳氧血紅蛋白，破壞了正常的輸氧功能異煙肼與維生素B及煙酸的結(jié)構(gòu)相似，因此，異煙肼在體內(nèi)可與維生素B競(jìng)爭(zhēng)，而取代其作用，因而引起中毒

5.Competitionreceptor第20頁/共164頁6.Interferecellororganellaphysiologicfunctioncarbontetrachloride（CCl4）－－CHCl3（trichlormethane)－－肝細(xì)胞膜中的unsaturatedfattyacid－－lipidperoxidation－－mitochondria(線粒體)、endoplasmicreticulum(內(nèi)質(zhì)網(wǎng))變性－－h(huán)epatocyte(肝細(xì)胞)deathPhenols(酚類)－－線粒體內(nèi)oxidativephosphorylation(氧化磷酸化)uncoupling(解偶聯(lián))－－inhibitingadenosinetriphosphate(三磷酸腺苷)synthesis(合成)、store(貯存)。第21頁/共164頁ThefactorofinfluencetoxicactionPhysico-chemicalpropertyofpoisonfineparticle,solubility,evaporabilitySusceptibilityofindividualsex,age,nutrition,healthstatus,livinghabit

第22頁/共164頁DiagnosispoisoningHistorySignandsymptomconsciousstatebreathingheartratebloodpressurepupil,skin,mucosa第23頁/共164頁Laboratory

examinationDetectionofpoison:blood,gastricjuiceandurineBlood,urineexamination第24頁/共164頁TherapeuticprincipleCPRGetridoftheenvironmentDecreaseAbsorptionSpecificantidotesCleaningpoisoningastrointestinaltractHeteropathyPreventComplication第25頁/共164頁EmergentmanagementBreathingsupportCirculationsupportTreatmentcomaTreatmentconvulsion第26頁/共164頁SPECIFICANTIDOTESOrgnaophosphorus-----PralidoximeIodide，AtropineBenzodiazepines－－FlumazenilPain-killer－－NaloxoneIsoniazid－－vitaminB6第27頁/共164頁EliminatepoisonEmeticGastriclavageActivatedcarbonadsorptionCatharsisWhole-bowelirrigation第28頁/共164頁Emetic壓舌板、刺激咽后壁飲溫水200-300ml吐根糖漿+200ml水休克、意識(shí)不清—禁用攝入腐蝕性毒物----禁用第29頁/共164頁P(yáng)urposeofGastriclavageEliminatepoisoningastric,preventabsorbPreparationforoperationorsomeexamination第30頁/共164頁IndicationandcontraindicationIndication

Non-corrosivepoisonContraindication

Corrosivepoison—strongacid,baseesophagealvarix,aneurysmofaortaSevereheartdisease，uppergastrointestinalbleeding，gastricperforation第31頁/共164頁P(yáng)rincipleofgastriclavage一般毒物的洗胃原則

一次性徹底洗胃（10000-20000ml）、停止洗胃標(biāo)準(zhǔn)為無色無味。有機(jī)磷中毒的洗胃原則

首次足量20000-30000ml持續(xù)胃腸減壓留置胃管接胃腸減壓器

反復(fù)少量洗胃

2000-5000ml/1-2h第32頁/共164頁洗胃的操作步驟洗胃步驟：1.先將胃內(nèi)容物盡量抽盡2.灌入300-500ml洗胃液3.再排出灌入液體4.反復(fù)灌洗直到洗胃液純清無味注意事項(xiàng):1.洗胃液每次進(jìn)入不宜過多，進(jìn)出要平衡。2.洗胃液性質(zhì)盡可能視毒物而定，液溫37℃3.掌握適應(yīng)癥與禁忌癥第33頁/共164頁洗胃要注意和觀察的幾個(gè)問題洗胃與胃出血的關(guān)系少量可給保護(hù)胃粘膜藥，大量停止洗胃、持續(xù)胃腸減壓觀察出血情況洗胃時(shí)要密切觀察生命體征、腹部情況、洗出液的性質(zhì)第34頁/共164頁CatharsisandWhole-bowelirrigation

硫酸鈉--15-20+水200口服硫酸鎂--15-20+水200口服（引起高血鎂）20%甘露醇250胃管內(nèi)灌入--1小時(shí)腹瀉、3小時(shí)排空。1%鹽水、肥皂水5000--高位連續(xù)灌腸清洗活性炭加入灌腸液，促進(jìn)毒物吸附排出第35頁/共164頁

EliminatepoisonForceddiuresis強(qiáng)化利尿Bloodpurification（血液凈化）

hemodialysisHD（血液透析）

hemoperfusion,HP（血液灌流）

plasmaexchangePE（血漿置換）Highpressureoxygen高壓氧第36頁/共164頁HemodialysisHD

血液透析機(jī)理：血液經(jīng)體外循環(huán)進(jìn)入透析器，通過透析膜和透析液之間形成的溶液濃度梯度，促使血液內(nèi)溶質(zhì)彌散至透析液內(nèi)?？赏肝龆疚锏男再|(zhì)：water-solubility水溶性、heavymetals,生物性毒物。種類：蛇毒、魚膽、利眠寧、diamorphine海洛因、撲熱息痛、Isoniazid異煙肼、aminoglycosides氨基糖甙類、arsenic砷、mercury汞等。第37頁/共164頁HemoperfusionHP

血液灌流機(jī)理：血液流經(jīng)灌流器，血液中的毒物被吸附到具有廣大表面積的吸附劑上。吸附劑：活性炭、合成樹脂毒物性質(zhì)：脂溶性、大分子化合物、易與血漿蛋白結(jié)合的藥物、毒物。種類：安定類、苯巴比妥類、抗抑郁類、有機(jī)磷類、伴有肝衰竭、腎衰竭者。第38頁/共164頁plasmaexchangePE

血漿置換機(jī)理：將血液引入血漿分離器中，使血細(xì)胞與血漿分離，棄去全部血漿，注入新鮮血漿和平衡液。毒物性質(zhì)：與血漿蛋白結(jié)合率高（大于60%）第39頁/共164頁AcuteOrganophosphatepoisoning第40頁/共164頁AcuteOrganophosphatepoisoningFeature：毒性大、起病快;發(fā)病迅速；中毒途徑多；診斷要快、準(zhǔn)確；搶救及時(shí)。Classify分類：劇毒、高毒、中毒、低毒

第41頁/共164頁AcuteOrganophosphatepoisoningEtiopathogenisis：Accidental

suicidePathogenesis：

Poisonmetabolism

mechanism

acutepoisoning;chronicpoisoning第42頁/共164頁Organophosphate

Absorption:readilyDistribution:bloodbrainbarrier

Metabolism:intheliverElimination:primarilyintheurineHalf-life:4hours第43頁/共164頁Mechanism體內(nèi)膽堿能神經(jīng)的化學(xué)介質(zhì)--乙酰膽堿交感、副交感神經(jīng)節(jié)前纖維副交感神經(jīng)節(jié)后纖維橫紋肌的運(yùn)動(dòng)神經(jīng)--肌肉接頭交感神經(jīng)節(jié)后纖維（支配淚腺、血管平滑肌）中樞神經(jīng)系統(tǒng)膽堿能神經(jīng)末梢----膽堿酯酶第44頁/共164頁CENTRALNERVOUSSYSTEMACh(nic)SkeletalMuscleSomaticEfferentsystemACh(nic)ACh(nic)ACh(nic)ACh(nic)NA

ACh(mus)

ACh(mus)BloodvesselsetcSweatGlandsAdrenalmedullaSympatheticsystemSalivaryglandsetcPara-sympatheticsystem第45頁/共164頁Cholinereceptor①M(fèi)uscarinicreceptor（M-R）毒蕈堿

heart:restrainbloodvessel：dilatation

smoothmuscle：contractsphincterpupillaemuscle:contractcontractglandularorgan:secrete②Nicotinicreceptor（N-R）煙堿

N1-R：gangliocyte;ganglioneure—excitedN2-R：skeletalmuscle——contract第46頁/共164頁第47頁/共164頁第48頁/共164頁急性有機(jī)磷中毒--機(jī)理

有機(jī)磷毒物與膽堿酯酶acetylcholinesterase(AchE)結(jié)合，形成磷?；憠A酯酶，失去水解活性，造成乙酰膽堿acetylcholine蓄積產(chǎn)生毒蕈堿（M）樣、煙堿（N）樣癥狀和中樞神經(jīng)系統(tǒng)的癥狀。第49頁/共164頁MECHANISMOFTOXICITY

Theorganophosphatesarepowerfulinhibitorsofcarboxylicesterhydrolases,includingacetylcholinesterase(foundinnervoustissuesanderythrocytes)andbutyrylcholinesterase(plasmaorpseudocholinesterase).Asaresultofthisenzymeinhibition,thesubstrateacetylcholineaccumulates

第50頁/共164頁急性有機(jī)磷中毒--機(jī)理中樞神經(jīng)系統(tǒng)：腦內(nèi)Ach含量增高---大腦多部位先興奮后抑制。驚厥、呼吸中樞抑制。神經(jīng)--肌肉接頭：神經(jīng)--肌肉接頭的傳遞阻斷，導(dǎo)致肌無力和肌麻痹。呼吸系統(tǒng)：呼吸肌麻痹、氣道分泌物阻塞。第51頁/共164頁急性有機(jī)磷中毒--機(jī)理循環(huán)系統(tǒng)：

*對(duì)心臟直接毒性：心動(dòng)過緩、心肌收縮力降低、各種心律失常

*抑制交感心血管中樞：外周血管擴(kuò)張、血壓下降。

*興奮心血管迷走中樞：心動(dòng)過緩、心肌收縮力降低、血壓下降。神經(jīng)節(jié)、腺體、平滑?。合袤w分泌增加、腸蠕動(dòng)增加。第52頁/共164頁中毒途徑及特點(diǎn)呼吸道吸收：有機(jī)磷沸點(diǎn)低、易揮發(fā)，易從呼吸道吸收,30min發(fā)病。消化道吸收：吸收快、10min－2h發(fā)病。皮膚黏膜吸收：有機(jī)磷是脂溶性，能透過皮膚黏膜入血，潛伏期長(zhǎng)、2－6h發(fā)病。主要致死因素：呼吸衰竭第53頁/共164頁SymptomsandSignsMuscarinic:SLUDGE,bronchorrhea,bradycardiaandmiosis.Nicotinic:muscleweakness,fasciculationorparalysistarchycardia,bronchodilation,mydriasis.CNS:restless,drowsy,confusion,tremor,ataxia,delirium,seizure,coma.第54頁/共164頁Muscariniceffects

毒蕈堿（M）UrinationMiosisBronchospasmEmesisLacrimationSalivationBradycardiahypotension尿頻、尿失禁縮瞳，視力模糊氣管痙攣，分泌增加嘔吐、腹瀉、腹痛流淚、流汗、流口水肺水腫心跳減慢，血壓下降第55頁/共164頁nicotinicmanifestations.musculartwitching,fasciculation,tachycardia,hypertension第56頁/共164頁centralnervoussystem

manifestations:Headache頭痛,Drowsiness

昏睡,Confusion

意識(shí)混亂,Slurred

speech言語不清,Emotional

lability

情感不穩(wěn),Ataxia

共濟(jì)失調(diào),Tremor

震顫,Delirium

精神錯(cuò)亂,Seizure

癲癇.

Restrain

centerofbreathand

circulate第57頁/共164頁degree

Slight：ChE50-70%。Muscarinicsymptomandsign;Midrange：ChE30-50%,

Muscarinicsymptomandsign,nicotiniceffectsHeavy：ChE30%,

Muscarinic,nicotinic，centralnervoussystemsymptomandsign第58頁/共164頁Delayedneuropathy急性中毒癥狀消失后2-3周motorius—thelowerlimbspalsy麻痹,amyotrophy肌萎縮Nervefibrofattydegeneration,nervecelldemyelinate脫髓鞘有機(jī)磷抑制神經(jīng)病靶酯酶（neuropathytargetesterase，NTE)第59頁/共164頁Delayedneuropathy－

stagesProgression：senseneuropathyStablephase：sensorydisabilitylast3－12monthremissivestage

：6－18monthmotorfunctionpartlyorcompleterecovery，spasm,motornervefunctionaldisturbance。第60頁/共164頁Intermediatesyndrome發(fā)生在急性中毒恢復(fù)后1－4天癱瘓（頸屈肌、腦神經(jīng)支配的肌肉、肢體近側(cè)肌、呼吸?。?－18天緩解嚴(yán)重者呼吸衰竭神經(jīng)肌肉接頭處突觸后功能障礙第61頁/共164頁LaboratoryexaminationserumcholinesteraseOrganophosphatemetabolicproduct

others第62頁/共164頁Diagnosis

Historygarlic-likeodor蒜臭味typicalsymptom：Pupilsizesmall,胃腸道癥狀、coma。Laboratoryexamination：serumcholinesterase,Organophosphatemetabolicproduct。Atropinetest：1-2mg---atropinization第63頁/共164頁DifferentialdiagnosisMuscarinicpoisonglobefishpoisonacutegastroenteritis;AGEHeatstrokeHypnoticintoxicationPesticideintoxication第64頁/共164頁TherapeuticprincipleGetridoftheenvironment

CannotusethehotwaterEliminatethepoisonqueasy、gastriclavageSpecificantidotesAtropine、PAMHeteropathyOxygentherapy、diuresis第65頁/共164頁EmergencyManagement

AirwayBreathingCardiopulmonaryresuscitation;CPRCNS：convulsionuse

valiumandphenobarbital，forbiduse

SuccinylcholineorMorphine。Cerebraledema：mannitol、glucocorticosteroidpneumonedema：Atropine，aminophyllineandmorphinecan’tbeuse第66頁/共164頁SpecificantidotesCholinesterase

resurrecter膽堿酯酶復(fù)活劑－N樣癥狀效果好碘解磷定(pyraloximemethoiodide)氯磷定（pyraldoximemethylchloride）Atropine,blockmuscarinicreceptors,causinginhibitionofallmuscarinicfunctions.

Early,enough,association,repetitions第67頁/共164頁阿托品類生物堿--莨菪堿顛茄曼佗羅第68頁/共164頁TheeffectofAtropine

atropinepoisoningBLURREDVISIONCONFUSIONrestlessness

coma;CONSTIPATIONURINARYRETENTION

atropinizationmydriasisTachycardiaBlushingSkinandmucousdrydrycrackles

disappear第69頁/共164頁Symptomatictreatment

keepingWater-Electrolyteandacid-basebalancePreventionandcurepulmonaryinfection

makeuseofsedativePlasmapheresisPreventionandcureintermediatesyndrome第70頁/共164頁Acutecarbonmonoxidepoisoning第71頁/共164頁Acutecarbonmonoxidepoisoning無色、無臭、不溶于水的窒息性氣體比重：0.967含碳物質(zhì)不完全燃燒產(chǎn)生的氣體空氣中最高允許濃度0.05%或30mg/m3吸入過量可發(fā)生急性中毒第72頁/共164頁Acutecarbonmonoxidepoisoning濃度，％ 暴露時(shí)間，min 癥狀0.0005 100 無明顯癥狀0.003 360 對(duì)中樞神經(jīng)有害0.04-0.05 短時(shí)間 呼吸困難0.05-0.1 短時(shí)間 頭痛、暈眩0.1-0.2 短時(shí)間 短時(shí)間內(nèi)死亡1 短時(shí)間 立即死亡第73頁/共164頁Acutecarbonmonoxidepoisoning

Etiology

livingpoisoning

burncoalwater-heateroccupationalpoisoningmisoperationNoprotectionAccidentalpoisonincoalmineaccidentSuicidalhomicdal第74頁/共164頁MechanismCO+HbCOHbCO+Fe++restraint

cellrespirationCan’tcarryingoxygenhypoxiaCO+HbO2+Hb=260CO-HbO2-Hb=36001第75頁/共164頁ClinicalmanifestationSlight：HbCO10-20%，頭痛、眩暈、心悸、惡心、嘔吐、短暫暈厥。吸空氣可好轉(zhuǎn)。Midrange：HbCO30-40%，昏迷、虛脫。皮膚櫻桃紅。吸空氣或高壓氧可很快清醒，數(shù)日恢復(fù)，不留后遺癥。Heavy：HbCO>50%，深昏迷、各種反射消失、瞳孔散大、血壓下降呼吸抑制。嚴(yán)重者昏迷數(shù)天出現(xiàn)臟器功能障礙。第76頁/共164頁臨床表現(xiàn)--遲發(fā)腦病意識(shí)障礙恢復(fù)后經(jīng)過2-60天的“假愈期”3%-10%病人出現(xiàn)腦病：

神經(jīng)意識(shí)障礙：癡呆、譫妄、去皮層狀態(tài)。

錐體外系神經(jīng)障礙：震顫麻痹綜合征。

錐體系神經(jīng)損害：偏癱、病理反射（+）

大腦皮層局灶性功能障礙：失語、失明、繼發(fā)癲癇。第77頁/共164頁Laboratoryexamination血COHb測(cè)定：特異性、判斷嚴(yán)重程度動(dòng)脈血?dú)夥治瞿X電圖：彌漫性低波幅慢波頭部CT：具有鑒別診斷意義第78頁/共164頁診斷和鑒別診斷有吸入CO病史典型臨床表現(xiàn)實(shí)驗(yàn)室檢查：定性或定量陽性、心肌酶增高其他：心電圖、頭顱CT、腦電圖除外：安眠藥中毒，其他有毒氣體中毒、腦血管意外、糖尿病酮癥酸中毒第79頁/共164頁EmergencytreatmentGetridoftheenvironmentOxygentherapy：Hyperbaricoxygentreatmentonlyafterseverecarbonmonoxidepoisoninginotherwisestablepatientsrespiratoryfailure：mechanicalventilationexchangeblood,bloodtransfusionDiuresis:preventionandcurebrainedema

promoterecoveryoffunction：sugar、vitaminATP、coenzymeA、cytochromeC。第80頁/共164頁acutesedatives-hypnoticspoisoning第81頁/共164頁Background

Sedative-hypnoticsareagroupofdrugsthatcauseCNSdepression.Benzodiazepines(BZD)barbituratesnonbarbituratenonbenzodiazepinesedative-hypnotics(NBNB)themostcommonlyusedagents第82頁/共164頁Backgroundacutesedative-hypnoticspoisoningwithdrawalsyndrome第83頁/共164頁EtiologyBenzodiazepines(BZD)Longacting(halflife>30h): chlordiazepoxide(利眠寧) diazepam（地西泮、安定）

flurazepam（氟安定）

Shortacting(halflife6-30h): alprazolam(阿普唑侖)Ultrashortacting: triazolam(三唑侖)第84頁/共164頁EtiologyBarbiturates

UltrashortactingMethohexital(Brevital甲己炔巴比妥)thiopental(Pentothal硫噴妥那)Shortactingpentobarbital(Nembutal戊巴比妥)secobarbital(Seconal司可巴比妥)IntermediateactingAmobarbital(Amytal異戊巴比妥)butalbital(Fioricet,Fiorinal異丁巴比妥) LongactingPhenobarbital(Luminal魯米那)第85頁/共164頁Nonbarbiturate,nonbenzodiazepinesedative-hypnotics(NBNB) Chloralhydrate(水合氯醛) Ethchlorvynol(乙氯維諾) Glutethimide(導(dǎo)眠能) Methyprylon(甲乙哌酮) Meprobamate(眠爾通)Etiology第86頁/共164頁一、Pharmacokinetics

：PharmacokineticsoftheBZDMostBZDareextensivelymetabolizedbytheliver.Somearemetabolizedtoproductswhichareactiveandmayhaveamuchlongerhalflifethantheparentdrug.ThemajorrouteofmetabolismisN-demethylation. intheelderly Cimetidine

Pathogenesis第87頁/共164頁P(yáng)athogenesis2、PharmacokineticsofBarbituratesBarbiturateswithlowlipidsolubilityareexcretedintheunchangedformbythekidneys.iephenobarbital（苯巴比妥）.Barbiturateswithhighlipidsolubilityaremetabolizedtomorepolarcompoundsintheliverbeforebeingexcretedviathekidneys.iethiopental（硫噴妥）.第88頁/共164頁3、PharmacokineticsofNBNBMostNBNBareextensivelymetabolizedbytheliverPathogenesis第89頁/共164頁

BZD IntheCNS,benzodiazepinesexerttheirclinicaleffectbyenhancingtheactivityoftheinhibitoryneurotransmitterGABA. (TheclinicaleffectsofGABAreleaseandGABA-gatedchloridechannelsincludesleepinductionandexcitementinhibition)Barbiturates inprolongationofthedurationofopeningofGABA-gatedchloridechannels,leadingtohyperpolarizationofthemembraneandsuppressionofneurotransmission.。NBNB similartotheactionofBarbiturates二、ThemechanismofactionPathogenesis第90頁/共164頁Benzodiazepines--PathogenesisBZD受體+GABA受體+CI+通道感覺運(yùn)動(dòng)區(qū)，有鎮(zhèn)靜催眠作用蛋白復(fù)合物BZD邊緣系統(tǒng)，抗焦慮和抗驚厥不清ω1ω2ω3抑制中樞神經(jīng)系統(tǒng)第91頁/共164頁BZDGABAchloridechannelCl-Cl-＋＋＋＋＋－－－－－h(huán)yperpolarization第92頁/共164頁ClinicalBenzodiazepineblurredvision,dizziness,confusion,drowsiness,anxiety,agitation,andunresponsivenessorcoma.BZDoverdoseinitselfisremarkablysafe.mostpatientswithbenzodiazepineoverdosecanbemanagedintheEDandreleasedhomeafterappropriatecare.Whencombinedwithothersedatives(mostfrequentlyalcohol),patientswithbenzodiazepineoverdosecanpresentwithprofoundlydepressedlevelsofconsciousness..

第93頁/共164頁ClinicalBarbituratesMildintoxicationischaracterizedbyataxia,incoordination,nystagmus,slurredspeech,andalteredlevelofconsciousness.Moderatepoisoningleadstorespiratorydepressionandhyporeflexia.Severepoisoningleadstoflaccidareflexiccoma,apnea,andhypotension.Occasionally,hyperreflexia,rigidity,clonus,andBabinskisignsarepresent.Miosisiscommon,butmydriasismaybepresentwithcertainagents.Generally,10timesthehypnoticdoseproducesseveretoxicity.第94頁/共164頁ChloralhydrateMildintoxicationischaracterizedbyataxia,lethargySeverepoisoningleadsto

stupor,coma,pinpointpupils,hypotension,sloworrapidandshallowrespiration,hypothermia,areflexia,andmuscleflaccidity.ArrhythmiasClinical第95頁/共164頁ClinicalGlutethimide(Doriden)LossofbrainstemreflexesFlaccidityAnticholinergiceffectsDelayedgastricemptyingMaycausehyperthermiaorheatstroke第96頁/共164頁Methaqualone(Quaalude)ResemblesbarbituratepoisoningHasmorepronouncedmotorproblems(eg,ataxia)andisknownaswallbangerbecauseofthisphenomenon.CanleadtoseveremuscularhypertonicityandseizuresClinical第97頁/共164頁LabStudies

Obtainacompletebloodcount(CBC),arterialbloodgas(ABG),glucose,chemistry,ImagingStudies:

Obtainanabdominalx-ray.Chloralhydrateisradiopaque.OtherTests:Obtainanelectrocardiogram(ECG);Co-ingesteddrugsmayhavedirectcardiaceffects(eg,tricyclicantidepressants).

第98頁/共164頁QuantitativeserumdrugconcentrationsarerecommendedforpatientswithserioustoxicityBarbiturates:Forshort-actingdrugs,thelethaldoseis3goraserumconcentrationhigherthan3.5mg/dL.Forlong-actingdrugs,thelethaldoseis5-10goraconcentrationhigherthan8mg/dL.Chloralhydrate:Thelethaldoseis10gandaconcentrationhigherthan100mg/mListoxicLabStudies

第99頁/共164頁DiagnosisHistorySymptomandsignserumdrugconcentrations第100頁/共164頁DifferentialsToxicity,AlcoholsHypoglycemiaDiabeticKetoacidosisNeoplasms,Brain第101頁/共164頁TreatmentEmergencyDepartmentCareEstablishABCs,obtainIVaccess,provideoxygenEnsureadequateairwayandventilation.Doendotrachealintubationifnecessary.Fluidresuscitationandanti-shockNaloxoneisrecommendedtothepatientswithcomma.第102頁/共164頁P(yáng)reventionofabsorptionGastriclavagemaybeperformedifthepatientpresentsobtundedwithin2hourofingestionActivatedcharcoalisrecommendedforsedative-hypnoticoverdoses.Multi-doseactivatedcharcoal(20-50gq4h)isrecommendedforoverdoseswithbarbiturates,glutethimide,andmeprobamate.Treatment第103頁/共164頁EliminationenhancementAlkalinediuresisenhanceseliminationofphenobarbitalandotherlong-actingbarbiturates.Itisrecommendedforallsymptomaticpatientswithlong-actingbarbituratetoxicity.Considerhemodialysisorhemoperfusioninglutethimide,methyprylon,phenobarbital,meprobamate,andchloralhydratepoisoning.Treatment第104頁/共164頁DetoxicantFlumazenilFlumazenilcompetitivelyandreversiblybindsbenzodiazepinereceptors(ie,GABA).Theuseofflumazenilforsuspectedbenzodiazepineoverdosesiscontroversial.Ifused,itshouldbeadministeredslowly(0.2mg/minupto3-5mg)becauselargedosescauseagitationandwithdrawal.Thisdrugiscontraindicatedinpatientswithincreasedintracranialpressure(ICP)orclosedheadinjury(CHI),thosewithahistoryofepilepsy,orthoseknowntohaveingestedatricyclicantidepressant(TCA)agentTreatment第105頁/共164頁TreatmentofcomplicationPneumoniaArrhythmiasAcuterenalfailure第106頁/共164頁P(yáng)rognosisprophylaxis第107頁/共164頁Acutealcoholicintoxication烴類羥基衍生物，屬于微毒品無色、易揮發(fā)、易燃液體，能與大多數(shù)有機(jī)溶劑混溶，更易溶于水，具有醇香氣味。分子量46.07，沸點(diǎn)78.5℃Overdose--acutealcoholicintoxication西方國(guó)家成人70％有飲酒史。美國(guó)成人中14％出現(xiàn)酒精依賴(alcoholdependence)第108頁/共164頁發(fā)酵微生物對(duì)糖類發(fā)酵而成，主要成分乙醇。蒸餾酒：烈性酒(如白酒、燒酒、大曲酒、白蘭地、威士忌)，含乙醇40％～60％發(fā)酵酒：果酒、啤酒和黃酒，乙醇20％以下配制酒：竹葉青酒、青梅酒、玫瑰酒等以蒸餾酒或發(fā)酵酒為酒基加用添加劑含乙醇含量低．酒精廣泛應(yīng)用于工業(yè)、醫(yī)藥、日?；瘜W(xué)制品和酒類飲料。許多產(chǎn)品酒精含量達(dá)50％～99％日常酒精中毒常為烈性酒引起第109頁/共164頁WhatisaStandardDrink?第110頁/共164頁Mechanism（1）Metabolismofalcoholinthebody

Spirits,beer,wineAbsorbedintheupperGItract說明I：1、吸收部位（腸道）2、是否與食物混合3、酒飲料的種類90%changeintoacetaldehydeintheliver,thenethanoicacid,CO2andwater10%byurinaryorrespiratorysystem說明II：1、正常人每小時(shí)可代謝7-20ml酒精2、嗜酒者可代謝25ml3、酒精為“燃燒食品”，嗜酒者靠飲酒獲得能量阻礙營(yíng)養(yǎng)物質(zhì)的攝入第111頁/共164頁Mechanism（2）Alcoholism:1、Lackofsomenutritionalelements2、IncreasethesecretionofACTH3、Damagestoliver4、Combineswithlecithinanddepositsinthenervoussystem.

第112頁/共164頁Mechanism（3）Possiblereasonsfordependence1、DecreasedactivityofMAOinCNS2、TetrahydroisowuinolinoccupancytotheopiatereceptorinCNS3、InfluencetotheGABAactivityandmetabolismintheCNS第113頁/共164頁P(yáng)hysicaleffectsofexcessiveuseofalcohol第114頁/共164頁Neuropsychiatriceffectsofexcessiveuseofalcohol第115頁/共164頁Clinicalfeatures（1）Acutealcoholism1、FirststageMildde-repressionofcortexElation,talkativeConcentrationofbloodalcohol:30-50mg/100ml第116頁/共164頁Clinicalfeatures（2）

2、SecondstageModeratede-repressionofcortexManiasyndrome,irritabilityConcentrationofbloodalcohol:60-100mg/100ml第117頁/共164頁Clinicalfeatures（3）

3、ThirdstageSevererde-repressionofcortexIn-congruentexcitementHallucinationanddelusionConfusionDeliriumConcentrationofbloodalcohol:100-150mg/100ml第118頁/共164頁Clinicalfeatures（4）

4、LaststageFullrepressionofCNSfunctionConsciousdisturbanceAbnormalsignsinNSEpilepsyInstabilityofvitalsignsConcentrationofbloodalcohol:150-200mg/100mlorhigher第119頁/共164頁Clinicalfeatures（5）AlcoholdependenceAlcoholdependencesyndromepsychologicaldependencephysicaldependenceWithdrawalsyndrome第120頁/共164頁Mechanism（1）Metabolismofalcoholinthebody

Spirits,beer,wineAbsorbedintheupperGItract說明I：1、吸收部位（腸道）2、是否與食物混合3、酒飲料的種類90%changeintoacetaldehydeintheliver,thenethanoicacid,CO2andwater10%byurinaryorrespiratorysystem說明II：1、正常人每小時(shí)可代謝7-20ml酒精2、嗜酒者可代謝25ml3、酒精為“燃燒食品”，嗜酒者靠飲酒獲得能量阻礙營(yíng)養(yǎng)物質(zhì)的攝入第121頁/共164頁Mechanism（2）Alcoholism:1、Lackofsomenutritionalelements2、IncreasethesecretionofACTH3、Damagestoliver4、Combineswithlecithinanddepositsinthenervoussystem.

第122頁/共164頁Mechanism（3）Possiblereasonsfordependence1、DecreasedactivityofMAOinCNS2、TetrahydroisowuinolinoccupancytotheopiatereceptorinCNS3、InfluencetotheGABAactivityandmetabolismintheCNS第123頁/共164頁P(yáng)hysicaleffectsofexcessiveuseofalcohol第124頁/共164頁Neuropsychiatriceffectsofexcessiveuseofalcohol第125頁/共164頁Clinicalfeatures（1）Acutealcoholism1、FirststageMildde-repressionofcortexElation,talkativeConcentrationofbloodalcohol:30-50mg/100ml第126頁/共164頁Clinicalfeatures（2）

2、SecondstageModeratede-repressionofcortexManiasyndrome,irritabilityConcentrationofbloodalcohol:60-100mg/100ml第127頁/共164頁Clinicalfeatures（3）

3、ThirdstageSevererde-repressionofcortexIn-congruentexcitementHallucinationanddelusionConfusionDeliriumConcentrationofbloodalcohol:100-150mg/100ml第128頁/共164頁Clinicalfeatures（4）

4、LaststageFullrepressionofCNSfunctionConsciousdisturbanceAbnormalsignsinNSEpilepsyInstabilityofvitalsignsConcentrationofbloodalcohol:150-200mg/100mlorhigher第129頁/共164頁Clinicalfeatures（5）AlcoholdependenceAlcoholdependencesyndromepsychologicaldependencephysicaldependenceWithdrawalsyndrome第130頁/共164頁醇濃度與臨床表現(xiàn)

血乙醇濃度臨床表現(xiàn)

rng／L非嗜酒者嗜酒者200~500精細(xì)運(yùn)動(dòng)失調(diào)500~1000欣快感、群集性、共濟(jì)失調(diào)無或輕度癥狀1000~2000情緒不定、言語不清清醒、欣快感共濟(jì)失調(diào)、嗜睡、惡心共濟(jì)失調(diào)2000~3000昏睡、恍惚、語無倫次情緒不穩(wěn)運(yùn)動(dòng)障礙3000~4000昏迷嗜睡5000呼吸抑制、死亡昏睡或昏迷第131頁/共164頁臨床表現(xiàn)無酒精耐受者酒醉清醒后，可有頭痛、頭暈、無力、惡心、震顫等癥狀；耐受者，癥狀較輕。重癥中毒輕度酸堿平衡和電解質(zhì)失常、低血糖和肺炎急性肌病，表現(xiàn)肌肉腫脹、疼痛或伴有肌球蛋白尿。第132頁/共164頁實(shí)驗(yàn)室檢查血清乙醇濃度測(cè)定成人乙醇LD50為5～8g／kg，兒童為3g／kg血液生化檢查急性中毒可出現(xiàn)低血糖、低鉀血癥、低鎂血癥和低鈣血癥動(dòng)脈血?dú)饧毙灾卸菊弑憩F(xiàn)輕度代謝性酸中毒心電圖可出現(xiàn)心律失常和心肌損害的心電變頭顱CT嚴(yán)重酒精中毒病人