鎮(zhèn)靜藥物中毒

鎮(zhèn)靜、催眠藥中毒

(sedative-hypnoticpoisoning)2021/5/71acutesedative-hypnoticpoisoning—coma,respiratorydepressionandshock。drugresistanceanddependencewithdrawalsyndrome2021/5/72病因

(reason)?苯二氮卓類

(Benzodiazepines,BZD)：

呼吸抑制作用小,不影響肝藥酶活性(enzymaticactivity),大劑量無麻醉(anesthetic)作用,耐受性和成癮性低超短效類：midazolam,temazepam,triazolum,brotizolam短效類：alprazolam,lorazepam,oxazepam,bromasepam,flunitrazepam,estazolam長效類：chlordiazepoxide,clonazepam,diazepam,flurazepam

2021/5/73?

巴比妥類

(barbiturate)：

作靜脈麻醉藥、抗驚厥藥(anticonvulsant)、腦復蘇治療(resuscitationtherapy)超短效類：methohexital,nembutal,pentothal短效類：secobarbital,pentobarbital,talbutal中效類：amobarbital,allybarbital,aprobarbital,butabarbital長效類：barbital,phenobarbital,methlphenobarbital,primidone2021/5/74?

非巴比妥非苯二氮卓類(Nonbenzodiazepine,Nonbarbiturate,NBNB)：

pharmacologicaction:pharmacokinetics:toxicreaction:chloralhydrote,glutethimide,meprobamate,methaqualone2021/5/75

藥代動力學(pharmacokinetics)liposolubilityabsorption、distribution、protienbinding、metabolismdischarging、starteffecttimeandactiontime易通過血腦屏障(blood-brainbarrier)2021/5/76?

Benzodiazepines,BZD：口服吸收迅速完全,1h—spikedensity,3h—peak蛋白結合率,分布容積變化在肝臟微粒體氧化系統(tǒng)(microsomaloxidizingsystem)

羥化(hydroxylation)、去甲基化(nor-methylation)和葡萄糖醛酸化(glucuronation)2021/5/77?

Barbiturate分布容積大,腦、肝、腎和脂肪組織(fattytissue)中濃度高cleaningway:

脂溶性高的巴比妥類:肝臟微粒體酶(microsomeenzyme)→無活性的產(chǎn)物+葡萄糖醛酸(glucuronate)→腎臟脂溶性低的巴比妥類→腎臟2021/5/78?

Nonbenzodiazepine,Nonbarbiturate,NBNB：大多經(jīng)肝臟微粒體酶系統(tǒng)(microsomeenzymaticsystem)

代謝2021/5/79

中毒機制

(poisoningmechanisms)?

Benzodiazepines,BZD：BZD+CNS特異性受體(w1,w2,w3)(toproduceamarkedeffect)W1:(sensorimotorarea),鎮(zhèn)靜、催眠(hypnosis);w2:(limbicsystem),抗焦慮(antianxiety)、抗驚厥(anticonvulsion)

w3:

notclearfacilitateBZD+receptor→GABA(gamma-aminobutyricacid—neurotransmitter)↓receptor

inhibitoryeffection2021/5/7109、人的價值，在招收誘惑的一瞬間被決定。2023/2/32023/2/3Friday,February3,202310、低頭要有勇氣，抬頭要有低氣。2023/2/32023/2/32023/2/32/3/20235:01:01PM11、人總是珍惜為得到。2023/2/32023/2/32023/2/3Feb-2303-Feb-2312、人亂于心，不寬余請。2023/2/32023/2/32023/2/3Friday,February3,202313、生氣是拿別人做錯的事來懲罰自己。2023/2/32023/2/32023/2/32023/2/32/3/202314、抱最大的希望，作最大的努力。03二月20232023/2/32023/2/32023/2/315、一個人炫耀什么，說明他內心缺少什么。。二月232023/2/32023/2/32023/2/32/3/202316、業(yè)余生活要有意義，不要越軌。2023/2/32023/2/303February202317、一個人即使已登上頂峰，也仍要自強不息。2023/2/32023/2/32023/2/32023/2/32021/5/711?

Barbiturate↗+GABA受體,氯離子通道復合物→開放t↑→抑制Barbiturate

(chloridechannelcompound)↘chloridechannel→擬GABA廣泛抑制CNS2021/5/712?

Nonbenzodiazepine,Nonbarbiturate,NBNB：

inhibitoryactionforCNS:similartobarbiturate2021/5/713

臨床表現(xiàn)

(clinicalsituation)?

Benzodiazepines,BZD：發(fā)音困難(dysarthria)、眼球震顫(nystaxis)記憶力減退、幻覺(illusion)、驚厥、昏睡(hypnody)、昏迷共濟失調(incoordination)、反射減退(hypopreflexia)或亢進(hyperreflexia)、肌張力障礙(myodystony)體溫降低(hypothermy)、呼吸抑制2021/5/714?

Barbiturate

★

light、midrangepoisoning:注意力、記憶力、判斷力減退、欣快(hyperhedonia)、情緒不穩(wěn)(emotionalinstability)、言語不清、共濟失調、眼球震顫(nystaxis)

★

severepoisoning:昏迷、瞳孔縮小(miosis)、腦干反射消失(areflexia)、肌張力(musculartension)降低、深部腱反射(deeptendonreflex)消失、腸梗阻(intestinalobstruction)、低血壓、休克2021/5/715?

Nonbenzodiazepine,Nonbarbiturate,NBNB：

輕者嗜睡(drowsiness)、共濟失調,重者昏迷水合氯醛(chloralhydrate):心律失常(arhythmia),肝腎衰竭格魯米特(glutethimide):抗膽堿(luridine)能綜合癥甲丙氨酯(meprobamat):CNS抑制,嚴重低血壓甲喹酮(methaqualone):錐體系征(pyramidalsystem):肌陣攣(myoclonus)、張力增強、腱反射亢進(tendonhyperreflexia)2021/5/716

實驗室檢查

(laboratoryexamination)concentrationmeasurement:

blood、urine、gastricfluidbloodgasanalysis:

PaCO2↑bloodbiochemistrydetect：

bloodglucose、ureanitrogen、creatinine、electrolyte2021/5/717

診斷

(diagnosis)historysingsandsymptomsconcentrationmeasurement

2021/5/718鑒別診斷

(differentialdiagnosis)cerebralvascularaccident:diabeticketoacidosis:uremiccoma:urinecreatinine、ureanitrogenpoisoning:alcohol2021/5/719?

Firstaidcoma:glucose,vitaminB1,naloxonerespiratoryfailure:airtube,oxygen,tracheacannula,mechanicalventilationshock:

hypovolemia2021/5/720?Togetridofpoison：gastriclavage：2hactivatedcarbonadsorption:

消化道透析diuresis：血液凈化(bloodpurification)：血液透析(hemodialysis):prolongedactionbarbiturates,BZD(no)

血液灌流(hemoperfusion):nonwater-solubility、highproteinbindingbarbituratesandothers2021/5/721?

ToxicideBarbiturates:no

BZD:

flumazenil—BZDreceptor競爭性拮抗藥(competitiveantagonist)

三環(huán)抗抑郁藥(tricyclicantidepressants)過量、長期應用BZD、

BZD(irritability)—to

prohibitsideeffect:

convulsion、arrhythmia、intracranialpressure↑2021/5/722?Totreatcomplicationpneumonia:antibioticsarrhythmia:electrocardio-monitoringacuterenalfailure:shockwater、electrolyte、acid-basebalance2021/5/723有機磷殺蟲藥中毒(organophosphorusinsecticidespoisoning)2021/5/724?

Effect:

inhibitinternal乙酰膽堿酯酶(acetylcholinesterase):↗Msample

acetylcholineacumulation→煙堿(nicotine,N)samplesymptom↘CNS→respiratoryfailure

→death.2021/5/725?

Characteristics:

★難溶于水(indissolvable)

★不易溶于多種有機劑(organism)

★揮發(fā)性(volatility),大蒜味(garlic)

★堿性(alkalinity)條件下易分解(resolve)失效.2021/5/726

分類(classification)rankpoisonedspecies:LD50<10mg/kg,甲拌磷(3911)、內吸磷(1059)、對硫磷(1605).highpoisonedspecies:LD5010-100mg/kg,甲基對硫磷(metacide)、甲胺磷(tamaron)、氧樂果(omethoate)、敵敵畏.Midrangepoisonedspecies:LD50100-1000mg/kg,樂果(rogor)、乙硫磷(ethion)、敵百蟲(Danex)等.lowpoisonedspecies:LD501000-5000mg/kg,馬拉硫磷(malathion)等.2021/5/727

病因(reason)acutepoisoning:

livingpoisoningchronicpoisonging:

occupational

poisoningabsorption—skin、gastrointestinalandrespiratorytractmembranes.2021/5/728

發(fā)病機制(poisoningmechanisms)?

Metabolism:

livercellsmicrosomaloxidizingenzymesystem: oxidize→virulence↑hydrolysis→virulence↓distribution:liver>kidney、lungandspleen>muscle、briantissure★

products→urine(24h)→lungtoexcrete(small),noaccumulation.2021/5/729

發(fā)病機制(poisoningmechanisms)?

Poisoningmechanisms:

真性膽堿酯酶(truecholinesterase乙酰-):foracetylcholine特異性高,水解作用(hydrol)強

假性膽堿酯酶(pesudocholinesterase丁酰-):

foracetylcholine特異性低,嚴重肝損時活力降低

2021/5/730

發(fā)病機制(poisoningmechanisms)organophosphorusinsecticides+cholinesterase酯解部位(esteraticsite)絲氨酸(serine)羥基(hydroxy)

↓

難以水解的磷?；憠A酯酶(organophosphate-cholinesterase)→cholinesterasecantresolve乙酰膽堿(acetylcholine)

↓

acetylcholineaccumulation→cholinergicnerve傳導功能障礙→toxicsymptom

2021/5/731direct

organophosphorusinsecticides

→acetylcholinereceptor2021/5/732

臨床特點(clinicalsituation)

?

Acutepoisoning

★

oraladministration:

tofallin(10min-2h)

inhaler:

tofallin(30min)

skinabsorption:

tofallin(2-6h)

★

light:

Msymptom,cholinesteraseactivity＜50%midrange:M+Nsymptom,cholinesteraseactivity10%-20%severe:M+N+CNSsymptom,cholinesteraseactivity＜10%2021/5/733Msamplesymptom:

parasympatheticnerveendingexcite→smoothmusclespasm,外分泌腺分泌(exocrineglandsecretion)enhanceNsamplesymptom:alloverthebodypresshard,vencricularfibrillation,強直性痙攣(toniccramp)→muscleforcedecrease,癱瘓(tobeparalyzed)CNSsymptom:

dizzy、headache、restlessness、譫妄(acuteconfusionalstate)、incoordination、convulsionorcoma2021/5/734?

Delayedneuropathysymptomdisappeared2-3w,toinvolvemotornervefibre→thelowerlimbstobeparalyzed,fourlimbsmuscle

萎縮(atrophy)—沃勒變性(Walleriandegeneration)2021/5/735progression:

periphsensoryneuropathy,lowerextremities→upperextremities→thelowerlimbsdeeptendonreflexdisappearheavy→遲緩性癱瘓(flaccidparalysis)stablephase:

sensorydisturbance3-12month,incompleteparalysiscatabasis:

6-18month,motorfunction→recover2021/5/736?

中間綜合癥(intermediatesyndrome)

☆

recover1-4d,4-18drelieve

☆

頸屈肌(flexor)、腦神經(jīng)支配的(innerv)肌肉、肢體近側(proximum)肌、呼吸肌癱瘓

☆脂溶性(liposolubility)多見

☆

reason:

organophosphorusinsecticidestobedelayeddischarging、redistributionorantidotenotenough2021/5/737

實驗室檢查(laboratoryexamination)?

cholinesteraseenergometry:

specificityindex—reflectpoisoneddegree、therapeuticefficacy、prognosisrepeattodeterminestoppyraloxime:todetermine/d,continous3d?

metabolicproduct:determination:

urine

antinitrophenol-most;ethapon-danex

others:electromyogram;nerveconductedfunction2021/5/738

診斷(diagnosis)

history,garlicflavor,musclebundleventricularfibrillation具膽堿(choline)能癥狀

contactinsecticide12hbloodplasmaandredbloodcellcholinesteraseactivityloss>50%post-treatmentatropine:Msamplesymptomrelieve2021/5/739

鑒別診斷(differentialdiagnosis)

heatstrokeacutegastroenteritis:diarrheacerebritis:stiff-neck;lumbarpunctureothers2021/5/740治療(treatment)?

Firstaid:respiratorydepressionpulmonaryedemaasystolecerebraledemacoma:mannitol?

Togetridofpoison：

gastriclavage:clearwater,normalsodium,2%bakingsoda

(danextobeprohibited),1:5000kalium

permanganicum(parathiontobeprohibited)2021/5/741?

Toxicide

膽堿酯酶復活藥(cholinesterasereactivators)碘解磷定(pyraloximeiodide),氯磷定(pyraloximemethylcholride),

雙復磷(obidoximechloride),雙解磷(trimedoxime)resolvephosphoryl_cholinesterase,recovercholi