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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(zhǎng)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(fù)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(zhǎng)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(dòng)力學(xué)(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(jié)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(jī)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(jià)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(qǐng)。2023/2/32023/2/32023/2/3Friday,February3,202313、生氣是拿別人做錯(cuò)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(gè)人炫耀什么,說明他內(nèi)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(gè)人即使已登上頂峰,也仍要自強(qiáng)不息。2023/2/32023/2/32023/2/32023/2/32021/5/711?
Barbiturate↗+GABA受體,氯離子通道復(fù)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(jì)失調(diào)(incoordination)、反射減退(hypopreflexia)或亢進(jìn)(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(jì)失調(diào)、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(jì)失調(diào),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(yán)重低血壓甲喹酮(methaqualone):錐體系征(pyramidalsystem):肌陣攣(myoclonus)、張力增強(qiáng)、腱反射亢進(jìn)(tendonhyperreflexia)2021/5/716
實(shí)驗(yàn)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(jìng)爭(zhēng)性拮抗藥(competitiveantagonist)
三環(huán)抗抑郁藥(tricyclicantidepressants)過量、長(zhǎng)期應(yīng)用BZD、
BZD(irritability)—to
prohibitsideeffect:
convulsion、arrhythmia、intracranialpressure↑2021/5/722?Totreatcomplicationpneumonia:antibioticsarrhythmia:electrocardio-monitoringacuterenalfailure:shockwater、electrolyte、acid-basebalance2021/5/723有機(jī)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(jī)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(nèi)吸磷(1059)、對(duì)硫磷(1605).highpoisonedspecies:LD5010-100mg/kg,甲基對(duì)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(jī)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(jī)制(poisoningmechanisms)?
Poisoningmechanisms:
真性膽堿酯酶(truecholinesterase乙酰-):foracetylcholine特異性高,水解作用(hydrol)強(qiáng)
假性膽堿酯酶(pesudocholinesterase丁酰-):
foracetylcholine特異性低,嚴(yán)重肝損時(shí)活力降低
2021/5/730
發(fā)病機(jī)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(dǎo)功能障礙→toxicsymptom
2021/5/731direct
organophosphorusinsecticides
→acetylcholinereceptor2021/5/732
臨床特點(diǎn)(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(qiáng)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(cè)(proximum)肌、呼吸肌癱瘓
☆脂溶性(liposolubility)多見
☆
reason:
organophosphorusinsecticidestobedelayeddischarging、redistributionorantidotenotenough2021/5/737
實(shí)驗(yàn)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(fù)活藥(cholinesterasereactivators)碘解磷定(pyraloximeiodide),氯磷定(pyraloximemethylcholride),
雙復(fù)磷(obidoximechloride),雙解磷(trimedoxime)resolvephosphoryl_cholinesterase,recovercholi
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