2toxico-overdose-lec07-1223099219105884-9-101219081153-phpapp02 [compatibility mode]

7/21/2019 2toxico-overdose-lec07-1223099219105884-9-101219081153-phpapp02 [Compatibility Mode]

1/15

Poisons&DrugPoisoning

DrMohamadshaikhani.

Poisoningclassification:

Accidental:mostcommoninchildren sedatives&hypnotics(barbiturates) >psychotherapeutics (tranquilizers) >CNSstimulants&depressants (amphetamines).

NarcoticsLomotil,anantidiarrhetic withasimilarlethaldoseasmorphine;duetoCNSdepression.

Propoxyphene,similareffectasmethadone OverdosetreatedwithNaloxone.

Majordrugsinvolvedinpoisoning:

Paracetamol.

Aspirin.

Benzodiazepines.

SSRIs.

TADs.

Antionvulsants.

Otheranalgesicsinculding NSAIDs.

Poisoning

by

substances

other

than

drugs:

Petrolium distilates.Naturetoxines asmushrooms.

Industrialchemicals.

Toiletries.

Householdproducts.

Agrochemicals.

Others.

General

Comments

Try&getasmuchhistoryaspossibleincludingwitnesses

Peopletruly

wanting

to

commit

suicide

oftenlie

RemembertheABCs: Airway Clearmouth&throat,gagreflex

Breathing O2saturation,ABGs

Circulation Venousaccess,IVfluidsifshocked

AssessGCS

Examination


2/15

History

When,what,howmuch?

Why?

CircumstancesPMHx,Drughistory

Psychiatrichistory

Assessmentalstatus&capacity

Care

with

names:

Generic

vs

Chemical

name

Dolostop:paracetamol+dextropropoxiphen.

Valium:diazepan.

Fluout:paraetamol +

diphenhydramine.

Investigations

Alwayscheckbloodglucose.

Sendblood&urinefortoxicologyscreening.

ALWAYSmeasureparacetamol &salicylatelevels

Failuretodiagnose&treatisnegligent.

CBP,LFTs,glucose,ABG,clotting,bicarbonateECG,CXR

Specificbloodlevels

Toxins

for

which

emergency

blood

levels

measurements

needed:

Paracetamol.

Aspirin.

Iron.

Lthium.

Theophylin.

Methanol.

Ethyleneglycol.

Management

Supportive Correcthypoxia,hypotension,dehydration,hypo

hyperthermia,andacidosis

Controlseizures

Ifcomatoseconsider;DONT(Dextrose,O2,Naloxone,Thaimine).

Monitor PR,BP,ECG,Oxygenation,GCS

General Absorption

Elimination

Specificantidotes

Principlesoftherapy:

1.Preventionofdrugabsorption

Washingtoremovecutaneouscontamination

by

acid

or

base

or

organophosphorous insecticides.

Inductionofvomitingtoremovepoisonfromstomachby:a.Mechanicalstimulationasinducinggag.b.Ipecacsyrup.c.Apomorphine.d.Warmsaltwaterorbiarbonate gastric

lavage.


3/15


1.Preventionofdrugabsorption

Bindingofthepoisonbyspecificchelatingagentse.g.EDTAinnheavymetalpoisoningasleadpoisoningordeferxamine inIronpoisoning.

Adsorptionofthepoisonontoactivatedcharcoal Shouldbegivenwithin30mmofingestion Charcoalhasnotoxicity,maybegivenbeforeinducing

vomitingorgastriclavage Itiswithauniversalantidote(activatedcharcoal:magnesium

oxide:tannicacid2:1:1) 50gsingleorrepeateddose( elimination) Doesntbindheavymetals,ethanol,acids

Drugsnotadsorbtoactivated

charcoal:

Iron.

Lithium.

Methanol.Ethyleneglycol(antifreeze).

Acids alkalis.

Petroleumdistillates.

Absorption

Gastriclavage Onlyifwithin1hour&iflifethreateningamount

Neverforcorrosivesasitmaycauserespiratoryirritation&moreGITdamagespeciallyoesophagus.

If LOCintubatebeforegastriclavage.

Elimination

Methodstoincreaseelimination:Multipledoseactivatedcharcoal

CanbindQuinine,phenobarbitoneCharcoalhaemoperfusion

CanbindBarbiturates,theophyllineDiuresisUrinaryalkalinisation:increaseexcretion

ofaspirin.

Dialysis:

can

remove

many

substances

fromblood.

Drugs

adsorb

to

activated

charcoal:

Aspirin.

Carbamezepine.Dapsone.

Digoxin.

Phenytoin.

Quinine.

Theophyline.

Barbiturates.


2.Alterationofdrugmetabolism

Theenhancementofmetabolismfor

drugsinactivated

by

metabolism

e.g.

use

ofthiosulfateincyanidepoisoning

Theinhibitionofmetabolismofdrugswhichproducetoxicmetabolitese.g.useofethanolformethanolpoisoning


4/15

Principles

of

therapy:

3.

Enhancement

of

excretion

Iontrapping&alterationofurinarypHforceddiuresis,dialysis[hemodialysis),peritonealdialysis,gastricdialysis(addacidicsolutiontostomach,pumpout)]

Haemoperfusion,pass

blood

over

charcoal

Laxatives(cathartics)e.g.sodiumsulfate,magnesiumsulfate,citrateorphosphate


4.Specificpharmacologicalintervention

Directchemicalantagonisme.g.acidbase

Receptorcompetitione.g.nalorphine inmorph

overdoseBlockadeofreceptorsthatcausesthetoxiceffe

e.g.atropineinorganophosphatepoisoning,Flumazenilinbenzodiazepinepoisoning.

Restorationofnormalfunctionusinganagentexertingadirectoppositeeffecte.g.barbituratCNSstimulantpoisoning

Antidotes

in

most

common

use

in

clinical

toxicology:

Paracetamol: nacetylcysteineormethionine.

Opioid: Naloxone.

Benzodiazepines: Flumazenil.

Iron: dexferoxamine.

Treatmentofshock

Shockisinallseriousaccidentalpoisoning

Arterialbloodpressureislowinshock

Theproblemofshockispoortissueperfusion

Presenttreatment:providefluid,increasearteriolarrelaxation&C.O.usingaadrenergicblocker(isoproterenol)&

antiinflammatomy steroids.

Causesofhypotensioninpoisoning:

Volumedepletionfromvomiting,diarrhea,GITB.

Druginduceddilationofthevenousbed.

MyocardialdepressionasinTAD&BBpoisoning.

Severebrady ortachyarrhythmia.

Druginducedmetabolicacidosisasinaspirinpoisoning.

Treatment of convulsion

ManydrugsstimulateCNScausingconvulsion.

Diazepam(Valium),atranquilizer,isthedrugofchoice


5/15

Specific drug poisoning:

ParacetamolOverdose

AcetaminophenisaleadingOTCanalgesics

IsoneoftheleadingcausesofdrugoverdoseintheUS&UK&aleadingcauseofliverfailure.

It ismetabolizedintheliver&relativelysafeintherapeuticdoses.

A smallfractionisconvertedtoareactivetoxicmetabolite,Nacetylpbenzoquinoneimine (NAPQI),bythecytochromeP450hepaticenzymes.

Withtherapeuticdoses,glutathionestorescandetoxifyNAPQIbyconjugation.

Glutathionestoresaredepletedinoverdoses,&NAPQIbindstocellularproteins,producinghepatocellularnecrosis.

Toxicityoccurafteraminimumof140mg/kg,orabout10g(20tabs)inanadult&muchlessinhighriskpersons(alcoholics,,onenzymeinducingdrugsasantipileptics&inmalnaurished&eatingdisorders.

ParacetamolOverdose ParacetamolOverdose:features.

Acetaminophenpoisoningclinicallyproducesonlynausea,vomiting,&anorexia12to24hoursafteringestion.

Hepaticcoma&coagulopathydonotoccuruntil48to96hoursafteringestion,afterirreversiblehepaticnecrosishasoccurred.

Patientwithsignificantparacetamol overdoseshould

notbe

discharged

early

from

Hospital,

even

ifappearingclinicallywellinthefirst4896hours.

ParacetamolOverdose:Treatment.

Nacetylcysteineisthedrugofchoice.

Iteffectivelypreventshepatotoxicityifgivenwithin8hours.

Itisstronglyeffectiveifgivenwithin16hours&maybe

effectiveup

to

&

beyond

24

hours.

Nacetylcysteinetherapyshouldbeinstitutedwitha4houracetaminophenlevelof150mg/mL,an8hourlevelof75mg/mL,ora12hourlevelof37.5mg/mL.

Becausethistherapymaybeeffective24hoursafteringestion,thepresenceofanymeasurableacetaminophenorbiochemicalevidenceofhepaticinjuryat24hoursisanindicationtostartNacetylcysteinetherapy.


Itcauseshepaticdamageinoverdose&rarelyrenalfailure.

Ifpresentswithin1hourofoverdose,activatedcharcoalgiveniadditiontoNAC.

AntidoteisIVNacetylcysteine,providescompleteprotectionifgivenwithin810hoursofoverdose;efficacydeclinesthereafter

So,ifapatient

presents

>8hours

after

ingestion,

N

acetylcyste

shouldnotbedelayedtoawaitaparacetamolbloodresult,soitgiven&onlystoppedifthelevelsubsequentlyshowntobebelothetreatmentline.

Methionine12gorally4hourly,toatotaloffourdoses,isasuitablealternativewhenNacetylcysteineisnotavailable.

Ifapatientpresents>15hoursafteringestion,liverfunctiontests,PT(orINR)&renalfunctiontestsshouldbeperformed&tantidotestarted.

InsomecasesABGswillneedtobetaken.

Livertransplantationshouldbeconsideredinindividualswhodevelopacuteliverfailure.


6/15


BecausetheP450enzymeispresentinthefetusbythe14thweekofpregnancy,acetaminophenishighlytoxictothefetus,&Nacetylcysteinetherapyshouldbegiventothepregnantpatient

assoon

as

possible.

Donotcheckaparacetamol

level

before4hourshave

elapsed;

it

is

uninterpretable.

Ifmorethan8hourssince

ingestion,

start

Nacetylcysteine

immediately

only

stop

itiftheconcentrationis

belowthetreatmentline

Thesalicylates (aspirin).

Isaleadingcauseofanalgesicdrugoverdose.

TheassociationofReye'ssyndromewithaspirinproducedadramaticfallinuse&accidentalpoisoninginthepediatricagegroup.

Salicylatesinhibitthecyclooxygenaseenzymeoftheprostaglandinsynthetasecomplex,uncoupleoxidativephosphorylation,&producerespiratoryalkalosis&ahighaniongapmetabolicacidosis.

Salicylatesaremetabolizedbyfirstorderkinetics&areconjugatedwithglycine&glucuronicacid;asplasmaconcentrationsriseinoverdose&glycinestoresaredepleted,

zeroorder

kinetics

prevail

&

renal

excretion

of

salicylate

becomesprominent.

Thesalicylates (aspirin).

Salicylateingestionatdoses>150,250&500mgaspirin/kgbodyweightproducesmild,moderate&severepoisoningrespectively.

Salicylatepoisoningcanalsooccurwithingestionofoilofwintergreenorwhensalicylicointment(e.g.wartremover)isappliedextensivelytoskin.

Salicylates (aspirin):

Clinical

presentation.

Includesnausea,vomiting,tinnitus,hearingloss,sweating, facialflushing,hyperpyrexia,&hyperventilation.

Withseverepoisoning:progressivedehydration,hypernatremia,pulmonaryedema,purpura,GIB&death.

Directstimulationofrespiratorycentreproduceshyperventilation

Peripheralvasodilatation withboundingpulses&profusesweatingoccursinmoderatelyseverepoisoning.

Petechiae&subconjunctivalhaemorrhagescanoccurduetoreducedplateletaggregationbutthisisselflimiting.

Signsofseriouspoisoningincludemetabolicacidosis,renalfailure&CNSeffectsasagitation,confusion,coma&fits.

Rarely,pulmonary&cerebraloedemaoccur.

DeathcanoccurasaresultofCNSdepression&CVcollapse.

The developmentofametabolicacidosisisabadprognosticsign,becauseacidosisresultsinincreasedsalicylate transferacrossthebloodbrainbarrier

A plasmalevelof>30mg/dLindicatessalicylatetoxicity&80100mg/dLindicatescriticalsalicylate poisoning.


treatment.

Itisimportanttomeasureaplasmalevelinallbutthemosttrivialoverdosebestat6hoursorlaterafteringestionbecauseofcontinuedabsorptionofthdrug.

Thesalicylateconcentration needstobeinterpretedinconjunctionwiththeclinical

features&

acid

base

status.

Thetreatmentofchoiceforsalicylatepoisoningisanalkalinediuresiswithsodiumbicarbonate.

AnysignificantmetabolicacidosisshouldbetreatedwithIVsodiumbicarbonate(8.4%)&thevolumegiventitratedtogiveanarterialPhof7.47

Patientsareoftenverydehydrated&fluidlossfromvomiting&sweating&mustbereplaced,butoveruseofIVFmayprecipitatepulmonaryoedema

Theuseofmultipledosesofactivatedcharcoalinsalicylatepoisoningiscontroversial, butthisapproachiscurrentlyrecommendedunlesssalicylatelevelhaspeaked.

Urinaryalkalinisationisindicatedforadultpatientswithsalicylateconcentrations of600800mg/l.


7/15


treatment.

Haemodialysisisveryeffectiveatremovingsalicylate&correctingacidbaseandfluidbalanceabnormalities&consideredwhen:

1.Serumconcentrations

are

>800

mg/l

in

adults

&>

700mg/lintheelderly.

2.Metabolicacidosisresistanttocorrection.

3.SevereCNSeffectsascomaorconvulsions, pulmonaryoedema&acuterenalfailure

VitaminKsupplementation shouldbegiven.

Supportivecareisparamount.

Other(NSAID)poisoning.

Ibuprofenistheleading(NSAID).

UsuallycauseslittlemorethanminorGIupsetincludingmildabdominalpain,vomiting&diarrhoea.

1020%haveconvulsions;usuallyselflimiting&needsonlyairwayprotection&oxygen,ifpersistIVdiazepam.

Seriousfeaturesincludecoma,prolongedfits,apnoea,bradycardiabutveryrare.

Deathshavebeenreportedaftermassiveoverdoseofibuprofen,butnotwithmefenamic acid.

Rarely,renalfailureensues.

Featuresoftoxicitytendtooccurearly&unlikelytodeveloplaterthan6hoursaftertheoverdose.

Liver/renalfunctionmaybeaffected,soelectrolytes,liverfunctions&CBPshouldbecheckedinallunlesstrivialoverdoses.

The 1/2tofmostNSAIDsare100mg/kgBWibuprofenor>10tabletofanyotherNSAIDtakeninthelasthour.

GI irritationistreatedwithoralH2blockers(e.g.ranitidine).

nticholinergic poisoning.

Theclassicanticholinergicsyndromeisproducedbyblockadeofacetylcholinewithcentral&peripheraleffects:

Psychosis,delirium,seizures,flushing,drymucousmembranes&skin,hyperpyrexia,dilatedpupils&urinaryretention.

Theantidotephysostigmine shouldbereservedforseverecasesofpureanticholinergicpoisoning.

Physostigmine shouldnotbeusedforagentswithonlysomeanticholinergicproperties,astricyclicantidepressants.

Theinitialdoseofphysostigmine is0.52mgIVslowlyinadults&0.02mg/kginchildren,maximumdoseisnottoexceed4mgin30minutesinadults.

Cardiacmonitoring

is

essential,

because

physostigmine has

causedasystole,bradycardia, &seizures.

Barbiturates poisoning.

Stillconstituteamajorsourceofoverdose&mortalityalthoughlargelyreplacedassleepmedicationbybenzodiazepines.

Theyarestillpresentinheadacheprescriptions&sleepmedications&remaincommondrugsofabuse.

Phenobarbitalisoneoftheleadinganticonvulsantmedications.

ThiopentalisusedasanIVanesthetic forinhospitalrapidsequenceintubationorasasedativebeforecardioversion&surgery.

Phenobarbitalisexcreted

primarily

unchanged

by

thekidney,whereasmostotherbarbituratesaremetabolizedbytheliver.

Barbiturates poisoning:features.

OverdoseisassociatedwithdepressionofCNS&CVsystem,coma,hypotension,lossof

reflexes,hypothermia,

respiratory

arrest

&

death.

2characteristicofabarbiturateoverdoseis:

1.ThepersistenceofthepupillarylightreflexevenwithstageIVcoma.

2.Bullousskinlesionsoftenoccuroverpressureareas.

Barbiturates poisoning:treatment.

Treatmentofthecriticallyillpatientinvolvesmechanicalventilation,resuscitationofCVstatus,gastriclavage&activatedcharcoal(aftersecuringtheairway)&

supportivecare

in

an

ICU.

Analkalinediuresiswithsodiumbicarbonateisspecificallyindicatedforphenobarbital,whichisaweakacidthatisexcretedunchangedintheurine.

Multipledoseactivatedcharcoalevery46hoursisalsospecificallyindicatedforphenobarbital,asitdiffusesintotheGITlumen.

Charcoalhemoperfusion &hemodialysis havearoleinbarbiturateoverdoseforcriticalpatientswhodonotrespondtoconservativetherapy.


8/15

Thebenzodiazepines poisoning.

Extremelypopular&havereplacedothersedativehypnotics.

Allareeffectiveanxiolytics&sedatives&aremusclerelaxants,anticonvulsants&amnestics.

Diazepam,lorazepam,&midazolam,havemajortherapeuticrolesasIVdrugsforinhospitaluseasanticonvulsants,preanesthetics &sedatives.

Althoughcommonagentsofoverdose,causeonlycoma&ataxia;mortality

is

rare

&

supportive

care

is

all

that

usually

necessary.

Theantidoteflumazenilisreservedonlyforreversingpureinhospitalbenzodiazepineconsciousanalgesia&reversing comainzolpidemoverdose.

Itsuseinthegeneraloverdosepatientorinapatientwithheadinjuryorcomaofunknownetiology isnotrecommended,reportedtocauseseizuresinpatientswhohavecoingestedbenzodiazepines&cyclicantidepressants&hascausedincreasedintracranialpressureinpatientswithheadinjury.

Cardiotoxicdrugs:

Cardiotoxic

drug

poisoning:

CCBs.

BBs.

Digoxin.

TAD.

The

calcium channel blockers poisoning.

Commonantihypertensiveagents

themostcommoncauseofcardiovasculardrugdeathbyoverdose.

Aspecialproblemispresentedbythesustainedreleasepreparations,whichallowforcontinuedabsorption.

Persistenthypotension,bradycardiawithatrioventricularblock(especiallywithverapamil),coma,pulmonaryoedema,&cardiacarrestconstitutetheclinicalpicture.

Thecalcium channel blockers poisoning.

Treatmentmustbeaggressiveifthesepatientsaretosurvive.

Wholebowelirrigationwithpolyethyleneglycolisindicatedifsustainedreleasepreparationshavebeeningested.

Anintravenous

10%

calcium

chloride1

gbolus

(over

5

minutes)maybelifesaving,and1gramIVevery15minutesoverthefirsthourmaybenecessaryincriticallyillpatients,followedby10%calciumchlorideviacontinuousintravenousinfusion(thedosageandratedependingontheclinicalcondition)untilbloodpressurestabilizes.

Thecalcium channel blockers poisoning.

Forpatientswhodonotrespondtohighdosecalciumtherapy,dopamine,dobutamine,amrinone,epinephrine,and/orglucagon.

Glucagonisindicatedinpatientswithconcomitantbbloc

overdose.

Pacingmaybenecessary,especiallywithverapamiloverdose.

SymptomaticpatientsandpatientswhohaveingestedsustainedreleasepreparationsshouldbeadmittedtothecriticalcareunitforcontinuousECGmonitoringforatlea24hoursafterstabilization.


9/15

Digitalis poisoning.

Stillcommon.

Patientswhosufferyelloworblurredvision,nauseaorvomiting,&sinusbradycardiamayimprovesimplybystoppingthedrug.

Significantdigitalisintoxicationisheraldedbyhyperkalaemia&avarietyofmajorcardiacarrhythmias.

DigoxinspecificFabantibodies(Digibind)offeradefinitivemeansof

therapy&are

indicated

for:

Lifethreateningcardiacarrhythmia.

Hyperkalaemia.

Aserumdigoxinlevelof10ng/mL,

Amassiveoverdoseof10mgorgreaterinadultsor4mginchildren.

Antidotetherapyshouldbeinstitutedbeforeconventionaltherapyinlifethreateningsituations.

Antidiabetics:

Sulphonylureas (e.g.chlorpropamide,glibenclamide, gliclazide,glipizide,tolbutamide)

Biguanides (metformin,phenformin)

Insulins.

Causehypoglycaemiawhentakeninoverdose.

Theonset

&

duration

of

hypoglycaemia

vary,

but

can

last

severaldayswithlongactingagentsaschlorpropamide&isophane /lente insulins.

Hypoglycaemiamaymanifestasagitation,sweating,confusion,tachycardia,hypothermia,drowsiness,comaoconvulsions

Permanentneurologicaldamagecanoccurifthehypoglycaemiaisprolonged.

Antidiabetics:

Metformincancausealacticacidosisinoverdose,particularlyinelderly&thosewithrenalorhepaticimpairment,orwhencoingestedwithethanol.

Itisassociatedwitha>50%mortality.

Metforminoverdosemayalsocausenausea/vomiting,diarrhoea,abdominalpain,drowsiness,coma,hypotension&CVcollapse.

Antidiabetics:

Management

Activatedcharcoalshouldbegiven&gastriclavageconsideredinapatientswhopresentwithin1hourofingestionofmorethanthenormaltherapeuticdoseofanoralhypoglycaemicagent.

Formalmeasurementofvenousbloodglucose(notjustvisuallyreastripsormeter),urea&electrolytesshouldbeperformed&repeatregularly.

Formedicolegalpurposes,abloodsamplemayberequiredforsubsequentmeasurementofinsulin,proinsulinandCpeptide.

Hypoglycaemiashouldbecorrectedurgentlywith50ml50%dextrgiveni.v. ifthepatientisunconsciousorwithasugarydrinkifthepatientisconscious,followedbyaninfusionof10%or20%dextrostitratedtothebloodglucosetopreventfurtherhypoglycaemia&mbenecessaryforseveraldays,dependingontheagentingestedorinjected.

Potassiumreplacement

should

be

guided

by

frequent

measuremenurea&electrolytes.

Antidiabetics:Management

Failuretoregainconsciousnesswithinafewminutesofnormalisationofthebloodglucoseindicateeither:

1.CNSdepressanthasalsobeeningested

2.Hypoglycaemiahasbeenprolonged.

3.Anothercauseforthecoma(e.g.cerebralhaemorrhage)orcerebraloedema.

Incasesofseveresulphonylurea overdoseresistanttodextroseinfusions,useofIVoctreotide asanantidotemaybeconsidered.

Carbon monoxide poisoning.

IstheleadingcauseofdeathfrompoisoninginU

COisacolourless,odourless,tastelessgasproducedbyincompletecombustionofcarbon

materials.

COhasa200timesgreateraffinityforhaemoglothanoxygen&thusproducescellularhypoxia&death.

Fires,smoke,woodburningstoves,gasspaceheaters&engineexhaustaresourcesofunintentionalpoisoning.


10/15


Becausetheheart&brainarethemostsensitivetohypoxicinsult,clinicalpresentationusuallyinvolvesCNSorcardiacsymptomsheadache, alteredmentalstatus,convulsions,chestpain,cardiacarrhythmia,&/orAMI.

MildCOpoisoningoftenismistakenforinfluenza,asbothoccurprimarilyinthewintermonths&causeheadache/GIsymptoms.

Becausemostpatientsreceiveoxygeninanambulanceonthewaytothehospital,thecarboxyhemoglobin levelisusuallyanunreliableindicatoroftheextentofpoisoning.

Ingeneral,thedeeperthelevelofcoma,thegreaterthechanceofneuropsychiatricsequelae.


COpoisoningistreatedwithoxygen:

Breathingroomair,ittakesapatient6hourstohalvecarboxyhemoglobin level(T);breathing10oxygen,90minutes;withhyperbaricoxygenat2.5atmospheresofpressureabsolute,40%

Cardiovascular involvement (chest pain, ECG changes,

arrhythmias)

Pregnant patients with carbon monoxide levels >15%

Patients who do not respond to 100% oxygen

Patients with recurrent symptoms up to 3 weeks after exposure

Caustic alkali

poisoning.

Accidentallyswallowingbuttonbatterieslargertha20mmindiameter&intentionalingestionofalkasubstancesarethemajorcausesofmorbidity.

Becausesolidcrystalsadheretothetongue&cauburning,theyuncommonlyproduceoesophagealburn.

Droolinginchildren&inabilitytoswallowarehighsuggestive.

Mouthburnsarealsosuggestive,buttheabsencemouthburnsdoesnotexcludeoesophagealburn.

Caustic alkali poisoning.

Milkistheonlypossiblehomeantidote,butitmustbegivenimmediately.

Todetectsignificantburns,somesuggestUGI

oesophagoscopy within

12

hours,

whereas

others

prefertowait242hoursfollowingingestion.

A3weekcourseofmethylprednisolone,2.5mg/kg/day,topreventoesophagealstricturehasbeenthemainstayoftherapy,butitsefficacyhasbeenquestioned.

Oesophagealdilation&gastrictubeesophagealreplacementareindicatedfortreatingesophagealstricture.

Cyanide poisoning.

Mostcommonlyisduetosmokeinhalation.

Onepublicsourceisacetonitrileinacrylicnailremover.

Hydrogencyanide

gas

is

afumigant

rodenticide.

Prolongedadministrationofnitroprusside canresinelevatedcyanidelevels.


11/15

Cyanide poisoning.

Producescellularhypoxiabybindingwiththeferricironofmitochondrialcytochromeoxidase&disruptingtheelectrontransportchain&theabilityofcellstouseoxygen.

Rapidlydevelopcoma,shock,seizures,lactic

acidosis,respiratory

&

cardiac

arrest.

Mildexposuresfollowingsmokeinhalationmaybedifficulttodiagnose&Emergencyadministrationofantidotemaybelifesaving.

Cyanidepoisoningshouldbesuspectedinpatientswhohaveinhaledsmoke&whohaveevidenceoflacticacidosis.

Cyanide poisoning.

Thecyanideantidotekitcontainsamylnitrite,ampulesofsodiumthiosulfate,&ampulesofsodiumnitrite.

Thebodyhasanaturalenzyme,rhodanese,thatcancomplexcyanide&sulfur toformthiocyanate,whichisomildlytoxic.

IVsodium

thiosulfateprovides

the

sulfur necessary

to

producethiocyanate &isrelativelysafe.

Becausesodiumnitritecauseshypotension&methemoglobinemia, itsuseisreservedforthemostcritcases.

Thenewantidotehydroxocobalamin (initialadultdosageIV),notyetapproved,isasaferalternative.

Iron

poisoning.

Hasadirectcorrosiveactiononthestomach&proximalsmallbowel

Onceabsorbed,producesshock,metabolicacidosis,liverfailure&death.

Initially,GIsymptoms prevailwithpersistentvomiting,abdominalpain&hemorrhage.

Aquiescentphasemaybeobserved,followedbyshock,coma,metabolicacidosis&liverfailure.

Laboratorydatamayrevealleukocytosis,

hyperglycemia&radiopaque

tablets

on

aflat

plate

of

theabdomen.

Iron

poisoning.

Aserumironlevelshouldbedetermined(duringpeaklevels)at24hoursafteringestion:>300mg/dL indicatesmildintoxication,,>500mg/dLindicatesseriousintoxication,butaserumironlevinexcessofthetotalironbindingcapacitydoesnoserveasausefulpredictorofironpoisoning.

Iron poisoning.

Managementofironpoisoningincludesgastriclavagewithnormalsaline.

Wholebowelirrigationmaybeindicatedafteringestionofsustainedreleasecapsules.

Thetreatment

of

choice

is

the

antidote

deferoxamine,

which

chelatesfreeserumironintheplasmatoformferrioxamine,whichisreadilyexcreted&impartsavinroscolourtotheurine.

Iron poisoning.

Deferoxamine isindicatedfor:

Allcriticalpatientswhopresentwithcoma,shock,orhemorrhage,

Allpatientswithaserumironlevelhigherthan500mg/d

Patientswhoaresymptomaticwithaserumiron>300mg/dL.

IVdeferoxamine 15mg/kg/houristhepreferred;upto6maybegivenin24hours.


12/15

Iron poisoning.

Chelationtherapyshouldcontinueuntil:

Thepatientbecomesstableforatleast24hours.

Vntil thevinrosurine(whenpresent)becomesclear.

Untiltheserumironlevelhasfallen50 mg/dL,

or with intractable metabolic acidosis.

Methanol ethylene glycol poisoning.

Ethylene Glycol

Signs and symptoms Early

Altered mental status; seizures; hypocalcemic

tetany12 hr after ingestion

Congestive heart failure

2472 hr after ingestion

Profound renal failure

Treatment Treat ethylene glycol with:

aggressive gastric lavage;

ethanol infusion or 4-methylpyrazole,

sodium bicarbonate to correct metabolic acidosis,

Correct hypocalcemia with calcium chloride,

Hemodialysis


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Theorganophosphates poisoning.

Highlypopularinsecticidesbecausetheyareeffective,disintegratewithindaysofapplication&donotpersistintheenvironment

Evenminutequantitiescanpenetratetheskin&belethal,asevidencedbytheuseoforganophosphate

nervegases

sarin,

soman,

tabun,

&

VX

in

chemical

weapons.


Theorganophosphatesirreversiblyinhibitacetylcholinesterase, resultinginanoverabundanceofacetylcholineatsynapses&themyoneural junction.

Theacetylcholineinitiallyexcites&thenparalyzestheCNtheparasympathetic nerveendings&thesweatglands(muscariniceffects),somaticnerves&ganglionicsynapse

autonomicganglia

(nicotinic

effects).

Initialsymptomsresembleaflulikesyndromewithabdominalpain,vomiting,headache,dizziness.

Thefullblownpicturegenerallydevelopsby24hours,includescoma,convulsions,confusion,orpsychosis;fasciculation,weaknessorparalysis;dyspnea,cyanosis,pulmonary edema;sometimespancreatitis.

Torsades depointesVFhasalsobeendescribed.

The

organophosphates

poisoning.

Emergencymanagementincludesdecontaminationoftheskin,&removalofclothes;establishinganairway&ensuringproperventilatory support,cardiacmonitoring;&administeringthespecificantidotepralidoxime &thephysiologicantidoteatropine.

A25%reductioninredbloodcellcholinesteraseconfirmsorganophosphatepoisoning.

Atropineshouldbegivenasaphysiologicantidotetoreversethemuscariniceffects&todrytheexcessivepulmonarysecretionsseeninpatientswithrespiratorydistress.

Atropineuserequirescardiacmonitoring&properoxygenation.

Pralidoxime isthetreatmentofchoicefororganophosphatepoisoning&shouldbebegunonclinicalgroundsbeforereturnofanybloodstudies.

Tobeeffective,pralidoxime mustbegiveninthefirst48hoursbeforeirreversiblebindingofacetylcholinesterase occurs.

The

organophosphates

poisoning.

Theinitialdoseis1gIVgivenover15to30minutes;theeffectmaybedramatic.

Pralidoxime bycontinuousinfusionofupto500mg/hourmaybenecessaryincriticallyillpatients.

Pralidoxime mayobviatetheneedforhighdoseatropinetherapy&reducetheincidenceoflateonsetparalysis.

Neithertherapiesexcludetheuseoftheother.


Thecarbamate insecticidesincludecarbaril,methomyl,&propoxur

arereversiblecholinesteraseinhibitors.

Theyproduceclinicaleffectssimilartothoseofthe

organophosphatesbut

without

CNS

signs;

Theyareconsiderablymorebenign&shorterduration.

Atropineisthedrugofchoiceforcarbamatepoisoning.

Pralidoxime isnotindicatedbecausethecarbamatecholinesterasecomplexisquitereversible.

Theophylline poisoning.

Mortalityfrombothplain&sustainedreleasepreparationsoccurfacuteoverdose&longtermunintentionalintoxication.

Vomitingisoftenthefirstsymptom, sinustachycardiaisthemostcommonsigninbothacutechronictoxicity.

Seizuresmay

be

common

when

the

serum

concentration

is

higher

40mg/mLinchronictoxicityorhigherthan80to100mg/mLinacuoverdose.

Cardiacarrhythmia,CVcollapse,respiratoryarrestareseeninfrequentlyunlesstheconcentrationishigherthan50mg/mLinchronictoxicityorhigherthan100mg/mLinacuteoverdose.

Profoundhypokalemia,hyperglycemia,metabolicacidosisarealsoseen.

Serumtheophyllineishigherinacuteoverdosecomparedwiththoinchronictoxicity.


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Treatmentincludes

withdrawingthedrug,cardiacmonitoring,supportivecare.

Gastriclavage&activatedcharcoalareindicatedforacuteoverdose.

Theserumhalflifeoftheophyllinecanbereducedbyserialadministrationofactivatedcharcoal,asitdiffusesintotheGITlumen;

dosageis

1g/kg

every

4hours.

Wholebowelirrigationmaybeindicatedforingestionofsustainedreleasecapsules.

CardiacarrhythmiasareoftendifficulttomanagebutmayrespondtoIVpropranolol.

Correctionofhypokalemia,metabolicacidosis&fluidelectrolytebalanceisindicated.

AlthoughseizuresmayrespondtoIVdiazepam,statusepilepticus &rhabdomyolysis mayoccur&signifyapooroutcome.


Charcoalhemoperfusion isthetreatmentofchoicforsignificanttheophyllinetoxicity.

Hemodialysis isbecominganoptionequaltocharcoalhemoperfusion.

Charcoal

hemoperfusion is

most

beneficial

for

patientswithaserumtheophylline>80to100mg/mLinacuteoverdoseor>40mg/mLinchrontoxicity(especiallyintheelderlyorpatientswithhepaticdiseaseorotherconditionsthatdelaytheophyllineclearance)orpatientsincriticalcondition.

Tricyclic (or cyclic)

poisoning.

Stilltheleadingcauseofprescriptiondrugdeath.

CVtoxicity(arrhythmia/hypotension),CNSeffects(especiallycoma/seizures),anticholinergicsignsareseen.

Thecardiotoxic effectsareseenwithingestionof1g(10to20mg/kg)&accountforthehighmortalityrate.

Tricyclic (or cyclic)

poisoning.

ThehallmarkonECGisprolongationoftheQRScomplex.

AQRScomplex>100ms isasignofseveretoxicity&correlateswithaplasmalevel>1000ng/mL.

Althoughsinustachycardia&anticholinergicsignsareevidentwithmildtoxicity,QRScomplexprolongationisassociatedwiththedevelopmentofventriculararrhythmseizures,death.

Ventriculartachycardiaisthemostcommonventricularrhythm,althoughventricularbigeminy,slowventricularrhythms,torsades depointesVFalsohavebeendescribe

VF/suddencardiacarrestarenotuncommon.

Tricyclic (or cyclic) poisoning.

ThetreatmentofchoiceIVsodiumbicarbonate.

TomaintainabloodpHof7.5reducetheincidenceofcardiacarrhythmia.

IV

bolus

of

sodium

bicarbonate(1

to

2

mEq/kg)

is

the

treatmentofchoiceforthesuddenonsetofventriculartachycardia,ventricularfibrillation&cardiacarrest.

Sodiumbicarbonatealsomaybeusefulforcorrectinghypotension,althoughvasopressorsmaybenecessary.

Airway,properoxygenation&ventilation,fluidreplacement(butavoidpulmonaryedema),gastriclavagewithseriallyadministeredactivatedcharcoal&supportivetherapyareindicated.


PhenytoinreverseQRScomplexprolongation,butreservedformanagingseizures.

ProphylacticIVphenytoin(15mg/kg)beforetheonsetofseizuresbegivenincasesofamoxapineoverdose,whichhasahighincidenof

status

epilepticus.

Diazepamisquiteeffectiveincontrollingseizures,althoughintenstherapyincludingthiopental&rapidsequenceintubationmaybenecessarytomanagestatusepilepticus.

Physostigmine isnolongerusedintricyclicoverdose,becausebyititcancauseseizures,bradycardia, asystole.

Deathgenerallyoccurswithinthefirst24hoursafteroverdose.

Becausesuddendeathhasoccurredafterapparentstabilization,cardiacmonitoringisindicatedforatleast24hoursafterstabilizati&normalizationoftheQRScomplex.


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Newerantidepressantsthatarenotstructurallyrelatedtothecyclicagentsincludetheserotoninreuptakeinhibitorsfluoxetine(Prozac),sertraline(Zoloft),paroxetine(Paxil),andfluvoxamine(Luvox),

generallycauseonlysedationinoverdose.

Fatalserotoninsyndromefromconcomitantoverdoseofselectiveserotoninreuptakeinhibitors(SSRIs)andmonoamineoxidaseinhibitorsisnowbeingreported.

2toxico-overdose-lec07-1223099219105884-9-101219081153-phpapp02 [compatibility mode]

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