I

Antidotes

II

ISBN

1 2555

3,000

270610400

0220110840220110851

/

022144660026124509

E-mail:smprt2005@yahoo.com

III

4 (CalciumDisodiumEDTA), (Botulinum antitoxin), (Digitalis Fab Fragment) (Diphtheria antitoxin) 4

.

( )

IV

V

2553

2554

2555

6 10

DiphtheriaantitoxinBotulinumantitoxin

2555

( )

VI

2555 1 (CalciumDisodiumEDTA) 7 (Botulinumantitoxin) 11 (DigitalisFabFragment) 17

(Diphtheriaantitoxin) 23

(LEADPOISONING) 29 (Botulism) 31 (DIGOXINPOISONING) 37

1. Antidotes 45 BotulinumantitoxinDiphtheriaantitoxin 2. 51 3. 53 4. 55 5. 3 57 6. 3 59

1

2555

1.

.. 2550 15 2550

5052antidotes

Antidotes

2553

2555

10

VMI

G antidotes G (highriskarea) G G / 2.

antidotes 2555 10

2

2555

1. Dimercaprol(ampule) 50mg/mL

arsenic,gold,mercury,lead,

copper

2. Sodiumnitrite(ampule) 3%w/v Cyanidepoisoning

3. Sodiumthiosulfate(ampule) 25%w/v Cyanidepoisoning

4. Methyleneblue(vial) 1%w/v Methemoglobinaemia

5. Glucagon(vial) 1mg/mL Beta-blockerandcalcium

channelblockerpoisoning

6. Succimer(capsule) 100mg/cap

leadpoisoninginchildren

7. Botulinumantitoxin(bottle) C.botulinumantitoxin botulinumantitoxin

TypeA750I.U.,

TypeB500I.U.,

TypeE50I.U.

permL

8. Diphtheriaantitoxin(ampule) 1,000I.U./mL diphtheria

toxin

9. Digoxinspecificantibody 40mg/vial digoxin,cardiac

fragment(vial) glycoside

10. CalciumDisoduimedetate 200mg/mL lead,

(ampule) zinc,cadmium,manganese

.

. botulism diphtheria botulinum antitoxin

diphtheriaantitoxin 1

3

3.

4.

/ /

/Geographic Information

System (GIS)

/ antidotes10

Dimercaprol ..1-2

.

Sodiumnitrite3% ,,.,.,

.

Sodiumthiosulfate25% ,,.,.,

.

Methyleneblue1% ,,.,.,

.

Glucagon .,.,.

Succimer

Botulinumantitoxin .,.

Diphtheriaantitoxin .,.,

.4

Digoxinspecificantibodyfragment ., Calciumdisoduimedetate .,

.

2

4

.

.

3 . 4 5.

5.1 ( 24 )

1)

G G

2) internet

G G

3)

4)

5)

G ........ 1

610400

G :1367 G :0-2-201-1084-61 G Email:poisrequest@hotmail.com G URL:www.ra.mahidol.ac.th/poisoncenter/PoisonCenter.mahidol.ac.th

5

5.2 ( 24 ) 1) :3

2) :02-4197317-8

3) :02-418-1493

4) URL:http://www.si.mahidol.ac.th/th/division/shtc/

6.

6.1

6.2

1

6.3 . . 3

5

3 6 6.4

6

7.

m m . :02-141-4297

:084-387-8045

E-mailaddress:wannapa.s@nhso.go.th

E-mailaddress:tanl_rx@yahoo.com

mdlCross-Out

7

OO

O

O-

Ca2+

Na+

N Na+

-O -O

O- O

N

(Calcium Disodium EDTA)

CalciumdisodiumEDTA(ethylenediaminetetraaceticacid)CaNa

2EDTA

CaNa2EDTA

extracellular fluid

cerebrospinalfluid

(metabolized)

(glomerularfiltration)

1 24

CalciumCaNa2EDTAdivalenttrivalent

EDTA affinity (chelate)EDTAcomplex

complex

CaNa2EDTA

8

CaNa2EDTAchelatingagents

1. leadencephalopathy

2. (bloodleadlevel)70

3. / 45 100

CaNa2EDTA cerebrospinal fluid

leadencephalopathydimercaprol(BAL)

chelating

agents /

CaNa2EDTA EDTAmobilization test

CaNa2EDTA248

0.6 1CaNa2EDTA

1.

2.

1.

2.

1.

2.

3.

4.

5.

9

6. disodiumEDTA calciumdisodiumEDTA

severehypocalcemia

CaNa

2EDTA15

1000-1500 50-75

2

normal saline 5%dextrose250-500 110%dextrosesolution

2-311

(continuousvenousdrip)

(deep intramuscular

injection)

25

5 1 2

1000

lead encephalopathy dimercaprol CaNa

2EDTA4

EDTAmobilizationtest1/2

CaNa2EDTA5(200)

10

1. Cory-SlechtaDA,WeissB,CoxC.Mobilization and redistribution of leadover the course of

calciumdisodiumethylenediaminetetraacetatechelationtherapy.JPharmacolExpTher1987

Dec;243(3):804-13.

2. LahayeD,EveraetE,RooselsD.Valueof thediagnosticsodiumcalciumedetatemobilization

testasacriterionofleadabsorption.JSocOccupMed1989Winter;39(4):136-40.

3. RadwanH,BraunH,Bar-SelaS,KottE.Leadencephalopathytreatedbyversenate(CA-EDTA).

EurNeurol1982;21(3):157-60.

4. Treatmentguidelinesforleadexposureinchildren.AmericanAcademyofPediatricsCommittee

onDrugs.Pediatrics1995Jul;96(1Pt1):155-60.

5. WilliamsDR,HalsteadBW.Chelatingagents inmedicine.JToxicolClinToxicol1982;19(10):

1081-115.

11

(Botulinum antitoxin)

(Botulism) (botulinum toxin) Clostridium botulinum

(botulinumantitoxin)

7 Clostridium botulinum

A,B,C,D,E,FGA,BE

FCDG acetylcholine (ACh)

(parasympathetic) AChanticholinergic (anticholinergictoxidrome)

1. (Foodborne botulism)

Clostridium botulinum

2. (Woundbotulism) Clostridium botulinum

3. (Infantile botulism Adult intestinal toxemia

botulism) Clostridium botulinum

4.

12

5. A

(botulinumantitoxin) (serum)

immunoglobulin

Fab

(t)5-7

AB(bivalent)A,BE(trivalent)

7(heptavalent)

1.

2.

(absolutecontraindication)

(hypersensitivity)

immune

13

1. AnaphylacticAnaphylactoid

23 (urticaria)

(bronchospasm)

2.

2

3. Serumsickness

13

immunoglobulin Fc

Fab immune

9 17

anaphylactic 1 9 immune(antivenin)

(lyophilized) (concentrated

solution)

250

21

epinephrineantihistamine

desensitization

(desensitization)

immune

250

2 8

14

Botulismus-AntitoxinBehring 1 A750 (international unit), B500

E50250

1. Pricktest

1:1,000

(positivecontrol)histamine(negativecontrol)

15-20 histamine(erythema)3

2. Intradermaltest

1

1:1,0000.02

1:100 (

1)

1:1001:1,000

epinephrine(1:1,000)

immune

15

Desensitization

desensitization

desensitization

15

desensitization

* normal saline (.)

1 1:1,000 0.1

2 1:1,000 0.3

3 1:1,000 0.6

4 1:100 0.1

5 1:100 0.3

6 1:100 0.6

7 1:10 0.1

8 1:10 0.3

9 1:10 0.6

10 0.1

11 0.2

12 0.6

13 1.0

*15

immuneanaphylaxisadrenaline

immune desensitization

immune

1. Anaphylaxis

anaphylaxis

1.1

1.2

1.3

16

1.4

- Adrenaline

- Corticosteroid

- H2antagonist

1.5(vitalsigns)

2.

2.1

2.2

2.3pethidine

3. Serumsickness

3.1

3.2corticosteroid

3.3plasmaphoresis

1. Geyer HL. Botulism. In: Nelson LS, Lewin NA, HowlandMA, Hoffman RS, Goldfrank LR,

FlomenbaumNE, eds.GoldfranksToxicologicEmergencies. 9th ed.NewYork:McGraw-Hill;

2011:p682-94.

2. GoldfrankLS,GeyerHL.Botulinumantitoxin. In:NelsonLA,LewinNA,HowlandMA,Hoffman

RS,GoldfrankLR,FlomenbaumNE,eds.GoldfranksToxicologicEmergencies.9thed.NewYork

:McGraw-Hill;2011:p695-7.

3. GomezHF. Botulism. In: Brent J,WallaceKL, Burkhart KK, Phillips SC,Donovan JW, eds.

CriticalCareToxicology:Diagnosisandmanagementof thecriticallypoisonedpatient.1sted.

Philadelphia:ElsevierMosby;2005:p1351-8.

4. ChalkC,BensteadTJ,KeezerM.Medicaltreatmentforbotulism.CochraneDatabaseSystRev.

2011Mar16;(3):CD008123.

5. TacketCO,ShanderaWX,Mann JM,HargrettNT,BlakePA.Equineantitoxin useandother

factorsthatpredictoutcomeintypeAfoodbornebotulism.AmJMed.1984May;76(5):794-8.

6. JonesRG,CorbelMJ, SesardicD. A review ofWHO International Standards for botulinum

antitoxins.Biologicals.2006Sep;34(3):223-6.

7. GottliebSL,KretsingerK, TarkhashviliN,ChakvetadzeN,ChokheliM,ChubinidzeM, et al.

Long-termoutcomesof217botulismcasesintheRepublicofGeorgia.ClinInfectDis.2007;45 (2):174-80.

8. ArnonSS,SchechterR,InglesbyTV,etal.Botulinumtoxinasabiologicalweapon:medicaland

publichealthmanagement.JAMA2001;285(8):1059-70

17

(Digitalis Fab Fragment)

Digitalis Fab Fragment (DSFab) (antibody) (cardiac glycoside) (digoxin) (digitoxin) DSFab (digoxin-

dicarboxymethoxylaminehapten)

Fab

(antigen)

DSFab

DigiFab DSFab

DSFab

(volumeofdistribution)0.3-0.4

(receptor)digoxin-Fabcomplex(DFC)

DSFab (DigiFab) 40 0.5 DFC 15-18

DFCreticuloendothelial

DSFab 20

(totalserumdigoxin)

1-2 (free serumdigoxin)

18

150

0.5 6

88

DSFab /

(steadystateconcentration)(

8-10)

DSFab (oleander)

1. ventricular tachycardia,

ventricular fibrillation,cardiacarrestsymptomaticbradyarrhythmiaheartblock

atropine

2. 5.5

3. 10

4. 6

DSFab

( 150)

1. (hypokalemia)(4)

(2.5)

2. rapid ventricular response atrial fibrillation

(3)

3. (1)

4. FDApregnancycategoryC

19

1. DSFab

DSFab2-3 7-10

2. DSFabdigoxin-Fabcomplex immunoassay

DSFab 4

1

2

3 4

(1)

(2)

DSFab

DSFab

DSFab

-(bioavailability)

80

-DSFab1

0.5

5(

8)

: 10-20

: 3-6

1-2

DSFab1-3

1

DSFab

20

10.2530

0.25x307.5

1(vial)DSFab400.5

DSFab

= (7.5)/DSFab(0.5) = 15

2 60 10

(Vd)5

DSFab()

= ()/DSFab(0.5)

= [()xVdx()]/[1000x0.5

]

= [10x5x60]/[1000x0.5] = 6

DSFab6

: 1.

2. 8-10

3.

51

DSFab

(oleander) DSFab

DSFab

1 (vial)

4 10

2-8 4

0.2230

21

DSFab(DigiFab)(lyophilizedform)40

1. Ujhelyi MR, Robert S. Pharmacokinetic aspects of digoxin-specific Fab therapy in the

managementofdigitalistoxicity.ClinPharmacokinet.1995Jun;28(6):483-93.

2. Schmidt TA, Kjeldsen K. Enhanced clearance of specifically bound digoxin from human

myocardialandskeletalmusclesamplesbyspecificdigoxinantibody fragments: subsequent

completedigitalis glycoside receptor (Na,K-ATPase) quantification. JCardiovascPharmacol.

1991Apr;17(4):670-7.

3. WardSB,SjostromL,UjhelyiMR.Comparisonofthepharmacokineticsandinvivobioaffinityof

DigiTAbversusDigibind.TherDrugMonit.2000Oct;22(5):599-607.

4. Antman EM,Wenger TL, Butler VP, Jr., Haber E, Smith TW. Treatment of 150 cases of

life-threateningdigitalisintoxicationwithdigoxin-specificFabantibodyfragments.Finalreportof

amulticenterstudy.Circulation.1990Jun;81(6):1744-52.

5. Marchlinski FE,HookBG,CallansDJ.Which cardiac disturbances should be treatedwith

digoxinimmuneFab(ovine)antibody?AmJEmergMed.1991Mar;9(2Suppl1):24-8;discussion 33-4.

6. HowlandMA.Digoxin-SpecificAntibodyFragments(Fab).In:NelsonL,LewinN,HowlandMA,

Hoffman R, Goldfrank L, FlomenbaumN, editors. Goldfranks Toxicologic Emergencies. NewYork:McGraw-HillProfessionalPublishing;2010.

7. KearneyTE.Digoxin-SpecificAntibodies. In:OlsonK, editor. PoisoningandDrugOverdose.

NewYork:McGraw-HillProfessional;2011.

23

(Diphtheria antitoxin)

(Diphtheria) Corynebacterium diphtherriae

(toxogenicstrain)

(exotoxin)

(Bull neck)

(diphtheria antitoxin,DAT)

penicillin erythromycin

streptococci

phenol 0.25%

SerumInstituteofIndiaVinsBioproducts

( and globulin)

b g

24

0.1 DAT1:100normalsalinesolution(NSS)201

DAT1:10NSS15

(anaphylaxis)serumsickness

serumsickness

Serum Institute of IndiaVinsBioproducts

10,000-30,000

(Intravenous:IV)40,000-100,000302

DAT NSS 1 : 20 1/ DAT

m 4820,000-40,000 m 72 80,000

m bullneck100,000-120,000 m 10,000-20,00020,000-40,000 IV

DATNSS250-500ml2-4

m Pharyngealorlaryngealdiseaseof2daysduration:20,000-40000units m Nasopharyngealdisease:40,000-60,000units m Systemicdiseaseof3ormoredaysdurationoranypatientwithdiffuseswellingoftheneck:80,000-100,000units

m Skinlesionsonly:20,000-40,000units

28

25

:10,000(10)

1. .

. :

.2547.

2. UseofDiphtheriaAntitoxin (DAT) forSuspectedDiphtheriacases.Available from:URL:http://

ww.cdc.gov./vaccines/vpd-vac/diphtheria/dat/downloads/protocol_032504.pdf/cited inApril

2012

3. LeafletofDiphtheriaantitoxin,SwissSerumandVaccineInstituteBerne,Switzerland.

4. LeafletofDiphtheriaantitoxin,SerumInstituteofIndiaLimited,India.

5. LeafletofDiphtheriaantitoxin,VinsBioproductsLimited,India.

27

29

(LEAD POISONING)

45

CC :

PI : 2 85

1.

m m

m m 2.

m *** m Leadline() m Neurologicaldeficitsperipheralnervoussystem 3.

m CBC,BUN/Cr,serumuricacid,liverfunctiontest m Serum/urineALAD,erythrocyticprotoporphyrins 4. chelatingagents

30

: 20 6

5 50-60

mildpaleconjunctiva

CBC: Hb9.2gm/dL,Hct28%,WBC4,500/cumm,platelet250x103/cumm,

normochromicnormocyticanemiawithbasophilicstippling

CaNa2EDTA 1 12 5

1CBC:Hb11/

bloodleadlevel6047

31

(Botulism)

- 5

2-3

1. RotavirusStaphylococus aureusVibrio

parahemolyticus

2.

Amanita pantherina, Amanita phalloides

1

(intravenous fluid)

(conscious)

(ptosis) (shallow breathing)

1.

2. (Tetrodotoxin)(Saxitoxin)

3. (Botulinumtoxin)

32

?

acetylcholine (cholinergic syndrome) (alteration of consciousness)

1

1

()

1-8

:

(Descendingparalysis)

6-8

,

() 1/2-12

:

(Ascendingparalysis)

-

2-3

,

33

balbar palsy

anticholinergic

(Botulism)

?

Clostridium botulinum (gram positive bacilli)

(obligated anaerobic)

120 30 (botulinumtoxin)Clostridium botulinum7A,B,

C,D,E,FGA,BEF

CDG

polypeptide2 light chain heavy

chain heavy chain light chain

zincdependentendoproteasepolypeptideSNAREproteins(soluble

N-ethylmaleimidesensitive factor attachment protein receptor) exocytosis

acetylcholineacetylcholine

(irreversible inhibition)

(botulism) (botulinum toxin ) 5

1.1 Foodborne botulism :

1.2 Intestinal botulism : Clostridium botulinum (infantilebotulism)(adultintestinaltoxemiabotulism)

1.3 Wound botulism : Clostridium botulinum

34

1.4 Biological weapon : 2

1.5 Iatrogenic botulism : A

1-8(2)

1:

2 : (descendingparalysis)anticholinergicsyndrome

anticholinergicsyndrome

(braindeath)

?

1.

m Mousebioassay m Immunoassayfortoxin m Polymerasechainreaction(PCR)fortoxin m CultureforClostridium botulinum 2

m (Pulmonary function tests) negative inspirationforce(NIF)

m (Electromyography)

35

?

m m m m

1.

(endotracheal tube)

negative inspiration force (NIF)

2.

paradoxicalmovement(diaphragm)

3.

4.

5. 1

6.

5-8

2 26 .. 2493-2502 (.. 1950-1959)

6 .. 2533-2539 (.. 1990-1996) .. 2549

190 42

6-9

36

1. Geyer HL. Botulism. In: Nelson LS, Lewin NA, HowlandMA, Hoffman RS, Goldfrank LR,

FlomenbaumNE, eds.Goldfranks ToxicologicEmergencies. 9th ed.NewYork:McGraw-Hill;

2011:p682-94.

3. GomezHF. Botulism. In: Brent J,WallaceKL, Burkhart KK, Phillips SC,Donovan JW, eds.

CriticalCareToxicology:Diagnosisandmanagementof thecriticallypoisonedpatient.1sted.

Philadelphia:ElsevierMosby;2005:p1351-8.

4. SwaddiwudhipongW,Wongwatcharapaiboon P. Foodborne botulism outbreaks following

consumptionofhome-cannedbambooshootsinNorthernThailand.JMedAssocThai2000;83 (9):1021-5.

5. Botulism fromhome-cannedbamboo shoots--NanProvince, Thailand,March 2006.MMWR

MorbMortalWklyRep.2006Apr14;55(14):389-92.

6. KongsaengdaoS,SamintarapanyaK,RusmeechanS,WongsaA,PothiratC,PermpikulC,etal.

AnoutbreakofbotulisminThailand:clinicalmanifestationsandmanagementofsevererespiratory

failure.ClinInfectDis.2006Nov15;43(10):1247-56.

7. WongtanateM,SucharitchanN,TantisiriwitK,OranrigsupakP,ChuesuwanA,ToykeawS,etal.

Signs and symptomspredictive of respiratory failure in patientswith foodbornebotulism in

Thailand.AmJTropMedHyg.2007Aug;77(2):386-9.

8. WitoonpanichR,VichayanratE,TantisiriwitK,WongtanateM,SucharitchanN,OranrigsupakP,

ChuesuwanA,NakarawatW,TimaA,SuwatcharangkoonS,IngsathitA,RattanasiriS,WananukulW.

Survivalanalysisforrespiratoryfailureinpatientswithfood-bornebotulism.ClinToxicol(Phila).

2010;48:177-83.

11.GottliebSL,KretsingerK, TarkhashviliN,ChakvetadzeN,ChokheliM,ChubinidzeM, et al.

Long-termoutcomesof217botulismcasesintheRepublicofGeorgia.ClinInfectDis.2007;45 (2):174-80.

12..:

, . . :

;2552.51-9.

13. . (Botulism). : , . .

CommonproblemsinInternalMedicine.:2551:79-94.

14.. Botulinum toxin .

.2549.

37

(DIGOXIN POISONING)

60

atrial fibrillation

glipizide 5 / humulin-N 20 unit/

enalapril 10 / atorvastatin 10 / isosorbide dinitrate 30 / aspirin

81 / furosemide 40 / digoxin 0.25 /

100/60 52 / 20 /

1

serum sodium 136 potassium 2.8

chloride 102 bicarbonate 21 BUN 82

/ creatinine 3.8 / serum digoxin 5.4 / (

digoxin 10 )

1 atrial fibrillation with complete heart block

junctional ectopy, 53/ QRS QTc interval 102 486 millisecond

38

(digoxin)

supraventicular tachycardia

(digitoxin)(yellowoleander,Neriumspp.)(Bufotoads)

sodium-potassium

adenosine triphosphate (Na-KATPase) pumps

Na-KATPaseNa-KATPase(membranepotential)

Na-KATPase

- (sodium

calciumexchanger)

1.

2. AV node supraventicular tachycardiaheartblock

3. ventricle

(automaticity) (excitability)

ectopicbeats,prematureventricularcontraction(PVC),bigeminy,ventriculartachycardia

fibrillationbidirectionalventriculartachycardia

4. (hyperkalemia)

1. (

80)

2. (confusionanddelirium)

39

3.

m Bradyarrhythmias : AV blocks (1st, 2nd, 3rd degree), atrial fibrillationwith slowventricularresponse(