antidote 2
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I
Antidotes
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II
ISBN
1 2555
3,000
270610400
0220110840220110851
/
022144660026124509
E-mail:smprt2005@yahoo.com
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III
4 (CalciumDisodiumEDTA), (Botulinum antitoxin), (Digitalis Fab Fragment) (Diphtheria antitoxin) 4
.
( )
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IV
-
V
2553
2554
2555
6 10
DiphtheriaantitoxinBotulinumantitoxin
2555
( )
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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
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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
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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
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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
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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
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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(
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