Antidote book1_download.pdf

8/11/2019 Antidote book1_download.pdf

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Antidotes

2554

.

1.

.. 2553 54 Antidotes

4/2553 19

2553 1. Antidotes

3 (2) 2552 5 Antidotes 6

2. .

Antidotes . 1. Antidotes 6

. (2) 2552 5 /

2. .

2554


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20 4 .

VMI Antidotes (High risk area)

2.

Antidotes 2554 10

(1) Dimercaprol inj, (BAL) 1,000 ampules(2) Sodium nitrite inj. 5,000 vials(3) Sodium thiosulfate inj. 5,000 vials(4) Methylene blue inj. 5000 vials(5) Glucagon inj. 600 vials(6) Succimer cap. (DMSA) 1,350 capsules(7) Digoxin-specific antibody fragment inj. 30 vials(8) Calcium disodium edetate inj. 250 vials(9) Botulinum antitoxin inj 10 vials(10) Diphtheria antitoxin inj 2,000 vials

.

3.

Antidotes


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4.

Geographic Information System(GIS)

Antidote 10

()

Dimercaprol 50 mg/ml

Sodium nitrite 3%Sodium thiosulfate 25%Methylene blue 1%Glucagon 1 mg/ml

Succimer 100 mg/capDigoxin-specific antibodyfragment inj.Calcium disodium edetate inj.Botulinum antitoxin injDiphtheria antitoxin inj

. . 1- 2 . ., , . , , . , , . ., . .

20

1071071071

11

121

22-44 ampules

10 vials10 vials20 vials200 vials

1,350 capsules30 vials

250 vials8 2 vials

2,000 vial

5.

5.1 ( 24 ) 1)

: . , . ,.


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2) internet

3) 4)

5)

. ........ 1

6 10400

. : 0-2354-7272, 0-2201-1083. : 1367. : 0-2201-1084-6 1. Email : [email protected]. URL : http://www.ra.mahidol.ac.th/poisoncenter/

5.2 ( 24 ) . : 3 . 0-2419-7317-8. 0-2419-7007. : 0-2418-1493. URL : http://www.si.mahidol.ac.th/th/division/shtc/

6.

.

www.nhso.go.th Online

24


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1. Antidotes .

2. Antidotes

Program . Program . 1

3. Antidotes .

Antidotes www.nhso.go.th

download

1. 2. .

02-141-5019 081-170-4112E-mail address : [email protected]

3. . 02-141-4201 084-387-8045E-mail address : [email protected]

[email protected]


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(Sodium nitrite)

(cyanide poisoning) (sodiumnitrite) (hydroxocobalamin) (cobalt edentate)

Na 2NO2 -

(aerobic respiration) (mitochondria) (electron transportation) (cytochrome oxidase) (ATP, adenosinetriphosphate) (Fe3+) (ferric)

CN

(histotoxichypoxia)

(oxidizing agent) oxidize (Fe2+) (ferrus) (Fe3+) (methemoglobin)

(cyanomethemoglobin)


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1. 8-15

2. 3.

1.

2. (methylene blue)

1.

300 (10 3% ) 3-5

2. 10 / 0.33 / 3%

10 (300 )

/78910111213

3% /5.86.67.58.39.110.010.8

3% /0.190.220.250.270.300.330.36


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30 30 1

3% 10 (30 / )

1. WHO: Antidotes and other substances used in poisonings. 2008. Chapter:4. WHO Model Formulary. Page65-66. www.who.int/selection_medicines/list/WMF2008.pdf Date accessed:07/12/2009

2. US DHHS: Medical Management Guidelines for Hydrogen Cyanide. 2007. Medical Management Guidelinespage12,18. http://www.atsdr.cdc.gov/MHMI/mmg8.html Available from:14/12/2009

3. Holdstege CP, Isom GE, Kirk, MA. Cyanide and hydrogen sulfide. In: Flomenbaum NE, Goldfrank LR,Hoffman RS, Howland MA, Lewin NA, Nelson LS, eds. Goldfrank toxicologic emergencies.8thed. New York:McGraw-Hill; 2006:p1712-24.

4. Curry SC. Cyanide: hydrogen cyanide, inorganic cyanide salts and nitriles. In Bent J, Wallace KL, Burkhart KK,Phillips SD, Donovan JW, eds. Critical care toxicology: Diagnosis and management of the critically poisonedpatient. Philadelphia: Mosby Inc;2005:p987-98.

5. Howland MA. Sodium and Amy nitrite. In: Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, LewinNA, Nelson LS, eds. Goldfrank toxicologic emergencies.8thed. New York: McGraw-Hill; 2006:p1725-27.

6. Andreson BD. Nitrites. in Bent J, Wallace KL, Burkhart KK, Phillips SD, Donovan JW, eds. Critical caretoxicology: Diagnosis and management of the critically poisoned patient. Philadelphia: Mosby Inc; 2005:p1539-42.

7. Mullen WH. Nitrire, sodium and amyl. In Olson KR, ed. Poison & Drug overdose. 5th ed. New York:McGraw-Hill;2007:p484-5.

8. Wananukul W, Kaojarern S. Acute Cyanide Poisoning: A case report with toxicokinetic study. J Med AssocThai 1992;75:304-309.


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(Sodium thiosulfate)

Na 2S2O3

(borate) (cisplatinum)

(sodium nitrite) (hydroxocobalamin)

(volume of distribution, Vd) 0.15 / (metabolise) (unchanged) 30-50

(sulfur) (CN) (SCN) (CN) 2 (divalent bond) sulfane-sulfur

mercaptopyruvate sulfer transferase rhodanese

albumin (SCN) 2


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2

1. 2.

2.1 (smoke inhalation)2.2

2.3

3.


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1. 1.1

12.5 (50 25%)

10-20 1.2

400// (1.6 / 25% ) 50 1

2. (sodium nitroprusside) 25 % 10 1

25% 18 (250 )

1. WHO: Antidotes and other substances used in poisonings. 2008. Chapter:4. WHO Model Formulary. Page

65-66. www.who.int/selection_medicines/list/WMF2008.pdf Date accessed:07/12/20092. US DHHS: Medical Management Guidelines for Hydrogen Cyanide. 2007. Medical Management Guidelines

page12,18. http://www.atsdr.cdc.gov/MHMI/mmg8.html Available from:14/12/20093. Holdstege CP, Isom GE, Kirk, MA. Cyanide and hydrogen sulfide. In: Flomenbaum NE, Goldfrank LR,

Hoffman RS, Howland MA, Lewin NA, Nelson LS, eds. Goldfrank toxicologic emergencies.8th ed. NewYork: McGraw-Hill; 2006:p1712-24.

4. Curry SC. Cyanide: hydrogen cyanide, inorganic cyanide salts and nitriles. In Bent J, Wallace KL, Burkhart KK,Phillips SD, Donovan JW, eds. Critical care toxicology: Diagnosis and management of the critically poisonedpatient. Philadelphia: Mosby Inc;2005:p987-98.

5. Howland MA. Sodiumthiosulfate. In: Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA,Nelson LS, eds. Goldfrank toxicologic emergencies.8th ed. New York: McGraw-Hill; 2006:p1728-30.

6. Stork CM. Thiosulfate. in Bent J, Wallace KL, Burkhart KK, Phillips SD, Donovan JW, eds. Critical caretoxicology: Diagnosis and management of the critically poisoned patient. Philadelphia: Mosby Inc; 2005:p1543-5.

7. Burkhardt C. Thiosulfate, sodium. In Olson KR, ed. Poison & Drug overdose. 5th ed. New York: McGraw-Hill;2007:p514-5.

8. Wananukul W, Kaojarern S. Acute Cyanide Poisoning: A case report with toxicokinetic study. J Med AssocThai 1992;75:304-309.


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(plasma glucose) 1 2 dose 1. cyanosis 2. (abnormal hemoglobin)

(sulfhemoglobin)3. 4. G-6-PD deficiency5. hemolysis 6.

7 /

(exchange transfusion)

1% 5 (10 /)

1. Curry S. Methemoglobinemia. Ann Emerg Med 1982; 11(4): 214-21.2. Peter C, Hungwan d, Kupfer A, lauterberg BH. Pharmacokinetics and organ distribution of intravenous and

oral methylene blue. Eur J Clin Pharmacol 2000; 56(3): 247-50.3. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management.

Ann Emerg Med 1999; 34 (5): 646-56.


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(Dimercaprol)

(Dimercaprol) 2,3-dimercaptopropanol British anti-Lewisite agent (BAL)2

3 sulfhydryl group 2

30 metabolized inactive metabolites

glucuronidation 4 sulfhydryl thiol groups

sulfhydryl group affinity affinity (chelate) heterocyclic ring mercaptidecomplex complex


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(oxidation)

(Arsine, AsH3) (mercury salts)

methyl mercury severe gold dermatitis gold-induced thrombocytopenia

edetate calcium disodium (EDTA) lead encephalopathy

(Tellurium) complex

G-6-PD

sterile abscess


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unbound dimercaprol complex

2.5-3 / 4-5 / 4-6 1-2 5-10

2.5 / 4 4-6 12 1 10 50 5 / 2.5 / 1

2.5- 5 / 2.5 / 4-6

1-2 1 7-10 4-6

d-penicillamine, dimercaptosuccinate (succimer), 2,3-dimercaptopropanesulfonate (DMPS)

1-2


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2 (50 /)

1. Baum CR. Treatment of mercury intoxication. Curr Opin Pediatr 1999; 11(3): 265-8.2. Gorby MS. Arsenic poisoning. West J Med 1988; 149(3): 308-15.3. Kuffner EK. British Anti-Lewisite. In Dart RC, Hurlbut KM, Kuffner EK, Yip L eds. The 5 minute toxicology

consult. 1st ed. Philadelphia: Lippincott Willans & Wilkins; 2000: 94-5.4. Muckter H, Liebl B, Reichl FX, Hunder G, Walther U, Fichtl B. Are we ready to replace dimercaprol (BAL) as

an arsenic antidote? Hum Exp Toxicol 1997; 16 (8): 460-5.

5. Williams DR, Halstead BW. Chelating agents in medicine. J Toxicol Clin Toxicol 1982; 19(10): 1081-115.


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(Succimer)

(meso-2,3-dimercaptosuccinic acid [DMSA]) (chelation) (dimercaprol; BAL)

mercaptan calcium disodium EDTA

(bioavailability)

20 3 95 mixed disulfides 90 10 2.8 3.2 1.7 2.2

sulfhydryl

D-aminolevolenicacid dehydratase ferrochelatase 30-40 60-80 2


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(lead) calcium disodium EDTA

(arsenic)

(mercury) (inorganic mercury) methylmercury methylmercury

1. 1.1 (18 ) 45 / 1.2 20-45 /

1.3 20-45 /

1.4 1.5 60 /

2 2 4 45 /

2.

24 24


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1. 2.

1.

2. 3. 4. neutropenia eosinophilia

5. mercaptan 6. hemolysis G-6-PD deficiency

1. 5 350 /3 () 5 350 /3 14

2. 5 10 / 5 10 / 14

3. category C

(US FDA)

100 200


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1. Dart RC. Succimer. In: Dart RC, editor. Medical Toxicology. 3 ed. Philadelphia: Lippincott William & Wilkins;2004.

2. Dart RC, Hurlbut KM, Maiorino RM, Mayersohn M, Aposhian HV, Hassen LV. Pharmacokinetics of meso-2,3-

dimercaptosuccinic acid in patients with lead poisoning and in healthy adults. J Pediatr. 1994 Aug;125(2):309-16.

3. Bradberry S, Vale A. Dimercaptosuccinic acid (succimer; DMSA) in inorganic lead poisoning. Clin Toxicol(Phila). 2009 Aug;47(7):617-31.

4. Bradberry S, Vale A. A comparison of sodium calcium edetate (edetate calcium disodium) and succimer(DMSA) in the treatment of inorganic lead poisoning. Clin Toxicol (Phila). 2009 Nov;47(9):841-58.

5. Aposhian HV, Aposhian MM. Arsenic toxicology: five questions. Chem Res Toxicol. 2006 Jan;19(1):1-15.6. Blanusa M, Varnai VM, Piasek M, Kostial K. Chelators as antidotes of metal toxicity: therapeutic and experi-

mental aspects. Curr Med Chem. 2005;12(23):2771-94.7. Boscolo M, Antonucci S, Volpe AR, Carmignani M, Di Gioacchino M. Acute mercury intoxication and use of

chelating agents. J Biol Regul Homeost Agents. 2009 Oct-Dec;23(4):217-23.


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(Glucagon)

polypeptide hormone alpha cell beta-adrenergic antagonist calcium channel blocker

glucagon receptorGs protein cyclic adenosine monophosphate (cAMP) cAMP 4 cAMP beta 1-adrenergic receptor beta-adrenergic antagonist beta-adrenergic antagonist calcium channel blocker receptor

1. gluconeogenesis glycogenolysis

2. 1, 12 20

subcutaneous

(volume of distribution, Vd) 0.20 0.25 / (half-life) 8 18 1 3 5 7 10 15 subcutaneous 1030

1-2 tachyphylaxis


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4

1. beta-adrenergic antagonist:

2. calcium channel blocker: (calcium gluconate calcium chloride)

1. 2. hypokalemia3. hyperglycemia hypoglycemia hyperglycemia

hypoglycemia

(warfarin)

hypoprothrombinemia prothrombin time international normalized ratio (INR)


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1. 3 5 (50 /) 5-10

2. 3 5

3. 2 10

4. 24

5. 1-2 2-4 hypokalemia

recombinant DNA

glycerin hydrochloric acid 1

1. Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J ToxicolClin Toxicol. 2003;41(5):595-602.

2. DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker andbeta-blocker toxicity. Toxicol Rev. 2004;23(4):223-38.

3. Shepherd G. Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J HealthSyst Pharm. 2006 Oct 1;63(19):1828-35.

4. Gilman AG. Nobel Lecture. G proteins and regulation of adenylyl cyclase. Biosci Rep. 1995 Apr;15(2):65-97.5. Levey GS, Epstein SE. Activation of adenyl cyclase by glucagon in cat and human heart. Circ Res. 1969

Feb;24(2):151-6.6. Murad F, Vaughan M. Effect of glucagon on rat heart adenyl cyclase. Biochem Pharmacol. 1969 May;18(5):1053-9.7. Chernish SM, Maglinte DD. Glucagon: common untoward reactions--review and recommendations.

Radiology. 1990 Oct;177(1):145-6.8. Koch-Weser J. Potentiation by glucagon of the hypoprothrombinemic action of warfarin. Ann Intern Med.

1970 Mar;72(3):331-5.


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(CYANIDE POISONING)

4 1 1/2 . :

: 19 .10 . .

coma BP 86/58 mmHg ET tubedopamine 5mg/kg/min, dobutamine 20 mg/kg/min

consciousness:response to pain, BP drop IV fluid endotracheal tube refer 2 : PICU . 19 .

- BP 100/60 mmHg, RR 48/min, PR 120/min- Alert, pallor, ashen gray color- Status on endotracheal tube with ventilatory setting (FiO2 1, PIP/PEEP 18/2 mmHg, MIV 20/min)- Otherwise -within normal limit- Arterial blood gas (ABG) 1 hypocapnea hypoxemia wide

anion gap lactic acidemia cyanide level antidote 3% sodium nitrite 4 ml IV drip

20 2.5% sodium thiosulfate 150 ml IV drip 30 antidote 50 lactic acid cyanide level

cyanide poisoning lactic acid methemoglobin 3.95%antidotes cyanide level off endotracheal tube partial airway obstruction vocal cord granuloma pneumonia 2

22 . - BP 90/63 mmHg, PR 108/min, RR 30 /min

- Alert, not pale, no cyanosis


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1

- , status on endotracheal tube with ventilator setting FiO21, PIP/PEEP 12/2 mmHg, MIV 25/min

- ABG lactic acid antidote cyanide 1- Gastric lavage activated charcoal

- off endotracheal tube discharge

0.56

0.02

0.32

Arterial blood gasArterial blood gas Lactic acid Blood cyanide

pH PO2

PCO2

CO2

(normal < 3.4 mmol/L) (normal < 0.03 /ml)

19 . 50 antidote43 .22 .

7.3527.376

7.467

118471

276

2126.4

25.2

11.715.6

18.3

7.45.2

2.7

Discussion

cyanide poisoning cyanide (HCN) cyanide NaCN, KCN cyanide 1 cyanide cyanide cyanide cyanogenic glycoside linamarin cyanide

Cyanide electron transport mitochondria anoxia (histotoxic anoxia) ( 5) hypoxia cyanide hypoxia central cyanosis cyanide cyanide cytochrome oxidase electron cyanide hemoglobin cyanohemoglobin central cyanosiseye ground retinal vein retinal artery retinal vein


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artery eye ground blood gas study arterial mixed venous blood O2tension tissue O 2 arterial blood gas venous blood gas PvO2>40 mmHg venous O 2saturation > 70%

O2saturation artery venous 10 cyanide central cyanosis central cyanosis cardio-vascular collapse bitter almond 40% 2

5 Pathway of cyanide toxicity and detoxification

Systems ManifestationsOdor Bitter almond breath (not always present)Skin Cherry red color or cyanosis

CNS disturbance Headache, agitation, disorientation, lethargy, seizures, coma, cerebral deathCardiovascular Hypotension and tachycardia, hypertension and bradycardia, ST-T wave changes, dysrhythmias,

instability AV block, cardiovascular collapseChanges in Tachycardia --> apnea, venous hyperoxemia: red venous blood, increased mixed venous O2

oxygenation content (SvO2), decreased O

2consumption (vO

2), narrow arteriovenous O

2difference (AvO

2diff)

Metabolic acidosis pH-elevated blood lactate and/or elevated lactate: pyruvate ratio

2 cyanide poisoning


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Level (g/ml) Symptomatology< 0.03 Normal

0.5 - 1.0 Hyperventilation, tachycardia1.0 - 3.0 Decreased mental state, may be fatal> 3.0 Fetal unless treated

3 cyanide

cyanide cyanide cyanide3 lactic acidosis hypoxia

arterial blood gas arterial blood gas venous blood gas () cyanide supportive treatment specific treatment

Supportive treatment

1. Establish airway intubate O 2 PaO2

hypoxia hypoventilation tissue O 2 mouth to mouth resuscitation cyanide antidote

2. hypotension start IV fluid, maintain BP fluid load vasopressor3. severe acidosis pH < 7.16 NaHCO 34. diazepam 0.2-0.5 mg/kg 5

5. arrhythmia

Specific treatment

1. Decontamination: cyanide cyanide linamarin cyanide

2. Enhance elimination: hemodialysis, hemoperfusion hyperbolic oxygen cyanide


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3. Antidote: 3% sodiumnitrite 10 ml/ampule sodium thiosulfate 18 ml/vial

sodium nitrite IV 5 monitor BP vasodilate 30 methemoglobin

methemoglobin hydroxocobalamin (vitamin B 12a) hydroxy group cyanide cyanocobalamin cyanide rhodanese hydroxocobalamin 5 30 cyanide 1.04 ./ 20 sodium thiosulfate 2-7

1. Kerns II WP, Kirk MA. Cyanide and hydrogen sulfide. In: Goldfrank LR, Flomebaum NE, Lewin NA, et al (eds).Goldfranks toxicologic emergencies. 5th ed. Connecticut: Appleton & Lange, 1994:1215-29.

2. Hall AH, Linden CH, Kulig KW, Rumack BH. Cyanide poisoning from laetrile poisoning: Role of nitrite therapy.Pediatrics 1986;78:269-72.

3. Poisindexstaff editorials. Cyanide. Poisindex Micro-medex: Denver 1998.

4. Hall AH, Rumack BH. Clinical toxicology of cyanide. Ann Emerg Med 1986;15(9):1067-74.5. Bermudez RA, Romero AM, Belzunegui MVG, Lorite AB, Cabrera CA. Venous blood arteriolization and

multiple organ failure after cyanide poisoning. Intensive Care Med 1997;23:1286.


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(METHEMOGLOBINEMIA)

24 . 3 central cyanosis

(cyanosed)

methemoglobinemia methemoglobin (chocolate brown) hemoglobin carbon dioxide deoxyhemoglobin methemoglobin

ferrous ion (Fe

++

) (oxidize) ferric ion (Fe

+++

) hemoglobin oxygen hemoglobin oxygen oxygen (the oxyhemoglobin dissociation curve shifts to the left) oxygen (hypoxia) (cyanosed) methemoglobin 10-15% hemoglobin 2 gm% (15% 14 gm%) oxygen

(hypoxia) deoxy-hemoglobin deoxyhemoglobin 5 gm% partial pressure 75-80% oxygen 2.5 methemoglobinemia oxygen oxygen

methemoglobinemia oxidizing agent

( 4) methemoglobin


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dapsone methemoglobinemia deoxy-hemoglobin methemoglobin oxygen deoxyhemoglobin methemoglobin methemoglobin sulfhemoglobin

4 methemoglobin

AGENT USE/SOURCEAniline Ink, dyes, shoe polish, photo developers, varnish, paints, fuel additiveBenzocaine Topical anestheticBetanaphthol disulfonate R salt

Chlorate salts Matchheads, toothpaste, throat soothantsChloroquine AntimalarialCopper sulfate Emetic, fungicide, astringentDapsone Dermatologic, antimalarialLidocaine Local and IV anesthetic, antiarrhythmicMetoclopramide AntiemeticMethylene blue Medical dye, methemoglobin therapyMonolinuron Urea herbicide

Naphthalene Mothballs, deodorizersNitrates

Ammonium nitrate Diuretic, fertilizerBismuth subnitrate AntidiarrhealCalcium, potassium, Contaminated water, fertilizers, food preservatives, vegetables

sodium nitrateIsosorbide dinitrate/ Vasodilator

tetranitratesSilver nitrate Topical burn therapyNitrites

Amyl nitrite Cyanide therapy, vasodilator, abused inhalantButyl nitrite Room odorizer, abused inhalantEthyl nitrite Folk medicineIsobutyl nitrite Room odorizer, abused inhalant

Sodium nitrite Cyanide therapy, anticorrosive, food preservative


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AGENT USE/SOURCENitrobenzene Solvent, polishesNitrogen oxide Fires, silageNitroglycerin Vasodilator, explosives

Permanganate salts Folk remedyPhenacetin AnalgesicPhenazopyridine Urinary tract analgesicPhenols DisinfectantsPrilocaine Local, caudal, epidural anesthesiaPrimaquine AntimalarialSulfonamides AntibacterialToluidine Methemoglobin antidote, dye, artificial fingernails

methemoglobin methemoglobin 3% 10% 20-30% 30-40% oxygen 50-70% 70%

methemoglobinemia 2 decontamination

methemoglobinemia oxygen

activated charcoal ()

Methylene blue cofactor methemoglobin reductase G6PD ferric ion (Fe+++) ferrous ion (Fe++) methylene blue oxygen methemoglobin 30% methemoglobinemia 1 methylene blue 1 methemoglobin sulfhemoglobin ( ), G-6-PD, methemoglobin methylene blue methyleneblue methemoglobin G-6-PD exchange transfusion methemoglobin ascorbic acid methylene blue methylene blue


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1. Smith RP. Toxic responses of the blood. In: Klaassen CD, Amdur MO, Doull J (eds). Casarett and DoullsToxicology: The basic Sciences of Poisons. McGraw-Hill,1996: 344-8.

2. Donovan JW. Nitrates, nitrites, and other sources of methemoglobinemia. In: Haddad LM, Winchester JF

(eds). Clinical Management of Poisoning and Drug overdose. 2nd ed. Philadelphia: W.B. Sauders Company,1990: 1419-30.


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(ACUTE ARSENIC POISONING)

37 : 2

: 2 2

: : Good consciousness

VS: BP 130/70 mmHg, PR 96/min, RR 20/min, BT 37oCHeart: normal

Lung: normalAbdomen: normalNeurological: unremarkable

: Termicide ingestion

?

1. Diflubenzuron benzoylphenyl urea

2. Pyrethroid

4-48


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3. Organophosphate Carbamate organophosphate carbamate

cholinergic , , , , , , 12

4. FipronilGABA receptor

5. Arsenic trioxide arsenic

arsenic trioxide arsenic trioxide

6 (arsenic trioxide 79.4% w/w)

6. Organochlorine status epilepticus

organochlorine

?

?

diflubenzuron, pyrethroid fipronil


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organophosphate, carbamate, organochlorine arsenic trioxide

1. Vital signs

2. cholinergic effects organophosphate carbamate3. 4. heart failure arrhythmia arsenic5. arsenic arsenic

arsenic arsenic arsenic 3 60-80% arsenic 4-6

7 log arsenic

arsenic arsenic arsenic 24 (24-hours urine arsenic) arsenic (spot urine arsenic) 24-hours urine arsenic arsenic 100 g/24 arsenic 24 spot urine arsenic

100 g/gram creatinine


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arsenic organoarsenic arsenic

arsenic arsenic arsenic

arsenic 30 arsenic arsenic

arsenic (spot urine) 2,275 g/gram creatinine 201 g/L (< 5 g/L)

arsenic arsenic chelating agent BAL (Britishanti-Lewisite) Dimercaprol

1. . [Computer program] , 2549.

2. Bradberry SM, Cage SA, Proudfoot AT, Vale JA. Poisoning due to pyrethroids. Toxicol Rev 2005;24(2):93-106.

3. Diflubenzuron, Fipronyl. [Toxicology Information on CD-ROM] POISINDEX system. Micromedex Healthcareseries Volume 130, 2006.

4. Mohamed F, Senarathna L, Percy A, Abeyewardene M, Eaglesham G, Cheng R, et al. Acute human self-

poisoning with the N-phenylpyrazole insecticide fipronil-a GABAA-gated chloride channel blocker. J ToxicolClin Toxicol 2004;42(7):955-63.


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(CHRONIC ARSENIC POISONING)

62 : 2

: 2 2 1 2 3 2 1

: 10

2-3 : Good consciousness, not pale, no jaundiceLung: no adventitious soundHeart: no murmurNeuro: pupil 3 mm react to light both sides,

Motor power: upper grade 4, lower grade 3 both extremitiesSensation: glove & stocking patternAbdomen: not tender, liver & spleen impalpable

Extremities: no pitting edema, white band on nails both extremities:

CBC: Hct 36%, WBC 7,300 mm3, PMN 44%, lymphocyte 46%, monocyte 7%, eosinophil 3%BUN/Cr 7.6/0.5 mg/dl

Live function test: within normal limitedElectromyelography: polyneuropathy, demyelination with axonal involvement

Urine arsenic 345.7 /gm Creatinine (normal 0-50)

Hair arsenic 27.9 /gm (normal 0-3)


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2 glove &stocking chronic toxic neuropathy

axonopathy acrylamide, arsenic, disulfiram, hexacarbons,organophosphate, thallium hypo-hyperpigmentation (hyperkeratosis) white band Mees line

2-3

1-2 keratin

Arsenic arsenic

1.

, melarsoprol trypanosomiasis, arsenic trioxide (As2O3) acute promyelocytic leukemia

4 element, , 2 trivalent arsenic (As3+, arsenite) pentavalent (As5+, arsenate) arsenite arsenate fish arsenic 2

2. (Toxicokinetics)


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arsenate arsenite 90% radioarsenic isotope (As74)

3 1 (2-3 )

1-2 90% 2 (3 7 ) 30 10 3 : 1

3 ( 10 ) 300

arsenate arsenite 46-68.9% 4-5 30% 1 1 1-2

keratin 2-4

3.

arsenite sulfhydrylgroups (reversible) sulfhydryl groups pyruvate succinate oxidation lipoate

Krebs cycle Krebs cycle oxidative phosphorylation ATP

Arsenate arsenolysis arsenate oxidative phosphorylation ATP arsenate phosphate ester ATP arsenate ester ATP arsenite Kerbs cycle oxidation endothelialcellular capillary integrity permeability transudation


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50

4.

arsenic trioxide arsenate

5 64.1

30

transudation mucosal vesicle (rice-water stools) hypovolemic shock

5

Systemic Thirst Minutes

Hypovolemia, hypotension Minutes to hoursGastrointestinal system Garlic or metallic taste Immediate

Burning mucosa ImmediateNausea and vomiting MinutesDiarrhea Minutes to hours

Abdominal pain Minutes to hoursHematemesis Minutes to hoursHematochezia, melana HoursRice-water stools Hours

Hematopoietic system Red cell hemolysis Minutes to hoursHematuria Minutes to hoursIsolated bolld element decrease (i.e., lymphopenia) Several weeksPancytopenia Several weeks


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Pulmonary system (primarily Cough Immediatein inhalational exposures) Dyspnea Minutes to hours

Chest pain Minutes to hours

Pulmonary edema Minutes to hoursLiver Jaundice DaysFatty degeneration DaysCentral necrosis Days

Kidneys Proteinuria Hours to daysHematuria Hours to daysAcute renal failure Hours to days

Central nervous system Confusion, delirium Minutes to hours

Encephalopathy Minutes to hoursSeizures Minutes to hours

Peripheral nervous system Sensory and motor neuropathy Several weeks

(: Yip 2002, 860)

6

Systemic ThirstHypovolemia, hypotension

Skin, mucous membranes EczemaHyperkeratiosis, plams and solesWartsMelanosis or vitiligo (or both)Mucous membrane irritation, ulceration

AlopeciaSquamous cell cancers

Gastrointestinal system StomatitisDiarrhe

Hematopoietic system LeukopeniaAnemiaPancytopeniaAcute myelogenous leukemia


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Kidneys Acute renal failure

Central nervous systemConfusion, delirium

EncephalopathySeizures

Peripheral nervous system Sensory and motor neuropathy

(: Yip 2002, 862)

non-specific

ST T wave hyperkalemia QTc prolongation 30 8 Torsades de pointes ventricular tachycardia

pulmonary edema, acute respiratory distress syndrome (ARDS)

(hemotopoietic system) pancytopenia nadir 1-2 2-3

1-3 diffuse, symmetric painful sensorimotor neuropathy

(glove and stocking distribution) painful burning sensation vibration positional sense

confusion, delirium, encepha-lopathy coma cerebral edema micro-hemorrhage


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capillary integrity

glomerular capillary permeability proteinuria hypovolemic shock

4.2

aresenic

peripheral neuropathy (glove and stocking anesthesia) axonal degeneration

hyperpigmentation

hypopigmentation raindrop pattern (hyperkeratosis) squa-mous, basal cell Bowens disease (sun protected area) 20-40

(gangrene foot) blackfoot dis-ease

aplastic anemia agranulocytosis

DNA repair,methylation DNA free radical

5.

1-2

24


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1-2 (false positive) 30

0.4 ./ 0.1 ./6.

6.1

chelating agent chelating agentchelator 7 Dimercaprol (British Anti-lewisite, BAL) 3-5 ./. 4 12 chelator succimer 10 ./. 8 5 10 ./. 12 2 sodium 2,3-dimercapto-1-propane sulfonate (DMPS) 5 ./. 6-8 8-12 2 12-14 BAL succimer D-penicillamine 25 ./. 6 1 / chelator 50 ./.

6.2 chelator

gastric lavage whole bowel irrigation (WBI) WBI

activated charcoal


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BAL

3- 5 mg/kg every 4- 6 hoursEnding point:24 hour urinary arsenic < 50 ug/ml or untilanother agent is substituted

Succimer

10 mg/kg per dose every 8 hours for 5 days then 10 mg/kg per dose every 12 hoursEnding point:24 hour urinary arsenic < 50 ug/ml

DMPS5 mg/kg per dose IM, administered as a 5% solution

Day 1: q 6- 8 h (3- 4 doses)Day 2: q 8- 12 h (2- 3 doses)Day 3 and thereafter: q 12- 24 h (1-2 doses daily)Ending point:24 hour urinary arsenic < 50 ug/ml

Hypertension

Febrile reaction, diaphoresisNausea, vomiting, salivationLacrimation, rhinorrheaHeadachePainful injection, injection site sterile abscessHemolysis in G-6-PD deficient patients

Nausea, vomiting, diarrheaAbdominal gas, pain, Transient elevations in hepaticaminotransferase and alkaline phosphataseRash, pruritus, sore throat, rhinorrhea, drowsiness,paresthesias, thrombovytosis esosiophilia

Allergic reactionsIncrease copper and zinc excretionNauseaPruritusVertigoWeakness

7 chelating agents

1. Ford M. Arsenic. In: Goldfrank LR, Flomenbaum NE, Lewun NA, Howland MA, Hoffman RS, Nelson LS,editors. Goldfranks toxicologic emergencies. 7thed. New York: McGraw-Hill, 2002: 1183-99.

2. Lewis R. Metals. In: LaDou J, editors. Current occupational & environmental medicine 3rded. New York:McGraw-Hill, 2004: 429-59.

3. Ratnaike RN. Acute and chronic arsenic toxicity. Postgrad Med J 2003; 79: 391-6.4. Yip L, Dart RC. Arsenic. In Sullivan JB, Krieger RG, editors. Clinical environmental health and toxic exposure

2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2001: 858-66.


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57

(LEAD POISONING)

48 1

ultrasound CT scan abdomen, liver function test Family history -

- Physical exam: - good consciousness, BP 160/100 mm/Hg

- moderate pale conjunctiva, no icteric sclera- no lead line at gum

- heart and lung within normal limited- Abdomen - soft, mild tender right upper quadrant- liver and spleen impalpable

- Extremities - no pitting edemaCBC : Hb 10.9 gm% Hct 32% WBC 8,400/mm3PMN 55%, band 4%, lymphocyte 13%, monocyte 6%, eosinophil 1%, platelet 333,000 /mm3

RBC morphology: anisocytosis 1+, microcyte 1+, polychromasia 1+, basophilic stripping 2+Uric acid 8.5 mg/dl

ALA D (Delta aminolevulinic acid dehydratase)= 10.89 Unit/ml RBC (50-115)Erythrocytic prophyrin (EP) = 346 g/100 ml RBC (< 100)ALA = 11.5 mg/L (0-6)Coproporphyrin III (CP3) = 832.59 g/L (0-200)

red blood cell morphology basophilic stripping


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heme synthesis

0.002%

1.

tetraethyl lead .. 2541 .

. 8

8

2. (Toxicokinetics)

20-30% 50% tetraethyl lead tetramethyl lead

0.5 1


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30-40% 2-3 1

99% trabecular cortical 35 , 40 20-30 bone matrix

blood brain barrier gray matter 65% 35%

3. (Pathophysiology of lead poisoning)

3

3.1 electron-donor ligands sulfhydryl groups sulfhydryl groups

3.2 mitochondria second messenger systems

voltage-sensitive calcium channels membrane-bound Na+-K+-ATPase calcium dependent protein kinase-C

3.3

4.

8

9 9


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60

blood brainbarrier tight intercellular junctions endothelial

(proteinaceous fluid) cerebellum cerebral occipital lobe

(encephalopathy)

9

(: Staudinger 1998)


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10 heme synthesis ()

Glycine + succinyl coenzyme A

5- aminolevulinic acid synthase

5- aminolevulinic acid (ALA)

ALA dehydratase (ALA-D)

Porphobilinogen

Porphobilinogen deaminase

Uroporphyrinogen

Uroporphyrinogen decarboxylase

Coproporphyrinogen

Coproporphyrinogen oxidase

Protoporphyrinogen

Protoporphyrin oxidase

Protoporphyrin IX + iron

Ferrochelatase

Heme

(: Henretig 2002, 1208)

energy dependent transport

mitrochondrial respiration phosphorylation acute lead nephropathy

Fanconi-like syndrome aminoaciduria, glycosuria phosphaturia nuclear inclusion body renal tubule 60 ./. fibrosis

40-59

Na+-K+ATPase Na+-Ca2+exchange pump Ca2+


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renin

60 ./. VACTERL vertebral anomalies, anal atresia, cardiac defect, tracheoesophageal fistula, renal limb abnormalies

(skelatal system) 1, 25-dihydroxyvitamin D3

osteocalcin osteoblast osteoclast metaphyseal lead line 11 calcium deposit provisional calcification

11 lead line

(: Traughber 2004, http://health.yahoo.com/topic/emergency/poison/article/healthwise/popup/zm6084)

lead colic (spasmodic contraction) purple-blue gingival lead line lead sulfide lead line


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5.

5.1

complete blood count, urinalysis,blood urea nitrogen, creatinine, liver function test X-ray lead line

5.2 5.2.1 heme

heme ALA-D ALA-D ALA-D 50%

15 ./. ALA 40 ./. erythrocyte protoporphyrin (EP) 120 EP EP (steady state) EP

5.2.2

35 heme 5.2.1

5.2.3 chelatable lead

chelating agent CaNa2EDTA 28% 40-49 ./. 60% 50-69./. CaNa 2EDTA 1 CaNa2EDTA 8 0.7 ./. CaNa2EDTA chelatable lead 6


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6.

chelating agent

chelating agent 10 BAL CaNa 2EDTA succimer (dimercaptosuccinic acid) chelator 3 D-penicillamine 10 ././ 20 ././ 2-3

1 D-penicillamine


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67

(: Henretig 2002, 1219)

Doses expressed mg/kg: BAL 450 mg/m2(24 mg/kg) ; 300 mg/m 2(18 mg/kg). CaNa 2EDTA 1000 mg/m2(25-50

mg/kg) : 1500 mg/m2(50-75 mg/kg) adult maximum 2-3 g/d). Succimer 350 mg/m 2(10 mg/kg).Subsequent treatment regimens based on postchelation BPb and clinical symptoms (see text) . BPb=blood lead(g/dL); EP=erythrocyte photoporphyrin; IM=intramuscular; IV=intravenous

(g/dL)

AdultsEncephalopathy

Symptoms suggestive ofencephalopathy or > 100

Mild symptoms or 70-100Asymptomatic and < 70

ChildrenEncephalopathy

Symptomatic, or > 70

Asymptomatic: 45-69

20-44< 20

BAL 450 mg/m2/da

CaNa2EDTA 1500 mg/m2/da

BAL 300-450 mg/m2/da

CaNa2EDTA 1000-1500 mg/m2/da

Succimer 700-1051 mg/m2/daUsually not indicated

BAL 450 mg/m2/da

CaNa2EDTA 1500 mg/m2/da

BAL 300-450 mg/m2/da

CaNa2EDTA 1000-1500 mg/m2

/da

Succimer 700-1051 mg/m2/da

or CaNa2EDTA, 1000 mg/m2/da

(or rarely, D-penicillamine)

Routine chelation not indicatedChelation not indicatedAttempt exposure reduction

75 mg/m2IM every 4 h for 5 dContinuous infusion, or 2-4 divided IV doses,for 5 d (start 4 h after BAL)50-75 mg/m2every 4 h for 3-5 dContinuous infusion, or 2-4 divided IV doses,for 5 d (start 4 h after BAL)Base dose, duration on BPb, severity of symptoms

350 mg/m2tid for 5 d, then bid for 14 dRemove from exposure

75 mg/m2IM every 4 h for 5 dContinuous infusion, or 2-4 divided IV doses,for 5 d (start 4 h after BAL)50-75 mg/m2every 4 h for 3-5 d

Continuous infusion, or 2-4 divided IV doses,for 5 d (start 4 h after BAL)Base dose, duration on BPb, severity of symptoms350 mg/m2tid for 5 d, then bid for 14 dContinuous infusion, or 2-4 divided IV, for 5 dAwait current studiesIf succimer used, same regimen as per abovegroup

10


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68

1. Gordon JN, Taylor A, Bennett PN. Lead poisoning: case studies. Br J Clin Pharmacol 2002; 53: 451-8.2. Henretig FM. Lead. In: Goldfrank LR, Flomenbaum NE, Lewun NA, Howland MA, Hoffman RS, Nelson LS,

editors. Goldfranks toxicologic emergencies. 7thed. New York: McGraw-Hill, 2002: 1200-27.

3. Lewis R. Metals. In: LaDou J, editors. Current occupational & environmental medicine 3rded. New York:McGraw-Hill, 2004: 429-59.

4. Needleman H. Lead poisoning. Annu Rev Med 2004; 55: 209-22.5. Piomelli S. Childhood lead poisning. Pediatr Clin N Am 2002; 49: 1285- 1304.6. Staudinger KC, Roth VS. Occupational lead poisoning. Am Fam Physician 1998; 57: 719-32.7. Traughber P. X-ray of lead poisoning in a child. 2004. Available at: http://health.yahoo.com/topic/emergency/

poison/article/healthwise/popup/zm6084. Accessed December 12, 2004.


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69

(CHRONIC LEAD POISONING)

50 : 1 : 1

plain film abdomen, long GI series, ultrasound CT scan whole abdomenendoscopic study mild degree gastritis serum amylase, lipase liver function test opiates morphine, pethidine tramadol 100 mg (2 ) 6

: 30

: :

CBC: Hb 10.9 gm% Hct 32% WBC 8,400/ml PMN 55% Band 4% Lymph 13%, Mono 6% Eos 1% Plt 333,000/mlRBC morphology: anisocytosis 1+, microcytosis 1+, polychromasia 1+ Basophilic strippling 2+

classic case colicky pain acute intermittent porphyria 2 porphobilinogen (PBG)

PBG acute intermittent porphyria 134 mg/dl ( 40


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70

mg/dl) 24 92 mg calcium disodium edetate(CaEDTA) 1000 mg iv fluid 2 3 24 1429, 1192 441 mg 2 tramadol

hemoglobin 15 gm% 2 referred pain metabolic abdominal crises metabolic hyperlipidemia (pancreatitis) uremia, lead poisoning, acuteintermittent porphyria

porphyria acute intermittent porphyria metabolic colickypain (investigation) ultrasound, CT scan, endoscopic examination 2

heme metabolite 2 3 "-aminolevulinic acid dehydratase (ALA-D), uroporphyrinogen decarboxylase ferrochelatase "-aminolevelinic acid (ALA), Copropor-phyrinogen III (CP3) protoporphyrin acute intermittent porphyria porphobilinogendeaminase porphobilinogen (PBG) ALA PBG, ALA CP3 PBG PBG (polymerize) uroporphyrin porphobilin pigment PBG acuteintermittent porphyria


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71

12 heme (lead) acute intermittent porphyria

, (lead salt)

30 (clinicalpoisoning) (subclinical)

(subclinical)

(Intelligence Quotient, IQ) (behavior) cognitive function

Center for Disease Control 10 g/dl 2539

2.0-9.7 g/dl 40 g/dl 60 g/dl


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72

(chelating agents) dimercaprol (BAL), CaEDTA D-penicillamine succimer BAL CaEDTA

CaEDTA CaEDTA () 24 g mg 1

Succimer D-penicilla-mine 1000-2000 mg/ 500 mg

1. Silen W. Abdomimal pain. In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci SA, Kasper DL (eds).Harrisons priniciples of Internal Medicine. 13rded. New York: McGrow-Hill, Inc. 1994:61-4.

2. Nadig R. Lead. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds). Goldfranks Toxicologic Emergencies.5thed. Connecticut: Appleton & Lange, 1994:1029-50.

3. Meyer UA. Porphyrias, In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci SA, Kasper DL (eds).Harrisons priniciples of Internal Medicine. 13rded. New York: McGrow-Hill, Inc., 1994:2073-9.

4. Wananukul W, Sirivarasai J, Sriapha C, et al. Lead exposure and accumulation in healthy Thai: Assessed bylead levels, EDTA mobilization and heme synthesis-related parameters. J Med Ass Thai 1998 ;81(2):110-6.


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73

(MERCURY POISONING)

44 10 : 1

: 2 2 : : not pale, no jaundice

Heart: no murmurLung: no crepitationAbdomen: soft, not tender, liver and spleen impalpable

Neurological exam: cranial nerve intact, motor power grade V, DTR 2+ all, Babinsiki showed plantarresponse, postural intention tremor of extremities positive, diadochokinesia negative:

Na 139 mEg/L, K 3.7 mEg/L, Cl 100 mEg/L, CO2 26.1 mEq/LBUN 19.2 mg/dL, Cr 1.0 mg/dL, uric acid 8.6 mg/dLCBC: Hct 44.6%, WBC 1,2000 mm3, Platelet 355,000 /mm 3

PMN 52%, lymphocyte 29%, monocyte 8%, eosinophil 9%24-hr urine for mercury = 1021. 87 g/gm creatinine (normal range 0-35)

Parkinsons

diseases, cerebella lesion


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74

1.

3 1.1 (elemental mercury)1.2 (inorganic mercury)

1.3 (organic mercury)

11

11

Elemental Inorganic (salt) Organic (alkyl)

Primary route of

exposurePrimary tissuedistributionClearance

Clinical effectCNS

PulmonaryGIRenalAcrodynia

Inhalation

CNS, kidney

Renal, GI

Tremor

+++ (acute)+++

Oral

Kidney

Renal, GI

Tremor, erethism

- - - - -++ (caustic)+++ (ATN)

++

Oral

CNS, kidney, liver

Methyl: GIAryl: renal, GI

Paresthesia,

ataxia, tremor, tunnelvision, dysarthria- - - - -

++

- - - - -

(: Sue 2002, 1241)

Elemental mercury , , (amalgum)

Inorganic mercury mercuric chloride (HgCl2), calomel mercurousion mercuric compounds


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Organic mercury 2 1. Alkyl mercury compounds 2 short chain methylmercury,

ethylmercury long chain methoxyethylmercury2. Aryl mercury compounds phenylmercury

short chain alkyl mercury long chain alkyl mercury aryl mercury compounds

2.

elemental mercury

interstitial pneumonitis, patchy atelectasis emphysema pulmonary edema, respiratory failure elemental mercury inorganic mercury inorganic mercury

inorganic mercury hemorrhagic gastroenteritis acute tubular necrosis

inorganic mercury elemental mercury aryl mercury compound long chain alkyl organicmercury 3 inorganic mercury 3 organic mercury 3

1. gingi-

vostomatitis2. chronic inorganic mercurialism tremor, neurasthenia,

erecthism tremor central intention tremor 12 choreoathetosis spasmodic ballismus neurasthenia erethism


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77

chelator inorganic mercury dimercaprol (BAL) 5 ./. 2.5 ./. 8-12 2.5 ./. 12-24 7-10 BAL

- 15-30 BAL 2,3 dimercaptosuccinic acid (DMSA, succimer) 10 ./. 3 5 DMSA DMSA DMSA D-penicillamuine (DPCN) methylmercury organic compound chelator methyl mercury DMSA

1. Bates BA. Mercury. In: Haddad LM, Shanon MW, Winchester JF editors. Clinical management of poisoningand drug overdose. 3rd ed. Philadelphia: W.B.Saunders company, 1998: 750-6.

2. Lewis R. Metals. In: LaDou J, editors. Current occupational & environmental medicine 3rded. New York:

McGraw-Hill, 2004: 429-59.3. Sue YJ. Mercury. In: Goldfrank LR, Flomenbaum NE, Lewun NA, Howland MA, Hoffman RS, Nelson LS,

editors. Goldfranks toxicologic emergencies. 7thed. New York: McGraw-Hill, 2002: 1239-48.4. Yip L, Dart RC, Sullivan JB. Mercury. In Sullivan JB, Krieger RG, editors. Clinical environmental health and

toxic exposure 2nded. Philadelphia: Lippincott Williams & Wilkins, 2001: 867-78.


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79

(CALCIUM CHANNEL BLOCKERS POISONING)

25 : verapamil (40 mg) 25 30

: 2 verapamil sensitive ventricular tachycardia Wolffe-Parkinson-White syndrome verapamil (40 mg) verapamil 25 30

: ventricular tachycardia 3 : BT 37C, PR 125 --> 72 /min, RR 20/min, BP 80/50 --> 100/70 mmHg

Good consciousness, others within normal limits

:Hb 12.3 gm%, Hct 38%, WBC3 10,580/10 cells/mm3(N 47%, L 42%), platelet 340,000/103cells/mm3

BUN/Cr 150/8 mg%, plasma glucose 125 mg%, Na+138, K +4.2, Cl -102, HCO 3-19 mEq/LEKG wide QRS complex tachycardia rate 120-130 /min

45 EKG sinus arrest with accelerated junctional rhythm delta wave 10% calcium gluconate10 . EKG normal sinus rhythm junctional rhythm normal sinus rhythm 24

Wolffe-Parkinson-White syndrome

verapamil calcium channelblockers mild transient hypotension junctional rhythm sinus arrest normal sinus

rhythm


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Calcium channel blockers (CCBs)

CCBs 3

phenylalkylamines verapamil dihydropyridines nifedipine benzothiazines diltiazemCCBs second generation selective

CCBs amlodipine, nicardipine,nitrendipine dihydropyridines

10% calcium chloride (13.6 mEq/L) 10 . 10% calcium gluconate(4 mEq/L) 30 . 5 10-20 hypercalcemia

glucagon 3-10 . 1-5 /. myocardial depression verapamil, nifedipine diltiazem glucagon catecholamine-independent receptor adenyl cyclase intracellular cAMP calcium flux

calcium channel4-aminopyridine verapamil 4-amino-pyridine

calcium influx potassium influx

1. Pearigen PD, Benowitz NL. Poisoning due to calcium antagonists: Experience with verapmil, diltiazem andnifedipine. Drug Saf 1991;6:408-30.

2. Ramoska EA, Spiller HA, Winter M, Borys D. A 0ne-year evaluation of calcium channel blokcer overdose:Toxicity and treatment. Ann Emerg Med 1993;22:196-200.3. Kenny J. Treating overdose with calcium channel blockers. Br Med J 1994;308:992-3.4. Spiller HA, Meyers A, Ziemba T, Riley M. Delayed onset of cardiac arrhythmias from sustained release

verapamil. Ann Emerg Med 1991;20:201-3.5. Morris DL, Goldschlager N. Calcium infusion for reversal of adverse effects of intravenous verapamil. JAMA

1983;249:3212-3.


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: 0-2201-1083, 0-2354-7272

1367


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: 0-2419-7317-8

: 0-2419-7007

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