organophosphate paraquat

8/16/2019 Organophosphate Paraquat

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19 !"#$%! 2556

'($)*$++, *-$*$+./0 +, 12$+34-

Organophosphate &56 Paraquat

#3.78+!9: 78; 5

&3(9? 8+6@A$10 $#B, C #8;(" D 3 2$E$F$B"'?


2/38

• Insecticide

• Organophosphates

• Carbamates

• Organochlorines

• Pyrethrins

• Rodenticide

• Coumarin

• Thallium

• Zinc phosphine

• Herbicide

• Paraquat

• Glyphosate

Pesticides


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• Parathion

• Malathion

• Fenthion

• Dimethoate

• Monocrotophos

• Methamidophos

Organophosphate


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LD50

!" #$%&'( ) !" #$*&+,- & LD50(mg/kg)

Parathion ./012$3,4&+&5'6 4-13

Monocrotophos $7.82+13.'/$% 8-23

Methamidophos 4&+&.*+.'3159$+: 5$/ 5 19-21

Malathion '&0&/$%,'&0&6;$*8: 1000

Dimethoate 5265'6 215


5/38

• Inhalation

: unlikely at ordinary temperatures, low volatility

: sprays or dusts

• Skin/eye contact

: rapidly absorbed through intact skin and eyes,contributing to systemic toxicity

• Ingestion

: acute toxicity and rapidly fatal systemicpoisoning

Route of exposure


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• Inhibit enzyme acetylcholinesterase (AchE)

• Blockade of AchE lead to excessive acetylcholine at• Muscarinic receptors

• Nicotinic receptors

• Central nervous system (CNS)

Mechanism of toxicity


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• Muscarinic Cholinergic

• Parasympathetic nervous system and Sweat gland • Excessive Ach lead to

• Sweating (7H)I DFFF*!$*)

• Lacrimation (#C A$G$.H5)

• Salivation (#C A$5$9.H5) • Bronchorrhea (24 D)%,/H5, D)J#H5F/5!) • Bronchospasm (H5F/5!G"1) • Nausea&Vomiting (%5I D#.20 F$7@"9#) • Diarrhea ((0 F)72"9)

• Urination (8K22$'6+$/) • Miosis (+L!M$#G$75N*) • Bradycardia (H, 'J@7G0 #B0 $)


SLUDGE

DUMBELS

Salivation, Lacrimation, Urination, Diarrhea,

Gastrointestinal distress , Emesis

Diarrhea, Urination, Miosis,Bronchospasam, Bronchorrhea, Bradaycardia,

Emesis, Lacrimation, Salivation


8/38

• Nicotinic Cholinergic

• Muscle Motor End-plate and Sympathetic nervoussystem

• Excessive Ach lead to • Fasciculation (*50 $!7#I C F3+4 C ')

• Weakness (*50 $!7#I C FFMF#&+)) • Paralysis (F, !3$G) • Tachycardia (B"3@+7G0 #7+N')

• Hypertension (%'$!/, #O5H4G2L))

• Adrenal Stimulation(*+6G> 0 #*$+(A$)$#EF)GMF!H!'*.G)



9/38

• Central Nervous System (CNS)

• Muscle Motor End-plate and Sympathetic nervoussystem

• Excessive Ach lead to • Seizure (B, *)

• Coma (H!/2G4) • Respiratory depression (*/*$+H$9J@)



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• Onset

• Chemical warfare • Sarin = 5 mins

• Agriculture chemical• 15 mins – 24 hrs

• Mostly within 8 hrs



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$&*&+


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• !, *7*4/G$!H5, )F$*$+34-7T"9135, #@$* Organophosphate 1-3', # J#UL 0 8V'9(" D!"P$'6 Cholinergic Crisis +>#&+)

• !"F$*$+FMF#&+)EF)*50 $!7#I C F1+47'SJ1H#0 $&56:"+-6(" D%'1%>!/0 '9720 #

8+62$(2!F) 7BM# 9, *%4 C '.!M ./0 5I!G$.!MEW C # *5F*G$.!M ./0 7+"9*'M$ “Bulbar Palsy” • 78Q#2$7HG>(" D(A$JH0 UL 0 8V'9H9M$7%+I DF)BM'9H$9J@.!M ./0 (Weaning of

respirator) (A$JH0 G0 F)3W D)7%+I DF)BM'9H$9J@#$#EW C # 1-3 2,8/$H?

• .!M!"*$++, *-$(" D@A$73$6 9$*5> M! oxime .!M(A$JH0 /"EW C # *$++, *-$&118+6%, 18+6%F)O/97T3$6*$+JB07%+I DF)BM'9H$9J@78Q#24 D)(" D2A$%, X(" D2>/

Intermediate Syndrome


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• Biomarker

1.Biomarker of exposure

1.1 Acetylcholinesterase (AchE) in RBC

1.2 Butyrylcholinesterase (BChE) in Plasma

2.Biomarker of effect

2.1 Electromyogram 78Q#*$+G+'@%5I D#.RRY$EF)*50 $!7#I C F O/9@6G+'@31 Spontaneous fasciculation

Laboratory


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+72( >?$=*&+6@ &=&3 cholinesterase 6A #020= - C " D

,F&'+G3


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• E0 F3W)+6', )J#*$+G+'@

• .!M2$!$+ZJB0 G4/G$!/L*$+/A$7#4#EF)O+% O/97T3$6BM')R[ \#G, 'EF)O+%./0

• P$'61$)F9M$)H+IF9$1$)B#4/ 7BM# P$'6]"/@$* hemoglobinopathy H+IF 9$ Chloroquine (A$JH0 +6/, 1*$+(A$)$#EF) AchE 5/5)./0

• *$+(A$)$#EF) AchE J#7!N/75IF/&/)J#P$'68*G4!"*$+&*'M)G, 'J#&GM56', #./0 8+6!$S+0 F956 10

• *$+7*N1G, 'F9M$)75IF/G0 F)JB0H5F/(" D!" D EDTA H+IF Heparin 7(M$#, C # H$*JB0H5F/(" D!" NaF @6(A$JH0 7*4/U5U4/35$/GD A$*'M$%'$!78Q#@+4)./0

Laboratory


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• Supportive treatment

• Primary assessment

• Airwar –Breathing–Circulation assessment • Oxygen therapy

• Semiprone position • Endotracheal intubation

• Secretion removal • Inadequate breathing • Shock

• Intravenous fluid resuscitation

• Observe seizure (Benzodiazepine)

• EKG 12 lead (Arrhythmia, QTc Prolongation)

Treatment


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• Specific treatment

• Decontamination • Remove clothing

• Cleansing

• GI Decontamination

• Do not induce vomiting ! Aspiration Pneumonitis

• Gastric lavage ! Must be within 1 hr

• Activated charcoal! Should be within 1 hr

• Antidote! Atropine , Pralidoxime (2-PAM)

• Control seizure! Diazepam

Treatment


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• FF*^(=4 _ 78Q#9$G0 $#7T3$6^(=4 _ Muscarinic cholinergic 7(M$#, C #

• E0 F1M)B" C • UL 0 (" D!"F$*$+&2/)EF) Muscarinic !$*@#F$@78Q#F,#G+$9GMFUL 0 8V'9

(DUMBELS, SLUDGE)

• 78Y$H!$9 • 5/24 D)%, /H5, D)J#($)7/4#H$9J@ 5A$.20 &56U4'H#, )

• &*0 P$'6H, 'J@7G0 #B0 $&56(A$JH0 +L!M$#G$E9$9G, '

• E#$/9$ :• Loading dose 1.8 mg IV &50 '8+67!4#]C A$J# 3-5 #$(" 8+, 1E#$/78Q#7(M$

G, '@#*'M$@6ZW)78Y$H!$9 (72!H6J#H5F/5!&H0 ) , PR > 80 bpm , SBP >80 mmHg)

• Maintenance dose JH0 ./0 78Q#%+, C )` H+IF IV drip (10-20% EF) loading doseGMFB, D'O!)) &56%'+G4/G$!(>* 15 #$("@#F$*$+%)G, '

Atropine


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• 9$*5> M! Oxime (A$H#0 $(" D reactivate 7FN#.]!? AchE J#8+67(:.(9!"B#4/7/"9'%IF Pralidoxime H+IF 2-PAM

• E0 F1M)B" C

• UL 0 (" D!"F$*$+&2/)EF)P$'678Q#34-@$* Organophosphate ( .!M#A$JH0 JB0 J#

P$'678Q#34-@$* Carbamate)

• 78Y$H!$9

• Reactivate 7FN#.]!? AchE JH0 *5, 1!$(A$)$#./0 F"*%+, C)O/98+67!4#@$*F$*$+&2/)($) Muscarinic &56 Nicotinic O/9#A$JH02, )7*GF$*$+ Fasciculation &56 Muscle Weakness 78Q#H5,*

• E#$/9$ :• Loading dose 1,000-2,000 mg IV in 10 mins • Maintenance dose 1,000 mg/hr H+IF 8-10 mg/kg/hr IV drip • %'+JH0 9$GMF7#I DF) @#R[ \#@$*P$'678Q#34-7T"9135, #.8&50 ' 12-24 B, D'O!)

Pralidoxime (2-PAM)


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• 78Q#9$2A$%, X(" D+, *-$F$*$+($)2!F) 7BM# B, * 2, 12# P$'6H9>/H$9J@]W D)7*4/@$**$+*/:L#9? %'1%>!*$+H$9J@J#2!F) 78Q#G0 #

• E0 F1M)B" C • %'1%>!P$'6B, *

• 5/F$*$+*+62, 1*+62M$9 (Anxiety, Agitation, Restless)

• 78Y$H!$9 • UL 0 8V'9H9>/B, *J#*+S"(" DB, *H+IF UL 0 8V'9H9>/3, *./0 J#*+S"(" D*+62, 1*+62M$9

• E#$/9$ :• 10-20 mg IV

Diazepam


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'($)*$+/L&5+, *-$• Flow chart.docx

• Standing order.docx

http://localhost/var/www/apps/conversion/tmp/scratch_5///ppt/slides/Standing%20order.docxhttp://localhost/var/www/apps/conversion/tmp/scratch_5///ppt/slides/Standing%20order.docxhttp://localhost/var/www/apps/conversion/tmp/scratch_5///ppt/slides/Flow%20chart.docxhttp://localhost/var/www/apps/conversion/tmp/scratch_5///ppt/slides/Flow%20chart.docx


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• 78Q#2$+*A$@, /:, G+L3IBJ#*5> M! Dipyridil compound

• !"%>S2!1, G4(" D/"*'M$2$+B#4/FI D#` %IF FF*^(=4 _ 7+N' !"8+624(=4P$32L) /, )#, C #@W)78Q#2$+*A$@, /:, G+L3IB(" D#49!JB0 !$*(" D2>/J#8+67(:.(9

• !"5, *-S678Q#2"#C A$7)4#7E0 ! !"*54 D#T># 25$9G, '(" DF>SHPL!4 300°c 565$9 ./0 /" J##C A$ %)(#J#P$'6(" D78Q#*+/ 72IDF!^(=4 _ 7+N'7!I DFF9L M J#/4#H+IFJ##C A$ (" D%'$!7E0 !E0 #2L)2$!$+Z*,/*+MF#O5H6./0

Paraquat


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• J#!#>-9? *$+*4#3$+$%'F((20%) 73"9) 10-15 cc (A$JH0 72"9B"'4G./0

LD50

!" #$%&'( ) !" #$*&+,- & LD50(mg/kg)

Paraquat *+( '';$*.83 20-50


24/38

• Inhalation

: no volatility , spray droplets are too large to beinhaled into the lungs

: occasionally cause of nausea or headaches

• Skin/eye contact

: intact skin is an effective barrier to paraquatabsorption

: irritation, blistering, burns

: severe corneal/conjunctiva inflammation

• Ingestion

: acute toxicity and rapidly fatal systemic poisoning

Route of exposure


25/38

Paraquat Lung

O2 O2.

OH.

Lipidperoxidation

Type I and II pneumocyte cell death & alveolitis

Lung fibrosis

GSH* GSSG**


*GSH : Glutathione **GSSG : Glutathione disulfide


26/38

• H5, )*4# Paraquat 7E0 $.8&50 ' UL 0 8V'9!, *!"F$*$+F$7@"9# 7#I DF)@$* Paraquat (" DE$9G$!(0 F)G5$/(, D'.8@6!"9$(A$JH0 F$7@"9#U2!F9L M/0 '9 73I DF5/%'$!78Q#34-EF)2$+#" C

• P$9J# 24 B,D'O!)&+* @6!"F$*$+($)+611($)7/4#F$H$+2M'#G0 # 7#I DF)@$*^(=4 _ +6%$97%IF)EF) Paraquat

• &U51'!&/)J#8$*&5654 C# 78Q# patch E$'%5>!&U5 • J#+$9(" D+>#&+)F$@31 Ruptured Esophagus

• 8'/(0 F) F$7@"9# (0 F)72"9

Clinical Presentation


27/38

• P$9J# 1-3 ', #GMF!$@6!"F$*$+($) Systemic

• Renal failure Oliguria , Uremia Acute tubular necrosis

• Liver failure Elevated SGOT,SGPT

Hepatocellular damage • Respiratory failure

Pulmonary hemorrhage Pulmonary edema

Pulmonary fibrosis



28/38

• Mild or subacute poisoning:

< 30 mg/kg- Asymptomatic or vomiting and diarrhoea.- Renal and hepatic lesions are minimal or absent.- An initial decrease of the pulmonary diffusion

capacity may be present.

• Complete recovery would be expected.



29/38

• Moderate to severe acute poisoning:

31-50 mg /kg- Immediate: vomiting.- Hours: diarrhea, abdominal pain, mouth and throatulceration.

- One to four days: renal failure, hepatic impairment,hypotension and tachycardia.- One to two weeks: cough, hemoptysis, pleuraleffusion, pulmonary fibrosis with deteriorating lung

function.

• Survival is possible, but in the majority of cases deathoccurs within 2 - 3 weeks from pulmonary failure.



30/38

• Fulminant:

>40 - 55 mg/kg mg/kg- Immediate: vomiting#- Hours to days: diarrhoea, abdominal pain, renal andhepatic failure, gastrointestinal ulceration,

pancreatitis, toxic myocarditis, hypotension, coma,convulsions.

• Death from cardiogenic shock and multi-organ failureoccurs within 1-4 days



31/38

• Biomarker

1.Biomarker of exposure

1.1 Paraquat Spot Test : Urine , Gastric content • 1. #A$8K22$'6H+IFEF)7H5'(" D/L/@$**+673$68+4!$S 10 ]"]" J2M5)J#H5F/(/5F)

• 2. 7G4!/M$) 7BM# sodium hydroxide 5).8@# pH 2L)*'M$ 9 (F$@JB0 sodiumbicarbonate 8+6!$S 2.5 - 5 ]"]" &(#./0 )

• 3. 7G4! sodium dithionite E#$/7(M$85$9B0 F#B$5)J#G, 'F9M$) 7E9M$71$` • 4. #A$H5F/(/5F).82MF)/L*, 13I C #2"E$' Z0 $!"2"#C A$7)4#H+IF2"7E"9'7*4/EW C # &2/)'M$!"3$+$%'F(F9L M J#G, 'F9M$)#, C # &5678Q#*$+9I#9, #*$+'4#4@T, 9O+% H$*J#G, 'F9M$)!"3$+$%'F(F9L M J#%'$!7E0 !E0 #2L) 2"(" D7*4/EW C #F$@@6*5$978Q#2"/A$ JH0 G+'@]C A$F"*%+, C ) O/97@IF@$)G, 'F9M$)5)

1.2 Paraquat level : Plasma , Urine

Laboratory


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H#M'934-'4(9$ +3.+$!$=41/"


33/38

• Supportive treatment

• Primary assessment • Ensure Airway, Breathing and Circulation are intact

• Do not give supplemental oxygen unless serious

hypoxia is present.• Rehydrate the patient to optimise renal clearance of

paraquat.

• Control vomiting

• Ondansetron 8mg by slow IV injection or IV infusion over15 mins

Treatment


34/38


• Skin Decontamination

• GI Decontamination • Gastric lavage

• Prevent absorption

• Fuller’s Earth 150 gm + Water 1 L

• 7.5% Bentonite 100-150 gm

• Activated Charcoal 100-150 gm

• Milk of Magnesia 30 cc q 4-6 hr

• Increase elimination • Hemodialysis / Hemoperfusion

Treatment


35/38


• Modification of tissue toxicities • Modulate inflammatory responses

• Cyclophosphamide 5mg/kg/day IV divided to every 8 hr

• Dexamethazone 10 mg IV q 8 hr

• Chlorpheniramine 4 mg 1 tab po qid

• Prevent oxidation • Vit C (500mg/amp) 6 g/day IV

• Vit E (400 i.u./ tab) 2 tabs qid

• N-acetylcysteine (300mg/amp) 50mg/kg divided to every 8 hr

Treatment


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• J#8K@@>1, #($):L#9? 34-'4(9$ +3.+$!$=41/" #A$ regimen (" D JB0 *$++, *-$34-@$*3$+$%'F(/, )#" C

• Cyclophosphamide 5 mg/kg/day ($)H5F/75IF//A$ &1M)JH0 (>*

8 B, D'O!)

• Dexamethasone 10 mg IV (>* 8 B, D'O!)

• Vitamine C (500 mg/amp) 6 gm/day ($)H5F/75IF//A$

• Vitamine E (400 IU/tab) 2 tabs ', #564 %+, C )

Treatment


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• Standing order for paraquat.docx

'($)*$+/L&5+, *-$
http://localhost/var/www/apps/conversion/tmp/scratch_5///ppt/slides/Standing%20order%20for%20paraquat.docxhttp://localhost/var/www/apps/conversion/tmp/scratch_5///ppt/slides/Standing%20order%20for%20paraquat.docx

organophosphate paraquat

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