paraquat toxicity
DESCRIPTION
Sept 2008 - My elected 3rd Year Prestation; reviews paraquat toxicity in dogsTRANSCRIPT
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PARAQUAT TOXICITY
Katie Krimetz
Western University of Health SciencesCVM DVM 2010
September 8, 2008
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Headlines
July 2003 – Laurelhurst Park, Portland, OR(11)
August 2004 – Willamette Park, Portland, OR(11)
Images: http://www.aspca.org/site/DocServer/vetm0904_755-762.pdf?docID=5581&AddInterest=1101
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WHY CAN’T WE FIX THIS?
HOW DO I RECOGNIZE/DIFFERENTIATE CLINICAL SIGNS?
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1,1’-dimethyl-4,4’-bipyridylium Uses
Non-selective contact herbicide Allowed no-till farming
Sources Restricted Use
Pesticide CommercialApplicator License(13)
Today products have <0.44% paraquat(4)
Older products with 50% paraquatcan be found(4)
Protective Measures Emetics, Bitters, Odor, Color
Image: http://agri.astate.edu/weeds/select_images.html
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Toxicity Exposure(4,5)
Ingestion Absorption at brush border Primarily absorbed in the jejunum
Skin – blisters, burns, nail damage Eyes – stinging sensation, inflammation, corneal ulcer Inhalation – nausea, headache, epistaxis
Toxic Levels(4)
Oral LD50 – dogs: unknown
cats: 30-50 mg/kg I.V.
LD50 – dogs: 7.48 mg/kg cats: ??
Image: http://www.broyhill.com/images/interior/safety.gif
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Mechanism of Toxicity
Paraquat is taken up actively and selectively Polyamine transporter(4,15)
Required for maintenance of high metabolic activity levels
Cells depend on them for growth, renewal and metabolism
Type I and II Alveolar cells most commonly affected by toxicity(4)
Damage mostly confined to areas with high accumulations of paraquat
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Mechanism of Toxicity Absorbed portion accumulates in tissues Cyclic oxidation-reduction rxns free
radicals Oxygen and hydroxyl
Free radicals overwhelm cellular defense Cause damage to tissues, esp membrane
lipids
Image: http://www.syngenta.com/pqmedguide/downloads/paraquat_booklet.pdf
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Clinical Signs & Pathophysiology
GI upset and vomiting present at all levels of toxicity Remember: emetics
added to formulation “Early” Signs:
Compromised renal function Mild hypertension Pulmonary alveolar damage
Edema Hemorrhage
Inevitable: Death by respiratory failure
Image: 2007 MS ClipArt
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Clinical Signs & Pathophysiology
“Moderate” dose (>20-30mg/kg but <40-50mg/kg)(5)
Immediately: vomiting Hours: diarrhea, abd pain, throat/mouth ulcerations 1-4 d: renal failure, hepatic fxn impaired,
tachycardia 1-2 wk: cough, hemoptysis, pleural effusion,
pulmonary fibrosis
“High” dose (>40-50 mg/kg) (Systemic poisoning) (5)
Immediately: vomiting Hours-days: Acute pulmonary edema, renal failure,
hepatocellular damage, intra/extrahepatic bile duct and gall bladder necrosis, adrenal failure
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Diagnosis
Histologic examination of tissues (lungs!)(4,5,6)
Spectrophotometry, gas/liquid chromatography(4,5)
HPLC Fluorescense(5)
Radioimmunoassay(4)
Dithionite reaction/dithionite spot test(4,5)
Solid Phase Extraction(5)
Elevated Serum Lipase(4)
Radiographs?(4)Image: http://picasaweb.google.com/aluapa/PathGallery/photo#5102345173274680146
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[Realistic] Diagnosis Histologic examination of tissues Dithionite reaction/dithionite spot
test Elevated Serum Lipase Radiographs
CAUTION – Misdiagnoses/Complications Ingestion of unknown food Vomiting may be only clinical sign Serum lipase – ddx: pancreatitis Radiographs – usually appreciate
abnormalities in late stage of toxicity
Images: http://www.achilles-online.com
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Treatment EARLY! Within hours in order to be effective
Adsorbent(4)
Fullers Earth, Activated Charcoal (rodent - add Mg citrate!) (4)
ER? Kitty litter Caution with esophageal tubes
Remove it(4)
Emesis – but then control Gastric lavage
Fluids/Forced Diuresis(4,5)
Analgesics – opiates best(5)
NO OXYGEN!(4,5)
Nitrous Oxide improves gas exchange
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Treatment in Research
Taurine @CRI, followed by hemodialysis(8)
Antioxidants(4,5)
N-acetyl cysteine(5)
Desferriozamine(5)
Propanolol(5)
Collagen synthesisinhibitor(4)
Radiotherapy(5)
Lung Transplant(5)
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Prognosis
Prognosis – Grave
Depends on circumstance of poisoning:
Good circumstances: inhalation, skin exposure, dilute formula
Bad circumstances: ingestion
Image: http://www.syngenta.com/pqmedguide/downloads/paraquat_booklet.pdf
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Prognosis
Indicators of a better prognosis:
•Young Age•Recent Last meal/size•Accidental Ingestion
•Lack of lesions
•Lack of:Renal, hepatic, pancreatic,
or respiratory failureImage: http://farm1.static.flickr.com/66/187783004_db3362fd81.jpg?v=0
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But there IS hope!!
Different Formulation Alginate Additive Gramoxone Inteon(7,14)
First used in human medicine for acid reflux Gelling action extends paraquat retention in stomach 0.79% absorbed/hour
Other Possibilities… A higher concentration
(10g/L) would be better(7)
Require mixing prior to use?(2,17)
Image: www.syngentacropprotection-us.com
Image: 2007 MS ClipArt
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Resources1. AG PICoboSCP. Paraquat: Get the Facts at the Paraquat Information Center. 2008; http://www.paraquat.com/, 2008.
2. Betman ND. New Formulation of Paraquat: A Step in the Wrong Direction? Public Library of Science. 2008.
3. Broyhill I. Personal Safety Procedures. 2006; http://www.broyhill.com/images/interior/safety.gif.
4. Cope RB, BCs, BVSc, PhD. Helping animals exposed to the herbicide paraquat. Veterinary Medicine. 2004;September 2004:755-762. http://www.aspca.org/site/DocServer/vetm0904_755-762.pdf?docID=5581&AddInterest=1101.
5. CTL S. Paraquat Poisoning a practical guide to diagnosis, first aid and hospital treatment2008.
6. Hampson EC, Pond SM. Ultrastructure of canine lung during the proliferative phase of paraquat toxicity. Br J Exp Pathol. Feb 1988;69(1):57-68.
7. Heylings JR, Farnworth MJ, Swain CM, Clapp MJ, Elliott BM. Identification of an alginate-based formulation of paraquat to reduce the exposure of the herbicide following oral ingestion. Toxicology. Nov 20 2007;241(1-2):1-10.
8. Izumi K, Nagata R, Motoya T, et al. Preventive effect of taurine against acute paraquat intoxication in beagles. Jpn J Pharmacol. Jun 1989;50(2):229-233.
9. Paula. Path Gallery. In: Paraquat Toxicity l, dog, 20x, ed. Picasa Web Albums. Vol 2007.
10. Prevention CfDCa. Facts about Paraquat. 2006; http://www.bt.cdc.gov/agent/paraquat/basics/facts.asp, 2008.
11. Robben J. Test on dead dog points to paraquat. Portland Tribune. 7/25/2003, 2003.
12. Spradley P. Pesticide Commercial Applicator License for Applying Restricted Use Pesticides. 2006; http://www.aragriculture.org/pesticides/training/commlicense.htm.
13. Syngenta. Gramoxone Inteon Label2008.
14. Wallace HM, Fraser AV, and Hughes A. A Perspective of Polyamine Metabolism. Biochemical Journal. 2003(376):1-14.
15. Wiesbrook M. Recent Happenings with Paraquat. May 2006 Newsletter. 2006. http://web.extension.uiuc.edu/ipr/i4147_829.html#2.
16. Wilks MS, al e. Improvement in Survival After Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka. PLoS Medicine. 2008;5(2).
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QUESTIONS&
DISCUSSION