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Paraquat Toxicity


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Sept 2008 - My elected 3rd Year Prestation; reviews paraquat toxicity in dogs

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Paraquat Toxicity

  1. 1. ParaquatToxicity<br />Katie Krimetz<br />Western University of Health Sciences<br />CVM DVM 2010<br />September 8, 2008<br />
  2. 2. Headlines<br />July 2003 – Laurelhurst Park, Portland, OR(11)<br />August 2004 – Willamette Park, Portland, OR(11)<br />Images:<br />
  3. 3. Why can’t we fix this?How do I recognize/Differentiate clinical signs?<br />
  4. 4. 1,1’-dimethyl-4,4’-bipyridylium<br />Uses<br />Non-selective contact herbicide<br />Allowed no-till farming<br />Sources<br />Restricted Use<br />Pesticide Commercial<br /> Applicator License(13)<br />Today products have <0.44% paraquat(4)<br />Older products with 50% paraquat<br /> can be found(4)<br />Protective Measures<br />Emetics, Bitters, Odor, Color<br />Image:<br />
  5. 5. Toxicity<br />Exposure(4,5)<br />Ingestion<br />Absorption at brush border<br />Primarily absorbed in the jejunum<br />Skin – blisters, burns, nail damage<br />Eyes – stinging sensation, inflammation, corneal ulcer<br />Inhalation – nausea, headache, epistaxis<br />Toxic Levels(4)<br />Oral<br />LD50 – dogs: unknown <br /> cats: 30-50 mg/kg<br />I.V.<br />LD50 – dogs: 7.48 mg/kg <br /> cats: ??<br />Image:<br />
  6. 6. Mechanism of Toxicity<br />Paraquat is taken up actively and selectively<br />Polyamine transporter(4,15)<br />Required for maintenance of high metabolic activity levels<br />Cells depend on them for growth, renewal and metabolism<br />Type I and II Alveolar cells most commonly affected by toxicity(4)<br />Damage mostly confined to areas with high accumulations of paraquat<br />
  7. 7. Mechanism of Toxicity<br />Absorbed portion accumulates in tissues<br />Cyclic oxidation-reduction rxns free radicals<br />Oxygen and hydroxyl<br />Free radicals overwhelm cellular defense<br />Cause damage to tissues, esp membrane lipids<br />Image:<br />
  8. 8. Clinical Signs & Pathophysiology<br />GI upset and vomiting present at all levels of toxicity<br />Remember: emetics<br /> added to formulation<br />“Early” Signs:<br />Compromised renal function<br />Mild hypertension<br />Pulmonary alveolar damage<br />Edema<br />Hemorrhage<br />Inevitable: Death by respiratory failure <br />Image: 2007 MS ClipArt<br />
  9. 9. Clinical Signs & Pathophysiology<br />“Moderate” dose (>20-30mg/kg but <40-50mg/kg)(5)<br />Immediately: vomiting<br />Hours: diarrhea, abd pain, throat/mouth ulcerations<br />1-4 d: renal failure, hepatic fxn impaired, tachycardia<br />1-2 wk: cough, hemoptysis, pleural effusion, pulmonary fibrosis<br />“High” dose (>40-50 mg/kg) (Systemic poisoning)(5)<br />Immediately: vomiting<br />Hours-days: Acute pulmonary edema, renal failure, hepatocellular damage, intra/extrahepatic bile duct and gall bladder necrosis, adrenal failure<br />
  10. 10. Diagnosis<br />Histologic examination of tissues (lungs!)(4,5,6)<br />Spectrophotometry, gas/liquid chromatography(4,5)<br />HPLC Fluorescense(5)<br />Radioimmunoassay(4)<br />Dithionite reaction/<br /> dithionite spot test(4,5)<br />Solid Phase Extraction(5)<br />Elevated Serum Lipase(4)<br />Radiographs?(4)<br />Image:<br />
  11. 11. [Realistic] Diagnosis<br />Histologic examination of tissues<br />Dithionite reaction/dithionite spot test<br />Elevated Serum Lipase<br />Radiographs<br />CAUTION – Misdiagnoses/Complications<br />Ingestion of unknown food<br />Vomiting may be only clinical sign<br />Serum lipase – ddx: pancreatitis<br />Radiographs – usually appreciate abnormalities in late stage of toxicity<br />Images:<br />
  12. 12. Treatment<br />EARLY! Within hours in order to be effective<br />Adsorbent(4)<br />Fullers Earth, Activated Charcoal (rodent - add Mg citrate!)(4)<br />ER? Kitty litter<br />Caution with esophageal tubes<br />Remove it(4)<br />Emesis – but then control<br />Gastric lavage<br />Fluids/Forced Diuresis(4,5)<br />Analgesics – opiates best(5)<br />NO OXYGEN!(4,5)<br />Nitrous Oxide improves gas exchange<br />
  13. 13. Treatment in Research<br />Taurine @CRI, followed by hemodialysis(8)<br />Antioxidants(4,5)<br />N-acetyl cysteine(5)<br />Desferriozamine(5)<br />Propanolol(5)<br />Collagen synthesis<br />inhibitor(4)<br />Radiotherapy(5)<br />Lung Transplant(5)<br />
  14. 14. Prognosis<br />Prognosis – Grave <br />Depends on circumstance of poisoning:<br />Good circumstances: inhalation, skin exposure, dilute formula<br />Bad circumstances: ingestion<br />Image:<br />
  15. 15. Prognosis<br />Indicators of a better prognosis:<br /><ul><li>Young Age
  16. 16. Recent Last meal/size
  17. 17. Accidental Ingestion
  18. 18. Lack of lesions
  19. 19. Lack of:</li></ul>Renal, hepatic, pancreatic, or respiratory failure<br />Image:<br />
  20. 20. But there IS hope!!<br />Image:<br />Different Formulation<br />Alginate Additive  GramoxoneInteon(7,14)<br />First used in human medicine for acid reflux<br />Gelling action extends paraquat retention in stomach<br />0.79% absorbed/hour<br />Other Possibilities…<br />A higher concentration (10g/L) would be better(7)<br />Require mixing prior to use?(2,17)<br />Image: 2007 MS ClipArt<br />
  21. 21. Resources<br />AG PICoboSCP. Paraquat: Get the Facts at the Paraquat Information Center. 2008;, 2008.<br />Betman ND. New Formulation of Paraquat: A Step in the Wrong Direction? Public Library of Science. 2008.<br />Broyhill I. Personal Safety Procedures. 2006;<br />Cope RB, BCs, BVSc, PhD. Helping animals exposed to the herbicide paraquat. Veterinary Medicine. 2004;September 2004:755-762.<br />CTL S. Paraquat Poisoning a practical guide to diagnosis, first aid and hospital treatment2008.<br />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.<br />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.<br />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.<br />Paula. Path Gallery. In: Paraquat Toxicity l, dog, 20x, ed. Picasa Web Albums.Vol 2007.<br />Prevention CfDCa. Facts about Paraquat. 2006;, 2008.<br />Robben J. Test on dead dog points to paraquat. Portland Tribune. 7/25/2003, 2003.<br />Spradley P. Pesticide Commercial Applicator License for Applying Restricted Use Pesticides. 2006;<br />Syngenta. GramoxoneInteon Label2008.<br />Wallace HM, Fraser AV, and Hughes A. A Perspective of Polyamine Metabolism. Biochemical Journal. 2003(376):1-14.<br />Wiesbrook M. Recent Happenings with Paraquat. May 2006 Newsletter. 2006.<br />Wilks MS, al e. Improvement in Survival After Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka. PLoS Medicine. 2008;5(2).<br />
  22. 22. Questions&Discussion<br />