1 2 3 4 5 6 Pesticide are also classified based on hazard level. - PDF document

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Pesticide are also classified based on hazard level. The hazard classification may help in assessing the risk/severity of a poisoning involving pesticides. IN MALAYSIA, label for pesticides are using different colour coding for each class. Black indicate with a skull – indicate the extremely hazardous class. Basis of classification The classification distinguishes between the more and the less hazardous forms of each pesticide in that it is based on the toxicity of the technical compound and on its formulations. The hazard referred to in this Recommendation is the acute risk to health. The classification is based primarily on the acute oral and dermal toxicity to the rat since these determinations are standard procedures in toxicology 7

Here are some examples – pesticide labels 8

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In those suffering less severe poisoning, death is still likely from progressive pulmonary fibrosis. 14

Common strength of paraquat in Malaysia ~ 13% Most of cases referred in our centre patient have no corrosive effect. 15

(A) ‘Paraquat tongue’ early lesion, within 24 h after ingestion. (B) ‘Paraquat tongue’ late lesion, 2 weeks after ingestion with extensive ulceration 16

Chest radiograph demonstrating diffuse alveolar shadowing of a patient 7 days after ingestion of paraquat 17

Sodium dithionite urine test (Urine Paraquat test) This test should be undertaken as soon after ingestion as can be arranged, but not more than 24 hours following exposure, and may be conducted on either urine or gastric aspirate. If initially negative, a urine qualitative test should again be repeated at 6 hours post ‐ ingestion. While this test can confirm an exposure, and a series of two negative tests indicate that a significant exposure is unlikely, potential toxicity cannot entirely excluded.[2][3] (TOXINZ) 18

Gastric lavage may be useful when performed within one hour of ingestion, No antidote is accepted as proven effective by an adequate randomized controlled trial.[ 3] However, there are some that have theoretical potential to reverse toxicity including N ‐ acetylcysteine. Due to its relative safety it seems reasonable to initiate treatment with N ‐ acetylcysteine. While pulse treatment with steroid and immunosuppressant has been advocated,[4] research has not demonstrated efficacy.[5] 19

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The infusion can be maintained indefinitely in patients whose clinical features and plasma levels indicate they are at high risk of toxicity OR meaning you can give until plasma creatinine levels, liver function tests, and chest x-ray films have returned to normal. 21

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Absorb well through all routes – ingestion, inhalation, dermal, conjuctiva 26

Mechanism of Action Cholinesterase inhibiting pesticides ‐ preventing hydrolysis and inactivation of acetylcholine Poisoning results in accumulation of acetylcholine (ACh) at (nerve / neuromuscular juctions) muscarinic and nicotinic cholinergic receptors = cause excessive stimulation (syndrome of cholinergic excess) – secretion Most organophosphate are indirect inhibitor – required partial metabolism within body to become active – delayed symptoms The active form is able to combine with cholinesterase – inactivating the enzyme OP – the complex – irreversible – aging – de novo synthesis of AChE is required to replenish its supply Carbamate – the complex ‐ reversible – aging cannot occur – the complex will hydrolyzed spontanously – reactivate the enzyme – duration of symptoms less than 24hours TOXICOKINETICS Extremely well absorbed from lungs, gastrointestinal, skin, mucous membranes and conjuctiva following inhalation, ingestion or topical contact. The presence of broken skin & dermatitis and higher environmental temperatures enhances cutaneous absorption. Inadequate skin & respiratory protection during pesticide applications may be responsible 27

for OP poisoning. Most of OP are lipophilic. Distributed and stored in adipose tissue, liver, kidney. Can cause cholinergic crisis recur when redistribution of Op from adipose tissue 2 main characteristics that distinguish carbamate from OP: 1) Carbamate do not easily across into CNS, thus the effect at CNS are limited 2) Carbamate – cholinesterase bond does not “age” , thus it is reversible, symptoms resolve earlier 27

Delayed onset – some OP need to be metabolized into active /toxic metabolite. Clinical findings in OP poisoning are typically cause by excessive stimulation of muscarinic and nicotinic receptors by Ach at: 1) AUTONOMIC CENTRAL NERVOUS SYSTEM – Parasympathetic (miosis, lacrimation, salivation, bradycardia, bronchorrhea, urinary incontinence) and Sympathetic (Mydriasis, Tachycardia, Hypertension, Urinary retention, Hyperglycemia, Bronchodilation, Ketosis) 2) SKELETAL NEUROMUSCULAR JUNCTIONS – Muscle weakness, fasciculation, paralysis 28

There is generally poor correlation between cholinesterase levels and severity of clinical effects (Brown SS, 1989a). 29

Antidote Endpoint Atropinization must be maintained until the clinical manifestations of muscarinic stimulation have resolved.[9] In severe cases treatment may need to continue for days. Atropinization must be maintained until all of the absorbed organophosphate has been metabolized. Therapy must be withdrawn slowly to prevent recurrence or rebounding of symptoms or signs, often in the form of increased secretions. Therefore with apparent clinical improvement, dose rates should be gradually decreased at a rate dictated by response, while avoiding atropine toxicity. This tapering process may require up to 24 hours, at least in the extreme case where atropine was required for several days.[23] This is most likely with poisonings from highly lipophilic compounds. 30

In most cases – patient may have muscarinic symptoms – so treatment with atropine is a must. In severe cases – patient will have nicotinic symptoms –pralidoxime is indicated. 31

ALTERNATE ADULT: An alternate initial dose for adults is 1 to 2 grams diluted in 100 mL of 0.9% sodium chloride infused over 15 to 30 minutes. Repeat initial bolus dose in 1 hour and then every 3 to 8 hours if muscle weakness or fasciculations persist (continuous infusion preferred). In patients with serious cholinergic intoxication, a continuous infusion of 500 mg/hr should be considered. In patients with acute lung injury, a 5% solution may be administered by a slow IV injection over at least 5 minutes (Howland, 2006). Intravenous dosing is preferred; however, intramuscular administration may be considered using a 1 ‐ g vial of pralidoxime reconstituted with 3 mL of sterile water for injection or 0.9% sodium chloride for injection, producing a solution containing 300 mg/mL (Howland, 2011). 32

Type I – older – less effective , but safe, easily degrade Type II – newer – more effective, stable & toxic Common pyrethroids include permethrin which is available to treat head and body lice. 33

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As compared to other pesticide – pyrethroids in aerosol form may potentially cause inhalation/ocular/dermal exposure 36

Activated charcoal is not routinely recommended as most exposures are trivial. With large ingestions patients are at risk for abrupt onset of seizures or mental status depression. 37

Unregistered rodenticide : • Tetramethylenedisulfotetram ine (TETS) = banned rodenticide • Sodium monofluoroacetic acid (SMFA) • Fluoroacetamide 38

Zinc Phosphide •Its toxicity is secondary to the release of phosphine gas on contact with moisture or moist air. • Phosphine is a very strong reducing agent and is highly reactive . • Inhibition of cellular respiration ( cytochrome oxidase ). 39

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Answer: PatientA 41

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Anticoagulant • Anticoagulant rodenticides are vitamin K antagonists. • When vitamin K cannot be regenerated, clotting factors cannot be activated and a coagulopathy results involving both the extrinsic and intrinsic pathways 45

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1. MICROMEDEXSOLUTION. [Database on the internet]. Colorado: Thomson Reuters (Healthcare); c 2015; [cited 2015 Oct 26]. Available from: http://www.micromedexsolutions.com. 2. Patocka J, et al. Toxic potential of superwarfarin: brodifacoum. Mil. Med. Sci. Lett. 2013,82(1), p.32-8. 3. Gunja N, et al. Management of intentional superwarfarin poisoning with long-term vitamin K and brodifacoum levels. Clinical Toxicology (2011), 49, 385–90. 47

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