Insecticides, Herbicides, Rodenticides

1. Insecticides, Herbicides, Rodenticides Chapter 182 Feb. 23, 2006

2. Poisonings • 2001 – 90,000 pesticide exposures reported • Of these, 46, 929 were children under the age of 6 • There were 17 deaths

3. Types of Exposure • Three kinds… • Intentional • Accidental • Occupational • Multiple formulations of the different compounds – always consult Poison Control

4. Insecticides • Toxic to nervous system • Four kinds • Organophosphates • Carbamates • Organochlorines • Pyrethrins

5. Organophosphates • Diazinon, Malathion, Orthene, Parathion and chlorpyrifos have been used as chemical warfare agents since WWII • Sarin, another compound used in the Tokyo subway in 1995

6. Organophosphates • Poisoning usually results in accidental exposure in the home, industrial accidents, agricultural sprayings, and in transport of these chemicals • But also involved in intentional poisonings in homicides

7. Organophosphates • If patient presents with poisoning, clinician should ask about first-aid, prehospital interventions, decontamination, product name, manufacturer, product concentration and formulation, circumstances of exposure, amount , onset of symptoms and patient age and medical history

8. Pathophysiology • Inhibits the enzyme cholinesterase in the nervous system leading to an accumulation of the neurotransmitter acetylcholine in the CNS, the autonomic nervous system and at neuromuscular junctions.

9. Pathophysiology • This accumulation results in overstimulation of the receptors • The initial overstimulation is followed by paralysis of cholinergic synaptic transmission in the CNS and autonomic ganglia • A cholinergic crisis results

10. Aging • Aging describes the permanent irreversible binding of the compound to the cholinesterase • Once aging occurs the enzymatic activity is permanently destroyed • Can take weeks to synthesize new enzyme

11. Clinical Features • CNS symptoms of cholinergic excess include anxiety, restlessness, emotional lability, tremor, HA, dizziness, confusion, delirium, hallucinations and seizures

12. S – Salivation L – Lacrimation U – Urination D – Defecation G – GI Pain E - Emesis D – Defecation U – Urination M – Muscle wkness B – BBB (Killer B’s) E – Emesis L – Lacrimation S - Salivation Mnemonic Heaven

13. Nicotinic Receptors • Overstimulation results in pallor, mydriasis, tachycardia, HTN, muscle cramps and fasiculations, and then weakness and paralysis

14. Special Considerations • Children are at a greater risk of toxicity due to their size and lower baseline levels of cholinesterase activity

15. Diagnosis • Suspicion based on history • Presence of a suggestive toxidrome • Laboratory assays • Testing for specific compounds

16. Diagnosis • Diagnosis can be difficult due to a constellation of clinical findings • Misdiagnoses such as flu or viral syndrome have occurred

17. Diagnosis • Noting a hydrocarbon or garlic odor may help • An initial test dose of atropine that does not result in expected improvement may help in making the diagnosis

18. Diagnosis • Unless 2-Pam (pralidoxime) is given before aging occurs, plasma cholinesterase takes up to 4-6 weeks and RBC acetylcholinesterase as long as 90-120 days to return to baseline

19. Routine Labs • Routine labs are non-diagnostic but may include evidence of pancreatitis, hypo or hyperglycemia, leukocytosis, and liver function abnormalities • CXR may show pulmonary edema in severe cases

20. EKG • Common abnormalities include ventricular dysrhythmias, torsade de pointes, and idioventricular rhythms. Heart blocks and prolongation of QTC interval are common

21. Treatment • ABC’s • Protective clothing must be worn to prevent contamination of health care workers (use neoprene or nitrile gloves instead of latex) • Patient’s clothing must be removed and then disposed of in hazardous waste

22. Treatment • Patient must be washed in copious amounts of soap and water, with possible a second washing of dilute ethanol • Body fluids are contaminated as well • Runoff water must be contained and disposed of in hazardous materials

23. Treatment • Place patient on 100% O2, cardiac monitor and continuous pulse ox • Suction airway as needed for bronchorrhea or emesis • Coma, respiratory failure or seizures may necessitate intubation

24. Treatment • A nondepolarizing agent should be used for intubation, as Succinylcholine is metabolized by cholinesterase. Therefore prolonged paralysis may result

25. Treatment • Hypotension may need fluid boluses • Charcoal is recommended for all ingestions • Protect airway if you lavage, as lavage can be considered in recent or in large ingestions • Hemodialysis has no proven value

26. Treatment • Atropine and pralidoxime are antidotes • Atropine is used to reverse muscarinic and central effects • Large amounts may be needed – the dose is titrated until copious bronchial secretions attentuate • Pupillary dilatation is NOT the endpoint

27. Atropine • Atropine should not be withheld in the face of a tachycardia (heart rate may be the result of hypoxia) • Initial test dose – 1 mg IV in adults, 0.01 to 0.04 mg/kg in children (but never less than 0.1mg)

28. Atropine • Normally that dose should produce antimuscarinic symptoms, but if no response to trial dose, then this is indicative of an organophosphate poisoning

29. 2-Pam • Restores acetylcholinesterase activity by regenerating phosphorylated acetylcholinesterase • Clinically, improves the muscarinic, nicotinic and CNS symptoms

30. 2-Pam • Administer as soon as possible, though is still can be administered 24 to 48 hours after exposure • Can reverse muscle paralysis if given soon enough before aging has occurred

31. 2-Pam • Dose: 1-2 grams for adults and 20 to 40mg/kg – up to 1 gram in kids • This is infused in NS over 5-10 minutes • Can also be given IM • A continuous infusion can be done (500 mg/hr in adults – 5-10 mg/kg/hr for kids) if paralysis does not resolve

32. 2-Pam • Not administered to asymptomatic patients or to patients with known carbamate exposures presenting with minimal symptoms • Response should occur within 10-40 minutes of administration

33. Disposition • Minimal exposure may just be decontamination and observation in ER for 6-8 hours • Do not return clothing and discarded items to patient – DISCARD in hazardous waste

34. Disposition • For significant poisonings – ICU • If toxins are fat soluble, then patient may be symptomatic for weeks • Supportive care will be needed during this time, such as respiratory support • End point of therapy is determined by absence of signs and symptoms

35. Death • Death usually occurs in 24 hours if patient is not treated • Respiratory failure secondary to resp. muscle paralysis, CNS depression or bronchorrhea is usual cause of death

36. Carbamates • Sevin, Baygon, Lannate, Carbaryl, Aldicarb • Cholinesterase inhibitors that are structurally related to organophosphates • Medicinal forms include physostigmine, pyridostigmine and neostigmine

37. Pathophysiology • Transiently and reversibly inhibit cholinesterase • Regeneration of enzyme occurs within minutes to hours, therefore aging does not occur

38. Clinical Features • Symptoms of intoxication are similar to organophosphates, but are of shorter duration • Carbamates do not effective penetrate into CNS, so less central toxicity and no seizures

39. Diagnosis • Cholinesterase levels may return spontaneously to normal after 4-8 hours • Measurement of cholinesterase activity generally is not useful as it will be relatively normal

40. Treatment • Atropine therapy usually not needed for longer than 6-12 hours • Avoid 2-Pam. Since irreversible binding does not occur, it is not needed, and potentially can worsen some carbamate poisonings

41. Organochlorines • DDT is prototype • Most have been restricted or banned in US due to their long half-life and toxicity • Lindane is another common one used to treat head lice and scabies

42. Pathophysiology • CNS stimulant that can be toxic after dermal, inhalation and GI exposure • Toxicity results from repetitive neuronal discharge following the action potential due to a decrease in the sodium channel permeability

43. Pathophysiology • Capable of inducing hepatic enzyme system, so the efficacy of other chemicals and drugs that use this system is reduced

44. Clinical Features • Neurologic symptoms predominate • Mild poisonings present as dizziness, malaise, HA, irritability, delirium, myoclonus and facial paresthesias. Fever is common

45. Clinical Features • Severe poisonings may have seizures, coma, respiratory failure and death • Seizures may occur early, have no prodromal syndromes and are short-lived • Organochlorines are delivered dissolved in hydrocarbon solvents that can cause sedation, coma and pneumonitis

46. Clinical Features • Sensitization of the myocardium to endogenous cathecholamines with cardiac dysrythmias can occur from both the organochlorines and the solvents • Chronic effects from low-level exposure to chlordane include deficits in balance, reaction times and verbal recall

47. Diagnosis • History is important! • Read package label for the chemical involved and the vehicle involved • Differential includes other causes of CNS stimulation and other insecticides • Basic labs are not helpful but organochlorines can be detected in serum and urine by special laboratories

48. Treatment • O2, intubation if needed to treat hypoxia secondary to seizures, aspiration or resp. failure • Benzos for seizure control • Dysrhythmia control may be indicated but avoid atropine and epinephrine as the myocardium is sensitized to endogenous catecholamines

49. Treatment • Removal of clothing and washing skin with soap and water are important • Avoid oils on skin as they promote absorption • Charcoal and possibly gastric lavage in large recent ingestions are indicated • Exchange resin Cholestyramine should be used in symptomatic Chlordecone exposures

50. Disposition • Observed for 6 hours and admitted to hospital if signs of significant toxicity develop or if ingestion involved a hydrocarbon solvent