Pesticides/Insecticides/Rodenticies


Insecticides

Organophosphates and carbamates are insecticides used extensively in agricultural and commercial applications.

Mechanism

  • Inhibition of cholinesterase → increased activity at all nicotinic and muscarinic receptors.
  • Carbamates bind cholinesterase transiently (minutes to hours).
  • Organophosphates can undergo “aging” → irreversible binding of the insecticide to cholinesterase.

Symptoms/Exam

  • Cholinergic toxidrome
  • Altered mental status (delirium to coma), seizures
  • Muscarinic Effects of Cholinesterase Inhibition:
S Salivation
L Lacrimation
U Urinary incontinence
D Defecation
G GI pain
E Emesis
 
Killer Bees Bradycardia
Bronchorrhea
Bronchospasm
 

Differential

  • Toxicity from nerve agents (VX, Soman, Tabum) or nicotine

Diagnosis

  • Usually apparent from clinical symptoms and a history of exposure
  • Measured RBC cholinesterase or pseudocholinesterase (plasma cholinesterase) levels
    • Reduced in toxicity, but are not available in a timely manner

 

Treatment

  • Immediate surface decontamination, as indicated
  • Supportive therapy
    1. 100% O2
    2. Airway management, w/ gentle suction of secretion.
    3. Use of Succinylcholine for intubation = prolonged paralysis.
  • Benzodizepines or phenobarbital for seizures
  • Antidote = Atropine, used for
    • Hemodyamically unstable bradycardia
    • Excessive secretions (endpoint is drying of airway secretions)
    • Very high doses often needed (>10 mg), titrate to decrease Tracheobronchial secretions.
    • Tachycardia and dilated pupils are NOT contraindication to atropine.
    • Substitute: High dose diphenhydramine
  • Antidote = Pralidoxime (2-PAM)
  • Can potentially reactivate inhibited cholinesterase
  • Indicated in organophosphate poisoning, but is ineffective in after aging has occurred
Treatment for Organophosphate Poisoning:
Decontami-
nation
Protective clothing must be worn to prevent secondary poisoning of health care workers.
Handle and dispose of all clothes as hazardous waste.
Wash patient with soap and water.
Handle and dispose of water runoff as hazardous waste.
Monitoring Cardiac monitor, pulse oximeter, 100% oxygen.
Gastric lavage No proven benefit
Activated charcoal No proven benefit
Urinary alkalinization No proven benefit
Atropine Adult: 1 mg or more IV
Children: 0.01-0.04 mg/kg (but never <0.1 mg) IV.
Repeat every 5 min until tracheobronchial secretions attenuate.
Pralidoxime Adults: 1-2 g
Children: 20-40 mg/kg (up to 1 g), mixed with NS and infused IV over 5 to 10 min.
Continuous infusion often necessary.
Seizures Benzodiazepines.

 

DISPOSITION:

  • Minimal exposure require 6 - 8 hr Observation
  • Recurrence of symptoms can occur due to re-exposure to contaminated clothing, particularly leather.
  • Significant poisonings require ICU monitoring

Herbicides

Herbicides are agents used to kill weeds. In addition to intrinsic toxicity, they may also be packaged with surfactants or solvents with their own toxic effects. The most dangerous are bipyridyl herbicides, namely paraquat and diquat.

Paraquat is especially toxic with lethal with oral doses of 20% solution being only 10-20 ml in an adult & 4-5 ml in children. Both agents are toxic via inhalation, dermal exposure, or ingestion. Due to their caustic properties, ulceration of skin and mucous membranes and GI corrosion can occur.

Paraquat ingestions result in renal, cardiac, & hepatic failure along with progressive pulmonary fibrosis. Due to the latter treatment often includes restriction of supplemental O2. .Decontamination of skin is important to prevent continues absorption.

Early after ingestion, GI decontamination with activated charcoal, fuller's earth, or bentonite may be helpful. Charcoal hemoperfusin may remove paraquat. Because of poor prognosis, especially with paraquat ingestions, admit pt with ingestion for future observation and treatment.

Agent Example Clinical Feature Treatment
Chlorophenoxy 2/4-dichloro-
phenoxyacetic acid
Mucous membrane irritation, pulmonary edema, muscle toxicity, hyperthermia Urine alkalization
Hemodialysis
Glyphosate   Mucous membrane irritation, erosion, multiorgan failure, respiratory distress Observe asymptomatic pt for 6 hr
Urea-substituted Chlorimuron, diuron, fluomenturon, isoproturon Methemoglobinuria Methylene blue

 

Organophosphate Butiphos SLUDGE Same as pesticides
N,N-Dietyl-3-methylbenzamide DEET Seizures Benzodiazepines.

 

Rodenticides

Superwarfarins:
Most home rodenticide products contain a superwarfarin such as brodifacoum.
Symptoms occur 1-2 days following ingestion and last for weeks to months.

Mechanism

  • Superwarfarins act similarly to warfarin by inhibiting production of vitamin K dependent clotting factors (II, VII, IX, X); however, the duration of anticoagulation may extend for weeks.

Symptoms/Exam

  • Symptoms are due to bleeding (brain, GI, vaginal, hematuria, epistaxis etc.).
  • Onset of symptoms is 1-2 days following ingestion.

Diagnosis

  • PT/INR measurement can determine the extent of anticoagualation from superwarfarins.
  • INR > 2 is abnormal

Treatment

  • Vitamin K supplementation for elevated INR (>2).
    • Adults: 20 mg po qd
    • Children: 1 - 5 mg po qd
    • Continue for up to 10 months.
  • Large ingestions may require high doses for prolonged periods of time.
  • Prophylactic vitamin K (prior to elevation of INR) is NOT indicated (duration of action of superwarfarin is much longer than that of vitamin K).
  • Acute bleeding:  Requires FFP, IV Vitamine K, addition of prothrombin complex, recombinant activated factor VII for refractory hemorrhage or Cryoprecipitate to reverse anticoagulation.
Disposition
  1. Admit
    • Massive ingestion
      • Hydroxycoumarin > 0.05 mg
      • Indandione > 5 mg
      • Warfarin 0.5 mg/kg
    • Rapid incr in PT, any significant bleeding, severe incr PT, fall risk
  2. Discharge
    • Pt who is taking warfarin with an unintentional overdose, hemodynamically stable with no evidence of active bleeding, f/u regularly
    • Routine INR monitoring pts on stable warfarin dosing extend q4wk
    • Pediatrician f/u
      • Children with acute unintentional ingestions either in office or by telephone at 48 hrs

 

Rodenticide Toxicity Clinical Effects Treatment
Arsenic Severe Dysphagia, muscle cramps, N/V,
Bloody diarrhea, Cardiovascular collapse,
Altered mental status,
Seizures, and late peripheral neuropathies.
Gastric lavage, activated charcoal, catharsis, chelation therapy using Succimer, dimercaprol, or penicillamine.
Barium carbonate and other soluble forms such as barium chlorides, hydroxides, and sulfides Severe Onset occurs within 1-8 h with N/V/D, abdominal pain, dysrhythmias, respiratory failure, muscular weakness, paresthesias, and paralysis. Gastric lavage with sodium or magnesium sulfate added to lavage solution to convert carbonate to less toxic sulfate; potassium replacement.
Elemental or yellow phosphorus Severe Skin irritation, severe burns, oral burns, abdominal pain, hematemesis, possible "smoking" luminescent vomitus and stool, garlicky odor, direct toxic effects on the myocardium, kidney, peripheral vessels, cardiovascular collapse. Late neurologic depression with multisystem toxicity and hepatorenal syndrome. Gastric lavage with dilute potassium permanganate solution may convert phosphorus to less toxic phosphates; activated charcoal; avoid emesis.
N-3-Pyridylmethyl-N'-p-nitrophenylurea (PNU or Vacor) Severe Within 24 h of ingestion, GI symptoms, perforation, autonomic nervous system dysfunction, insulin-deficient hyperglycemia or diabetic ketoacidosis, dysrhythmias, neuropathies. Nicotinamide (niacinamide) IV or IM is an antidote; lavage for recent ingestions; activated charcoal and insulin for treatment of hyperglycemia and ketoacidosis.
Sodium fluoroacetate (SFA) Severe Nausea, vomiting, apprehension, lactic acidosis, seizures, coma, respiratory depression, cardiac dysrhythmias, and pulmonary edema. Electrocardiographic abnormalities include ST-segment and T-wave changes, tachycardia, premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation. Hyperkalemia and hypocalcemia are common. Activated charcoal, seizure and dysrhythmia control, and supportive care. Experimental regimens include glycerol monoacetate, calcium gluconate, sodium succinate, and ethanol loading. Consultation with a toxicologist is recommended.
Strychnine Severe Restlessness, muscle twitching, painful extensor spasms, opisthotonos, trismus, inability to swallow, and facial grimacing. Medullary paralysis and death can follow. Airway control, quiet environment (minimize sensory stimulation), and activated charcoal.
Avoid lavage (may precipitate seizures). Benzodiazepines, barbiturates, analgesia. Neuromuscular blockage if necessary.
Thallium sulfate Severe Early GI symptoms, then after 2–5 d, painful paresthesias, myalgias, muscle weakness, headache, lethargy, tremors, ataxia, delirium, seizures, and coma. Death from respiratory failure and dysrhythmias. Alopecia after approximately 2 wk. Chronic neurologic sequelae. Supportive care. Multiple doses of activated charcoal or Prussian blue PO (potassium ferric hexaniacinate) interrupt enterohepatic circulation and increase elimination in stool.
Zinc phosphide Severe Immediate nausea, vomiting, epigastric, phosphorous or fishy breath, black vomitus, and GI irritation or ulceration. Myocardial toxicity, shock, and noncardiogenic pulmonary edema; agitation, coma, seizures, hepatorenal injury, metabolic acidosis, hypocalcemia, tetany. Intragastric alkalinization with sodium bicarbonate, dilution with water or milk, activated charcoal, a cathartic, treatment of hypocalcemia, and supportive therapy.
α-Naphthyl-thiourea (ANTU) Moderate Dyspnea, cyanosis, cough, pleuritic chest pain, noncardiogenic pulmonary edema, and pleural effusion. Supportive care; activated charcoal.
Cholecalciferol (vitamin D3) Moderate Hypercalcemia, osteomalacia, and systemic metastatic calcifications. Treat hypercalcemia with IV normal saline, furosemide, steroids, calcitonin, and biphosphates as needed.
Bromethalin Low Muscle tremors, myoclonic jerks, contractions of flexor muscles, ataxia, and focal motor seizures; personality changes, confusion, and coma. Decontamination; benzodiazepines for seizures.
Norbormide or dicarboximide Low Tissue hypoxia and ischemia. Supportive care; decontamination.
Red squill Low Nausea, vomiting, diarrhea, abdominal pain.
Hyperkalemia, atrioventricular block, ventricular irritability with dysrhythmias, and death.
Treat as digoxin toxicity:
Atropine, external pacing, digoxin-specific antibody fragments, activated charcoal

Strychnine

A rodenticide with significant human toxicity, its use in home products has largely been supplanted by the superwarfarins.

Mechanism

  • Inhibits glycine receptors within the spinal cord → uncontrolled muscular contraction

Symptoms/Exam

  • Strychnine poisoning produces rapid onset involuntary muscle contractions, opsithotonus, hyperreflexia, clonus, and trismus. Mental status is not affected.

Diagnosis

  • Specific testing for strychnine is not available.

Treatment

  • Benzodiazepines or barbituates are administered to relieve excessive muscular activity.
  • More severe cases may require intubation and neuromuscular blockade.
Generalized, uncontrolled muscular activity with normal mental status is suggestive of strychnine poisoning.