Rodenticide Poisoning

1. Rodenticide Poisoning

2. DEFINITION • Rodenticides are a category of pest controlchemicals intended to kill rodents • Rodents are difficult to kill with poisons because of their feeding habits. • They will eat a small bit of something and wait, and if they don't get sick, they continue. • An effective rodenticide must be tasteless and odorless in lethal concentrations, and have a delayed effect.

3. Types • Anticoagulants • Metal phosphides • Agents causing Hypercalcemia • Others

4. Anticoagulants • Anticoagulants act by effectively blockingthe vitamin K cycle, resulting in inability to produce essential blood-clotting factors -mainly coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor) and X ( Stuart Factor). They can be • chronic (death occurs after 1 - 2 weeks post ingestion of the lethal dose, rarely sooner), • single-dose (second generation) or • multiple-dose (first generation) rodenticides,

5. First generation agents • 4-hydroxycoumarin type: warfarin, coumatetralyl • indandione type: pindone, They generally require higher concentrations (usually between 0.005 and 0.1%) and consecutive intake over days in order to accumulate the lethal dose, and less toxic than second generation agents. Second generation Agents They are derivatives of 4-hydroxycoumarin: brodifacoum, bromadiolone and 4-hydroxy-1-benzothiin-2-one,

6. Pathophysiology • Metabolic disruption of Vit K pathway • Massive toxic doses of 4-hydroxycoumarin or other anticoagulants cause damage to capillaries, increasing their permeability, causing diffuse internal bleedings (haemorrhage). These effects are gradual, developing over several days. • In the final phase of the intoxication, the exhausted rodent collapses in hypovolemic circulatory shock or severe anemia and dies calmly.

7. Second generation agents are far more toxic than first generation. They are generally applied in lower concentrations in baits (usually in order 0.001 - 0.005%), are lethal after a single ingestion of baitand are also effective against strains of rodents that became resistant to first generation anticoagulants; thus, the second generation anticoagulants are sometimes referred to as superwarfarins

8. Toxicity in humans • They are absorbed through GIT and damaged skin • They cause clinical effects by affecting Vit K metabolism • Repeated dosages are necessary to cause symptoms • Signs and symptoms occur early in persons having underlying coagulatiom abnormalities

9. Modes of Exposure: • Accidental exposure, • Suicide attempts with the substance, • Munchausen's syndrome, • Exposure of factory workers, and • Exposure from smoking marijuanaor "crack" cocaine. • Homicidal

10. Vitamin K Metabolism

11. Vitamin K1 (also called phylloquinone or phytonadione), acquired from the diet or from medical administration, is reduced to its active form (hydroquinone) by one of two reductases. • One of the reductases is not sensitive to warfarin and requires NAD(P)H; the other reductase is partially sensitive to warfarin. • Active vitamin K is required for carboxylation of coagulation factors II, VII, IX, and X (as well as protein C, protein S, protein Z, and certain bone proteins).

12. A carboxylase enzyme performs the carboxylation step using oxygen and carbon dioxide, and in the process, active vitamin K becomes oxidized to an inactive form called vitamin K2,3- epoxide. • Epoxide reductase reduces vitamin K2,3- epoxide back to vitamin K1, which permits the regeneration of active vitamin K. • Epoxide reductase is inhibited by warfarin or warfarin-like agents, including superwarfarins such as brodifacoum.

13. Brodifacoum is the most commonly used superwarfarin • Brodifacoum is lipophilic. It is 100 times as potent as warfarinand has a very long half life. • carboxylation reaction requires a new vitamin K1 molecule,because vitamin K1 cannot regenerate • For thesereasons, the treatment of brodifacoum poisoning requires largedoses of vitamin K1, ranging from 50 to 800 mg per day, administeredfor an extended period.

14. Signs and Symptoms • I Generation: Symptoms are likely to occur after 5-7 days of repeated exposure. Initially there is back and stomach pain, followed later by nose and gum bleeding, bruising and haemorrhage. All symptoms are associated with haemorrhage either into body cavities or tissues. Haemorrhagic shock may occur terminally. • II Generation: Poisoned victims may show evidence of excessive blood loss. The lengthened prothrombin time is usually apparent within 24 hours and reaches a maximum of 36-72 hours after exposure.

15. Laboratory • The prothrombin time should be determined. There is a lengthening of this time at doses below those necessary to cause haemorrhage. • The extended clotting time may indicate the extent of the poisoning, but may also be affected by an intrinsic deficiency of clotting factors in the patient's blood.

16. Phosphides • aluminium phosphide (fumigant only) • calcium phosphide (fumigant only) • Magnesium Phosphide (fumigant only) • zinc phosphide (in baits)

17. Properties • Metal phosphides have been used as a means of killing rodents and are considered single-dose fast acting rodenticides (death occurs commonly within 1-3 days after single bait ingestion). • Zinc phosphide is typically added to rodent baits in amount of around 0.75-2%. • The baits have strong, pungent garlic-like odor characteristic for phosphine liberated by hydrolysis. The odor attracts (or, at least, does not repulse) rodents, but has repulsive effect on other mammals

18. Phosphine poisoning can also happen when: • People live or work near grain warehouses where phosphide is used. • People work in the holds of boats carrying cargo treated with phosphides • Welders use acetylene containing phosphine as an impurity

19. Pathophysiology • It is readily absorbed by the gastrointestinal tract and may be absorbed by inhalation in dust form or as phosphine gas. • Although it is not absorbed through the unbroken skin, it may be absorbed through cuts or abrasions. • Its toxicity is related to its liberation of phosphine on decomposition, following absorption which is an inhibitor of mitochondrial cytochrome oxidase. • Organs that may be affected include the heart, lung, liver and kidney.

20. Signs and Symptoms • Latent period of about 60 minutes following ingestion and the appearance of symptoms. • Earliest symptoms are usually nausea, abdominal pain, chest tightness, excitement and agitation and a feeling of chilliness, of being "cold all over". Vomiting is constant. • Later symptoms may include shock, dyspnoea, thirst, oliguria and kidney failure, convulsions and coma. Purpura and asymptomatic thrombocytopenia have been observed. • Early deaths may occur from pulmonary oedema. • The majority of fatal cases die after 30 hours as a result of cardiac damage

21. Identification • The patient's breath may smell of phosphine (garlic odour). • Serum zinc levels will be raised and the urine will contain reducing substances, which may be hypophosphite, dissolved phosphine or due to zinc glycosuria. • On stomach aspiration, a black fluid with a pungent smell of phosphine is typical of ingestion of this compound.

22. Treatment • Treatment is mainly symptomatic. • Vomiting should be induced immediately followed by gastric lavage with 2-4 litres of water. • Using non-oily purgatives to avoid absorption of zinc phosphide particles. • Correction of fluid loss and electrolyte disturbances.

23. Suggested treatments • Use of 0.5 gm of copper sulfate (as a 1% aqueous solution) which has the additional theoretical benefit of forming insoluble copper phosphide. • Gastric lavage with a 1 in 1000 potassium permanganate solution, which has been suggested as a means of oxidizing the phosphide.

24. Arsenic and arsenic containing chemicals • Arsenic trioxide, arsenic pentoxide • Calcium arsenate, copper aceto arsenate • Arsenic trioxide dimethylarsinic acid • Arsenic pentoxidelead arsenate • Calcium arsenate methylarsonic acid • Copper acetoarsenite sodium arsenite

25. Common Uses • In farming and forestry to kill weeds, ants, termites, insects, rats, and mice; • To protect wood from decay; • In the microelectronics industry; • For worming animals

26. Ayurvedic kushtay is an indian aphrodisiac containing arsenic • Copper smelting and industrial manufacture of glass, pigments, pesticides, wood preservatives, and silicon chips.

27. Mechanism Of Action • Arsenic is irritant to skin, lungs and gut. • It interferes with life-processes in cells in many parts of the body. • Combine with suplhydryl group of mitochondrial enzymes • uncoupling mitochondrial oxidative phosphorilation • Fatal dose:0.2 gms arsenic trioxide

28. Arsenic compounds • Exposure may also occur via ingestion of herbal remedies or in industry.. • Topical - Irritant to skin and mucous membranes. Systemic arsenic poisoning may occur after substantial exposure. • Ingestion – • Very small ingestions are likely to cause only mild gastro- intestinal upset. • Substantial ingestions: - Rapid onset (within 1-2 hours) of burning of the mouth and throat, hypersalivation, dysphagia, nausea, vomiting, abdominal pain and diarrhoea. • In severe cases gastrointestinal haemorrhage, cardiovascular collapse, renal failure, seizures, encephalopathy and rhabdomyolysis may occur.

29. Other features: facial and peripheral oedema, ventricular arrhythmias (notably torsade de pointes), ECG abnormalities (QT interval prolongation, T-wave changes), muscle cramps. • Investigations may show anaemia, leucopenia, thrombocytopenia or evidence of intravascular haemolysis. • Death may occur from cardiorespiratory or hepatorenal failure. The adult respiratory distress syndrome (ARDS) has been reported.

30. Monitor breathing, pulse, blood pressure, fluid and electrolyte balance, and liver and kidney function. • Supportive care, including oxygen and ventilation. • If the patient has symptoms, an antidote should be given as soon as possible. Dimercaprol can be given by deep intramuscular injection. • Dose: • Days 1 and 2: 2.5-3 mg/kg of body weight every 4 hours.  • Day 3: 3 mg/kg of body weight every 6 hours.  • Days 4-10: 3 mg/kg of body weight every 12 hours until symptoms of poisoning are gone

31. Other agents • Red squill • The botanical preparation of red squill, containing a cardiac glycoside as an active ingredient, was used as a rodenticide for many years. In theory, rodents ingest the product, and because they are incapable of vomiting, develop glycoside intoxication and pulmonary edema. Because humans are capable of vomiting, red squill was considered harmless, even to children. This product is not used much today because of its limited effectiveness as a rodenticide. • Strychnine • Strychnine is a plant alkaloid that, in the past, was used widely as a rodenticide. This agent is not used much today. Consider strychnine toxicity if an individual presents with generalized seizure like appearance but without loss of consciousness or extensor posturing with risus sardonicus. Strychnine is also used as an adulterant in some street drugs sold as lysergic acid diethylamide (LSD).

32. Thallium • Many case reports document thallium intoxications in third world countries where this product is still used as a rodenticide. Consider thallium toxicity when treating a patient with a neuropathy and hair loss. • Cholecalciferol-containing rodenticides • They produce hypercalcemia and require extremely large doses to create a toxicologic situation in humans. • Yellow phosphorus • Yellow phosphorous was once used as a rat poison. Symptoms include a garlic odor, oral burns, vomiting, and phosphorescent smoking feces.

33. Barium-containing rodenticides • Interest in these rodenticides is purely academic. Drive potassium intracellularly, may lead to hypotonia • Yellow phosphorus • Yellow phosphorous was once used as a rat or roach poison. Symptoms include a garlic odor, oral burns, vomiting, and phosphorescent smoking feces

34. Blood tests for arsenic, thallium, mercury, and lead may be useful but are usually considerably time consuming • X-Ray: Abdominal plain film x-ray may be helpful because these metals are radio-opaque.

35. Emergency Department Care • Patients who present or develop renal failure may require hemodialysis. • Patients with severe respiratory compromise from zinc phosphide, arsenic, or barium may require endotracheal intubation for ventilatory support. • Severe hemolysis from phosphine gas (released from zinc phosphide) may require exchange transfusion of RBCs.

36. GI evacuation is rarely useful; however, consider it for exceptional cases in which a huge overdose is suspected and in which the patient presents early to an emergency facility. • Give all patients with rodenticide overdose activated charcoal as soon as possible to prevent further absorption of ingested toxins. With anticoagulant overdoses, perform a careful physical examination to look for any sign of bleeding.

37. Other medical therapy depends on identification of specific substances involved. • If a heavy metal is suspected, institute chelation therapy • Phosphides have no specific antidotal therapy that has been of any consistent advantage. Only supportive care is available. • If a coagulopathy is documented, institution of vitamin K therapy is suggested. If frank bleeding occurs, the administration of fresh frozen plasma and concentrated clotting factors, may be warranted. Since all of the vitamin K–dependent clotting factors may be affected, the hemolytic factors C and S may be affected early and might cause the presentation to be one of acute thrombosis rather than anticoagulation.

38. THANK YOU