Transcript Rodenticide Poisoning

Rodenticide Poisoning
DEFINITION
 Rodenticides are a category of pest control
chemicals 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.
Types
 Anticoagulants
 Metal phosphides
 Agents causing Hypercalcemia
 Others
Anticoagulants
 Anticoagulants act by effectively blocking the
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,
 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,
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.
 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 bait and 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
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
Modes of Exposure:
 Accidental exposure,
 Suicide attempts with the substance,
 Munchausen's syndrome,
 Exposure of factory workers, and
 Exposure from smoking marijuana or "crack"
cocaine.
 Homicidal
Vitamin K Metabolism
 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).
 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 warfarinlike agents, including superwarfarins such as
brodifacoum.
 Brodifacoum is the most commonly used superwarfarin
 Brodifacoum is lipophilic. It is 100 times as potent as
warfarin and has a very long half life.
 carboxylation reaction requires a new vitamin K1
molecule, because vitamin K1 cannot regenerate
 For these reasons, the treatment of brodifacoum
poisoning requires large doses of vitamin K1, ranging
from 50 to 800 mg per day, administered for an extended
period.
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 3672 hours after exposure.
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.
Phosphides
 aluminium phosphide (fumigant only)
 calcium phosphide (fumigant only)
 Magnesium Phosphide (fumigant only)
 zinc phosphide (in baits)
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
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
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.
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
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.
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.
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.
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
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
 Ayurvedic kushtay is an indian
aphrodisiac containing arsenic
 Copper smelting and industrial
manufacture of glass, pigments,
pesticides, wood preservatives, and
silicon chips.
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
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 gastrointestinal 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.
 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.
 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
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).
 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.
 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
 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.
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.
 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.
 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.