Anticholinesterase
Insecticides
• Organophosphates
• Carbamates
• Variable toxicity
• Toxicity usually occurs from misuse
of products or improper storage
Mechanism of Action
Inhibition of acetylcholinesterase
Signs of Toxicity
• Muscarinic
• Salivation, lacrimation, urination,
diarrhea, miosis, dyspnea, bradycardia
• Nicotinic
• Muscle fasciculations beginning with
face, generalized tremors, weakness
• CNS
• Respiratory depression, clonic-tonic
seizures
Diagnosing Toxicity
• Clinical signs
• Decreased AChE activity (Blood,
Brain)
• Test dose of atropine
• Chemical analysis for specific
compounds
Treatment of Anti-Esterase
Toxicity
• Atropine sulfate for muscarinic
signs, dose to effect; will not stop
nicotinic signs
• Oximes can reactivate AChE before
aging
• Diazepam or barbiturates for
seizures
Ethylene Glycol
• Major ingredient in normal antifreeze
• Toxicity usually in small animals
• Exposure most common in Spring
and Fall
• Animals often “like” ethylene glycol
Mechanism of Action
• Ethylene glycol acts like ethanol,
producing early signs of
“drunkeness”
• Metabolism to glycolic acid causes
acidosis
• Metabolism to oxalic acid which
combines with calcium to form
insoluble crystals
Signs of Toxicity
• 3 stages of intoxication
• Stage I (30 minutes-3 hours)
• “drunkeness”, ataxia, depression. Often not
observed
• Stage II (12-24 hours)
• Tachypnea, tachycardia (or bradycardia)
• Often not observed
• Stage III (12-72 hours)
• Oliguric renal failure. Prognosis is poor
here.
Diagnosing Toxicity
• Acidosis
• Anion and osmolal gap
• Crystalluria
• Crystals in kidney and urine.
• Clinical sign.
Oxalate Crystals
Granular appearance.
Oxalate Crystals
Treatment of Ethylene
Glycol Toxicity
• Traditional treatment is ethanol and
bicarbonate
• Ethanol is competitive inhibitor of
Alcohol Dehydrogenase (ADH) which is
initial 1st step in EG metabolism. 3hours
• Bicarbonate used to correct acidosis.
Good for CNS signs.
• 4-methylpyrazole and Antizol® are ADH
inhibitors that can replace ethanol
Acetaminophen
• Present in many OTC pain and cold
remedies (Tylenol)
• Metabolized extensively by the liver
by Glucuronidation, sulfation.
• Activated by P450 to reactive
compound detoxified by GSH
• When GSH is depleted, toxicity
occurs
Signs of Toxicity
• Methemoglobinemia, ( brown blood)
Heinz body formation in cats
• Cyanosis, dyspnea.
• Facial and paw edema *
• Anorexia, vomiting
• Humans and dogs develop hepatic
necrosis in overdoses.
Acetaminophen
Facial Edema
Acetaminophen
Hepatic Necrosis
Acetaminophen
Hepatic Necrosis
Treatment of APAP
Toxicity
• GI Decontamination, emesis
,charcoal
• N-acetylcysteine (Mucomyst®) to
replenish and substitute for GSH
• Ascorbic acid used to treat
methemoglobinemia in cats,
methylene blue in other animals
Methylxanthines
• Caffeine, theobromine, theophylline.
• Usually a problem with dogs due to
eating habits.
• Found in chocolate, coffee,
medications
• Unsweetened baking chocolate is
especially toxic; as little as 0.2 oz/kg
may kill a dog
Mechanism of Action
• Antagonist of adenosine receptors;
causes CNS stimulation,
vasoconstriction, and tachycardia
• Prevents Ca++ reuptake
• Inhibits phosphodiesterase
Signs of Toxicity
• GI… Vomiting, diarrhea
• Hyperactivity
• Tachycardia, PVC, hypertension
• Ataxia
• Tremors, seizures
• Coma
Treating Methyl-Xanthine
Toxicity
• Monitor EKG
• Treat tachyarrhytmias with lidocaine
(not in cats) or metoprolol
• Treat seizures with diazepam or
barbiturates
Anticoagulant Rodenticides
• First generation compounds
• Warfarin
• Short-half life (15 hours), low potency,
required multiple feeding.
• Second generation compounds
• Brodifacoum, bromodialone, diphacinone
• Long half-life (15-20 days); high potency (one
feeding)
• 0.25 mg/kg often toxic
Anticoagulants
• Usually a problem in small animals.
• If cat or wild animal eat rat who has been
poisoned. They will be poisoned as well.
• Large animals can develop similar
problems from moldy sweet clover
Mechanism of Action
• Inhibits vitamin K epoxide reductase.
• Results in depletion of vitamin K
dependent clotting factors (II, VII, IX,
X).
Signs of Toxicity
• Delayed onset as clotting factors are
consumed (3-5 days).
• Initial signs are often depression,
anorexia, and anemia.
• Pale mucosa, dyspnea, nosebleeds, and
bloody feces.
• Abdominal pain.
• Hemorrhage and hematoma. (carful when
you give an injection).
Diagnosing Toxicity
• Increased prothrombin (PT) time
• Increased activated partial
thromboplastin time (APTT or PTT)
• Chemical analysis
Treatment of Anti-Coagulant
Toxicity
• Vitamin K1 administration (giving
oral is more effective than injectable
V.K )
• Therapy should be continued for 10-
14 days with warfarin; 21-30 days for
second generation compounds.
• Transfusion.
Strychnine
• Alkaloid used as pesticide to control
gophers, moles, rats, and coyotes
• Controlled in most states
• Still commonly used as a malicious
poison
• All species are sensitive but dogs are
most commonly poisoned.
Mechanism of Action
• Competitive inhibitor of glycine at
postsynaptic neurons
• Glycine NT is inhibitory so result is
disinhibition (stimulation)
Signs of Toxicity
• Initial signs are anxiety and stiffness
• “Grinning” muscle pull back around the teeeth.
• Violent tetanic seizures usually initiated by
sudden noise or light , normal between seizure
• Saw horse stance
• Persistent rigid extensions of all limbs (extensor
muscle are stronger so they dominate).
• Apnea due to rigidity of muscle.
Treating Strychnine
Toxicity
• Control seizures with pentobarbital
(as much as anesthesia level to be
effective) or Methocarbamol
(Robaxin), muscle relaxing.
• Prevent asphyxiation
• May require intubation and
respiratory support.
Metaldehyde
•Slug and snail baits
•Generally 3.5%
metaldehyde
•Ingestion of 1-4 oz of bait
will cause toxicity in
average dog
•Toxicity is most common
in dogs
Mechanism of Action
• Metaldehyde is hydrolyzed to
acetaldehyde by gastric acids
• Further metabolism of acetaldehyde
to acidic products thought to
account to acidosis
• Exact mechanism is unknown
Signs of Toxicity
• Initial signs are anxiety, nystagmus
• Progresses to salivation, vomiting,
ataxia, seizures, hyperthermia
• Profound acidosis.
• “Formaldehyde”-like smell
Treating Metaldehyde
Toxicity
• Control seizures with diazepam or
barbiturates
• GI decontamination
• Treat acidosis with fluids and
bicarbonate
• Treat hyperthermia . Ice packs.
Cholecalciferol
• Vitamin D3
• Used as a rodenticide
and psoriasis
treatment
• Usually sold as a bait
preparation
• Toxicity occurs at
doses above 0.5mg/kg
Mechanism of Action
• Metabolized to 1,25-
dihydroxycholecalciferol
• Increases serum Ca by increasing GI
absorption, decreasing renal
excretion, and stimulating bone
resortpion
Signs of Toxicity
• Vomiting, diarrhea
• Polydipsia, polyuria, radio-opaque
kidneys
• Elevated serum Ca (>11.5 mg/dl),
BUN, and creatinine
• Mineralization of soft tissues.
Tissue Mineralization
Tissue Mineralization
Treating Vit D Toxicity
• IV saline and furosemide (excretion)
• Cortisone (work opposit of PTH )
• Calcitonin immediate reverse
• Low Ca diet and avoid sunlight
• Continue treatment until Ca
stabilizes in normal range (up to 2
weeks).
Lead Toxicosis
• Affects large and small animals;
waterfowl.
• Sources include old paint, motor oil,
grease, batteries, lead shot and
fishing sinkers.
• Toxicity usually results from acute
oral exposures to lead.
Mechanism of Action
• Multiple actions, many based on the
reaction of Pb with –SH groups of
key enzymes and effects on calcium
regulation (important to CNS).
• Lead inhibits delta-aminolevulinic
acid dehydratase and heme
synthetase, both involved in heme
synthesis (blood signs)
Signs of Lead
Poisoning
• Lead causes a mixture of neurologic,
GI, and hematopoietic signs
• Neurologic signs include blindness,
seizures, ataxia, head-pressing,
“roaring”-horses.
• GI signs include anorexia, vomiting,
constipation then diarrhea (often
bloody), colic
Signs of Lead Poisoning
• Hematopoietic signs include
regenerative anemia with nucleated
RBCs,
• Basophilic stippling of RBCs (dogs).
• Increased zinc protoporphyrin
(dogs),
• elevated plasma porphyrins (cattle)
might florence if hold under black
light.
Diagnosing Lead Poisoning
• Clinical signs
• Whole blood lead levels of 0.6part
per million (ppm) or greater
• Decreased serum d-ALAD activity,
increased urine d-ALA
Treating Lead Toxicity
• GI decontamination using a cathartic
or surgical removal of large objects
• Chelation therapy with Ca-EDTA,
DMSA (Succimer) (more effective but
not approved for vet use),
• d-Penicillamine
• Thiamine may improve symptoms in
cattle
• Control seizures with barbiturates.
Oxalate Containing Plants
• Many members of the Areaceae family of
plants contain preformed Ca-oxalate
crystals that cause mechanical injury
(needle shape ) to the mouth resulting in
pain, salivation, vomiting, dyspnea
(mostly cats)
• Dieffenbachia, Caladium, Philodendron,
Calla lily
Oxalate Containing
Plants
• Plants containing soluble oxalates
produce hypocalcemia and renal injury
due to precipitation of Ca-oxalate crystals
• Examples are Rhubarb, Beets, Lamb’s
quarters
• Detoxification with limewater (calcium
hydroxide) and supportive treatment of
hypocalcemia and nephrosis.
Nitrates
• Sources are plants and fertilizer
• Ruminants are most susceptible due
to conversion of nitrate to nitrite in
rumen
• Nitrite oxidizes hemoglobin to
methemoglobin
Signs of Nitrate Toxicity
• Methemoglobinemia, “chocolate”
brown blood
• Brownish cast to membranes
• Cyanosis, dyspnea
• Tachycardia
Treating Nitrate
Toxicity
• Convert methemoglobin to
oxyhemoglobin with methylene blue
(except cats) (ascorbic acid) .
• Avoid overdosing as methylene blue
can cause methemoglobinemia
• Avoid stressing animals
Cyanide
• Released from cyanogenic glycosides
found in some plants (wild cherry and
other Prunus spp., Sudan and Johnson
grass, arrowgrass) ruminant most
susceptible.
• Acts by inhibiting cytochrome oxidase
which inhibits oxidative phosphorylation
Signs of Cyanide Poisoning
• Initial signs are salivation and
tachypnea
• Progress to dyspnea, weakness,
seizures, tachycardia
• Death in 20-120 minutes
• *Cherry-red blood that clots slowly*
(over oxygenated)
Treating Cyanide
Toxicity
• Cyanide binds tightly to Fe(III)
• Convert hemoglobin to
methemoglobin with sodium nitrite
• Promote detoxification of cyanide
with sodium thiosulfate.
Other Sources of
Information
• American Board of Veterinary
Toxicolgy
– www.abvt.org
• ExToxNet
– http://ace.orst.edu/info/extoxnet/