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Toxicology

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Pam Boutilier

on 9 June 2014

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Transcript of Toxicology

Nicotine
Toxicosis
Phenoxy Derivatives of Fatty Acids
(2,4-D)
Toxicology
MOLLUSCICIDES
HERBICIDES
FUNGICIDES
Meth-aldehyde Toxicosis
INSECTICIDES
Organo-
phosphates
Chlorinated
Hydrocarbons
(Organochlorines)
Carbamates
Pyrethrins and Pyrethroids
Rotenone
Toxicosis
D-Limonene
Toxicosis
RODENTICIDES
Anti-
coagulant
Rodenticides
Amitraz
Toxicosis
DEET
(Diethyltoluamide)
Toxicosis
Napthalene
Toxicosis

Ivermectin
Toxicosis
Chole-
calciferol
Bromethalin
Rodenticide
Strychnine
(Zn3P2) Zinc Phosphide


Fluoroacetate
(Compound
1080)

Dipyridyl
Herbicides
(Paraquat & Diquat)
Pentachloro-phenol
(PCP)
Pesticides:
HOUSEHOLD
Ethylene
Glycol (Antifreeze)
Poisoning
Propylene
Glycol Toxicosis
Alcohols
(Ethanol and Methanol)
Phenolic Compounds
Detergents
Toxicosis
Bleaches
Toxicosis
Xylitol
Toxicosis
Methyl-xanthine
(Chocolate)
Toxicosis

Non-Toxic Household Chemicals
FEED/WATER:
Non-Protein
Nitrogen
Ionophore Toxicosis
Water Deprivation/
Sodium Ion Toxicosis
Nitrate and Nitrite Poisoning
Cyanide
Poisoning
Soluble Oxalate Poisoning

Toxic Principles in Plants
Toxic GaseS:
Ammonia
(NH3)
Hydrogen Sulfide
(H2S)
Carbon Monoxide
(CO)
Nitrogen Oxide
(NO2)
(N2O4)
Sulfur Oxide
(SO2)
(SO3)
INDUSTRIAL:
Petroleum Products Toxicosis
Fluoride
Toxicosis
Nitrate and Nitrite
Poisoning
Cyanide
Poisoning
Soluble Oxalate POisoning
METALS/
MINERALS:

Lead (Pb)
Toxicosis
Zinc (Zn)
Toxicosis

Inorganic Arsenic Toxicosis
Organic Arsenic Toxicosis
Iron (Fe) Toxicosis
Copper (Cu) Toxicosis
(Acute and Chronic)
Molybdenum
(Mb) Toxicosis
Selenium (Se) Toxicosis
PLANT RELATED:
Zootoxins:
Frogs
Snakes
ILLICIT DRUGs:
Amphet-amines
Cocaine
Marijuana
USES/Sources:
Names contain 'phosphate', 'phos', 'phoro' or sometimes 'thione'
chlorpyrifos (Dursban)
coumaphos (Co-Ral)
diazinon (Diazinon)
fenthion (Bayte, Tiguvon)
malathion (Cythion)
methyl parathion(Penncap-M)
temephos (Abate)
Properties:
Most persist in the environment for 2-4 wks
Which is far less than the Chlorinated hydrocarbons that preceded OPs
Some can last longer
Poorly soluble in water but soluble in organic solvents and in fats/oils (somewhat lipophilic)
Can penetrate intact skin, waxy coatings of leaves and fruits
Factors Affecting Toxicity:
Toxicity decreases (degredation) out in the environment
Subject to 'storage activation' (increased potency over time when stored in sealed container)
Technical grades more toxic (heat isomeration, impurities)
Inorganic solvents, oils, etc can enhance toxicity
Various drug-drug interactions:
Malation+Coumaphos show synergism
Malathion+Parathion show antagonism
Other muscle relaxants or neuromuscular blocking drugs will worsen signs
Other similar pesticides (ie. Pyrethrins)
Enzyme inducers have variable effect
Toxicokinetics:
Absorbed from the GIT, skin and mucous membranes or by inhalation
No accumulation in a particular tissue
Most need enzymatic activation ("Lethal synthesis") in the liver
Bind to esterases, metabolized by other liver enzymes
Continued exposure can lead to tolerance due to:
Enzyme induction
Functional adaptation to decreased esterases
Adaptation of ACh receptors to excessive amounts of ACh (receptor downregulation)
Mechanism of action:
Irreversible inhibition of cholinesterases
Increase ACh at all cholinergic sites
Muscarinic receptors are most sensitive
Then ganglionic stimulation, neuromuscular stimulation and CNS stimulation
Last, ganglionic blockade, neuromuscular blockade, and CNS depression
The cause of death in high exposure is respiratory failure
Myopathy (hemorrhage/necrosis of muscle in acutely poisoned animals from elevated ACh)
Some are teratogenic in chickens (Diazinon, parathion, dichlorvos)
Impurities may suppress the immune system
Clinical signs:
Acute toxicity
Signs of muscarinic stimulation: DUMBELS (Diarrhea, Urination, Miosis, Bronchoconstriction, Emesis, Lacrimation, Salivation)
Signs of nicotinic stimulation: Muscle fasciculation, tremors, twitching, spasm, hypertonicity, stiff gait
CNS signs: Anxiety, restlessness, hyperactivity, may proceed to tonic-clonic seizures (not in ruminants)
LATER: Nicotinic blockade causing paralysis, CNS depression, coma, dyspenea and death (resp. failure)

Delayed toxicity
Peripheral neurotoxicity can occur if survive acute poisoning (variable)
Signs are muscle weakness, ataxia, rear limb paralysis that progresses.
Other problems can develop - myopathy causing lameness, weight loss, secondary infections
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions if acute death
Few nonspecific lesions such as pulmonary edema and congestion, cyanosis, hemorrhages, congestion and edema of various organs (including brain), necrosis in skeletal muscle.
In delayed neurotoxicity there is degeneration and demyelination of peripheral and spinal motor neurons
Pancreatitis has been reportedly found in some dogs with the more lipophilic compounds

OP can be detected in stomach or rumen contents, in hair/skin with dermal exposure
Usually do not test liver/kidney because metabolism is rapid
With Chlorpyrifos may find residues in fat
Acetylcholinesterase activity level can be measured
Usually in blood - which correlates well to brain cholinesterase activity
Refrigerate and assess ASAP to preserve activity.
Usually <50% activity is 'suspicious' and <25% activity is diagnostic
History of recent exposure, clinical signs, lesions, laboratory diagnosis
Response to specific therapy (atropine response test)
Administer Atropine 0.02mg/kg
If full mydriasis, significant increase in HR or dry mouth within 15 minutes then most likely NOT OP toxicity
Other intoxications
Pyrethrins and pyrethroids
Tremorgenic mycotoxins
Amitraz toxicosis
Blue-green algae
Muscarinic mushrooms
Diphenhydramine (Benadryl) **Controversial** - has been suggested to antagonize nicotinic effects in small animals
1-4mg/kg IM, PO q8h (SA)
Supportive care as needed
Oxygen, Fluids, address acidosis, vitamins
There is no specific treatment for neurotoxic effects such as degeneration and demyelination
Atropine sulfate (specific physiologic antagonist)
0.2 mg/kg Small animals/horses
0.5 mg/kg Food/large Animals
Give 1/4 dose IV then rest IM or SC
Repeat with decreasing doses q3-6h based on clinical signs
Neuromuscular blockers, muscle relaxants, phenothiazines, aminoglycosides, opioids and other drugs that depress respiration are contraindicated
2-PAM chloride (pralidoxime, Protopam)
25-50mg/kg 10% solution IM or slow IV (SA), 20% IV drip (LA)
Repeat treatment q12h if improvement is seen
Discontinue if no response after 3-4 doses (May not be effective against some OPs)
Not effective if 'aging' has occurred
If they are alive prognosis is better
Depends on dose and how long it's been since exposure
If clinical signs are already present it may depend on finances
Overall mild to moderate signs are treatable
USES/Sources:
Generally similar to organophosphates
Names contain 'Carb'
carbaryl (Sevin)
aldricarb (Temik)
bendiocarb (Ficam)
carbofuran (Furadan, Curateer)
methiocarb (Mesurol)
propoxur (Baygon, Sendran)
methomyl (Golden Malrin)
Properties:
Young animals more sensitive (discussed further in toxicokinetics)
Toxicity:
Do not undergo storage activation like OPs
Toxicokinetics:
Do not require enzymatic activation
More toxic in young animals
More toxic to animals that are deficient in liver enzymes
Metabolize very rapidly
Mechanism of action:
Reversible
inhibition of Acetylcholinesterase
AChE can hydrolize carbamates but at a slower rate than it does ACh
Toxicosis occurs when carbamylation >> hydrolysis of carbamate
Results in too much ACh (thus clinical signs same as for OPs)
Specific effects of large doses of carbaryl may be by another mechanism:
Chickens: Leg paralysis
Swine: Muscular degeneration and
necrosis, cerebral edema
Clinical signs:
Similar to organophosphates but usually less severe and/or shorter duration
Earlier onset than OPs
Tres Pasitos "Three Steps"
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
Prognosis:
Same as for OPs
Similar to OPs
Acetylcholinesterase levels:
Blood samples should be undiluted, refrigerated immediately, analyzed ASAP (using rapid method)
Because binding is reversible 'reactivation' of ACh can occur during transit (giving false negative result)
Detection of drug residues
May not be detectable in tissues, blood or secretions because of rapid metabolism
Generally based on history, clinical signs, lesions (or absence of lesions)
Response to atropine therapy
As for OP toxicity
Generally good if treatment started soon after onset of clinical signs
Because of faster onset the most extreme dose exposures may die too quickly to reach you
Animals with low exposure may survive without treatment (if signs are not severe)
OTHER TREATMENT:
As for organophosphates
USES/Sources:
Diphenyl aliphatics (DDT, methoxychlor)
Aryl hydrocarbons (Lindane)
Cyclodienes (aldrin, toxaphene)

Commonly used from the 1950's through the 1970's
as insecticides and ectoparaciticides.
Methoxychlor was used in dogs, cats and horses.
(Banned from use in the US in 2003)
Lindane was used in dogs, cattle, horses, swine, sheep and goats (Licensed as a 'second-line' pharmaceutical for lice in US)
Exposure:
Ingestion of contaminated feeds, sprayed foliage or pesticide containers
May be absorbed through the skin, MMs, or inhaled if applied topically
Properties:
Highly lipophilic and soluble in oils and organic solvents (insoluble in water)
Very persistent in the environment because they resist chemical or microbial decomposition (there are exceptions if they are protected by a layer of soil)
Residues may appear naturally in animal tissues due to environmental contamination (bioaccumulation in food chains)
Toxicity:
Generally have low toxicity to mammals
All animals are susceptible but CATS are the most sensitive
Toxicokinetics:
After absorption (oral, skin, MMs, inhalation) the insticide may be bound to serum lipoproteins
Distributed to body tissues (mainly fat, then brain and fetus)
Metabolized by liver microsomal enzymes (enzyme inducers)
Metabolites of diphenyl aliphatics and cyclodienes are more toxic
The half life is very long (may be several weeks)
Fat is the main storage tissue
Excreted in bile (enterohepatic recycling), feces, urine and milk
Mechanism of action:
Diphenyl aliphatics interfere with sodium channels in nerve membranes causing CNS stimulation and seizures
Lindane may inhibit GABA binding
Cyclodienes stimulate the CNS by an unknown mechanism
Clinical signs:
Mainly CNS stimulation including salivation, nausea, vomiting, apprehension, tremors, hyperthermia, incoordination, intermittent clonic-tonic seizures and opisthotonos
Also abnormal postures and walking backward in cattle
Birds show depression, abnormal postures, apparent blindness and death
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
Carcasses may be bruised, lacerated and dirty from convulsions
Congestion and edema may be found in several organs
Chemical analysis
Confirms acute toxicosis if the insecticide is in blood, liver or brain at appropriate PPM
Brain concentrations are better correlated with toxicosis than fat concentrations
Not correlated with severity of clinical signs
Samples should be packaged separately to avoid contamination
History of exposure
Clinical signs (esp. convulsive seizures)
Neuromuscular signs
Few lesions
Chemical analysis of tissues
Swine:
Water deprivation (Salt toxicity)
Pseudorabies
Dogs/Cats:
Strychnine, fluroroacetate, lead, OP, metaldehyde
Rabies
Cattle
OP, lead, urea,
Nervous forms of coccidiosis, infectious thromboembolic meningoencephalitis
Polioencephalomalacia (PEM), ketosis
Decontamination:
Emetics, gastric lavage, activated charcoal, mineral oil and saline cathartics
Bathing in soap/water for dermal exposure
Symptomatic treatment:
Diazepam or barbituates to control CNS stimulation/seizures
Chloral hydrate in large animals
Respiratory assistance/Oxygen
No specific antidote
Guarded to Good
acetylcholinesterase
I'm
Free!
acetylcholinesterase
Atropine Sulfate
As for OPs

2-PAM is not reliably effective against Carbamates
Reversible binding of other carbamates reduces benefit
Contraindicated with Carbaryl
(Sevin) as it can potentially increase the carbamylation process!!
OP
2PAM
OP
Carbamate
acetylcholinesterase
OP
2PAM
USES/Sources:
Flea and tick control in dogs and cats
Sprays, dips and shampoos against fleas, ticks, lice, mosquitoes, flies and gnats
Dairy and farm insecticide
Home insecticide

Sources of exposure:
Excessive use of sprays/dips
Inappropriate species application
(esp. using canine products on cats)
Inhalation in closed places
Accidental ingestion of concentrated pesticide
Properties:
Pyrethrins are extracts of pyrethrum flowers
Crysanthemum cinerariifolium
Sometimes advertised as 'Natural'
Pyrethrins are esters
Pyrethrin I and II, Cinerin I and II, Jasmolin I and II
Pyrethrin content is low in the USA
Pyrethroids are synthetic, chemically related compounds
Type 1 pyrethroids do not contain an alpha-cyano moiety
Allwethrin, bifenthrin, permethrin, phenothrin, remethrin, sumithrin, tefluthrin, tetramethrin
Type 2 pyrethroids contain an alpha-cyano moiety
Cyfluthrin, cyhalothrin, cypermethrin, deltamein, fenvalerate, flumethrin, fluvalinate, tralomethrin
Very unstable in air and light
Toxicity:
Only acute (usually mild)
No subacute or chronic toxicity
Piperonyl butoxide or MGK-264 may be added as a synergist
Inhibit pyrethrin metabolism by insects
Not supposed to have as much effect in mammals, however an EPA report stated
"There appears to be a greater risk of moderate or major symptoms among those exposed to products containing pyrethrins and piperonyl butoxide than those exposed to pyrethrins alone."
Low toxicity to mammals
Dogs, cats and large animals can be poisoned
Very toxic to fish (and some birds)
Toxicokinetics:
Pyrethrins are lipid soluble
Absorption is oral, dermal, or by inhalation
Very rapidly inactivated by plasma and liver esterases and liver oxidases
Also rapidly metabolized in the intestinal tract
Conjugated metabolites are excreted in urine
No residual effect
Mechanism of action:
Pyrethrins and pyrethroids delay closure of sodium ion channels in the axonal membrane of the insect "knockdown effect"
May inhibit ATPase leading to repetitive firing
Type 2 pyrethroids (containing an alpha-cyano moiety) interfere with binding of GABA and glutamic acid
Allergic reactions can be seen in animals (including humans)
Clinical signs:
Some dogs may show "Acute Paralysis" due to paresthesia caused by topical application
Salivation, vomiting, diarrhea, hyperexcitability
Generalized muscle tremors, depression, blindness (reversible), ataxia, seizures, dyspnea, prostration and death
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
Low tissue levels
Difficult to detect
Best specimens for detection are liver and brain
Tissue levels are not well correlated with severity of clinical signs
History of exposure, clinical signs, ruling out other diseases
Other neurotoxicants:
Strychnine, methaldehyde, fluoroacetate, caffeine, theobromine, amphetamine, cocaine, tremorgenic mycotoxins, organophosphate, carbamate and organochlorine insecticides.
Acute death from unrelated causes
Occult cardiomyopathy, neoplasia, etc
Symptomatic treatment
Wash the skin with soap and water!
Activated charcoal NOT typically used
Diazepam or pentobarbital as anticonvulsants
Methocarbamol for tremors
Phenothiazines (acepromazine, chlorpromazine)are contraindicated
Monitor and control temperature!
Severe hyperthermia from tremors
Overcorrection and hypothermia can prolong clinical signs and alter Na-channel kinetics
No specific antidotes.
Generally excellent
USES/Sources:
Used as a piscicide
Used for ear mites in dogs, cats and rabbits
General pesticide (used on cranberries)
Also used combined with other insecticides
Properties:
Factors affecting Toxicity:
Formulation
Emulsified concentrate is highly toxic (DANGER)
Other formulations slightly toxic (CAUTION)
Route of administration
Inhalation is more toxic than ingestion
Species
Low toxicity for mammals
Pigs, birds and cats are sensitive (chickens resistant)
Extremely toxic to fish and cold-blooded animals
Toxicokinetics:
Oral absorption is poor, increased by fats and oils
Absorbed more by inhalation
Metabolized in the liver by hydroxylation to toxic metabolites and by demethylation to nontoxic metabolites
Eliminated within 24hrs mainly in feces
Mechanism of action:
Affects cellular respiration
Inhibits the oxidation of nicotinamide adenine dinucleotide dehydrogenase (NADH) to NAD
Resulting in blocking the oxidation by NAD of substrates such as glutamate and pyruvate
Clinical signs:
Acute
Local irritation including conjunctivitis, congestion and dermatitis
Ingestion causes signs of irritation of the GI mucosa and vomiting in dogs and cats
Inhalation of high doses causes respiratory stimulation followed by respiratory depression, convulsions and death
Chronic
Liver and kidney damage
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
Fatty changes in the liver and kidney with chronic exposure
Parkinsonian changes in rat models with chronic IV administration
Chemical analysis
Vomitus, blood, urine or feces
Hypoglycemia may be present
History, clinical signs, laboratory diagnosis
If investigating a fish poisoning ask if there have been any DFW officials or indiginous New Guinea fisherman around recently.
Ingestion of other irritating substances
Severe signs unlikely to be encountered normally (ie large amounts inhaled, IV administration) in mammals
Detoxification
Supportive treatment
Diazepam or barbituates for seizures
(Phenothiazines contraindicated)
Dextrose IV for hypoglycemia
No specific antidote
Excellent (for mammals)
USES/Sources:
Used for control of lice, fleas, ticks
Usually shampoos
Also a food fragrant (flavoring agent)
More recently popular as essential oils

Properties:
Citrus oil extract (from citrus peel)
Monocyclic terpene
Toxicity:
Toxic to all life stages of the flea
Primarily as a desiccant
Dogs and cats are susceptible
Cats more sensitive than dogs
Potentiated by piperonyl butoxide and other enzyme inhibitors.
May be combined with other essential oils such as linalool
Toxicokinetics:
Lipid soluble
Readily absorbed through GI and skin
Wide distribution in body
Metabolized by the liver
Metabolites excreted in urine
Mechanism of action:
Unknown
May be by central and peripheral vasodilation due to a neuronal mechanism
Clinical signs:
Ataxia, weakness, recumbence, paralysis, CNS depression, hypothermia and hypotension.
Smell like citrus
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
No specific tests are available
History
Usually easy to determine based on exposure history and scent
Decontamination:
Shampoo with mild dishwashing liquid
Monitor temperature (esp. hypothermia)
Other supportive care as needed
No specific antidote
Excellent in sublethal toxicosis which usually is resolved in 6-12 hours
Worse if skin reaction (e.g necrotizing dermatitis, etc) - rare
USES/Sources:
Contaminated feed with nicotine sulfate as plant insecticide
Ingestion of excessive amounts of tobacco leaves, cigarettes or cigars
Ingestion of nicotine patches or gum
Properties:
An alkaloid from the dried leaves of
Nicotiana tabacum
plant (2-8%)
Caustic
Toxicity:
Highly toxic
LD50 (oral) for dogs 9.2mg/kg
Toxicokinetics:
Absorbed well by inhalation and from intact skin
Absorbed poorly following ingestion
Distributed all over the body
Metabolized in the liver
Excreted in bile and urine
Mechanism of action:
Ganglionic and neuromuscular stimulation at small doses
Ganglionic and neuromuscular blockade at high doses
Stimulation of the CNS followed by depression
Cause of death is respiratory failure
Stalks of the tobacco plant have a teratogenic effect to sows
Nicotiana glauca has anabasine which is teratogenic to cows
Clinical signs:
Excitement, rapid respiration, salivation, vomiting, diarrhea, muscle twitching, hypotension, convulsions, clonic seizures, depression, collapse and death from respiratory failure
The course of signs is very rapid (minutes)
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
May be signs of anoxia
Odor of nicotine in stomach contents (crude nicotine smells like an old cigar)
Urine, gastric contents, kidney, liver and blood can be tested for nicotine.
History, clinical signs, no lesions, nicotine odor
Elevated nicotine levels in urine, blood, liver and kidney
At low doses (and early in high doses) may resemble anticholinesterase (OPs, Carbamates)
Late stages and high dose similar to other CNS depressants
Diazepam or barbituates for seizures
Fluid therapy for hypotension
Artificial respiration with oxygen in severe cases
Removal of the source
Gastric lavage with diluted potassium permanganate, tannic acid or tincture of iodine, or activated charcoal
Washing the skin with water and soap in dermal exposure
Mecamylamine as a ganglionic blocker only can have some benefits in early cases
Atropine for parasympathetic effects
Poor with large doses
USES/Sources:
Used in flea and tick collars (Preventic), and topical liquid for generalized demodicosis (Mitaban) in dogs
Miticide/insecticide in swine (Point-guard, Taktic) and cattle (Taktic)
Contraindicated in cats and horses
Plant insecticide

Exposure through ingestion of dip or accidental ingestion of collar
Dermal absorption after skin exposure
Properties:
A formamidine insecticide
Mild irritant
Concentrate is flammable
Toxicity:
Acute toxicity
Acute oral LD50 is 100-250mg/kg for dogs
Subacute toxicity
Causes sedation in some dogs at 20mg/kg
Meperidine or sympathomimetic amines increase toxicity
Stress increases toxicity
Debilitated, geriatric or toy breeds possibly more susceptible
Toxicokinetics:
Readily absorbed orally
Also absorbed by inhalation and skin
Distributed throughout the body including the CNS
Rapidly metabolized by the liver and excreted in urine
Mechanism of action:
Alpha-2 adrenergic agonist in the CNS
Alpha-1 and Alpha-2 adrenergic agonist in the ANS
Weak Monoamine Oxidase (MAO) inhibitor
Causes cardiovascular collapse and respiratory failure
Clinical signs:
Bradycardia, ataxia, CNS depression, hypothermia, mydriasis, anorexia, vomiting, diarrhea, urination, vocalization and possibly seizures.
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
Hepatomegaly
Chemical analysis
Liver, kidney, skin, brain, lungs, adipose tissue or spleen
Hyperglycemia (due to inhibition of insulin)
History, clinical signs and laboratory diagnosis
Other toxicants
Cholinesterase inhibitors (OP, Carbamates)
Pyrethrins.
Decontamination
Washing the skin with soap/water
Emetics, activated charcoal, cathartics
Removal of the collar (endoscopy) if ingested
Supportive care
Fluid therapy
Alpha-2 adrenergic antagonists
Yohimbine
Short acting
Atipamezole (50 mcg/kg IM)
Fewer cardiorespiratory effects than yohimbine
Good
USES/Sources:
Insect repellant (Off, Deep Woods Off, Cutters)
Has been combined with fenvalerate (pyrethroid) as a repellant and insecticide for dogs and cats
Not found commonly in current pet products in USA
Fly Repella in Australia
Properties:
Characteristic odor
May damage synthetic fibers or plastics
Toxicity:
Acute oral LD50 in rats is 2g/kg
Acute dermal LD50 in rabbits is 3g/kg
Subacute oral toxicity in rats/dogs
300mg/kg daily for 90 days did not cause gross or microscopic lesions
Subacute dermal toxicity in dogs
300mg/kg daily for 90 days caused mild irritation
Dogs and cats are susceptible but cats may be more sensitive
Young animals are more sensitive
CNS depressants may increase toxicity
Toxicokinetics:
Absorbed from the skin and GIT
7.9-12.8% absorbed from skin in dogs
Increases dermal absorption of fenvalerate (pyrethrin)
Metabolized in the liver
Excreted in the urine
Mechanism of action:
Unknown
May cause irritation of the skin and MMs
Clinical signs:
Salivation, vomiting, anorexia, tremors, excitation, ataxia and seizures, hypotension and bradycardia
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
Chemical analysis:
Specimens are stomach contents, urine, blood, skin and vitreous humor
Also can be detected in bile, kidney
20ppm is considered diagnostic
Urine concentration >1ppm or tissue concentration >10ppm 'supportive'
History, clinical signs, chemical analysis
Other toxins:
Metaldehyde, strychnine, lead, ivermectin, organochorines, anticholinesterases, mycotoxins, etc.
Other neurologic (nontoxic) diseases
Symptomatic treatment
Decontamination
Gastric lavage
Activated charcoal
Saline cathartics (not magnesium)
Bathing in soap and water for dermal exposure
No specific antidote
Usually recover with treatment if sublethal exposure with appropriate treatment (24-72 hrs)
USES/Sources:
Ingestion of mothballs
Napthalene vs. Paradichlorobenzene (organochlorine)
Properties:
Derived from the distillation of coal tar or petroleum hydrocarbons
Volatile (sublimates at room temperature)
Irritant
Toxicity:
>400mg/kg LD50 in dogs
Cats are more sensitive than dogs
Though dogs more likely to ingest
One mothball can weigh 2.7-4g
Of ~99% Napthalene
Toxicokinetics:
Absorbed orally, by inhalation and from intact skin
Oils increase skin absorption
Mechanism of action:
Irritation
Oxidation products cause hemolytic anemia and methemoglobinemia
Clinical signs:
Salivation, vomiting, diarrhea, characteristic breath odor, methemoglobinemia (chocolate brown MMs), hemolytic anemia, seizures, cataracts (in neonates)
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
Methemoglobinemia
Liver damage, renal damage
Hemolysis, Heinz bodies, methemoglobinemia
History, clinical signs (esp. methemoglobinemia), odor of mothballs
Very characteristic presentation
Other causes of oxidative RBC damage
Acetaminophen
Onions
Nitrates
Less commonly other drugs (benzocaine)
Other causes of cyanosis, hemolysis
Decontamination
Emetics, activated charcoal, saline cathartics
IV fluids
Sodium bicarbonate to reduce precipitation of HGB in the kidney
Other supportive care as needed
Blood transfusion, respiratory support
Ascorbic acid (20mg/kg) to treat the methemoglobinemia
Nonenzymatic conversion of MethHgB to HgB
Relatively slow process
Methylene Blue 1% 1.5mg/kg (controversial)
Reasonable if treated promptly
USES/Sources:
Endectocide for cattle, swine and sheep (Ivomec) and horses (Eqvalan)
Similar products: selamectin, moxidectin (
Prevention of heartworm disease in dogs and cats (Heartguard)
Exposure
Typically overdose
Use of large animal products on small animals
Properties:
Macrolide (macrocyclic lactone) antiparasitic agent
Toxicity:
Dogs are susceptible, especially collies and collie crosses
"White feet, don't treat!"
Other animals may be susceptible
Small birds such as parakeets also susceptible
Doses associated with clinical signs
Dogs: Collies 0.1-0.2mg/kg (15-30x therapeutic dose)
*MDR1 mutation
Dogs: Beagles 2.5-40mg/kg (>200x therapeutic dose)
Cats: 0.3mg/kg SC
Cattle: 4-8 mg/kg (20-40x therapeutic dose)
Horses: 2mg/kg (10x therapeutic dose)
Pigs: 30mg/kg (100x therapeutic dose
Toxicokinetics:
Up to 95% absorbed orally
Primarily excreted unchanged in the feces
Some metabolized in liver
Elimination half life is about 2 days in normal dogs
Longer with some topicals
Mechanism of action:
GABA Agonist
GABA is a major inhibitory neurotransmitter in the CNS of animals
Clinical signs:
Mydriasis, neurologic blindness, depression, stupor, ataxia, vomiting, drooling, tremor,coma and death
Pathologic Lesions:
Laboratory diagnosis:
Clinical Diagnosis:
Differential Diagnoses:
SPECIFIC ANTIDOTE:
OTHER TREATMENT:
Prognosis:
No specific pathologic lesions
Chemical analysis (generally not needed)
Samples are liver, body fat, GI contents and feces
Can also measure in serum
Levels to not correlate well to brain levels
History and clinical signs
Other toxins:
Cholinesterase inhibitors, mycotoxins, ethanol, methanol, ethylene glycol, xylitol, amitraz
Drugs with CNS depressing properties
Removal of ivermectin
Activated charcoal
Saline cathartics
Symptomatic and supportive treatment
IV fluids
Treat possible bradycardia
Physostigmine IV may have some effect in the comatose animal
Picrotoxin is a specific antidote (GABA receptor antagonist) but has a narrow safety margin
Seizures due to picrotoxin can be treated with barbiturates
Depends on exposure dose
Supportive care may be required for a long time (cost factors)
Generally no long-term sequelae
Older insecticide extracted from the roots of several tropical plants - esp. Derris elliptica, jicama seeds
Unstable in air and light, with some residual effect
Irritant
Shampoos: D-limonene 5%
(DEET, N-octylbicycloheptene, dicarboximide, pyrethrins, benzalkonium chloride, di-N-propyl isocinchromenorate)
Napthalene
Paradichlorobenzene
Salt Soln
(c) Vin.com
acetyl-
choline
acetyl-
choline
(For a great review of O2 binding check out:
www.youtube.com/watch?v=HYbvwMSzqdY )
SpECIAL TOXICOKINETICS:
MDR1 gene mutation
MDR1 encodes P-glycoprotien which is a component of the BBB
Lack of MDR1 results in ~ 50x concentration of certain drugs in the CNS
Can be congenital (e.g. Collie breeds) or acquired (certain drugs: Cyclosporine A, ketoconazole, Verapamil, Tamoxifen)
Neurotoxicity has been seen with coadministration of Comfortis (Spinosad) and off-label ivermectin
http://www.fda.gov/AnimalVeterinary/newsevents/CVMupdates/ucm047942.htm
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