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385 Cards in this Set

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what is the difference between a toxicant and a toxin?
A toxicant can be any substance a toxin is only a natural substance
All toxins are toxicants but not all toxicants are toxins (T/F)
True
toxins are biological toxicants
What is the difference between acute, subacute, subcronic and chronic toxicity?
acute toxicity- the effect of a single dose or multiple doses over 24 hours

Subacute= the effect produced by daily expures from 1 to 30 days

Subchronic = the effect produced from daily exposure from 30 to 90 days

chronic = the effect produced by daily exposures from 3 months or more
what is the chronicity factor?
chronicity factor is the ratio of acute LD50 to chronic LD50. A low chronicity factor means that chronic toxicity is unlikley. A low chronicity factor is generally due to rapid metabolism
What does a low chronicity factor indicate?
A low chronicity factor indicates that chronic toxicity is unlikely most likely due to rapid metabolism
What would the dose of a toxin that is extremely toxic be?
extremely toxic = 1mg/kg or less
What would the dose of a toxin that is highly toxic be?
> 1-50 mg/kg
What would the dose of a toxin that is moderately toxic be?
>50-500mg/kg
What would the dose of a toxin that is slightly toxic be?
>,5 -5 g/kg
What would the dose of a toxin that is pratcially non toxic be?
>5-15 g/kg
What is LD 0
highest dose that does not cause any death
What is LD 50
dose that kills 50% of animals in a group
What is LD 100
lowest dose that kills all the animals in a group
What is the risk factor?
the risk factor can be calculated as the ratio between toxicity and risk use level (dose used in therapy)
The closer the toxic dose to the use dose the greater the risk (or lower your factor)
What does a low risk factor indicate?
The lower the factor the higher the risk
Weak acids are more ionized in what pH
basic
What are the route of toxin exposure and what is the most common?
The most common route of exposure is ORAL. However dermal route (insecticides) and inhalation (insecticides and toxic gases) are also seen.
What effect will enzyme inhibitors and enzyme inducers have on toxins?
enzyme inhibitors can decrease lethal synthesis
Enzyme inducers can increase lethal synethesis
how does volume of distribution relate to drug diposition?
the larger the volume of distribution the morel ikely the drug is to leave the extracellular space and enter the intracellular space or concentrate in tissues. Drugs with a Vd <1 have limited distribution, Vd>1 have a wide distribution
What are common metabolism reactions in the liver? Which reactiosn are cats deficient in? Which reactions are cattle best at? What reactions are birds poor at ?
The liver is primary site of biotransformation. Reactions in the liver are generally divided into phase I and phase II.
Phase I includes oxidation, reduction and hydrolysis
Phase II includes conjugation
Cats are deficient in conjugation due to a deficiency in glucuronly transferase
Ruminants and horses have higher levels of oxidative enzymes.
birds lack oxidative enzymes
What is the importance of enterohepatic recirculation in toxicology?
important to note in toxins because it determines how we use absorbents like activated charcoal. Drugs with enterohepatic recirculaion need repeated doses of activated charcoal
What is first order kinetics
most drugs follow first order kinetics meaning that the rate of remvoal of the durg from the plasma is proportional to the concentration persent at the given time. Constant half life
What is zero order kinetics?
zero order kinetics means that the rate of elimination of the drug remains constant no matter the amount. Process is saturable. These drugs have a half life that changes based on concentration
If the 1/2 life of a drug that follows first order kinetics is 2 hours, how long will it take for the drug to reach 25% of its iniital blood level
4 hours
What is the strongest evidence of toxin diagnosis?
confirmed diagnoeses- reached by using all criteria of diagnosis. these include: history, clinical findings, identification of source and lab work. The diagnosis is confirmed when these agree. Tetative diagnoses is the least evidence and presumptive diagnoses is the middle
what are questions to ask to help determine if a toxicity has occured?
suspected toxin type
does owner have container
was exposrue witnessed or evidence suggestive of ingestion
maximum amount
route of exposure
when did exposure occur
for farm animals, pertinent questions would also include: number of affected, number dead, type of management
Do most toxins have a pathognomonic lesion, clinical signs or lab work?
no
often lesions are similar to other disease processes and toxins.
why might a postive chemical analysis not confirm toxicity or a negative chemical analysis not rule out a toxicity and why is chemical analysis often not useful in treatment?
positive results may not indicate toxicity only exposure.
What are general principles of sample submission?
speciments should be submitted with a complete signalment, weight, history, PE, lab work
source should be on label
containers should be labeled with waterproof ink
IMEF
Southern California & Arizona
what is the procedure for collecting and shipping blood and serum samples?
collect the appropriate quantity of sample
serum should be frozen
blood should be refrigerated
(freezing causing hemolysis)
separate serum from blood follow appropriate procedures
appropriate tubes should be used
What is the procedure for collecting and shipping forages and feed?
collect sample
do not wash
green and silages should be frozen
what factors should be addressed first in toxicologic emergencies?
life threatening problems first: seizures, respiratory distress, shock
what are things owners can do at home for toxicological emergencies?
minimize stress at facility until docotr arrives in LA
transport to hospital with minmal stress (SA)
decontaminate with bath, emetic, wash eye, etc
how do toxicological emergencies differ from other emergencies?
even stable patients need immediate tx with toxins that cause acute toxicity
methods of decontamination include??
removal of the suspected source of toxicity
removal of the posion from site of absorption
decrease the rate of absorption
enhance elimination of the poison
methods of removal of poison from the site of absorption include?
emetics
gastric lavage and enterogastric lavage
rumentomy/gastrostomy/endoscopy
purgatives
skin and eye decontamination
general rules of emesis ar>
emetics are helpful if used within 1 to 2 hours of ingestion of toxin
emetics may not completely empty stomach contents but the eariler the better
what are some contraindications of emetics
unconsciousness due to rik of aspiration, corrosive toxins may cause further injury to esophagus, species that can't vomit
what are some examples of at-home emetics?
3% hydrogen peroxide, syrup of ipecac, NaCl solution, fresh ground mustard
What are emetics used in the hospital?
apomorphine and xylazine
how does hydrogen peroxide work?
causes vomiting via irritation of GI system
in what species is hydrogen peroxide used?
dogs, can be used in cats but not offten
what are some adverse effects of hydrogen peroxide
potential gastric ulceration/perforation in particular if GIT is severely compromised by toxin.
air embolism
gastric irritation
how do at home emetics work (besides H2O2)
acts as direct irritant
why are some at home emetics not used?
some feel these cause excessive irritation
how does apomorphine work as an emetic?
opioid agonist acts directly on crtz to induce vomiting
in what species is apomorphine primarily used?
dogs
why is apomorphine not recommended in cats?
more likely to cause excitement, CNS and respiratory depression, and excessive vomiting
how is apomorphine administered
Subconjunctival sac, IV or IM
What are contraindications and side effects of apomorphine?
not recommended in animals that are depressed
may cause excitement and respiratory depression i ncats
how are side effects of apomorphine controlled
side effects can be reversed with naloxone except for vomiting
whaqt are some dopamine agonsits that can be used to reverse vomitting caused by apomorphine
metoclopramide-
chloropromazine
why are repeated doses of apomorphine not likly to be helpful if vomiting is not seen after first
additional doses may inhibit vomiting or cause side effects
how does xylazine cause vomiting
alpha 2 agonist that induced vomiting by stimulation crtz
in what species do we use xylazine for emesis
cats
how is xylazine administered for emesis
iv, im, sc
side effects for xylazine
may cause cns and respiratory depression for several hours
how can xylazine be revesred
yohimbine
how effective are purgatives in decreasing absorption?
not effective but may be good when combined with activated charcoal
side effects and contraindidcations of purgatives
purgatives may increase vomiting
hypovolemia, dehydration, intestinal obstruction and corrosive toxins are contraindicated
magnesium sulfate may increase mganesium levels
how does precipitation decrease absorption and what are some examples?
the use of chemicals that precipitate the toxicant thereby decreaseing absorption (make less soluble)
what is adsorption?
physical binding of toxicant in the GIT to an unabsorable carrier to that it cannot be absorbed and is eliminted in the feces.
what is an example of an absorbent?
activated charcoal
what substances are NOT bound by activated charcoal
ethanol, methanol, heavy metal salts, fluoride and nitrate and nitrite, NaCl, chlorate, bleach, fertilizer, ammonia and cyanide
What type of molecules does activated charcoal work best on
large non-polar molecules.
contrainidcations and side effects of activated charcoal
comatose patients
induces vomiting
how does ion trapping decrease intestinal absorption?
involves ionizing toxins to they are less likely to be absorbed
weak bases are ionized with strong acids
how effective is ion trapping
not effective
methods of enhancing the elimination of toxins/
fluids
urine pH modifers
peritoneal dialysis
when are fluids helpful in enhancing elimination?
fluids will help renal elimination of renal excreted toxins in particular if a patient is dehydrated
In what patients must fluids be used with caution?
use caution in patients with renal and heart toxicity or previous illness (may cause fluid overload)
what drugs are sometimes combined with fluid therapy to enhance elimination and what must be accomplished prior to giving these drugs?
sometimes patients are fluid loaded and then diuretics are used to increase urine output (mannitol and lasix).
- volume must be restored before giving diuretics. If not GFR and toxin clearence may actually decrease due to hypovolemia
- it is debatable as to if diuretics will actually help clear toxins/ GFR vs. just eliminate water
How do urin pH modifiers worK?
by ionizing the molecule in the renal tubules it becomes trapped and is excreted. It is trapped by ionizing because ionized molecules cannot easily cross lipid membranes
when does ionization work best, and when is it less effective?
- ionization works best for weak acids and weak bases
- ionization can be performed when the counpound is not highly lipid bound, suitable pKa and is primarily distributed to the extracelllular space
-countraindcated in drugs with large volume of distribution , protein bound, lipid soluble or drugs metabolized in the liver or other tissues.
what drugs can be used for acidification, when is it contraindicated and what are some examples?
Ammonium chloride or methionine is used to acidify and ionize weak bases such as alkaloids or amphetamines. Acididication therapy is contraiindicated in patients with metabolic acidosis.
What drugs can be used for alkalinziation, what are some potential adverse effects and what are some examples?
soidum bicarbonate
ionizes weak acids such as NSAIDS or phenobarbital
may cause hypokalemia, hypernatremia, decreased ionized calcium and paradoxical CNS/intracelullar acidosis, secreased O2 delivery to tissues and volume overlaod
when should hemodialysis or peritoneal dialysis be considered to eliminate toxins?
hemodialysis and peritoneal dialysis can be performed when renal function is poor or to increase toxin elimination
Methods of toxin dilution include
milk and water
when is toxin dilution recommended?
when a corrosive toxicant has been ingested
With what toxicants might lipid administration be beneficial and who would it help?
-Helpful with lipid soluble toxicants like ivermectin
- lipids may help bind the lipid soluble toxin in the blood and thereby prevent the toxin from getting to the site of action
If an animal presented to your hospital after being exposed to a toxicant which decontamination procedures would most likely be performed?
1. contact poison control
2. activatted charcoal if vomiting is not contraindicated.
why are organophosphates considered more dangerous than other insecticides?
most organophosphates are highly toxic range. Sensitivity depends on species and type. BIRDS and FISH
More dangerous due to a close treatment and toxic range. They are not as selective for insects. They have a lower risk ratio
What is the onset of clinical signs of organophosphates?
mostly acute (often minutes when ingested).
How does environment, quality of product, storage, vehicles, and age effect toxicity of organophosphates?
toxicity decreased by degradation of the compound in the environment
- technical grades are more toxic than pure
organic solvents increase toxicity
drugs that require activation are less toxic to young animals due to decreased biotransformation.
what sre some drug interactions with organophosphates?
-malathion and coumaphos are synergistic
muscle relaxants and neuromuscular blockers increase toxicty
Enzyme inducers such as phenobarbital and chlorinated hydrocarbon insecticides may decrease or increase toxicity.
Enzyme inducers increase toxicity in cases of lethal synthesis such as malathion and parathion
What is the difference between systemic or non-systemic organophosphatese and what are some examples?
non-systemic = malathion and parathion
systemic = coumaphos and dichlorvos
systemic forms have a longer recovery and may have a longer time until onset of action. Clinical signs of systemic are more simular to organochlorines at certain stages of toxicty. Systmeic have a molecular structure that is more similar to organochlorines.
What are some toxicokinetic concerns with organophosphates?
most need enzymatic activation by the liver (parathion, malathion)
- tolerance may develop with continued exposure due to enzyme induction
- protein binding, enzyme induction and adaptation/alteration of cholinergic receptors when exposed to chornic excessive amount of Ach (decreasd/down regulation of Ach receptors) may lead to tolerance
What is the mechanism of action of organophosphate in acute toxicosis?
IRREVERSIBLE inhibition of acetylcholineterase causes neurologic stimulation

See muscarinic signs before nicotinic signs and neuromuscular stimulation

Excessive depolarization eventually results in ganglionic and neuromuscular blockade --> neuromuscular depression
what is aging and why is it important in regards to organophosphates
when organophosphates are changed chemicallly by organophosphates so that they are permanently dysfunctional
important because once aged ACHase cannot be reactivated by 2 PAM.
what are the clinical signs of acute organophosphate toxicosis?
- PNS/muscarinic stimulation. PSN signs are typically seen first and predominant in most tissues. (DUMBLES, bronchoconstriction)
-later ganglionic nicotinic stimulation causes vasoconstriction due to predomination of sympathetic in blood vessels. may see other sympathetic signs in other organs but typically PSN predominates
- Neuromuscular nicotinic stimulation causes neurlogic stimulation signs (remor, muscle fasciculation, etc)
- Nicotinic blackade causes neurlogic depression and can cause respiratory paralysis resulting in death
-signs of cns stimulation causes neurlogic excitement (seizures)
- signs of CNS depression may also be seen in particular after prolonged CNS stimulation resutling in coma, depression, etc
what species are not reported to have seizures with organophosphates?
ruminants
can organophosphates be chemically tested for? If so is there a specimen of choice?
can test for OP in rumen stomach contents, hair, and skin
-can also test actylcholinesterase activity
Do oganophosphates have any specific antidote and what is the main type of supportive care require?
atropine (partial antidote) and 2 PAM (full antidote) are antidotes

2 PAM can reactivate ACHase if it is not aged

supportive care involves tx of seizures and respiratory support

always treat life threatehing conditions first
why is atropine only a partial antidote and is 2 PAM a full antidote?
-atropine only blocks muscarinic effects
-2 PAM can decrease muscarinic (decrease parasympathetic activity) and nicotinic activty (decrease sympathetic, parasympathetic and NMJ activation
Is 2 PAM or atropine needed in intermediate syndrome?
typically these patients do not have muscarinic signs (due to muscarinic receptor down-regulation) therefore atropine is not generally recommended.
how can atropine be used to confirm organophosphate toxicosis?
give smaller dose of atropine similar to that used in anesthesia. IF the animal responds to the atropine it is likely not organophosphate toxicosis.
what is the prognosis/recovery period for organophophates?
best if treated early but recovery period can be long in some cases. high doese = rapid death
Why are carbamates less toxic than organophosphates?
-similar relative toxicity to organophophates but relative toxicity depends on species ad type.

- however less toxic than OP due to reversible inhibition and rapid metabolism

- somewhat more used then organophosphates d/t decreased toxicity
what are some toxicokinetic concerns with carbamates?
do not require liver activation and rapidly metabolized
what is the mechanism of action of carbamates?
similar to organophosphates but inhibition of acetylcholinesterase is reversible
what are the clinical signs of carbamates?
similar to acute toxicity with organophosphates.
can carbamates be chemically tested for? If so, is there a specimen of choice and waht is the problem with acetylcholinesterase testing?
-chemical testing is possible but toxicant id quickly degraded once absorbed so testing tissues is not very useful. Stomach contents therefore may be better
-Acetylcholinestrase activity can be checked but due to reversbile inhibition they maay also be less useful
-In other words by the time the sample reaches the lab the ACHase may no longer be inhibited because inhibition is reversible.
-Response to treatment may also help confirm diagnosis
Do carbamates have any specific antidote and what is the main type of supportive care required?
-Atropine is partial antidote
-2PAM is not used- may be more harmful
What is prognosis/recovery period of carbamates
recovery and prognoses are better than organophosphates, but large amounts can result in a poor prognosis.
organochlorines toxicants include?
`
diphenyl aliphatics (DDT, methoxychlor)
aryl hydrocarbons (lindane)
cyclodienes (Aldrin, toxaphene)
what are some environmental concerns with organochlorines?
very persistent in enviornment because they resist chemical or microbial decomposition (there are exceptions espceially if they are protected by a layer of soil)
-residues may appear naturally in animal tisssues due to environment contamination
-environmental residues may cause BIOACCUMULATION
why is organochlorine toxicity less common currently?
used in 1950s and early 1970s as insecticide and ectoparasiticide.
what is the species sensitivity and susceptibility of organochlorines?
all animals are susceptible but CATS are most sensitive
what is the onset of clinical signs of organochlorines?
typically acute toxicity (few minutes to 1 to 2 days) but dose dependent and with sublethal doses toxicity may be subactue (over several days)
what are some toxicokinetic concerns with organochlorines?
mainly distributed to fat then brain
-rapidly taken up and sotred in fat (fat acts like a sink) and is slowly released
-distribution to fat to some degree protects brain. However with large doses enough can accumulate in the brain to cause toxicity. slow release from fat casuses long half life and can prolong toxicity
-initial distirubtion to fat causes quick decrease in blood levels but slow release from the fat resutls in a long half life (may be weeks to months)
-also distributes to fetus
-metabolized by liver
-enzyme inducer
- can increase the toxicity of organophosphates with lethal synthesis (malathion, parathion) and decrease the toxicity of organophosphates without lethal synthesis
- metabolites of diphenyl aliphatics and cyclodienes are more toxic (lethal synthesis)
- excreted in bile (undergoes enterohepatic rercycling), feces, urine and milk
what is the mechanism of action of organochlorines?
-diphenyl aliphatics interfere with mechanism where soidum influx is stopped and potassium efflux is started during the action ptoential, this results in repetitive nerve discharges
-lindane may inhibit GABA binding
-Cyclodienese stimulate the CNS by an unknown mechanism
what are the clinical signs of organochlorines?
-mainly see CNS excitement
-often see seizures (may see CNS depression between seizures)
- may be explosive or slowly progressive
- abnormal posture and walking backward is seen in cattle
- birds show depression abnormal postures apparent blindness and death
-early gastrointestinal signs may also be seen
Can organochlorines be chemically tested for?
chemical analysis confrims acute toxicosis if the insecticide is in the blood, liver or brain, but levels do not correlate with severity of clinical signs
- brain concentrations are better correlated with toxicosis than fat. Remeber the fat takes up toxin thereby decreasing level in the brain and blood. After uptake by the fat the toxin is released back into the blood but it is a slow release. So fat levels may be greater than the blood or brain levels. This leads to a situation of where no toxicity occurs depsite high levels in th fat. However, if high levels are found in the brain then the clinical signs are likely related to the toxin
do organochlorines have any specific antidote and what is the main type of supportive care required?
no specific antidote, need to control seizues
what is the prognosis/recovery period of organochlorines?
-poor if comatose otherwise guarded to good
-recovery time is moderate
-signs such as seizures may last 48 to 72 hours but residues can persist for months to years.
what is the definition of pyrethrins, pyrethroids, and pyrethrum?
- pyrethrins are from pyrethrum flowers (chrysanthemum) they are natural
- pyrethroids are synthetic and divided into type 1 and type 2
-pyrethrum includes natural and sythetic forms
what are some important differences between pyrethrins and pyrethroids?
unstable in light and air so environmental toxicity limited by pyrethroids are more stable
what is an important source of pyrethrins and pyrethroids?
flea product and tick control in dogs and cats
why are pyrethrums a relatively safe insecticides?
highly toxic but considered to have low toxicity to animals. Dose used to kill insects is much lower than toic dose in aniamls
what is species sensitivity and susceptibility of pyrethrins and pyrethroids?
-dogs, cats, and large animals are susceptible
-cats may be more sensitive and some individuals seem to be more sensitive
-very toxic to fish and some birds
how can the toxicity from pyrethrin and pyrethroids be increased? Which is more potent, pyrethrins or pyrethroids, and what type of pyrethroid is most toxic?
-piperonyl butoxide is added to inhibit enzymes that inactivate pyrethrins. This will increase toxciity and is used commercially as pyrethrin synergist
-pyrethroids are more potent than pyrethrins
-type 2 are generally more toxic than type 1
what are some toxicokinetics concerns with pyrethrins and pyrethroids?
-very rapidly inactivated by plasma esterases and by liver enzymes
-rapid metabolism will decrease toxicity
-also metabolized in GIT
what is the mechanism of action of pyrethrins and pyrethroids?
-prolonged opening of soidum channels--> impulse conduction
what are the clinical signs of pyrethrins and pyrethroids?
-pyrethrins and pyrethroids primarily cause CNS excitement
-tremors are more common than seizures
-weakness may be seen with Tpye 2
=Gastrointestinal signs may also be seen
-Dermal exposure may cause allergic skin reaction
-Systemic anaphylactic reactions are rare.
what are the clinical signs of pyrethrins and pyrethroids?
CNS excitement
tremors, seizures
weakness
GIT signs
dermal exposure- allergic skin reactions
systemic anaphylactic rxn =rare
can pyrethrins and pyrethroids be chemically tested for? If so, is there a specimen of choice?
can be tested for but often low tissue levels (due to rapid metabolism) and difficult to detect, in addition tissue levels are not well correlated with clincial signs
Do pyrethrins and pyrethroids have any specific antidote and what is the main type of supportive care required?
-no antidote
- need to control tremors
-may need to treat skin reactions with anti-inflammatories, rarely treatemnt for anaphylaxis is needed
what drug is considered more effective than valium in controlling pyrethrin induced tremors?
-methocarbamol (mainly for tremor and maybe seizure)
- for full on seizures (not tremor), diazepam or other anticonvulsant may be superior to methocarbamol but not all sources agree
what is the prognosis/recovery period of pyrethrins and pyrethroids?
-excellent in most cases unless signs are advanced
- moderate recovery time
- animals that recover generally take 24-48 hours
What are sources of rotenone?
-historically used to be placed on arrowheads to kill fish
-used as a pesticide in water to kill fish
-used for garden pest control
-used for ear mites in dogs, cats, and rabbits
what is the species sensitivity and susceptibility of rotenone toxicosis?
low toxicity to mammals
chickens are resistent
what is the onset of clinical signs of rotenone toxicosis?
acute most common
what factors can increase rotenoone toxicity?
formulation (emulsion is more toxic)
sometimes combined with pyrethrins
route more toxic by ingestion and inhalation
what is the mechanims of action of rotenone toxicosis?
-irritant to contact surfaces
-inhibits energy metabolism
- inhibition of NADH prevents formation of substances such as glutamate and pyruvate that need to oxidize by NAD to be fomred
-Rotenone also inhibits electron transport
What are the clinical sings of rotenone toxicosis?
in acute toxicosis inhibition of energy production results in gastrointestinal abnormalities and possibly neuroligc abnormalities (depression and excitment are seen)
-neurologic disease may lead to respiratory deprssion and death. Dyspnea may be seen prior to respiratory depression.
-local irritation to contact tissues such as the skin and eye may cause conjunctivitis, congestion and dermatitis
-chronic signs cause liver and kidney damage
does rotenone have any specific lesions or bloodwork findings?
-no specific findings
-not specific but may see hypoglycemia on bloodwork
does rotenone have any specific antidote and what is the main type of supportive car required?
no specific antitode
need to suppor GIT and treat seizures or respiratory depression.
what is the prognosis of rotenone?
excellent in most cases
what food is D limonene found in?
citrus peels
What are sources of D limonene?
control of lice, fleas, ticks
desiccant that destroyes insect cuticle
food additive and fragrance.
what is the relative toxicity od D limonene?
toxicity in cats occurs at 5x recmmoneded dose for dogs
what is the species sensitivity nd susceptibility of D limonene
dogs and cats are susceptible
cats are more sensitive than dogs
what is the onset of clinical signs of D limonene?
mostly acute for neurologic and cardiovascular abnormalities (minutes to hours)
how can D limonene toxicity be ptoentitated?
toxicity potentiated by piperonyl butoxise and other enzyme inhibitors
what is the mechanism of action of D limonene?
mechanism of neurologic and cardiovascular dysfunction is unknown
vasodilation caused by the toxin in central and peripheral vessels may be due to a neuronal mechanism.
idosyncratic skin leasions
what are the clinical sings of D limonine
nervous system dysfunction
cns dperession
may see neurlogic excietment
cardiovascular dysfunction
causes hypotension via vasodilation
hypotherma
acute necrotizing dermatitis
does D limonene have any specific lesions or bloodwork findins?
no
does D limonene have any specific antidtoe, and what is the main type of supportive care required?
no specific antidote
-cases with large skin lesions may need tx of vasodilation (fluids/vasopressors)
what is the prognosis for D limonene toxicosis
in animals with no skin lesions short recovery - 24 hours
skin lesions are longer recovery with poorer prognosis
what are ths oruces/uses fo napthalene?
found in mothballs, urinal disks and toilet bowel/diaper pan deoodarant blocks
what is the species senstivity ans suceptibility of naphthalene?
cats and dogs are suceptible
cats are more sensitive
onset of cllinical signs of napthalene?
acute but may be over several days
time may vary due to reate of absorption which is dependent on form. for exmaple whole moth balls take a dew days to be absorbed
what are some toxicokinetic concerns with naphthalene?
whole mothball in the GIT may take several days to be absorbed
what is the mechanism of action of naphthalene?
irritant to contact tissues like the GIT
metabolie causes oxidative injury to RC making them fragile resulting in hemolytic anemia (Heinz body)
oxidative injury - likely to cause liver and GIT issues
hemoglobinuria from red cell lysis can lead to secondary injury to kidneys
what are the clinical signs of naphthalene?
-primarily causes GI signs and evidence of hemolytic anemia (pale, yellow gums, tachycardia), but may also see liver damage and secondary renal injury
-seizures and cataracts (in neonates)
breath odor
what are specific bloodwork findings associated with naphthalene toxicosis
hemolytic anemia and heinz bodies. methemoglobin (brown blood)
what is the prognosis of napthelene toxicosis
depends on complications. can be poor if compilcations like liver and renal disease develop and prolonged recovery if severe hemolytic anemia
what are the sources of nicotine?
contaminated feed with nicotine sulfate as plant insecticide
wild tobacoo may be source in farm animals
sources of exposure in small animals include chewing tobacoo, nicotine patches, nicotine gum, cigarettes or cigars
onset of clinical signs of nicotine?
acute toxicity (course of signs rapid, within a few minutes to an horu)
what are some toxicokinetic concerns with nicotine?
urinary excretion decreased when urine is alkaline
what is the mechanism of action of nicotine?
GI irritation may be partly due to caustic effect
neurologic signs are due to nicotinic agonism
nicotinic agonism causes ganglionic and neuromuscular stimulation at small doses and intially at high doses.
Later nicotinic receptor agonism causes ganglionic and neuromuscular blockade because the persistentn depolarization leads to inability of the cell to repolarize
what are autonomic signs associated with nicotine
neurologic
-autonomic signs- neurologic stimulation. Parasympathetic signs tend to predominate in most tissues except blood vessels.
para= diarrhea, urination, miosis, bradycardia, emesis, lacrimation, salivation (DUMBLES).
Sympathetic = vasoconstriciton
later blockage of nicotine receptors occurs due to persistent situmation resulting in normal heart rate and vasodilation.
What are some neuromuscular signs of nicotine?
initially see stimulation- tremors, etc
followed by paralysis
central effects of nicotine include?
CNS stimulation results in excitement, seizure and tremor followed by depression.
CNS and nueromuscular depression- repsiratory paralysis- death
vomiting
Does nicotine have any specific antidote and what is the main type of supportive care required?
Decontamination- gastric lavage with diluted soluntion of potassium permangante, tannic acid or tincutre of iodine
acidification of urine may help excretion
mecamylamine as a ganglionic blocker only can have some benefit early in case
atropine therapy for PS effects
control neurlogical excitement
What is the prognosis of nicotine?
poor in large doses but typically in small doses recovery is generally short (<24 hours)
What are sources of DEET?
insect repellent
combined with fenvalerate as a repellant and insecticide for dogs/cats
what is the relative toxicity of DEET
acute toxicity
slightly toxic
what is the species sensitivity and susceptibility of DEET?
dogs and cats are susceptible but cats are more senstive
neonates are more sensitive
onset of clinical signs of DEET toxicity?
acute or subactue
what are some toxicokinetic concerns with DEET
neurotoxicity mechanism is unknown
may cause irritation of the skin and mucous membranes
what are the clinical signs of DEET toxicity?
primarily neurologic excitement
gatrointestinal signs
skin irritation
Does DEET toxicity have any specific antidote and what is the main type of supporitve care required?
no specific antidote
the main thing is to control CNS excitement
What is the prognosis for DEET toxicosis
toxicity is RARE
Amitraz sources and uses include?
flea and tick collars
sources include: ingestion of the dip or accidental ingestion of the collar and dermal absorption following dermal exposure
What is the species sensitivity and susceptibility of amitraz?
never used in horses due to induction of intestinal stasis
cats are also more sensitive
onset of clinical signs of amitraz?
acute to subacute
Amitraz is a good insect repellent in horses (T/F)
false, amitraz causes intestinal stasis
Onset of clinical signs of amitraz
acute to subacute
drugs and other factors tha can increase the toxicity of amitraz?
meperidine or sympathomimetic amines increase toxicity
stress increases toxicity
what is the mechanism of action of amitraz?
alpha 2 adrenergic agonist in the CNS is believed to result in sedation and cardiovascular instability
alpha 2 adrenergic agonist in the PNS is believeed to result in cardiovascular instability
weak MAO inhibition may also contribute to neurlogic toxicty
Mild irritant to the GIT and skin
what are the clinical signs of amitraz?
primarily CNS depression but may also see ataxia, possibly seizures and vocalization

cardiovascular instability can cause hypotension and is due to bradycardia and vasodilation
hypothermia
mydriasis
gastrointestinal abnormalities such as intestinal motility
urination/PU
death often due to CNS depression resulting in respiratory depression or colic in horses
does amitraz have any specific lesions or bloodwork findings?
HYPERGLYCEMIA (due to alpha 2 receptor activation) may be clue but is not specific
chemical analysis is possible
Does amitraz have any specific antidote and what is the main type of supportive care required?
- Alpha 2 adrenergic antagonists (yohimbine or atipamezole) are an antidote

- main supportive care is to monitor for respiratory depression and decontamination
What is the prognosis of amitraz?
good in most cases
moderate recovery period (24 to 72 hours)
What are some common macrocyclic lactone brand names?
includes drugs such as ivermectin (heart gaurd, Ivomec), moxidectin, selamectin, milbemycin, doramectin, eprinomectin, abamectin
what are uses/sources of macrocyclic lacones?
-endectocide from cattle, swine, sheep and horses
- prevention of heart worm disease in dogs and cats
-also used for treatment of various external and internal parasites, in dogs, cats, rabbits and other species
-abamectin
-sources include overdose and use of large dose of products formulated for large animals in dogs. Ingestion of ant traps by dogs will rarely causes toxicity, but can cause obstruction
what is the species sensitivity and susceptibility of macrocyclic lactones? why are some speciese more sensitives
many species are susceptible
certain dog breeds- collies and herding breeds
onset of clinical signs of macrocyclic lactones?
acute
what are some toxicokinetic concerns with macrocyclic lactones
ivermectin most known
long half life after skin administration
what is the mechanim of action of macrocyclic lactones?
GABA agonist- neuronal inhibiton
what are the clinical signs of macrocyclic lactone
mainly CNS depression seen, may also see stupor, coma, mydriasis, neurologic blindness, ataxia, tremor. Seizures can alos be seen.
-other signs may include GI signs, bradycardia and sinus arrhythmias
-may progress to respiratory/cardiac depression resulting in death
Do macrocyclic lactones have any specific antidote? What supportive care is required?
decontamination may need multiple doeses of activate charcoal
physostigmine IV
picrotoxin is specific antidote- but has narrow safety margin
What is the prognosis of macrocyclic lactones?
depends on dose, but may need long term care
can be very long (>1 week) due to long half life
what insecticides are long lived in the environment or have environmental concerns?
organochlorines- BIOACCUMULATION
what insecticides have an acute toxicity?
all of the them are primarily acute but some can also be subacute and chronic
what insecticides have a well recognized subacute to chronic toxicity?
organophosphates- delayed/intermediate syndrome
-organochlorines- chronic with low doses
-napthalene- whole moth balls slow absorption in GIT
what insecticides are highly to moderately toxic?
all of them except DEET and D Limonene
what insecticides are unsafe due to similar therapeutic and toxic doses?
organophosphates
to what insecticides are fish and/or reptiles and/or birds most sensitive?
pyrethrins very toxic to fish and birds
rotenone very toxic to fish and cold blooded animals
with organophosphates and carbamates some sources report birds and fish are more sensitive
to what insecticides are dogs or cats most sensitive?
cats= organocholrines, D limonene, napthalene

dogs= macrocyclic lactones in some K9
what insecticides are not used in horses, and generally not in cats?
horses- amitraz due to intestinal stasis
cats are also sensitive to amitraz and are more sensitive than dogs
to what insecticides are avians sensitive or resistant?
chickens are resistant to rotenone
some birds are sensitive to pyrethrins and organophosphates/carbamates
what insecticides are neonates more sensitive too?
- OP without lethal synthesis
-Carbamates
-DEET
are any insecticides not well absorbed or poorly distributed?
-all are well distributed
-absorption varies but most can be absorbed to some degree by all routes
where are most insecticides metabolized and excreted?
most are metabolized in the liver and excreted in urine and bile
OC have significant bile exretion
Rotenone is mainly excreted in feces
Macrocyclic lactones are excreted mainly unchanged in the feces (these also have long half life and long recoery time due to the long half life)
what insecticides have lethal synthesis
Organophosphates
Organochlorines
rotenone forms toxic metabolites in some liver reaction
why is bile or feces excretion important
important because excretion in bile or feces means repeated closes of activated charcoal should be given
what insecticides cause mainly CNS excitement
organophosphates, carbamates, organochlorines, pyrethrins (mainly tremors), nicotine, DEET
-sometimes depression can also be seen with some of these
what insecticides cause mainly CNS depression?
Ivermectin, amitraz, rotenone and D limonene= mainly CNS depression but may also see excitment
Which insecticides cause significant direct cardiovascular dysfunction?
amitraz (similar to xylazine)
D limonene (vasodilation)
what insecticides cause skin lesion?
D limonene (TEM or EM like)
Pyrethrins (type 1 hypersensitivity)
what insecticides and other toxins cause hemolytic anemia
napthalene
what insecticides and toxins cause hypoglycemia
rotenone
what insecticides cause mainly CNS depression?
Ivermectin, amitraz, rotenone and D limonene= mainly CNS depression but may also see excitment
Which insecticides cause significant direct cardiovascular dysfunction?
amitraz (similar to xylazine)
D limonene (vasodilation)
what insecticides cause skin lesion?
D limonene (TEM or EM like)
Pyrethrins (type 1 hypersensitivity)
what insecticides and other toxins cause hemolytic anemia
napthalene
what insecticides and toxins cause hypoglycemia
rotenone
What insecticides and toxins causing hyperglycemia?
amitraz
which insecticides have a specific lesion on necropsy or physical examination
none
what insecticides are associated with a poor prognosis?
most only have a poor prognosis in large doses but insecticides with higher relative toxicity, lethal synthesis or decreased metabolism tend to have a worse prognosis
prognosis is always poor once multiple organ failure develops. Insecticides that lead to CNS excitement such as organophosphates and organochlorines seem to quickly lead to this sequela in particular with large doses and delayed supportive care
what insecticides are associated with a good prognosis?
cabamates, pyrethrins, DEET, D limonene, Rotenone all tend to have a good prognosis in cases of limited exposure
For what insecticdes is chemical analysis possible? Do any have a specimen of choice?
only citrus oil has no test for chemical analysis
organophosphates- acetylcholinesterase activity and chemical analysis
-carbamates acetylcholinesterase activity, chemical analysis of stomach contents best due to rapid metabolism but can also test tissues
-organochlorine - brain
-pyrethrins- worry about rapid metabolism
which insecticides that are commonly used in veterinary products have limited toxicity?
fipronil- Frontline-GABA agonist
imidacloprid (advantage)
methoprene (Frontline plus)
nitenpyram (Capstar
how are anticoagulants classified?
First Generation: Warfarin, pindone, chlorophacinone

Second Generation: Brodifacoum, bromodiolone, diphenadione
what are sources/used of anticoagulants?
used to kill rodents as prepared baits or powders for mixing with bait material, some are used medically as anticoagulants, ingestion of baits or eating contaminated foods, swine, dogs, and cats can be poisoned by eating rats or mice killed by these, malicious
what is the species sensitivity ans suceptibility of anticoagulants?
dogs are most suceptible
order or sensitivity is pigs>dogs>cats>ruminants>horses>chickens
what is the onset of clinical signs of anticoagulants?
toxicity is subacute. It takes 3 to 5 days to see clinical signs. It is more acute with second generation, but it still generally takes a few days after ingestion to see clinical signs
what factors increase toxicity with anitcoagulants
factors that enhance bleeding
vitamin K deficiency, oral antibiotics/sufonamide therapy or high dietary fat, enzyme inhibitors, presence of other drug or diseases that causes hemorrhage, liver disease, presence of drugs that displace the anticoagulant from albumin
what factors decrease toxicity?
pregnancy or lactation, enzyme inducers
what are the clinical signs of anticoagulant toxicosis?
it depends on the site of bleeding
respiratory distress, neurologic, cardiovascular deterioration if severe blood losses
do anticoagulants have any specific lesions or bloodwork findings?
no specific lesions. Lesions will depend on the site of bleeding
blood work not specific but will often be consistent with blood loss
activated coagulation time (ACT)
PT/PTT
PIVKA
what will be elevated first with anticoagulant toxicosis PT/PTT and why?
PT b/c it tests the extrinsic pathway which involves factor VII. Therefore it is prolonged first because Factor VII has the shortest 1/2 life
which clotting test is least sensitive and which is most sensitive?
ACT is the least sensitive
PIVKA is said to be the most sensitive and specific. Other disease will increase the PIVKA test and some feel the PT is just as good for early detectioin
Can anticoagulants be chemically tested for if so is there a specimen of choice?
best for definitive diagnosis
detection in blood (preferred in live animal) serum, or plasma in a live animal
other smaples that may be submitted include liver (preferred in dead animals) GI contents, vomitus and baits
Do anticoagulants have any specific antidote? What is the main type of treatment for anticoagulant rodenticides?
stable patient
detoxification
antidote is vitamin K1. Vitamin K1 will not stop active bleeding
coagulation parameters should be checked a few days after cessation of therapy
unstable patient
decontamination is not helpful since posion is alreaady absorbed
antidote is fresh frozen plasma for aniaml with coagulopathy and minimal blood loss or while blood for animals in need of clotting factors and red blood cell. FFP will give immediate clotting factor. Vitamine K1 is alos given as in stable patient to help liver activate factors
-supportive care/monitoring, fluid therapy oxygen therapy, minimize restraint and handling, thoracocentesis/pericardiocentesis/abdomiocentresis should be avoided unless respiratory/cardiac distress from hemorrhage is life threatening
-coagulation monitoring as in stable patient
how long is vitamin K given and how long before the liver starts making new factors after giving vitamin K1?
-coagulation parameters are significantly shortened within 24 to 48 hours of vitamine K1 therapy
-Generally takes 12 to 48 hours for clotting factors to normalize depending only severity of toxicity.
why is vitamin K3 not used in treatment?
vitamin K3 (menadione) is not effective
vitamin K3 can cause heinz body anemia and is nephrotoxic. It is also poorly stored and requires metabolism for activity so its onset of action is slow and requires a larger amount
what is the prognosis and recovery period of anticoagulants?
generally a few days but it depends on the amount and location of bleeding.
Treatment is long for second generation 3 to 4 weeks and shorter for first generation 1 to 2 weeks. if unknown type should treat for long period
What is the other name of vitamine D3 what are vitamin D analoges?
Vitamin D3 is chloecalciferol
calcipotrol, calcipotriene are vitamine D analoges
what are sources/uses of vitamin D toxicosis? What is the most common source? What source rarely causes toxicity?
ingestion of cholecalciferol rate poisons
feeding on poisoned rodents
consumptiono f large doses of vitamin D
ingestion of psoriasis medications with vitamin d3 analogs creams
ingestion of poisonous plants containing vitamin D analogs
what is the sepcies sensitivity ans suceptibility of cholecalciferol
all animals are susceptible
dogs and cats are most frequently poisoned
cats are more sensitive than dogs
young animals are more sensitive than adults
what factors increase toxicity with cholecalciferol
predisposing factor include renal disease, hyperparathyroidism, ingestion of high calcium and phosphorus in diet
what are some toxicokinetic concerns with cholecalciferol?
absorbed from the GIT
binds to serum vitamin D binding protein and transported to the liver
cholecalciferol is metabolized in the liver by hydroxylation via 25 hydroxylase to 25 hydroxychloecalciferol
calcefidiol is converted to 1,25 dihydroxycholecalciferol by 1-alpha-hydroxylase in the kidney
-metabolites are very lipid soluble so they are slowly eliminated
-metabolism is dependent on form
-metabolites mainly excreted in the bile then in feces
-vitamin D can be excreted in milk at toxic level
what is the species sensitivity and susceptibility of cholecalciferol?
all animals are susceptible
-dogs and cats are most frequently poisoned
-cats are more sensitive than dogs
- young animals are more sensitive than adults
what factors increase toxicity with cholecalciferol?
predisposing factor include renal disease, hyperparathyroidism, ingestion of high calcium and phosphorus in diet
what are some toxocokinetic concerns with cholecalciferol?
absorbed from the GIT
binds to serum vitamin D binding protein and transported to the liver
cholecalciferol is metabolized in the liver by hydroxylation via 25 hydroxylase to 15
what form of the vitamin D3 metabolites is most active and which form predominated?
calcefidiol is the main vitamin D form in circulation becaues of inhibition of 1 alpha hydroxylase by calcitriol
calcitriol is the 500 times greater vitamin D receptor binding than calcifediol and 1000 times greater binding than cholecalciferol
what is the mechanism of action of cholecalciferol toxicosis?
toxicity is mainly the result of hypercalcemia and hyperphosphatemia

early mechanisms of action hypercalcemia of hypercalcemia are receptor and intracellular mediated events and are mainly seen in the gastrointestinal tract, kidenys, heart and nervous system

- later in toxicity increased calcium and phosphorus results in soft tissue mineralization in areas such as kidneys, cardiac and lung tissues, vascular walls and stomach
what are the clinical signs of cholecalciferol toxicosis?
generally appear within 24 to 36 hours. Main organs afffected include the gastrointestinal system, cardiovascular system, nervous system and kidneys
Gastrointestinal: GI injury is severe, anorexia, vomiting (bloody), abdominal pain, constipation, or bloody diarrhea
Renal: initially PU and PD, later in toxicity anuria can be seen with acute renal failure, weakness, renal disease can also worsen GI injury via uremia
Cardiovasuclar- cardiac arrhythmias (often causes bradycardia) and hypertension
CNS- mainly CNS depression: weakness, lethargy, depression, coma
other CNS signs may include twitching and seizure
What blood work abnormalities (CBC, chemistry, urinalysis) would be seen in cholecalciferol toxicosis?
CBC, chemistry and urinalysis
- hyercalcemia (>11 mg/dl in dogs and 12 to 18 mg/ dl in cats)
- hyperphosphatemia
- hypnatremia and hypokalemia
what lesions are seen in cholecalciferol toxicosis?
calcification of the kidneys, blood vessels, stomach and other tissues is the most specific lesion
what are differentials for cholecalciferol toxicosis?
differentials for hypervitiminosis D and hypercalcemia will be most useful
other differential list may also be helpful but they are most helpful when you see them with hypercalcemia
Differentials for hypervitaminosis D
why can it be difficult to make a diagnosis when you have hypercalcemia and renal failure?
hypercalcemia is a cause of renal failure and renal failure can cause hypercalcemia
why can it be difficult to make a diagnosis when you have hypercalcemia and renal failure?
hypercalcemia is a cause of renal failure and renal failure can cause hypercalcemia
what radiograph finding may be seen with vitamin d toxicosis?
calcification of tissue of radiograph
can cholecalciferol be chemically tested for if so is there a specimen of choice?
you can test serum serum levels of 25 hydroxycholecalciferol
how would PTH, PTHrp and phos levels possibly differ in renal disease, neoplasia, primary hyperparathyroidism and vitamin D toxicosis?
renal disease= high PTH, low PTHrP and high phos
vitamin D toxicosis= low PTH, low PTHrP and high phos
neoplasia = low PTH, high PTHrP and low phos
Primary hyperparathyroidism- high PTH, low PTHrP and low phos
Does cholecalciferol have any specific antidote and what is the main type of supportive care required?
no specific antidote but several drugs amy help to lower calcium levels such as
- normal saline IV
-furosemide
- glucocorticoids such as prednisone or prednisolone
-calcitonin
-sodium bicarbonate
-pamidronate disodium
-also consider low calcium diet
what should be done prior to lasix/furosemide administration and holwng is therapy givien
restore volume prior to lasix to protect kidney
therapy should continue until serum CA is normal
what is the prognosis/recovery period of cholecalciferol
good if treated early
guarded to poor in severe hypercalcemia
grave in animals with hematemesis
toxicity is short to long depending on degree of injury cause by toxin
treatment may be long due to slow elimination
does bromethalin look different from other rodenticides?
no it is often similar color /texture
what are sources/used of bromethalin
general use pesticide
ingestion of rat poison
secondary poisoning of non target animals (possible in cats)
what is the relative toxicity of bromethalin
highly toxic in dogs and cats
what is the species sensitivity and susceptibility of bromethaline
dogs and cats are susceptible
cats more senstive
guinea pigs are resistant
onset of clinical sings of bromethalin?
acute seen with dosees greater then the LD50
lower doses can cause slower onset
cats tend to have a more subacute toxicity
what are some toxicokinetic concerns with bromethalin?
highly lipophilic- rapidly absorbed
wide distribution with the highest concentrations in fat and brain
metabolized by N demthylation in the liver to the metabolite which is more toxic
what is the mechanism of action of bromethalin toxicosis
neurlogic abnormalities noted are thought to be due to uncoupling of oxidative phosphorylation resutling in lack of atp
insufficient energery fo atp depdent Na and K ion channel pumps results in cerebral edema due to accumulati onf Na in th cells, may also cause lipid perodidation resulting in brain injury
what are the clinical signs of bromethalin toxicosis?
clinical signs are varied and dose dependent cats tend to have a slower onset and lower doses cause a slower onset.
in acute toxicosis (w/in 24 hrs) CNS stimulation is most prominent. In some subacute cases in particular the cat the signs may be consistent with a spinal lesion.
Acute CNS signs are generally CNS excitement. Generalized seizures may be precipitated by light or noise.
Animals may also show CNS depression
does bromethalin have any specific lesions or bloodwork findings?
no but may see cerebral edema, myelin edema, myelin splitting, axonal swelling confined genally to CNS
can bromethalin be chemically tested for i?
chemical analysis is not routinely available can use several specimens including vomitus and bait
does bromethalin have any specific antidote and what is the main type of supportive care required?
no specific antidote
dexamthosone may be helpful
mannitol for cerebral edema
antioxidants for oxidative injury
what is the prognosis/recovery period of bromethalin
if exposure is not severe animals may recover but sever exposure is fatal
what are the sources/uses of strychnine?
restricited use pesticide
currently used to control gophers and squirrels
ingestion of bait intended for other animals
dogs and cats and wild birds eating poisoned rodents
malicious poisoining
what is the relative toxicity of stychine?
extremely toxic in horses, cattle, pigd, gods and highly toxic in cats.
what is the species sensitivity and suceptbility of strychnine?
all animals = susceptible
dogs- most frequently poisoned more sensitive than cats
horses, cattle, pigs are very sensitive
poultry are resistant
onset of clinical signs of strychnine
acute, signs seen to 10 to 120 minutes
what other factors alter strychnine toxicity?
vomiting decreases toxicity
presence of food in stomach may prevent emesis and enhance toxicity or may decrease toxicity by decreasing absorption
small amoutns ingested over time may not cause poisoning because of rapid elimination
what are some toxocokinetic concenrs with strychnine
rapidly abosrbed
does not accumulate
cross BBB
metabolized in liver
excreted in urine as unchanged and metabolites
most lethal dose eliminated in 24 hours
what is the mechanism of action of strychnine toxicosis?
blocks the postsynaptic effect of glycine in the spinal cord
tonic seizures
what are the clinical signs of strychnine toxicosis?
rapid onset and rapid death
neurologic system- excitement
seizures
respiratory failure
does strychnine have any specific lesions or bloodwork findings
none, may note rapid rigor mortis
can strychnine be chemically tested for if so is there a specimen of choice
urine in a live animal and stomach contents in a dead animal or specimens of choice. usually can be detected in the liver
does strychnine have any specific antidote and whats the main type of supportive care required?
no specific antidote
control seizures
useful anitconvulsants in strychnine poisoning?
pentobarbital to effect
thibarbiturates in cats
methocarbamol, guaifensin, xylazine
diazepam
what are some specific considerations in strychnine decontamination
specific considerations for decontamination
sodium bicarbonate is contraindicated in lavage, precipitation of alkaloid by diluted solution of tannic acid or potassium peermaganate
enhancing renal excretion with fluid therapy or ammonium chloride or methionine to acidfy urine
what is the prognoses/recovery period for strychnine?
good if treated early
does zinc phosphide persist in the environment?
stable when dry but decomposes in air or bait within 2 weeks
what are sources/uses of zinc phosphide
most products are restricted use pesticides
available as grain, bait, or tracking powder
sources include: accidental ingestion, caged birds exposed by ingesting food contaminated for killing mice
what is the relative toxicity of zinc phosphide?
highly toxic
what is the species sensitivity and suceptibility of zinc phosphide
birds are most sensitive
onset of clinical signs of zinc phosphide
tpyically acute within 15 minutess
sometimes delayed
what factors alter toxicity of zinc phosphide?
gastric acid enhances toxicity
an empty stomach may decrease toxicity due to decreased acidity
=dogs may survive after eating on an empty stomach
vomiting decreases toxicityq
what is the recovery period of zinc phosphide?
in hospital genrally 48-72 hours
what is the species sensitivity and susceptibility of bromethaline
dogs and cats are susceptible
cats more senstive
guinea pigs are resistant
onset of clinical sings of bromethalin?
acute seen with dosees greater then the LD50
lower doses can cause slower onset
cats tend to have a more subacute toxicity
what are some toxicokinetic concerns with bromethalin?
highly lipophilic- rapidly absorbed
wide distribution with the highest concentrations in fat and brain
metabolized by N demthylation in the liver to the metabolite which is more toxic
what is the mechanism of action of bromethalin toxicosis
neurlogic abnormalities noted are thought to be due to uncoupling of oxidative phosphorylation resutling in lack of atp
insufficient energery fo atp depdent Na and K ion channel pumps results in cerebral edema due to accumulati onf Na in th cells, may also cause lipid perodidation resulting in brain injury
what are the clinical signs of bromethalin toxicosis?
clinical signs are varied and dose dependent cats tend to have a slower onset and lower doses cause a slower onset.
in acute toxicosis (w/in 24 hrs) CNS stimulation is most prominent. In some subacute cases in particular the cat the signs may be consistent with a spinal lesion.
Acute CNS signs are generally CNS excitement. Generalized seizures may be precipitated by light or noise.
Animals may also show CNS depression
does bromethalin have any specific lesions or bloodwork findings?
no but may see cerebral edema, myelin edema, myelin splitting, axonal swelling confined genally to CNS
can bromethalin be chemically tested for i?
chemical analysis is not routinely available can use several specimens including vomitus and bait
does bromethalin have any specific antidote and what is the main type of supportive care required?
no specific antidote
dexamthosone may be helpful
mannitol for cerebral edema
antioxidants for oxidative injury
what is the prognosis/recovery period of bromethalin
if exposure is not severe animals may recover but sever exposure is fatal
what are the sources/uses of strychnine?
restricited use pesticide
currently used to control gophers and squirrels
ingestion of bait intended for other animals
dogs and cats and wild birds eating poisoned rodents
malicious poisoining
what are some toxocokinetic concerns with zinc phosphide?
gastric acid causes hydrolysis
gas in lungs may cause toxicity to persons txing animal
what is the mechanism of action of zinc phosphide toxicosis?
exact mechanism is unknown- irritation of the GIT due to corrosive effects resutls in vomiting blood early in intoxication
reducing compound- phosphine is reducing compound which can complex to metals such as copper, iron and other metals
enzyme dysfunciton also reuslts in inhibiton of oxidative phosphorylation and therefore decreased energy production
phosphine gas can increase damaging reacitve oxygen species formed by the reuction of oxygen
tissues affected are mainly the brain, heart, liver, kidney, and lungs
damage of the blood vessels and erythrocyte membranes and respiratory mucosa is also noted
acute toxicosis is due to absorbed phosphine gas and intact zinc phosphide may cause liver or kidney damage later
what are the clinical signs of zinc phosphide toxicosis
onset is rapid
mainly see GIT, resp, cardiovascular and neurologic signs but many organs can be affected
-neurologic signs are mainly CNS excitement, dogs may show CNS stimulation, signs such as "mad dog running", yelping and convulsions, gastroenteritis may be hemorrhagic
death is usually due to tissue anoxia and may be seen within 3 to 48 hours
in animals that recover may see delayed hepatic and renal injury with associated clinical signs
does zinc phosphide be chemically tested for if so if there is speciment of choice
zinc phosphide can be tested for in various issues
specimens should be rapidly frozen
does zinc phosphide have any specific antidote, decontamination procedures or supportive care
gastic lavage
alkalinzaiton of stomach
oral antacids
what is the progonsis/recovery time of zinc phopshide
animals that vomit may recover
animals with severe signs of tissue damage have a guarded to poor
what are sources/uses of fluoracetate?
currently it is only used in the US as a livestock protection collar (LPC) for controlling coyotes preying on sheep and goats
Sources- eat poisoned animals
what is the relative toxicity of flluoroacetate?
extremely to highly toxic
what is the species sensitivity and susceptibility of fluoroacetate
dogs are very sensitive
birds are most resistant
onset of clinical signs of fluoroacetate
acute
what is the recovery period of fluoroacetate
depends on degree of injury and death is common in animals that show clinical signs
death can occur in 3 to 5 hours with lethal doses rare to live more than 48 hours
what are some toxokinetic concerns with fluoracetate
readily absorbed from the GIT lung or open wounds but no intact skin
distributed throughout the body without accumulation in a particular tissue
fluroacetate is metabolized to monofluroacetic acid by hydrolysis.
-Fluoroacetate and its metabolites are eliminated in the urine within a few days
what is the mechanism of action of fluoroacetate toxicosis
GI signs partly due to direct GI irritant
Cardiac and neurologic signs are due to inhibition of energy production
-combines with acetyl coenzyme A to form fluroacetyl CoA which combines with oxaloacetate to form flurocitrate
-flurocitrate competes with citrate for the active site of the citric acid cycle enzyme
what are the clinical signs of fluoracetate toxicosis
rapid onset of clinical signs and signs are dependent on species
In dogs mainly see signs of CNS stimulation and GI irritation
other signs include hyperthermia due to seizures, and death within 2 to 12 hours
in horses, cattle, sheep, goats see signs of heart failure

in cats and pigs signs are a combination of cns and cardiac signs
does fluoroacetate have any specific lesions or bloodwork findings
non-specific
lesions typically due to CNS excitement and cardiac failure
may see rapid rigor mortis
blood chemistry may show hypocalcemia and other findings associated with shock and convulsions
can fluoroacetate be chemically tested for if so is there a specimen of choice
-chemical analysis for floroactetate is difficult
-specimens are gastric contents and vomitus
-can test for elevated citrate in the kidney tissue or blood but it is not diagnosic/specific for fluroacetate
Does fluoroacetate have any specific antidote and was is the main type of supportive care required
limewater precipitates fluoracetate and therefore may be helpful in decontamination
-acetate donors which compete with the poison at vital biochemical steps to reduce conversion to fluroacetate may be helpful these inlcude Glycerol monoacetate, ethanol 50% and acetic acid 5% soln is an alternative but is less effective, acetamide soln.
-Sodium bicarbonate may reduce toxicity
-other supportive care of seizures and shock
what rodenticides generally have an acute toxicity?
vitamin D, bromethalin, strychnine, zinc phosphide, fluroacetate
what rodenticides have a well recognized subacute to chronic toxicity
anticoagulant rodenticides are always subacute to chronic

bromethaline
zinc phosphide is often acute but can sometimes have delayed hepatic and renal injury
what rodenticides are highly to moderately toxic
all highly to moderate
choliceferol and strychnine is extremely toxic in some species
to what rodenticides are birds most sensitive
zinc phosphide
to what rodenticides are dogs or cats most sensitive
cats- vitamin D, bromethalin, fluoroacetate
dogs- anticoagulant (dogs more than cats but pigs are most sensitive) strychnine (dogs more than cats but large animals are more sensitive
to what rodenticides are large animals more sensitive
strychnine
pigs very sensitive to anticoagulants
what rodenticides are neonates more sensitive too
vitamin D
to what rodenticide are guinea pigs resistant
bromethalin
what rodenticides have lethal synthesis
vitamin D, bromethalin
what rodenticides cause mainly CNS excitement
zinc phosphide, fluoroacetate, bromethalin, strychnine
what rodenticides cause hypercalcemia
vitamin D toxicosis
which rodenticides cause bleeding
anticoagulant rodenticides
what rodenticides and other toxins have elicitable seizures
rodenticides - bromethalin, strychnine, zinc phosphide
other toxins = metaldehyde
what are the sources/uses of metaldehyde?
restricted use pesticide
used alone or in combination with other compounds- as a molluscicide
solid fuel in certain camp stove
what is the relative toxicity of metaldehyde
moderately toxic
what is the species sensitivity and susceptibility of metaldehyde
acute toxicty
usually seen within 1 to 3 hours of ingestion
what is the recovery period of metaldehyde
can last up to 5 days but generally only last about 12 to 72 hours
what factors increase toxicity with metaldehyde
more toxic by inhalation
what factors decrease toxicity of metaldehyde?
enzyme inducers such as phenobarbital may decrease toxicity
what are some toxocokinetic concerns with metaldehyde
metaldehyde is readily absorbed from the GIT
acetaldehyde is formed in the stomach when gastric acid hydrolyzes metaldehyde to acetaldehyde and therefore some acetaldehyde is also absorbed
-acetaldehyde is also formed via by metabolism of metaldehyde by liver microenzymes
-acetaldehyde is metabolized by hepatic aldehyde dehydrogenase to acetic acid which can enter the TCA cycle and be broken down to water and CO2
-both metaldehyde and acetaldehyde cross the blood brain barrier
what is the mechanism of action of metaldehyde in acute toxicosis?
causes direct GI irritation
neurotoxicity may be due to acetaldehyde or metaldehyde
decreased norepineprhine and serotonin appears to be due to increases MAO leading to break down of norepinephrine and serotonin. Decreased levels can lead to seizures
-decreased GABA levels may cause convulsive seizures
-Dogs that survive the acute phase may develop liver failure
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what are the clinical signs of metaldehyde toxicosis?
-primarily neurologic excitement
-convulsions are usually stimulated by external stimuli in cats and sometimes elicitable in dogs
-hyperthermia is likely due to muscle tremors and can be severe
-convulsions may lead to hyperthermia and CNS depression and death by respiratory failure
- other signs may inlcude GI and cardiovascular signs
- dogs that survive the acute phase may develop live failure within 2 to 3 days
Does metaldehyde have any specific lesions or bloodwork findings?
-no specific lesions or bloodwork
-formedaldehyde or acetaldehyde odor in the stomach contents
can metaldehyde be chemically tested for if so is there a specimen of choice
analysis of stomach contents for metaldehyde or acetaldehyde
what is the main treatment of metaldehyde and are their any specific antidotes
-Decontamination is standard and Milk or sidum bicarbonate to decrease absorption
-control seizures
-diazepam, pentobarbital (enzyme inducer), propofol
-Muscle relaxants such as methocarbamol and guiafensen
-xylazine and acepromazine in horses
-other supportive care control hyperthermia, fluid therapy for acidosis, diuresis and maintenance requirement
What are sources/uses of PCP
-only used by certified applicators as a wood preservative to protect lumbar from fungal rot and wood-boring insects

-Sources: licking wood treated with pentachlorophenol, inhalation of toxic amounts from treated walls in sheds and barns
-toxicity usually associated with fumes in crowded barns but is rare due to decreased use
what is the relative toxicity of PCP
high to moderately toxic
onset of clinical signs of PCP
acute or chronic
what factors increase toxicity with PCP
high ambient temperatures, oily or organic solvent
what factors decrease toxicity of PCP
cold temperatures, antithyroid drugs and presence of body fat
what are some toxocokinetic concerns with PCP?
-readily absorbed from the GIT by inhalation and from intact skin
-distributed throughout the body with some accumulation in body fat
-metabolized by conjugation to glucuronic acid
-excreted in urine
-residues in tissues and fat are depleted from teh body within 1 week of exposure
what is the mechanism of action of PCP in acute toxicosis?
-irritation of the respiratory tract mucousa and skin
-uncouples oxidative phosphorlyation and blocks or decrease ATP
-Uncoupling increases oxygen demand in an effort to produce ATP
-end result in neurotoxicity, hyperthermia and metabolic acidosis
What are the clinical signs of PCP toxicosis?
acute toxicosis, onset and duration may be so fast that no signs are seen.
acute- diffuse organ involvement- neurologic excitement (seizures) and hyperthermia
Does PCP have any specific lesions or bloodwork findings
acute and chronic toxicity findings are non specific
may see changes due to shock and seizures with acute. The blood may be very dark. Rapid rigor mortis
-with chronic toxicity hyperkeratosis of the skin and villous like hyperplasia of urinary bladder in chronic cases
Can PCP be chemically tested for if so there is a specimen of choice.
chemical analysis in blood and urine in live animals and kidneys and skin in dead animals
what is the main treatment of PCP and are their any specific antidotes
standard decontamination
supportive care for seizures and hyperthermia
what is the prognosis with PCP
if animal survives 24 hours, chances for complete recovery are fair
what are sources/uses of 2,4-D
generally sprayed forages
sources: include accidental ingestion of concentrations or sprays (cattle), grazing freshly sprayed pastures (Cattle), access to freshly sprayed lawns (pets)
what is the relative toxicity of 2,4-D
moderately toxic
onset of clinical signs of 2,4-D
acute
what species is most sensitive to 2,4-D and what species are susceptible
cattle and dogs are the most susceptible
dogs are more sensitive than othrspecies
what factors increase toxicity with 2,4-D
alter the metabolism of plants resulting in toxicity by increasing accumulation of nitrate and cyanide
improve palability of some poisonous plants thereby increasing toxicity to animals
what are some toxocokinetic concerns with PCP?
readily absorbed from the GIT
poorly absorbed from the skin
well distributed
metabolized in liver
excreted mainly unchanged in the urine y tubular secretion
meat residues in cattle and sheep are unlikely unless exposed to very high concentrations
what is the mechanism of action of 2,4-D acute toxicosis
=Gastrointestinal and neurologic signs
= irritation of the GI mucosa
= uncouple oxidative phosphorlation and depress ribonuclease synthesis
= in dogs may directly affect skeletal muscle membranes
what are the clinical signs of 2,4-D toxicosis?
-Ruminants: gastrointestinal signs, depression, muscle weakness, and emaciation with no convulsion

Dogs: gastrointestinal signs, neurolgic signs
does 2,4-D have any specific lesions or bloodwork findings
no specific findings
rumen stasis with ingested food is a characteristic finding
Does 2,4D have any specific lesions or bloodwork findings
no specific findings
rumen stasis with ingested food is a characterstic finding
Can 2,4-D be chemically tested for if so is there a specimen of choice
chemically analysis by analytical methods are expensive and time ocnsuming
what is the main treatment of 2,4-D and are their any specific antidotes
no specific antidote
need supportive care and during decontamination alkaline diuresis can be considered
what is the prognoses for 2,4D
good if exposure is moderate
what are the sources/uses of ipyridyl hericides
paraquat is RUP and diquat is GUP. It is a broad spectrum desiccant contact herbicide
concentrated forms for agriculture use and dilute forms for lawn and garden
what is the relative toxicity of dipyridyl herbicides
moderately to highly toxic
what species is most sensitive to dipyridyl herbicides and what species are susceptible
all animals are suceptible especially dogs
what is the onset of clinical signs with dipyridyl herbicides
acute GI but pulmonary toxicity delayed with paraquat
-chronic toxicity also described with smaller doses
what factors increase toxicity with dipyridyl herbicides
toxicity is enhanced by a selenium or vitamin E deficiency, depletion of tissue glutathione and oxygen therapy
what are some toxocokinetic concerns with dipyridyl herbicides
diquat is poorly absorbed from the GIT
paraquat is absorbed from the GIT and also from the skin
paraquat is distributed all over the body and achieves high concentrations in the lungs
energy dependent uptake of paraquat by the lungs occurs at a critical level and is time dependent
diquat is not taken up by the lungs like paraquat
minimal metabolism
paraquat is excreted within 24 hours mainly unchanged in the urine
small amounts can be detected in urine for up to 21 days
what is the mechanism of action of dipyridyl herbicides in acute toxicosis
caustic to mucous membranes resulting in severe GI ulceration
other organ injury is mainly respiratory with paraquat and gastrointestinal diquat due to reactive oxygen species formation
-production of free radicals results in membrane damage, damage to DNA and damage to cell enzymes ultimately resulting in cell death
-With paraquat the lung is particularly susceptible due to accumulation in lung tissue and the kidneys due to excretion
-in chronic cases there may be less all at once massive damage to the lungs but rather slow damage and healing with scar tissue
what are the clinical signs of dipyridyl herbicides toxicosis (paraquat)
Paraquat:
- acute toxicosis: early signs are mainly GI abnormalities (caustic so may see vomiting anorexia) but may also see neurologic abnormalities (seizures,depression, and ataxia) at high doses may cause dypsnea
-delayed: primarily due to respiratory dysfunction. Respiratory signs include tachypnea, dyspnea, harsh respiratory sounds and cyanosis
-liver and renal failure may be seen after 2 to 3 days

Subacute or chronic toxicosis: respiratory signs due to progressive pulmonary fibrosis
what are the clinical signs of diquat?
minimal pulmonary signs
mainly see GI, liver, renal, and neurologic signs
do dipyridyl herbicides have any specific lesions or blood work findings
nonspecific
pulmonary lesions with paraquat instertial pneumonia
GI, liver, renal
can dipyridyl heribcides be chemically tested for if so is there a specimen of choice
speciments are suspected plants, stomach, contents and urine in acute cases or lung in chronic
urine samples may be negative after 48 hours
what is the prognosis with dipyridyl herbicides
poor for paraquat