GIT toxins (Lectures 21-24; MT: Meat diapers, batteries, dryer sheets, cationic detergents)

What are the types of phosphides?

- Zinc phosphide

- Aluminum phosphide

- Magnesium phosphide

What are sources of zinc phosphide?

- Rodenticide

- Insecticide

- Grain fumigant (control rodents and insects; When feed is fumigated with these it needs to be covered and then aired out before being fed)

What animals are susceptible to zinc phosphide toxicity?

- All animals susceptible, but especially common in dogs, horses, and wildlife/birds

Are secondary zinc phosphide poisonings common?

- No; Except for in people (inhaling fumes)

What are some of zinc phosphide inhalation (phosphine gas) in people?

- May smell like ammonia, results in emesis, severe respiratory issues, and flu-like signs that can progress

What is the MOA of zinc phosphide?

- Contact with water and an acidic environment (i.e. stomach) results in production of phosphine gas; both phosphide and phosphine gas are severe irritants leading to inflammation and necrosis

- Phosphine gas blocks cytochrome C oxidase which blocks electron transfer and oxidative phosphorylation leading to a lack of ATP production -> Multiple organ involvement -> CV collapse and failure of multiple organs

Describe the onset of clinical signs associated with zinc phosphide toxicity.

- Acute onset with fast progression (15 mins to 4 hours; depends on stomach contents)

What clinical signs are associated with zinc phosphide toxicity?

- Severe GIT pain with distention, anorexia, salivation, diarrhea, vomiting (If GI signs are only signs observed -> Good prognosis)

- CNS signs including malaise, ataxia, tremors, seizures, altered behavior (poorer prognosis)

- Respiratory signs including labored breathing, increased RR, coughing, sneezing, pulmonary edema (poorer prognosis)

- Cardiovascular signs including increased HR, arrhythmias, hypovolemic shock (poorer prognosis)

- Acute death (especially in horses/birds/wildlife)

Broadly, what organs are targeted by zinc phosphide?

- GIT

- Heart

- Lung

- Liver

- Kidney

- CNS

How can a diagnosis of zinc phosphide toxicity be confirmed?

- Phosphine gas in stomach contents and source material (freeze in airtight bag)

How is zinc phosphide toxicity treated?

- Decontaminate asymptomatic patients with emesis, AC and sorbitol, gastric lavage (symptomatic patients will vomit themselves)

- In symptomatic patients, consider anti-emetics, control the diarrhea, IV fluids (e.g., hydration, correct electrolytes and acid/base abnormalities), corticosteroids, analgesics, antibiotics, GI protectants (sucralfate, H2-antagonist, PPIs)

- In both symptomatic and asymptomatic patents, consider PO 5% sodium bicarbonate or antacids (Magnesium aluminum hydroxide) to raise the pH of the stomach

True or false: All forms of arsenic are created equal. If false, how do they differ?

- False

- Organic forms are rare and affect the PNS (optic nerve -> Blindness; peripheral nerves -> Paresis/paralysis/recumbency)

- Inorganic forms affect the GIT

What are sources of arsenic exposure?

- Herbicides/insecticides/rodenticides (largely phased out)

- Wood preservatives (green color to wood)

- Ant baits (uncommonly)

- Natural elements (misc., toys, taxidermy, water)

What is the MOA of arsenic?

- Capillary poison which binds SH groups and affects the enzymes associated with cellular respiration/oxidative enzymes, affecting the GIT, kidney, liver, skin, and lungs leading to acute cardiovascular collapse, shock, and death

- In humans, it is mutagenic, embryotoxic, and carcinogenic

Describe the onset of clinical signs associated with arsenic toxicity. Is it commonly acute or chronic exposures?

- Acute, abrupt onset

- Rarely chronic in animals

What signs does the inorganic form of arsenic result in?

- Typical GI signs (abdominal pain, ataxia, weakness, lethargy, salivation, vomiting/regurgitation, diarrhea)

- Multi-systemic signs including severe fluids loss and shock, death may occur with few signs

What signs does the organic form of arsenic result in?

- Blindness

- Paresis/paralysis (demyelination and axonal degeneration)

- "Happy pig/poultry syndrome"

How can a diagnosis of arsenic toxicity be confirmed?

- Antemortem: Blood/urine (short half-life)

- Postmortem: Liver, kidney,

How is arsenic toxicity treated?

- Supportive (treating shock/fluids)

- Chelators (BAL (dimercaprol) or DMSA (succimer))

- Note: DMSA (succimer) is chelator of choice

What are some other names for Vomitoxin?

- Deoxynivalenol

- DON

Vomitoxin is a ________________ produced by ___________________.

- Mycotoxin

- Fusarium spp.

Mold growth and mycotoxin production are dependent on which factors?

- Mold growth and mycotoxin production are dependent on substrate and environmental factors

- Mycotoxin production is also depdendent on genetics

What type of feed is vomitoxin most commonly found in?

- Grain (wheat specifically)

- Less commonly: grass, hay (wet times)

Which species are susceptible to Vomitoxin toxicity?

- All species (swine most sensitive, some monogastrics like dogs are particularly sensitive)

What are some clinical signs associated with Vomitoxin toxicity (chronic/subclinical exposures?

- Some feed refusal

- Diminished immune responses

- Poor production with respect to weight loss

What is the prognosis of Vomitoxin toxicity?

- Rarely fatal

What clinicopathologic abnormalities and lesions are associated with Vomitoxin toxicity?

- None

What are methods to confirm a diagnosis of Vomitoxin toxicity?

- Test feed (Vomitoxin or other mycotoxins)

- Consider representative sampling of feed as there can be hot spots and feed may be gone by the time the animal is presenting

- Also, use caution when using labs that test for mycotoxins and sell binders

How is Vomitoxin toxicity treated?

- Remove source

- Prevention

Describe the signs/problems associated with meat diaper ingestion.

- Mild GI upset

- They absorb a lot of fluid, so make sure the animal has free access to water and is well hydrated

What are Phenoxy herbicides? Which is most common?

- A group of structurally similar herbicides

- 2,4-D is the #1 herbicide used in agriculture and for at home use ("weed and feed")

How can the term "weed and feed" be used to remember the ingredients of phenoxy herbicides?

- Weed: Phenoxyherbicide component

- Feed: N, P, and K

What animals are susceptible to phenoxyherbicide toxicity?

- All animals are susceptible but dogs are especially sensitive (may be due to lack of OAT transporter and poor ability to tubular secrete organic acids)

How do animals commonly access phenoxyherbicides?

- Appropriately treated areas (low risk) but access to puddles/piles/concentrated areas are a high risk

Describe the half-life of phenoxy herbicides.

- Short (except in dogs)

Describe the absorption and excretion of phenoxy herbicides.

- Rapidly absorbed from GIT

- Excreted primarily via the urine unchanged

Describe the onset of clinical signs associated with phenoxy herbicide toxicity.

- Abrupt onset

What are signs associated with phenoxy herbicide toxicity?

- Low exposures: Anorexia, vomiting-regurgitation, diarrhea; Self-limiting and gone in 24 hours)

- High exposures ("spills"): GIT signs as above, ataxia, reluctance to move, myotonia, weakness

- Overall: GIT and neuromuscular

Describe the prognosis of phenoxy herbicide toxicity.

- Excellent; Rarely fatal

How can an electromyogram be used to confirm a diagnosis of phenoxy herbicide toxicity?

- Myotonia (increased insertional activity, abnormally long muscle contractions with a slow relaxation - sounds like a dive bomber)

What sampling can be done for chemical diagnosis of phenoxy herbicide ingestion/toxicity?

- Serum

- Urine (excreted unchanged)

- Liver/kidney postmortem

How is phenoxyherbicide toxicity treated in an asymptomatic patient?

- Decontamination

How is phenoxyherbicide toxicity treated in a symptomatic patient?

- Anti-emetic, AC, cathartic, gastric lavage are options (not likely to be beneficial)

- Diuresis for 48 hours

- Analgesics/muscle relaxants or other supportive measures

What are NSAIDs?

- Analgesics

- Antipyretics

- Anti-inflammatories

When a patient presents for a possible NSAID toxicity, what is the first question to ask?

- What is the label (need dose, form, and there is concern for dual or triple exposure, commonly with acetaminophen and caffeine)

How do different NSAID products differ/how are they similar?

- Usually have similar MOA

- They have different half-lives, protein-binding, enterohepatic recirculation, excretory pathways, and lipophilicity (important to realize for treatment options)

What is the toxic dose of NSAID exposure?

- Hard to find (different doses depending on exposure duratio - do the math)

Cats and neonates are more or less sensitive to NSAID toxicity relative to dogs?

- 8-10 times more sensitive (low in glucuronidation and glycine conjugation)

True or false: Ferrets are sensitive to ibuprophen toxicity.

- True

Describe the absorption of NSAIDs.

- Rapid

Describe the major and minor MOAs of NSAID toxicity.

- Major: Inhibition of cylooxygenase (PH synthetase) activity leading to lack of PGI2 and PGE2 leading to gastric ulceration and renal necrosis

- Minor: Inhibits platelet cyclooxygenase leading to a decrease in platelet aggregation in more chronic exposures; At high doses there are CNS effects via opioid receptors

- Note: Carprofen and some other NSAIDs can elicit an immune mediated attack on an altered protein in the liver of dogs

What are the clinical signs associated with NSAID toxicity?

- GI upset (4 to 6 hours or less) - anorexia, vomiting, abdominal pain, diarrhea

- GI ulceration (12 hours to 4 days)

- Renal changes (12 hours to 5 days)

- Neurologic signs (dose dependent with respect to timing, but generally within first 12 hours resulting in seizures and coma)

- Depression and lethargy

What clinicopathologic abnormalities can be associated with NSAID toxicity?

- Increased ALT and ALP in some patients (Dr. T suspects this is a reactive hepatopathy secondary to gastroenteritis)

- Hemoconcentration

What gross lesions are associated with NSAID toxicity?

- Hemorrhage, inflammation, ulceration, and erosion of GIT

What histologic lesions are associated with NSAID toxicity?

- Inflammation, ulceration, necrosis of GIT

- Renal tubular necrosis and interstitial nephritis

- Perhaps hepatic necrosis (uncommon)

What is the goal in an asymptomatic patient presenting for NSAID ingestion.

- Prevent clinical signs

True or false: NSAID toxicity is commonly confirmed analytically.

- False; It is uncommon and usually only done in malicious poisonings; there are no well-established serum levels

What is the focus of treatment for a patient with NSAID toxicity that is asymptomatic?

- Prevent gastric ulceration and renal disease (possibly also liver disease and CNS effects)

What is the prognosis for NSAID toxicity? What are some prognostic indicators?

- Great is treated early and aggressively

- Duration of anorexia, age, and delay in treatment are prognostic indicators for death/euthanasia

True or false: Most patients with NSAID toxicity present asymptomatic.

- True

How is NSAID toxicity treated?

- Decontaminate (emesis - probably no good after 2 hours, anti-emetic, repeated AC to prevent enterohepatic recirculation for certain NSAIDs, sorbitol, gastric lavage)

- Establish baseline (CBC, panel, UA)

- Diuresis (2-2.5x maintenance to correct deficits and enhance excretion) for a minimum of 48 hours (72 hours for naproxen); If normal 24 hours later will be okay but discharge with GI protectants for an additional 7-10 days; aggressively diurese in horses

- Monitor BUN, Creatinine, USG, PCV, TP, liver enzymes (must be normal off fluids for 24 hours before discharge)

- Liver protectants

- Naloxone for CNS signs with ibuprofen

- IV lipid therapy depending on NSAID (symptomatic life saving measure or high dose exposures of ibuprofen and naproxen)

- Therapeutic plasma exchange for ibuprofen and others that are highly protein bound (high dose exposures where neuro signs are expected; not readily available)

Why is diuresis essential in patients with NSAID toxicity?

- Enhance excretion of toxin/metabolites

- Enhance GFR and decrease touch time to cells as well as prevent tubular reabsorption

True or false: Sucralfate is the best GI protectant for asymptomatic patients.

- False; It binds to damaged GI mucosa and is better for symptomatic patients (better for treatment than prevention)

What are the two types of batteries?

- Corrosive (dry cell batteries which have acidic (ammonium chloride or manganese dioxide) or alkaline (potassium/sodium hydroxide) dry cells)

- Current (Lithium disc/button batteries which are alkaline on the cathode side and acidic on the anode side as the current passes through the battery)

What is the effect of ingested batteries?

- Damage to mucosal lining

How should magnet ingestions be managed?

- As a non-toxic FB -> Consider radiographs, emesis or make sure they pass (one is usually okay, two or more is a serious problem)

In patients that ingest batteries (or magnets) we want to see them pass in ______________ hours. If not, one should do what?

- 36-48 hours

- Go and get battery if it doesn't pass because prolonged exposure or if battery is damaged will cause problems over time)

How should battery ingestion in animals be managed?

- Emesis if not damaged (make sure disc batteries don't get lodged in esophagus)

- Dilution

- Radiographs (may need to remove if there is suspected puncture or if it is not passing after 36-48 hours)

- GI protectants if the battery is not intact, there is suspected damage to the mucosa, or if lithium/disc/button battery

- Can also consider bulk of saccharide cathartics, analgesics, antibiotics, IV fluids, endoscopy, +/- surgery

True or false: Activated charcoal is a good treatment option for battery ingestion.

- NO

How many blister beetles nationwide present risk for Cantharidin toxicity?

- ~6 (not generally found in our area but recent information suggests there may be in the future)

What genus of blister beetles is most commonly concerned?

- Epicauta

Describe the lifecycle of blister beetles and how it relates to exposure sources.

- The beetles follow grasshoppers and feed on alfalfa. the beetle larvae feed on grasshopper eggs, overwinter, and emerge in late spring where adults feed on alfalfa blooms.

What are some sources of cantharidin toxicity?

- Used maliciously

- Alfalfa

- Potential biopesticide

- Aphrodisiac

Describe the biology of male and female blister beetles as it related to whether they contain Cantharidin.

- Males have glands in the reproductive tract which secrete Cantharidin that is transferred to the female during mating, which is then transferred to the eggs to protect them from predators.

How many blister beetles are required to cause a toxicity?

- A few to hundreds, depending on the species

What species are most susceptible to blister beetle/cantharidin toxicity?

- Horses and cows

Describe the MOA of Cantharidin.

- Lipid soluble substance which is highly irritating and penetration the skin to cause acantholysis (separation of stratum spinosum to form vesicles)

Describe the absorption and excretion of Cantharidin.

- Readily absorbed

- Excreted unchanged in urine primarily

What two clinicopathologic abnormalities are most associated with Cantharidin toxicity?

- Hypocalcemia

- Hypomagnesemia

Describe the onset of clinical signs associated with Cantharidin toxicity.

- Abrupt

What clinical signs are associated with Cantharidin toxicity?

- Severe GIT distress/colic involving restlessness, irritability, sweating, pawing, grunting, trembling, increased RR/HR, diarrhea, gastric reflux, frequent/straining urination (renal)

- CNS signs involving head pressing, disorientation, seizures, and lethargy in up to 20% of patients

- Myocardial signs in a small percentage of patients

- Shock and death

What clinicopathologic abnormalities are associated with Cantharidin toxicity?

- Hypocalcemia

- Hypomagnesemia

- Nonspecific signs such as dehydration and an inflammatory leukogram

What gross lesions are associated with Cantharidin toxicity?

- Congestion, inflammation, hemorrhage in the GIT (ulcers rarely) and renal system

- Vesiculation of the non-glandular stomach in horses

- Lesions are minimal to severe and generally do not match the severity of signs

What microscopic lesions are associated with Cantharidin toxicity?

- Gastroenteritis

- Nephritis

- Cystitis

- Myocardial necrosis

What organ systems are targeted by Cantharidin toxicity?

- GIT

- Renal

- CNS and myocardium

When identifying a beetle involved in Cantharidin toxicity, what information needs to be included?

- Genus and species

What sampling can be done to confirm a diagnosis of Cantharidin toxicity?

- Urine is best

- Can use serum

- Postmorte, sample GI contents, kidney

- The beetle itself

What are the 4 aims of treatment for Cantharidin toxicity?

1) Remove source

2) Correct fluid loss and provide maintenance/correct Mg/Ca

3) Assist excretion

4) Manage pain

What are two ways to assist excretion of Cantharidin?

1) Enhance excretion through the urine and prevent contact time and reabsorption through fluid therapy

2) Enhance fecal excretion via AC

What is the prognosis for Cantharidin toxicity?

- 50% even with aggressive and early intervention

In unused dryer sheets, what are some components which can be problematic with ingestion?

- Cationic detergents (25-50%, as high as 95% in some)

- Caustic/corrosive substances (with cationic detergents concentration is usually more problematic than pH)

What signs can ingestion of unused dryer sheets lead to?

- GIT inflammation and necrosis

What are potential problems associated with ingestion of used dryer sheets?

- FB possibility, most will pass, rarely cause issues

What are treatment options for ingestion of dryer sheets?

- GI protectants

- Analgesics

- Anti-inflammatories

- Feeding tube

- Endoscopy

- Antibiotics

- Other symptomatic care

What are some examples of products containing cationic detergents?

- Fabric softeners

- Germicides

- Sanitizers

- Dryer sheets

- Pot-pourris

Cationic detergents can be highly to extremely toxic due to the corrosive effect of _______________ (but one should also think about the ________).

- Concentration

- pH

What are cationic detergents?

- Quaternary ammonium compounds with groups attached

Cationic detergent solutions can be corrosive at concentrations as low as....

- Over 1%

What clinical signs can oral ingestion of cationic detergents lead to?

- Salivation/vomiting (most common sign)

- Muscle weakness and fasciculations

- CNS and respiratory depression

- Fevers

- Seizure

- Collapse

- Coma

- Note: There can also be corrosive lesions of the paws and oral cavity and further down the GIT resulting in swelling, ulceration, and sloughing of GI mucosa (can be noted on endoscopy)

What are treatment options for ingestion of cationic detergents?

- Dilution (milk, water, egg whites)

- Endoscopy to evaluate the esophagus, stomach, and upper intestinal tract

- Maintain fluid and electrolyte balance

- Analgesics

- Prophylactic ABX

- GI protectants

- Feeding tube placement

- Wash paws and hair

- Monitor for hyperthermia and inflammation