Toxicology - Exam 1: Too much kills 'em, Too little kills 'em, What can ya do?

A naturally occurring poison is what?

A toxin

A substance that produces adverse biological effects is what?

A toxicant

A toxicant that causes immediate death/illness in small amounts is what?

A poison

A chemical substance in an organism that is not naturally produced/expected is what?

A xenobiotic

The quantity of a toxicant that causes toxic effect is what?

Toxicity

The disease state that results from exposure to a toxicant is what?

Toxicosis

What are the most relevant target molecules of toxicants?

Nucleic acids, proteins, and membrane lipids

T/F: It is in your best interest to stabilize the patient and remove the animal from the potential source of toxicosis, and then treating the patient

True

Inducing emesis is best within what time period?

2 hours, limited value after 4 hours

T/F: An antidote is the cure to a specific toxicant or poison

False, antidote is an agent that has action against the toxicant, may not be 100% effective

What do consumed oxalates combine with to become insoluble?

Calcium

What is the main reason why ruminants get muscle tremors, weakness, and depression due to oxalate toxicity?

Hypocalcemia

What is a significant clinical sign of oxalate toxicity in horses?

Increased bone resorption (due to hypocalcemia)

How does oxalate toxicity affect the kidneys

Insoluble calcium oxalate can block tubules

What is the treatment of oxalate toxicity?

Calcium gluconate to correct hypocalcemia and limewater (calcium hydroxylate) to bind oxalates, preventing absorption

What supplement can help prevent oxalate toxicity?

Dicalcium phosphate (prevent absorption)

What are the four most common (or at least discussed) plants that cause oxalate toxicity?

Halogeton, Pigweed, Rhubarb, and Curly dock

Where are you most likely to find Halogeton?

In alkaline, disturbed soil (trails, roads)

What is a characteristic clinical sign of pigweed?

Knuckling of the pastern/fetlock

What is the most toxic part of Rhubarb?

Leaves

What is the mechanism of action for oak toxicity?

Hydro-soluble tannins denature proteins

T/F: The leaf is the toxic part of the oak tree

False, all parts of the plant are toxic

What two organ systems are most affected by oak toxicity?

Kidneys (tubular damage) and Gastrointestinal (irritation, constipation, diarrhea)

Bracken fern mostly affects what species?

Cattle

What is the main clinical sign of bracken fern toxicity?

Hematuria due to neoplastic formation in urinary tract

What is the toxin in bracken fern?

Ptaquiloside

Your horse started getting dehydrated, went into shock, and got renal damage. You also astutely notice necrosis of the mucus membranes. You, a genius, suspect cantharidin toxicity. Where do you suspect your horse got it from?

Blister beetles in alfalfa hay

ABPEE is caused when dry pasture suddenly becomes lush and green due to an increased amount of what?

L-tryptophan

L-tryptophan is converted into what toxin that leads to pulmonary edema and emphysema?

3-methylindole

What cattle type is most commonly affected by ABPEE

Beef cattle

T/F: Pasture type does not matter in ABPEE

True

T/F: Nursing calves are unaffected by ABPEE

True (immature rumen and just don't eat as much)

T/F: ABPEE takes a few days to show signs, and signs slowly progress

False, acute onset with severe dyspnea

T/F: Quickly moving the herd off the offending pasture is the best first step to treating ABPEE

False, exercise can lead to collapse and death

What methods can you use to prevent ABPEE?

Quality hay before turn out (so they aren't hungry?)

Gradual exposure to pasture

Pre-emptive ionophores

What is the initial compound in sweet potatoes that mold converts to a toxin, and what is the toxic compound?

4-hydroxymyoporone --> 4-ipomeanol

What sign is more indicative of moldy sweet potato toxicity than of ABPEE?

Coughing

What is the most toxic stage of perilla mint toxicity?

Seed and flower

What is the toxin in perilla mint?

Perilla ketone (similar to 4-ipomeanol)

T/F: Perilla mint is a lung toxicity just like ABPEE and moldy sweet potato

True

What is a major component of ensiled forages that smells like bleach and can cause outbreaks of ARDS?

Nitrogen dioxide

What toxin comes from welding in closed barns, leading to colloidal particles in terminal alveoli?

Zinc oxide

What are the five M's of a down animal?

Metabolic, Musculoskeletal, Metritis, Mastitis, and Massive sepsis

What is the most toxic part of Senna?

Seeds

What is the main clinical sign of Senna toxicity?

Myonecrosis (leading to myoglobinuria)

What findings on blood work would you expect with Senna toxicity?

Increased muscle enzymes (CK, AST)

What is toxicant associated with fescue toxicity?

Ergot alkaloids produced by the symbiotic fungus

What receptors do ergot alkaloids have an effect on?

α₂-adrenergic receptors

dopaminergic receptors

serotonergic receptors

What physiologic response does the body have to fescue toxicity?

Vasoconstriction, which can cause heat stress in warm climates or tissue ischemia in the distal limbs

What are the major clinical signs of black walnut toxicity in horses?

Limb edema and laminitis

Where might a horse obtain large amounts of black walnut?

In shavings

How does selenium toxicity cause disease?

Through oxidative tissue damage

What two compounds prevent oxidative damage, and thus are depleted in selenium toxicity?

Glutathione and S-adenosylmethionine

T/F: Selenium is most commonly an acute disease from ingestion of seleniferous forage

False, chronic ingestion leads to progressive disease

What can breath smell like in acute selenium toxicity?

Garlic

What physical signs are present from chronic selenium toxicity?

Hoof deformities and loss of mane/tail hairs

How can you diagnose selenium toxicity?

Whole blood Selenium (should be < 0.35 ppm)

What disease does Box Elder cause?

Lipid storage myopathy

What is the toxin in Box Elder and its MOA?

Hypoglycin A; irreversible binds acetyl CoA dehydrogenases

What signs are associated with Box Elder?

Muscle weakness, sweating, fasciculations, and myoglobinuria

What is the mechanism of action of cardiac glycosides?

Reversibly inhiibts Na/K ATPase, leading to increased intracellular sodium/calcium and cardiac contractions

What cardiac signs can you expect from cardiac glycosides?

Bradycardia and arrhythmias (due to increased vagal tone)

What plant causes cardiac glycoside toxicity?

Oleander

What part of oleander is cardiotoxic?

All of it

T/F: Oleander causes mostly just cardiac signs

False, gastrointestinal signs and pulmonary signs too

What is the main reason behind all of oleander toxicity's signs?

Failure of the heart leads to venous congestion and edema, as well as hypoxia in the tissues

What medication may be useful in oleander toxicity?

Atropine

What is the mechanism of action for grayanotoxin?

Binds voltage gated sodium channels

What plants contain grayanotoxin?

Rhododendron (azaleas)

What is the main sign of grayanotoxin in goats?

Vomiting!

What is the mechanism of action of cardiotoxic taxine alkaloids?

Inhibit sodium and calcium channels

What plant contains cardiotoxic taxine alkaloids?

Yew. Yes, Yew

T/F: The Yew berry is the most toxic part of the plant

False, least toxic

What are the four major clinical signs of Yew toxicity (not including death)?

Dyspnea, muscle tremors, collapse, and bradycardia

What is the normal mechanism of action of ionophores?

Bind electrolytes and transport across cell membranes, which can disrupt the normal ion gradient

How do ionophores cause muscle damage in horses?

By increasing intracellular calcium, leading to ATP depletion and cell death

What muscle type is most affected by ionophores in horses?

Cardiac

What part of the plant are nitrates most concentrated?

Bottom third (since nitrogen comes from the soil)

How does nitrite toxicity cause disease?

It converts hemoglobin to methemoglobin, which can't bind oxygen, leading to hypoxia

What characteristic of blood is suggestive of nitrate toxicity?

Dark brown blood

How can we diagnose nitrate toxicity?

Measure nitrate (>20 mcg/mL) or nitrite (>0.5 mcg/mL)

What is the treatment of nitrate toxicity?

Methylene blue IV to convert back into hemoglobin

What will cause a release of hydrocyanic acid in plants, and what will lessen its toxicity?

Damage; drying

How does cyanide cause toxicity?

It prevents conversion to methemoglobin, meaning oxygen remains bound to hemoglobin and can't reach tissues

What major clinical sign is indicative of cyanide toxicity?

Bright red mucus membranes

What will cyanide smell like in gastric contents?

Bitter almonds

What is the treatment plan for cyanide toxicity?

Sodium nitrite (to convert to methemoglobin) and sodium thiosulfate (so it can be excreted in urine)

What two things decrease copper accumulation in sheep so that it is not absorbed into circulation?

Molybdenum and sulfate

Where is copper stored?

Liver

When a stressful event releases copper into the system, what is the main disease it causes?

Intravascular hemolysis

T/F: Sheep with copper toxicity DIE!

True -Bennet

False -Stockler

Tralse -Benckler

Farue -Stonnet

eurT -tenneB

eslaF -relkcotS

Would you expect liver damage from a toxicity that is stored in the liver?

Yes

How does red maple cause disease?

Oxidative damage to RBCs

What is the toxin in red maple?

Gallic acid

What is a finding on blood analysis that would point to red maple toxicosis?

Heinz body anemia

What treatment option may be used for red maple toxicity that would reduce methemoglobin back to hemoglobin?

Ascorbic acid

What is the main toxin to cows in bracken fern?

Ptaquiloside

What is the characteristic sign of bracken fern toxicity in cows?

Bleeding disorders

What is the main toxin to horses in bracken fern?

Thiaminase

What is the treatment of bracken fern toxicity in horses?

Parenteral thiamine (vitamin B1)