Exam 1 (L1-10)

How do acute heart toxicities appear?

• Arrhythmias

• Bradycardia to tachycardia

• AV block

• QT prolongation →

• Decrease in cardiac function

How do chronic heart toxicities appear?

• Hypertrophy (eccentric) → enlarged LV

• Malignant arrhythmia → can cause cardiac arrest and is usually a ventricular origin

How do Xenobiotics cause heart toxicity?

1. Fetal Gene Expression → heart hypertrophy (eccentric hypertrophy)

2. Cell Death results in dilation → heart failure

What are some examples of drugs that can cause heart toxicity?

• Anti-arrhythmics

• Inotropics

• CNS drugs

• Local anesthetics

• ABX (aminoglycocides, macrolides, flouroquinolones)

What are some medications that can prolong heart QT complexes?

• Antihistamines

• Prokinetic drugs → cisapride

• Methylxanthines

• Sildenafil

What kind of toxin is monensin?

Ionophore - antibiotic

What kind of toxic agent are ionophores?

Cause heart issues in horse, cattle, sheep and goats → feed additive

• Horse: prolong depolarization, V tach, AV block

• Cattle: QT/QRS prolongation, AV block, muscle damage

What kind of toxin is amitraz?

tri-aza-pentadiene compound in dog flea collars

How does amitraz cause toxicity?

Inhibits MAO (monoamine oxidase) enzyme and works as a a2-adrenergic receptor agonist

• Bradycardia, AV blcok, diminished CO

What are the toxic components of blister beetles?

Can-thari-din, which inhbits serine-threonine protein phosphatase

• Blocks adenosine a1 receptors → regulates myocardial O2 consumption → anti-adrenergic eeffect

• Increased HR, myocardial dysfunction

• Colic in horses

How do blister beetles cause toxicity?

Swarm in alfalfa fields and are crushed into the hay when its baled

What is a characteristic feature of blister beetle toxicity?

“Thumps” → diaphragmatic contractions due to hypocalcemia

What are some signs of bufo toad toxicity?

• Salivation, head shaking, pawing at mouth, retching

• CNS and cardiac issues → can be life-threatening

If a dog eats or mouths a bufo toad, what should be done?

Rinse the mouth out ASAP and seek veterinary care

How does bufo toads cause toxicity?

Their glands secret bufotoxin, which includes glycosides (bufadienolies) as well as epinephrine, norepinephrine and serotonin

How do foxgloves (digitalis) cause toxicity?

• Digitalis glycosides

• Absorbed in GIT and elminated by heaptic metabolism/urine

• Inhibits N/K pump → calcium imbalance adn cardiac rhythm disturbances

What are the signs of foxglove (digitalis) toxicity?

Anorexia, colic, diarrhea (GI signs) precede cardiovascular signs

How does milkweed cause toxicity?

Cardenolides and Galitoxin

• Inhibits N/K pump → calcium imbalance and cardiac rhythm disturbances

How does oleander cause toxicity?

• Cardiac glycosides (oleandrin and neriine)

• Inhibits N/K pump → calcium imbalance adn cardiac rhythm disturbances

How does Lilly of the Valley cause toxicity?

Convallotoxin

• Cardiac glycosides

How do azaleas cause toxicity?

Grayanotoxins

• Bind to voltage-gated Na channel → state of depolarization

What are signs of azalea toxicity?

ADR, excess salivation, vomiting, bradycardia, arrhythmias, seizures

What is a toxic plant found in appalachia?

Mountain laurel and sheep laurel

What are the toxic components of mountain and sheep laurels?

Grayanotoxins

• Bind to voltage gated Na-channel → depolarization state

What are the signs of mountain and sheep laurel toxicity?

• Excessive salication, perspiration, vomiting, dizziness, weakness around mouth, low BP, sinus bradycardia

What do avocados cause toxicity?

• Persin

• Myocardial necrosis

In what animals are avocados toxic?

Cats, dogs, cattle, goats, rabbits, rats, guinea pigs, birds, fish, and horses

What is the toxic component of cotton plants/cottonseed?

Gossypol → acute heart failure, cardiac necrosis, monogastrics more affected

What animal is most predisposed to Yew toxicosis?

Livestock → eat in winter cuz evergreen

What’s the toxic component of Yews?

Taxine alkaloids → cardiac ion channels, sudden death

What is a common plant found in the Solanaceae family?

Deadly nightshade, tomato green part of plant

What is the toxic component of solanaceae?

• Hyoscyamine

• Scopolamine

• Atropine

• Inhibits PNS, colid, mydriasis, shock, hypotension

What is the toxic component of Death Camas?

Zig-a-cine (steroid alkaloid)

What is the toxic component of White Snakeroot?

Tremetone → found in milk, “acetone” smell to breath

High levels of ______ may cause fatal pulmonary edema in pigs within 1-4 hours post-exposure

Fumonisin

_______ is an irritant to upper airways and is the reaction of ammonia with ____ ______.

Chlorine/chroamine

Sodium hypochlorite

_______ irritates the eyes and respiratory membranes and can make bacteria and parasitic infections worse.

Ammonia

_______ gas becomes an asphyxiant at 85% and can be an expolosive hazard.

Methane gas

_______ _______ can paralyze the respiratory tract at high concentrations, is heavier than air and is common in manure pits and smells like ______.

Hydrogen Sulfide → smells like rotten eggs

Some cookware contains _______, which can cause pulmonary edema and hemorrhages in birds if heated above a certain degree.

PTFE-coated cookware

What is the toxic component of poison hemlock?

N-methyl coniine, coniine → blocks NM junctions

What is the toxic component of water hemlock?

Cicutoxin → inhibits GABAergic receptors → seizures

What is ABPEE?

Acute bovine pulmonary emphysema and edema

• When cattle turn over to more lush pastures, they get tryptophan from the feed, which can be degraded into 3-methylindole → absorbed to bloodstream → pneumotoxicity

How do Perilla mint and Alfatoxin 4-ipomeanol cause toxicity?

Damages pulmonary endothelum and type I pneumocytes (gas exchange) → proliferation of type II pneumocytes (surfactant production) → fill lungs → interstitial pneumonia → fatal

• Causes ABPEE

What are examples of cyanogenic plants?

Wild cherry, choke cherry, apricot, peach (need to be crushed), apple

Johnson grass, arrow grass, sudan grass

What are the most common toxic components of cyanogenic plants?

Amygdalin and prunasin → converted to HCN in GIT and absorbed → inhibits cellular respiration

What are the clinical signs of cyanogenic plant ingestion?

Onset of signs in peracute → hyperventilation, venous blood is bright cherry red

Typically if they ain’t dead, they fine

How is cyanogenic plant toxicity treated?

Not rarely done cuz animals typically just die → administer sodium nitrite

What are some plants that contain nitrates?

Lamb’s quarter, pigweed, Johnson grass

Oats, Corn, Wheat, Alfalfa

What conditions increase plant nitrate content?

Drought followed by rain, temperature extremes

What is the toxic component of plants that contain nitrates?

NO3 (nitrate) is reduced to NO2 (nitrite) → combines with Hb (Fe++) and oxidizes to methemoglobin (Fe+++) → can’t bind O2

___________ is a dye that converts methemoglobin to hemoglobin.

Methylene Blue

What is the toxic component of red maple?

Tannins, gallic acid, pyrogallol

What does red maple toxicity cause?

Methemoglobinemia and acute hemolytic anemia → damage to horse RBCs

Poison

a substance that is capable of causing illness or death of a living organism when introduced or absorbed

Poisonous

substance causing or capable of causing death or illness if taken into the body

Toxin

a poisonous substance that is a specific product of the metabolic activities of a living organism, is notability toxic when introduced into tissues of another organism

What is a toxin capable of inducing?

antibody formation

Toxic

substance containing or being poisonous material especially when capable of causing death or serous debilitation

Toxicant

any toxic substance

Toxicants can be ___ or ___ occuring.

synthetic, naturally

Where can different toxicants be found

in air, soil, water, food

Venom

a toxic substance produced by some animals that is injected into prey or an enemy chiefly by biting or stinging and has an injurious or lethal effect broadly

If YOU bite it and die it is _______

poison

If IT bites you and you die its ____

venom

Toxicosis

a pathological condition caused by the action of a poison/toxin

Intoxication

the state of being intoxicated

Should you specify the type of intoxication?

yes

Poisoning

the action of administering poison to a living organism

Toxicity

the quality of being toxic or poisonous

Does "natural", "organic", "non-artificial" tells you anything about safety?

NO

What are the seven most deadly (to humans) chemical substances?

botulinum toxin A, tetanus toxin A, diphtheria toxin, dioxin, muscarine, bufotoxin, sarin

Where does botulinum toxin A come from?

Clostridium botulinum

Where does tetanus toxin A come from?

Clostridium tetani

Where does diphtheria toxin come from

corynebacterium diphtheriae

Where does dioxin come from?

its manufactured

Where does muscarine come from?

mushrooms

Where does bufotoxin come from?

toad, bufo

Where does sarin come from?

manufactured

Hazard

something that has the potential to cause harm

What does hazard include?

element of magnitude (ex. “seizures” vs. “tremors”)

What are examples of hazards?

physical trauma, chemical effect, infection, neoplasia

Risk

the likelihood / probability that a hazard will cause harm

What does risk include?

element of probability

What is the calculation for risk?

hazard x probability

Risk assessment

the systematic process of identifying, analyzing and evaluating potential hazards or risks that could cause harm, determining the risk, and what can be done to reduce or eliminate it

Hazard is something that has the ___ to harm you

POTENTIAL

Risk is the _____ of hazard causing harm

LIKELIHOOD

Without context, hazard is ___

meaningless

What are the steps to toxicology analysis?

list toxicological differentials, obtain appropriate samples w/ appropriate extraction technique, determine appropriate analysis, interpret results

What are toxicological differential based on?

signalment, history, clinical signs, other diagnostics

If toxic etiology on the differential list is that ALWAYS the cause?

no

What are many toxicological diagnosis based on?

HISTORY and analysis is confirmatory

What things should you not assume in animal history?

that what you are told is the truth, that the owner will volunteer all info, and the case is cut and dry

What makes up the examination?

physical exam and postmortem exam

What are the things you collect in antemortem sampling

blood (whole and serum), urine, feces, vomit/gastric lavage, hair in topical exposure

Why is serum separation important?

prevents sample degradation and allows better testing

What organs do you collect for postmorem sampling

liver, kidney, brain, heart, skeletal muscle, fat, etc

What fluids should you collect postmortem?

urine, blood from heart, aqueous fluid

What GI contents should you sample postmortem?

stomach or rumen contents, cecal or intestinal contents, feces, crop or gizzard contents