Exam 1 Flashcards

Question 1

Q

What is Pharmacology

Answer

A

science that broadly deals with the physical and chemical properties, actions, absorption, and fate of drugs that modify biological function
Science of drugs

Question 2

Q

What is Clinical pharmacology

Answer

A

clinical science that integrates disease pathophysiology with fundamental concepts of pharmacology to provide a rational basis for drug therapy in patients
Applied to clinical patients

Question 3

Q

What is Veterinary pharmacology

Answer

A

science that describes the use of drugs in a clinical setting in different animal species

Question 4

Q

What is a drug

Answer

A

a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease

A substance (other than food) intended to affect the structure or any function of the body

Question 5

Q

What is a drug product

Answer

A

the finished dosage form that contains a drug substance, generally, but not necessarily in association with other active or inactive ingredients

Formulated for how it is administered (ex. Tablet, liquid, capsule, etc)

Question 6

Q

What is a pioneer drug

Answer

A

(legend drug)

demonstrated safety/efficacy; manufacturing under GMP
Brand name (patented version)
Long extensive drug approval process

Question 7

Q

What is a generic drug

Answer

A

bioequivalent to brand name drug; manufacturing under GMP
It is FDA approved but doesn’t go through safety
Tested so that when given, same blood concentration as pioneer → same efficacy and toxicity

Question 8

Q

What is a compounded drug

Answer

A

manipulation of drugs to obtain products that differ from the starting materials in an approved dosage form
Could be by vet or pharmacy manipulation of approved products to something else
not considered FDA approved products

Question 9

Q

What is the drug approval process

Answer

A

overseen by FDA CVM (Center of Vet Med)
Target animal safety- drug is safe and determine what concentrations are associated with adverse effects
Clinical efficacy- does what it is supposed to do
Environmental considerations- if it is dumped
Human food safety- important for food animal species
Composition, manufacturing, chemistry- have SOPs to show that they are following GMP

Question 10

Q

What is a dose

Answer

A

a specified quantity of a therapeutic agent, such as a drug or medicine, prescribed to be taken at one time or at stated intervals
Amount of drug administered
Dose found on label or package insert
Off brand use on plumbs
Important: be aware of units and know if amount given is based on body weight or set amount

Question 11

Q

What is toxicology

Answer

A

study of poisons, including their chemical properties, biological effects, and the diagnosis and treatment of poisoning cases

Question 12

Q

What is toxicity

Answer

A

a measure of the degree to which something is toxic, the amount of a poison that causes a toxic effect

Question 13

Q

What is toxicosis

Answer

A

poisoning, intoxication, a disease state that results from exposure to a toxicant

Question 14

Q

What is a toxicant

Answer

A

poison, any agent capable of producing a deleterious response in a biological system

Question 15

Q

What is a toxin

Answer

A

naturally occurring poison (except metals), a poison that originates from a living organism (fungal toxins, bacterial toxins, zootoxins, plant toxins)
Toxin is a type of toxicant

Question 16

Q

What is a lethal does (LD)

Answer

A

the lowest dose that causes death

Question 17

Q

What is LD50

Answer

A

the dose at which 50% of the animals die during some period of observation; derived from experimental studies

Question 18

Q

What is an effective dose (ED50)

Answer

A

drug concentration at which 50% of the test subjects respond (quantal) or in which a 50% response is observed (graded)

Quantal- all or no response (ex. Heart rate decreases by 10 bpm)
Graded- looking at one individual over a range of doses

Question 19

Q

What is a therapeutic index (TI)

Answer

A

LD50/ED50
an estimate that characterizes the relative safety of a drug or chemical

Question 20

Q

What is an effective concentration (EC50)

Answer

A

the concentration required to elicit 50% of the maximum effect

Question 21

Q

Why are the disciplines of pharmacology and toxicology so similar? What are some differences?

Answer

A

“The right dose differentiates a poison and a remedy”
Same discipline at 2 different ends of the spectrum

Pharmacology- study of chemicals used at doses to achieve therapeutic (beneficial) effects on an organism

Toxicology- study of chemicals (toxicants) that produce a harmful effect on an organism
Severity can be mild, moderate, or severe
Higher dose means higher magnitude of response (why drugs have side effects)

Question 22

Q

Describe the dose-response relationship

Answer

A

Establishes causality that the chemical has in fact induced the observed effects
Establishes the lowest dose where an induced effect occurs (threshold)

Three general assumptions
Interaction with a molecular or receptor site to produce a response
Degree of response is correlated to the concentration of the drug or toxicant at that site
Concentration of the drug/toxicant at the site is related to the dose of chemical received
Dose → concentration at site → response

Question 23

Q

What is the LD50 and the ED50?

Answer

A

LD50- the dose at which 50% of the animals die during some period of observation; derived from experimental studies

Effective dose 50 (ED50)- drug concentration at which 50% of the test subjects respond (quantal) or in which a 50% response is observed (graded)
Quantal- all or no response (ex. Heart rate decreases by 10 bpm)
Graded- looking at one individual over a range of doses

Question 24

Q

Would you rather take a drug with a high or low therapeutic index?

Answer

A

High TI because it would be a safer drug

Question 25

Q

What data is plotted in a dose response curve?

Answer

A

y axis- % individuals responding (could be mortality or toxicity)
X axis- log of dose (mg)
Allows to look at larger range of doses and gives sigmoidal shape
Threshold- start to see response
Below this dose the effect of a given agent is not detectable
Max effect (intrinsic efficacy)- where the graph flattens out
At this point, a higher dose doesn’t give an increased response (maxed out on response)

Therapeutic range (window)- the blood concentration range within which a drug is likely to produce its therapeutic effects
Plasma concentration (y) vs time (x)
Looks at concentration of drug over time

Question 26

Q

Explain the terms pharmacokinetics and pharmacodynamics. What is the relationship between them?

Answer

A

Pharmacokinetics- “effects of body on the drug”
Study of the movement of a drug in the body and how it is processed (ie. absorption, distribution, metabolism, and excretion)

Pharmacodynamics- “effect of drug on the body”
Desired and undesired clinical outcomes (physiologic, pharmacologic effect)
Ex. vomiting, diarrhea, death

Pharmacokinetics determines pharmacodynamics → this determines how much concentration there is at the site → this determines the response
Goal is to maximize beneficial effects (pharmacokinetic delivery to the target receptor and target receptor affinity and selectivity) and minimize detrimental side effects

Question 27

Q

What is nutrition

Answer

A

the qualitative and quantitative requirements of the diet necessary to maintain proper health

Question 28

Q

Define essential and conditionally essential nutrients

Answer

A

Essential nutrient- a substance that cannot be made or cannot be made in sufficient amounts by the animal to support optimum nutrition
Ex. omega 6 fatty acids (none made), biotin (not enough made)
Water
Energy (carbohydrates, fats, proteins)
Amino acids (or nitrogen source)
Common essential amino acids for monogastric animals, but ruminants can take nitrogen and make their own amino acids
Fatty acids
Linoleic acid (C18:2 n-6)
Linolenic acid (C18:3 n-3)
Minerals
Macrominerals (needed in large amounts) and trace minerals (needed in small amounts)
Vitamins- fat soluble and water soluble
Other nutrients

Conditionally essential nutrient- a substance that is only essential under certain conditions
Ex. vitamin D- summer vs. winter
Can be life stage- young vs adult

These terms are based on individual, not population level

Question 29

Q

What are the steps involved in proximate analysis? What information is given by this process?

Answer

A

Dry matter and moisture- determined by drying feed samples to a constant weight at 100-105 degrees celsius
moisture/water (g) = wet feed (g) - dry feed (g)
Limitations- dietary components which volatize are lost in this process

Ash (minerals)- weight of residue left after heating feed sample at 600 degrees celsius in a muffle furnace for 2 hours
Burn everything organic and left with inorganic/mineral/ash
Limitations- some minerals (Cl, Zn, Se, I) can volatize at this high temperature

Ether extract (fat)- a dry feed sample is extracted with diethyl ether; the ether is dried and the residue remaining in the beaker is weighed to indicate the amount of fat in the diet
Limitations- fat soluble vitamins, chlorophyll, waxes, and other lipid soluble compounds are measured as fat (so the value is slightly overestimated)

Crude fiber- following ether extract, the feed sample is boiled in weak acid (0.255 N H2SO4) filtered and then boiled in weak alkali (0.312 N NaOH); the undissolved material is filtered, dried, weighed, and ashed
Crude fiber is the organic material that is not dissolved by boiling in acid and alkali
Crude fiber = undissolved material (g) - ash (g)
Crude fiber consists of some cellulose and some lignin
Limitations- crude fiber does not measure soluble fiber
But people are interested in soluble fiber values since it ferments easily

Crude protein- Kjeldahl analysis of nitrogen
Feed samples are digested in concentrated H2SO4 to produce NH4SO4; the sample is neutralized with NaOH to produce NH3; the NH3 is distilled into an acid solution and titrated to the amount of NH3 in the sample
Protein is calculated as grams of nitrogen multiplied by 6.25 (this assumes protein contains an average of 16% nitrogen)
Limitations- any compound with nitrogen is considered to be protein

Nitrogen free extract (NFE)
Not determined by analysis
% NFE = 100 - % moisture - % ash - % crude protein - % ether extract - % crude protein
NFE is assumed to equal the carbohydrate (excluding fiber) portion of the diet
Limitations- NFE does not actually measure the carbohydrate portion of the diet (spillover of soluble fiber and other things that aren’t measured, like vitamins)

Question 30

Q

How is moisture content determined

Answer

A

Dry matter and moisture- determined by drying feed samples to a constant weight at 100-105 degrees celsius
moisture/water (g) = wet feed (g) - dry feed (g)
Limitations- dietary components which volatize are lost in this process

Question 31

Q

How is ash/mineral content determined

Answer

A

weight of residue left after heating feed sample at 600 degrees celsius in a muffle furnace for 2 hours
Burn everything organic and left with inorganic/mineral/ash
Limitations- some minerals (Cl, Zn, Se, I) can volatize at this high temperature

Question 32

Q

How is fat content determined

Answer

A

Ether extract (fat)- a dry feed sample is extracted with diethyl ether; the ether is dried and the residue remaining in the beaker is weighed to indicate the amount of fat in the diet
Limitations- fat soluble vitamins, chlorophyll, waxes, and other lipid soluble compounds are measured as fat (so the value is slightly overestimated)

Question 33

Q

How is fiber content determined

Answer

A

following ether extract, the feed sample is boiled in weak acid (0.255 N H2SO4) filtered and then boiled in weak alkali (0.312 N NaOH); the undissolved material is filtered, dried, weighed, and ashed
Crude fiber is the organic material that is not dissolved by boiling in acid and alkali
Crude fiber = undissolved material (g) - ash (g)
Crude fiber consists of some cellulose and some lignin
Limitations- crude fiber does not measure soluble fiber
But people are interested in soluble fiber values since it ferments easily

Question 34

Q

How is crude protein content determined

Answer

A

Kjeldahl analysis of nitrogen
Feed samples are digested in concentrated H2SO4 to produce NH4SO4; the sample is neutralized with NaOH to produce NH3; the NH3 is distilled into an acid solution and titrated to the amount of NH3 in the sample
Protein is calculated as grams of nitrogen multiplied by 6.25 (this assumes protein contains an average of 16% nitrogen)
Limitations- any compound with nitrogen is considered to be protein

Question 35

Q

How is nitrogen free extract content determined

Answer

A

Not determined by analysis
% NFE = 100 - % moisture - % ash - % crude protein - % ether extract - % crude protein
NFE is assumed to equal the carbohydrate (excluding fiber) portion of the diet
Limitations- NFE does not actually measure the carbohydrate portion of the diet (spillover of soluble fiber and other things that aren’t measured, like vitamins)

Question 36

Q

How do you convert between dry matter and “as fed”?

Answer

A

It is hard to compare diets with different water concentrations
Use the ratio method- calculate the percentage of dry matter in each diet → make a ratio with nutrient in question → compare with x/100 → solve for x for percentage on dry matter basis

Question 37

Q

How are nutrient requirements determined?

Answer

A

Determined by graph of amount of nutrient ingested (x) vs response (y)
Need to be able to see the response of nutrients (ex. Growth, enzyme, blood clotting)

D- deficiency range (suboptimal response)
Not enough nutrient for appropriate response
R- requirement
1st time achieving optimal response
O- optimal response
Some nutrients have a wide O response, while some have very narrow ones
T- toxicity
Feed too much and go over the optimal range
Limitations- some nutrients are involved in multiple things and all of them have different R and O values AND some nutrients can’t be measured for optimal effects
Ex. omega fatty acids being good for cognitive function and visual acuity

Question 38

Q

What are the different energy measurements? How does one convert between these units?

Answer

A

calorie = heat required to raise the temperature of 1 gram of water from 14.5 to 15.5 degrees celsius
Kilocalorie (kcal) or Calorie = 1,000 calories
Used in human, dog, and cat nutrition
Megacalorie (Mcal) = 1,000,000 calories
Used in large animal nutrition

Joule (J) = SI unit for energy (and work)
The energy required to displace 1 newton a distance of 1 meter
1 calorie = 4.184 joules
Kilojoule (kJ) = 1,000 J
Megajoule (MJ) = 1,000,000 J
Watt = 1 J/sec
Time comparison, used in exercise and nutrition
Horsepower = 745.7 J/sec

Question 39

Q

What is gross energy? How is it measured?

Answer

A

the heat of complete combustion of a food
Measured in a bomb calorimeter
The maximum energy that can theoretically be obtained from a food. It is not a physiological measures since no system is 100% efficient
Each compound (carbohydrate, protein, fats, etc) has its own standard units → these values are used to calculate energy content of food

Question 40

Q

What is digestible energy? How is it determined?

Answer

A

takes into account of energy lost through absorption from GI to feces
DE = GE - fecal energy (bomb calorimetry)
DE is a measure of “apparent” energy digestibility
DE is determined by measuring food intake and fecal output. GE is then determined on a sample of both food and feces. DE may also be calculated from GE using estimates of digestibility

Question 41

Q

What is metabolizable energy? How is it determined?

Answer

A

ME = GE food - GE feces - GE urine - GE gasses OR ME = DE - GE urine - GE gasses
Energy losses in urine range from 2-8% of GE and energy losses as gasses range from 0-12% of GE

Relationships between ME and DE:
ME = 0.93 DE for many dog and cat foods
ME = 0.82 DE for many ruminant feeds
Off by more due to fermentation

Atwater factors (human nutrition) for ME are
Carbohydrate = 4 kcal/g
Protein = 4 kcal/g
Fats = 9 kcal/g

AAFCO modified factors for dogs and cats
Carbohydrate = 3.5 kcal/g
Protein = 3.5 kcal/g
Fats = 8.5 kcal/g

Question 42

Q

What is the total digestible nutrient (TDN) system? How is it determined?

Answer

A

TDN is used for some livestock species
TDN = (%CP x dig) + (%NFE x dig) + (%Crude fat x dig) +2.25(%fat x dig)
Dig- digestibility
TDN does not account for gas losses
TDN tends to overestimate the energy value of hays and other roughages

Question 43

Q

What is the net energy system? How is it determined?

Answer

A

NE = GE food - GE feces - GE urine - GE gasses - heat increment OR NE = ME - heat increment
NE is a system developed for livestock rations that require extreme precision
NE is often expresses as NE for maintenance (NEm) or NE for product production

Question 44

Q

How is the energy content of a diet calculated?

Answer

A

AAFCO equation
ME (kcal/kg) = 10[(3.5x%CP) + (8.5x%Crude Fat) + (3.5x%NFE)]

Question 45

Q

How is energy requirement calculated?

Answer

A

Maintenance energy- the energy intake required to maintain a constant body weight (or body energy content)
Increased body weight = positive energy balance
Decreased body weight = negative energy balance
Constant body weight = maintenance
At maintenance, metabolizable energy intake = energy expenditure (or heat production)

Thermoregulation- energy expenditure required to maintain body temperature
Thermoneutral- temperature range where no additional energy expenditure is required to maintain body temperature
Cold stress occurs below thermoneutral
Heat stress occurs above thermoneutral
Summit metabolism is the maximum sustained rate at which energy expenditure can occur
This varies based on species, breed, and temperature

Body size- the primary factor determining energy expenditure
Used in all energy systems to predict energy requirements
Large animals expend more energy than small animals. When expressed per gram of tissue, large animals expend less energy than small animals
Body surface area plays a large role in the energy expenditure differences with body size (kg^0.67)
Regression experiments with animals ranging in size from mice to elephants showed that the mass exponent for energy expenditure is kg^0.75
Energy requirement equations on the slides

Question 46

Q

What are the physiochemical properties of drugs? How does this affect movement across cellular membranes?

Answer

A

concentration gradient- move from high to low concentration

blood flow- delivering drug and carrying it away

molecular size/weight
Small molecular weight ⇒ small molecules ⇒ passive diffusion easy (easily absorbed/distributed)
Large molecular weight ⇒ large molecules ⇒ diffusion more difficult ⇒ absorption/distribution difficult

Solubility (lipophilicity)- property of a compound that enables it to dissolve in a liquid
Biological membranes are a lipid bilayer → requires lipid solubility
octanol/water partition coefficient (P)= Co/Cw
Determines how lipophilic one compound is
Octanol is the lipophilic phase and the water is the aqueous phase (separate like oil and water) → drug is added → drug distributes based on lipophilicity vs hydrophilicity → calculate ratio
When the log P exceeds 3, the compound is designated as very fat soluble
Smaller- hydrophilic
Larger- lipophilic `
Lipophilic = hydrophobic
If too lipophilic → it gets stuck
Lipophobic = hydrophilic

degree of ionization (charge)
Most drugs are weak organic acids or bases
Weak acid
Conjugate acid- unionized (protonated) → lipid soluble
Conjugate base- ionized (unprotonated) → water soluble

Weak base
Conjugate base- unionized (unprotonated) → lipid soluble
Conjugate acid- ionized (protonated) → water soluble

protein binding

Question 47

Q

What are mechanisms of movement through cell membranes?

Answer

A

Passive diffusion- most common
Transcellular passive diffusion- moves straight through phospholipid bilayer; need to be more lipophilic than hydrophilic
Paracellular passive diffusion- through aqueous pores in between cells
These don’t exist in the blood brain barrier
Only small, hydrophilic molecules can pass through

Carrier mediated transport- using proteins
Passive facilitated diffusion- no energy required, with concentration gradient, uniporters (moving one substance in one direction)
Active transport- energy dependent; can move against concentration gradient (low to high concentration); uniporters (moving one substance in one direction), antiporters (moving two substances in opposite directions), symporters (moving two substances in the same direction)

endo/exocytosis- rare; large macromolecules use this process

Question 48

Q

Given the pH of the environment and the pKa of a drug, determine the relative amount of drug that is absorbed/distributed across a membrane.

Answer

A

Henderson Hasselbach equation

Drugs are preferentially absorbed/able to distribute in their unionized (non charged) form
Important: pKa does not tell us whether a drug is a weak acid or base
Can use environmental pH and drug pKa to determine [unprotonated]: [protonated]
Weak acid

If pH > pKa: ionized form predominates
If pH < pKa: unionized form predominates
Weak base

If pH > pKa: unionized form predominates
If pH < pKa: ionized form predominates

Question 49

Q

What are the physiochemical characteristics of drugs? How do they affect absorption and distribution?

Answer

A

Absorption- movement of drug (parent compound) from the site of administration to the systemic circulation

Distribution- transfer of drug between the vascular space (blood) and the extravascular space (tissue)
Systemic circulation
Most drugs in plasma and albumin is the primary protein
Capillary bed exchanges drug from blood to tissue
Once out of capillary, can go into fluid and can go into cells
Can diffuse into capillary bed (route of transport)
Move by passive diffusion or active transport
Compounds distribute differentially within the body
Dependent on drug properties (molecular weight, lipid solubility, ionization), concentration gradient, blood flow, plasma protein binding, and affinity for tissue constituents

Question 50

Q

Intravascular vs extravascular administration

Answer

A

Intravascular- administration within blood vessels (IV)
Extravascular- other than into the blood vessels

Question 51

Q

Enteral vs parenteral administration

Answer

A

Enteral- administration of a substance via the alimentary canal (oral and rectal → through the GI tract)

Parenteral- administration via a route other than the digestive system
Some discrepancy on this

Question 52

Q

local vs systemic administration

Answer

A

Local- close to/at site of action

Systemic- drug administered at a convenient location and absorbed into the bloodstream for delivery

Question 53

Q

How do you tell administration method and absorption from a concentration time curve

Answer

A

IV administration- Starts out with high concentrations in the blood and falls after that; no absorption phase

Extravascular- at time zero, concentration is low and starts to climb (absorption phase- goes in blood); beyond extravascular, can’t tell what route

Therapeutic window- when see effect, how long it will last, intensity

Absorption- often evaluated by visual inspection of the data
Cmax- maximum observed concentration in a concentration time profile
Tmax- time to reach Cmax

Question 54

Q

Describe the oral absorption process. What are some species differences and limitations?

Answer

A

most convenient for clients
Esophagus- little contact time and cells can’t absorb
Cranial stomach- can’t absorb since the cells cannot
Caudal stomach- can absorb because there are different cells but it is really acidic and there is a mucus lining → hard to absorb
Small intestine- drugs will absorb for most orally administered products here; epithelium is good for absorption, alkaline environment compared to stomach, spend a lot of time here and has increased SA (have folds, villi, and microvilli)

Species differences- gastric emptying, pH differences, different microflora, and anatomical differences (ruminants vs non ruminants; surface area)

Formulation of oral drugs- dosage → disintegration into granules → deaggregation into fine particles → dissolution in the gut lumen → goes into solution → transported into gut wall to portal blood vessel

How food affects oral absorption- changes in gastric emptying, stimulation of bile, changes in pH, effects on drug metabolism (P-gp), changes in bacterial microflora

When oral administration is unsuitable
Drug properties- instability in GI fluids, poor lipophilicity, and large molecular weight
Patient characteristics- unable to swallow medications, immediate response needed, nausea, vomiting, diarrhea, and incompatible medications

Question 55

Q

Describe buccal/sublingual administration

Answer

A

Buccal- absorption through cheek
Sublingual- under tongue
pH of saliva is important (determines ionized vs unionized concentration)

Question 56

Q

Describe pulmonary drug administration

Answer

A

absorption from the lungs
Things epithelial membrane/well perfused
Primarily in terminal bronchioles

Question 57

Q

Describe subcutaneous/intramuscular administration

Answer

A

Usually enter bloodstream faster and more completely than oral administration
Generally limited by blood flow (different muscles are perfused differently)

IM absorption within minutes; SC absorption slower
Paracellular- hydrophilic
Transcellular- lipophilic

Depot formulations- slows down absorption
Formulation- addition of esters
Ex. Procaine penicillin

Question 58

Q

Describe skin administration

Answer

A

Topical- delivery of drugs to skin to treat skin (local)
Liquids, ointments, gels

Transdermal- delivery of drugs systemically through the skin into the bloodstream
Slow process

Question 59

Q

Describe local administration

Answer

A

non systemic
High local concentrations
Less systemic side effects
Local oral administration- antacids, antibiotics
Intrathecal (spinal canal)
Ointments or creams for skin
Ophthalmic

Question 60

Q

What is the “first pass effect”?

Answer

A

Oral- Occurs from gastrointestinal tract to absorption

Pre systemic metabolism
Intestinal first pass effect- breaks down drug so that less reaches the blood
Digestive enzymes
Bacterial enzymes
Metabolic (intestinal) enzymes
Hepatic first pass effect- GI → portal vein → liver → blood (can be metabolized in the liver before circulation)
Metabolic enzymes

Intestinal drug efflux
P-glycoprotein pumps (efflux protein → pump things back into the lumen → goes out in excrement)

Overall: decreased absorption

Question 61

Q

What is bioavailability? What are some reasons for poor bioavailability?

Answer

A

Area under the curve (AUC)- an estimate of overall drug exposure
Bioavailability (F)- fraction of drug reaching the systemic circulation intact
IV is used as a reference because 100% of the drug is going into circulation
bioequivalence/relative F- generic vs brand name
Poor availability because it doesn’t meet minimum requirements or absorption too slow → need to increase dose

Question 62

Q

What are the implications of plasma protein binding?

Answer

A

Drugs exist in a free and plasma protein bound form and an equilibrium is maintained
Proteins- albumin and alpha1 acid glycoprotein
Binding of lipid soluble drugs facilitates movement

Large MW precludes movement from circulation
Only free drug molecules can leave the blood
If free exits circulation, the equilibrium is off → some of the bound ones dissociate from albumin and become free

Significant if > 80% bound

Endogenous compounds and other drugs may displace drugs
Can increase distribution of drug that is displaced and can also be eliminated
May have clinical implication if narrow TI

Changes in protein concentrations can affect free concentration

Limits interaction with receptor sites, crossing of cell membranes, metabolism, and excretion
Higher binding ⇒ lower clearance ⇒ higher half life

Binding in the tissue- drugs may bind to tissue proteins/components
Increase distribution of drug in body

Can act as a reservoir for drugs and increase toxicity
Fat can serve as reservoir for lipid soluble drugs
Bisphosphonates, tetracycline antibiotics- bone
Aminoglycosides- kidney/ear

Question 63

Q

What is the importance of components of the blood brain barrier? How does this affect CNS drug distribution?

Answer

A

Kidney and heart have the highest % cardiac output → highly perfused tissues → it will see drugs earlier and have a higher concentration

Question 64

Q

How does drug distribution change with changes in volume of distribution?

Answer

A

Vd- apparent volume of distribution
Proportionality constant relating plasma drug concentration to amount of drug administered
Conceptual example- Add known amount of drug to a tub → use the concentration of drug in tub and volume of total amount of water in the tub

Lower Vd- more in blood and bodily water
Higher Vd- more in the tissues
Clinical considerations- horses vs. foals
Foals have more volume of water than horses → distribution of hydrophilic drugs increases in the foal
Lipophilic drugs need to be given in a higher dose in foals than in horses because they have less fat compared to adults

Answer 65

A

removal of drug from the plasma resulting in a decrease in concentration

Answer 66

A

drug is chemically transformed into metabolites

Answer 67

A

process by which a drug is eliminated from the body without a chemical change

Answer 68

A

Metabolism vs excretion predominant depends on ionization and lipophilicity

Answer 69

A

Metabolism- enzymatic process that alters the chemical structure of a drug

Hydrophilic- more soluble in blood and urine; more easily eliminated and less likely to go into the tissue

Answer 70

A

species/breed
Environmental factors ex. Diet, drugs, etc

Age
Animals are not born with a full fleet of metabolic enzymes
Geriatric patients have less metabolic enzymes

Gender
Genetic polymorphisms ex. Prozac ,mutation and MRDI mutation in Collies

Answer 71

A

Metabolism results in

Formation of an inactive polar metabolite
Diclofenac to 4-OH diclofenac

Formation of an active metabolite
Metabolism of active drug to active metabolite
Metabolism of inactive drug to active metabolite (Prodrug)

Formation of a reactive/toxic metabolite
Acetaminophen to NAPQI (toxic and leads to cell death)

Answer 72

A

Speed up rate of reactions
Many require coenzymes/cofactors

Substrate specificity
Eg complementary shape

Multiple enzymes may metabolize a single drug
Multiple metabolites

Enzymatic activity and expression may differ between species

Site- mainly in the liver, but also in the small intestine, brain, skin, and the kidneys

Answer 73

A

Phase I reaction introduces/exposes a reactive group (-OH, -NH2, -COOH, -SH)
Makes a more polar metabolite
Excreted in urine or feces

Phase II reaction attaches a polar molecule
Makes it more water soluble
Faster than Phase I
Substrates often arise from Phase I metabolism
Usually, metabolites have decreased biologic activity
Metabolites are highly polar
Some metabolites are excreted in bile

Most common is phase I → phase II
Rare is phase II → phase I
Can go through either phase or both to be eliminated

Answer 74

A

Phase I reaction introduces/exposes a reactive group (-OH, -NH2, -COOH, -SH)
Makes a more polar metabolite
Excreted in urine or feces
Three different types
Hydrolysis- esterases, dehydrogenases, amidases
Reduction
Oxidation (most common)
Cytochrome P450s (CYP450)

Membrane bound on the ER
Has coenzyme and cosubstrate
Has a heme and could bind oxygen, which is needed for its reaction
Deactivation reactions are the most common
Activation reactions increase analgesic effect because there is an active parent drug and an active metabolite
Flavin-containing monooxygenases (FMOs)

Answer 75

A

Phase II reaction attaches a polar molecule
Makes it more water soluble
Faster than Phase I
Substrates often arise from Phase I metabolism
Usually, metabolites have decreased biologic activity
Metabolites are highly polar
Some metabolites are excreted in bile
Multiple types (from most important to least)

Glucuronidation
Catalyzed by UDP-glucuronosyl transferase (UGTs)
Requires cosubstrate UDP-glucuronic acid (UDPGA)
Incorporation of glucuronosyl molecule into substrate
Can glucuronidase different locations on same substrate/drug → can lead to different metabolites

Sulfation-
Catalyzed by sulfotransferase enzymes
Requires cosubstrate 3’-phosphoadenosine-5’-phosphosulfate (PAPS)
Not abundant in body and can be depleted if overwhelmed
Transfer of a sulfate group from PAPS to substrate

Glutathione conjugation-
Catalyzed by glutathione transferase (GSTs)
Requires glutathione cosubstrate
Not abundant in body and can be depleted if overwhelmed
Reacts with strong electrophiles to form glutathione conjugates
Further transformed/metabolized into mercapturic acids which are excreted in urine
Presence of mercapturic acids in the urine signify that a reactive metabolite was formed

Acetylation
Catalyzed by N acetyltransferases (NATs) enzymes
Requires cosubstrate acetyl coenzyme A (Acetyl-CoA)
Formation of acetate with the O, N, S-containing drug/xenobiotics
Not that water soluble but makes it inactive for further metabolism
Ex. Procainamide, sulfanilamide, histamine
Amino acid conjugation
Methylation

Species differentiation
Cat- some forms of glucuronidation missing
Ferret- some forms of glucuronidation missing
Dog- acetylation absent
Fox- acetylation absent
Pig- sulfation present but slow
If processes are missing, then compounds stay around for a long time

Answer 76

A

Hepatic clearance- volume of plasma flowing through the liver that is completely cleared of drug per unit time

Affected by
Hepatic extraction ratio of drug
Ranges from 0 to 1.0
metabolism by liver and biliary elimination (feces)
Blood flow to liver
Plasma protein binding of drug

Answer 77

A

High ER drugs
ER>0.7
“Flow dependent”
Cl hepatic changes are proportional to changes in blood flow

Low ER drugs
ER<0.3
“Capacity Limited”
Moderate effects on blood flow will have little effect on Cl hepatic

Answer 78

A

Induction- increased synthesis of enzyme
Leading to high metabolic activity
Can be another substance or its own metabolism
Drug cleared more quickly → lowered pharmacological effect
Takes time to develop (7-14 days to develop)

Self induction- drug stimulates its own metabolism

Inhibition- interference with the ability of an enzyme to bind to its substrate (drug)
Competitive inhibition
Substrate for the enzyme
Not a substrate but reversibly binds to the active site of the enzyme
Non competitive inhibition
Binds at site other than active site of enzyme = conformational change
Reversible or irreversible
Decreased clearance
Therapeutic failure- prodrug (due to inhibition of conversion)

Answer 79

A

Filtration- from glomerular capillaries to bowman’s capsule → urine aids in drug elimination
Approximately 25% of cardiac output reaches the glomerulus
Glomerular filtration barrier- substances MW <5,000 daltons are freely filtered; >70,000 are not
Increased MW ⇒ decreased amount filtered (decreased amount in bowman’s capsule)
For albumin, it stays in plasma and if the drug is bound to albumin, it will not be filtered; only the free is filtered
Filtration is driven by high hydrostatic pressure
Glomerular filtration rate- the volume of plasma filtered by the kidneys per minute

Answer 80

A

Secretion- movement from peritubular capillary to renal tubule which eventually becomes urine
Movement from blood to tubular fluid
Active transport process (need E and moving against concentration gradient)
Ionized drug- moving charged molecule through membrane bound protein
Not usually affected by plasma protein binding
Competition
Penicillin and probenecid (which was developed to be competition)- penicillin stays in the body while probenecid goes through tubular secretion → pen stays in for a longer amount of time (decreased dose needed for increased time in body)

Answer 81

A

Reabsorption- from renal tubule to capillary → back into systemic circulation (hinders elimination)
Passive process
Dependent on
Concentration gradient
Urine flow (faster rate → decreased contact → decreased change of reabsorption through epithelial cells)
Lipid solubility of drug
Urine pH and ionization
Drugs
Pathophysiology
Diet
Carnivores (pH 5.5-7.0)
Herbivores (pH 7.5-10.5)
If pH increases, there are less drug excreted (more in uncharged → reabsorbed)
Ig pH decreases, there are more drug excreted (ion trap = more soluble)

Answer 82

A

Bile travels through its normal route
Bile recirculates → conserves composition of bile
Can occur with drugs and metabolites as well
Encounter microflora → can use enzyme to cleave metabolites → active drug and goes to liver or feces → liver may let it go through to systemic circulation

Answer 83

A

Volume of distribution determines how much stays in the fluid and blood versus how much stays in the tissue
Clearance is how much drug is taken out by metabolism and elimination (decreases volume of distribution)
Elimination half life is how much is how long it takes for elimination (only in hydrophilic form)

Answer 84

A

Protein- Complex molecule consisting of a particular sequence of amino acids that form a peptide chain, which is folded in a specific 3D orientation. All proteins contain carbon, hydrogen, oxygen and nitrogen (N)

Answer 85

A

To provide the nitrogen required for the synthesis of dispensable amino acids, heme etc.
To provide essential amino acids (EAA)

Answer 86

A

Proteins and amino acids are unique due to the amount of nitrogen they contain – about 16% on average
One can determine the amount of protein based on measuring the amount of measured nitrogen

This Determined Amount Of Protein Is Called “Crude Protein” based on the following equation
% Crude Protein = % Nitrogen x 6.25
Note: 100 g protein ÷ 16 g N = 6.25
Measures nitrogen, not Protein
One can use the factor of 6.25 to convert measured values of nitrogen into corresponding amounts of protein

Answer 87

A

Ability of a particular protein, or mixture of proteins to meet the body’s amino acid requirements

Determined by
Digestibility
Bioavailability- Percentage of ingested nutrient in a food source that is absorbed in a form that can be utilized by an animal
Poor digestibility can result from a variety of factors
Antiproteolytic factors (antitrypsin)
Side chain destruction (oxidation)
Maillard reaction products- heat processing of foods in moist conditions
Sugars + lysine = unavailable lysine
Amino Acid Availability
Pattern of Amino Acids

Answer 88

A

No storage pool so all body protein is functional (muscles, enzymes, structural, others)

As energy intake decreases, more protein is directed toward meeting energy needs rather than being retained for other metabolic purposes
Negative nitrogen balance
Increase urea nitrogen

Body proteins are dynamic
Rapid turnover – albumin, gut mucosa, liver
Slower turnover – elastin and collagen

Body protein degrades and N & AA are released – some partially recycled for new protein synthesis

In order to maintain balance degraded AA must be replaced by dietary N and AA intake

In animals in a negative energy balance, the deficit between energy derived from food and energy expenditure is supplied by catabolism of body tissues

Answer 89

A

An organic compound characterized by having an amino group (NH2) and a carboxylic acid group (COOH) attached to the same carbon at the end of the compound

Building blocks of proteins; Intermediates in metabolic pathways; Synthesis of non-protein compounds

Answer 90

A

Can be synthesized from other amino acids

Answer 91

A

Required in the diet
Arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine → PVT TIM HALL

Answer 92

A

Normally is not essential but under certain conditions becomes essential
Taurine- Dogs under certain dietary conditions
Arginine- Premature infants, renal disease (human)
Glutamine- Gastrointestinal disease

Answer 93

A

Considered the amino acid that is most deficient in a protein relative to the animal’s requirement
Lysine- Cereals (corn, rice, wheat)
Methionine and Cysteine- Legumes and milk products
Tryptophan- Collagen and second limiting in corn

Answer 94

A

Essential amino acids are metabolized to a variety of end products, including other non- essential amino acids
The addition of these non-essential amino acids in the diet can reduce the amount of the essential parent amino acid needed.
Thereby “sparing” the amount of the essential amino acid required in the diet
Requirement for one essential amino acid can be partially mitigated by a NEAA
For example: cysteine sparing MET
Tyrosine spares PHE by about 50%
Non essential amino acids spare essential amino acids!

Answer 95

A

Malnutrition: imbalanced intake of protein +/- calories; has the potential to undermine proper medical or surgical care of the patient
Protein Energy (Calorie) Malnutrition- Loss of protein and energy stores
Protein Deficiencies- Inadequate dietary intake, Intake of incomplete proteins, Excessive losses
Loss- Intake of protein cannot meet need for maintenance plus replacement
Lost through GI tract, urinary tract, and skin

Consequences
Impaired growth and reproduction
Weight loss (+) muscle wasting
Anemia
Low albumin
Dull hair
Reduced immune function
Delayed wound healing
Chronic diarrhea

Two common forms of protein malnutrition

Kwashiorkor
Protein deficiency without severe energy restriction
Often seen with low protein and high carbohydrate diets
Carbohydrate intake stimulates insulin release
Insulin traps AA in muscle
Low albumin (edema)
Distortion of plasma amino acids profile

Marasmus
Protein and energy malnutrition
Essentially starvation

Diagnosing Protein Deficiency
Failure to grow
Decreased plasma albumin (Kwashiorkor– 1⁄2 life of albumin ~20 days)
Anemia
Fatty liver – Kwashiorkor
AA deficiency and altered PAA profiles

Amino Acid deficiencies
Initial signs usually: Decrease in food intake, Decreased growth rates

Arginine def ⇒ increased ammonia (ammonium toxicity)
Cats are sensitive to this because they did not evolve on a diet limiting in protein and it leads to decreased ornithine and decreased urea, which prevents excessive amino acid catabolism between meals

Histidine def ⇒ y suture cataracts and anemia

Methionine def ⇒ scaling and scabbing

Phenylalanine def⇒ for black coat in cats and dogs, Adequate phenylalanine is necessary to maintain black color
Requirement for adequate pigment is higher than that for growth- more than twice!

Pellegra- tryptophan def ⇒ scabbing and scaling
Trp is a precursor of niacin
Corn + alkali treatment = available niacin
Decreased serotonin, aggressiveness, decreased pain sensitivity

Answer 96

A

Maximum measured concentration

Answer 97

A

Time of maximum concentration

Answer 98

A

fraction of drug reaching the systemic circulation intact.

Answer 99

A

Measure of total systemic exposure.

Answer 100

A

Apparent volume within which a drug is distributed in the body.
Determines single/loading dose

Answer 101

A

Volume of plasma cleared of drug per unit time.
CL=Dose/AUC
Determines dose to maintain a target plasma Concentration

Answer 102

A

fraction of a drug removed per unit time.

Answer 103

A

time for half of administered drug to be absorbed.

Answer 104

A

time for the plasma concentration to decline by half
Time course of drug elimination
Time course of drug accumulation
Important for calculating dosing interval

Answer 105

A

Difference between first dose and steady state
Depending on half life
Takes 5 half lives to reach steady state

Answer 106

A

Five half lives for both instances

Answer 107

A

Loading dose- used when immediate drug concentration (effect is acquired)
Eg. phenobarbital, digoxin, bromide
eqn- DL = (TDC x Vd)/F

Maintenance dose- maintain the peak plasma drug concentration below the toxic concentration and the lowest drug concentrations above the minimally effective level
Maintain steady state of drug in the body
eqn- MD = (TDC x CL x DI)/F

Answer 108

A

Dose interval depends on acceptable amount of fluctuation and elimination half life
Increased half life → more frequent dose intervals
Decreased half life → less frequent dose intervals

Dosing Interval longer than t1/2:
Concentration–Dependent Antimicrobials
Drugs that accumulate in tissue
Drugs with active metabolites
Drugs with large therapeutic index

Dosing interval shorter than t1/2:
Drugs with narrow therapeutic index
phenobarbital, digoxin, potassium bromide

Answer 109

A

Decreased clearance → increased half life → decreased dose or dosing intervals
Increased clearance → decreased half life → increased dose or dosing intervals

Decreased volume of distribution → decreased half life → increased dose or dosing intervals
Increased volume of distribution → increased half life → decreased dose or dosing intervals

Answer 110

A

Information collection- patient, diet, environment (live with other animals, do they share food, person feeding the animals, economics, feeding philosophy, schedule)
Signalment, history, physical exam

Published guidelines available
American Animal Hospital Association (AAHA; 2010) and World Small Animal Veterinary Association (WSAVA; 2011)

Goal: recognize patients at risk of nutritional problems, accurately identify candidates for extended nutritional evaluation

Answer 111

A

Should be in every patient’s record and updated on every visit!
Also weight and BCS
Assess trends over time, historical weights prior to illness or while consuming a specific diet or amount
Name and amount of food
Amount and types of snacks/treats
How is the dog/cat fed?
Access to other food sources?
How are medications given?
Dietary supplements?
Does it meet the animals needs?
Life stage
Palatability and volume
Performance of pet
Owner needs: Availability, cost, philosophy
Animal factors
Age, Sex, Breed
Body weight (serial and historical)
Health status
What does the animal do for a living?
Body and Muscle Condition Score
Body- Primarily assess body fat
5 and 9 point scale BCS systems
Visual and tactile (palpation) data to assess adiposity and assign numerical score
Muscle- Help to identify at-risk patients and to establish interventional guidelines
AAHA and WSAVA guidelines propose 4 point system (normal; mild, moderate, or severe atrophy)
Visual and tactile examination of muscles over temporal bones, scapulae, ribs, pelvis

Answer 112

A

Diet +/- treats/supplements
Amount
Feeding method
How much food is based on
diet history- If you have a good diet history and animal is in good body condition and weight-stable, recommend that amount
bag/can directions- An estimate that is likely to overfeed in many cases
energy requirements (calculated)- it is easy to overestimate energy requirements; Closely monitor the animal (weight, BCS) and adjust recommendations as needed
WSAVA Nutrition Toolkit- energy requirement charts, diet history form, nutritional assessment checklist, body and muscle condition scoring, hospitalized feeding guide, client resources: selection of commercial diets, navigating internet info

Approaches to feeding

Free choice (AKA ad-libitum or ad lib) – relies upon the animal to regulate their energy intake
Advantages:
In cats allows them to consume multiple small meals throughout the day
Picky or slow eaters
Helps ensure subordinate animals eat
In kennels can help alleviate boredom
Easy – requires very little owner effort
Disadvantages
May miss anorexia/hyporexia due to a medical condition if not monitoring intake
Subordinate animals still may not get enough food (cats!)
Increases the probability of weight gain and obesity (bored animals, genetically predisposed animals)
Dry, extruded diets (kibble) are only type that can be used in this manner

Time restricted feeding
Similar to ad-libitum feeding - you rely on the animal’s ability to regulate its daily calorie intake
Surplus of food provided at meal time and the animal is given a set amount of time to eat
This form of feeding is most applicable to dogs
Most dogs will learn to consume their energy requirements in a 10-15 min time period, cats may have trouble with this depending on energy density of diet
Advantages
Does not require much effort on behalf of the owner
May be used with any type of pet food
Allows monitoring of food intake to some degree
Disadvantages
Not appropriate for finicky or slow eaters
May encourage gluttony and aerophagia
Has been shown to promote overeating in
puppies (increased risk for developmental orthopedic disease)

Portion controlled feeding- animals fed a specific amount often divided into 2 feedings per day
Advantages
Permits owner to carefully monitor animal’s food intake
Lowers probability of weight gain or obesity
Owner more likely to recognize reduced food intake sooner
Disadvantages
Requires more of a time commitment and effort on behalf of the owner

Snack and treats
~57% of dogs and 26% of cats received a treat at least one time per day
Important part of the human-animal bond
No more than 10% of daily calories should come from snacks/treats or unbalanced foods

Answer 113

A

Base recommendations off information obtained from diet history
Try to recommend specific brand names
Provide more than one recommendation
Recommendations in different price ranges can be helpful too

Dry pet food- Most Common Type Of Food Purchased
Contain 6–10% moisture (~90%DM)
Most economical
Most Energy Dense
Long shelf life
Can Be Fed Free Choice
Some Offer Dental Hygiene Benefits

Canned pet food- Contain about 75% water
Advantages
High palatability
Long shelf life
No preservatives
Lower Energy Density
Higher Quantities Of Animal Protein And Fat
Disadvantages
High palatability → obesity in some cases
Cost– often most expensive
High processing temperature
Fixed food preferences in some animals

Semi-moist pet foods- Contain about 15 – 30% water
Softer texture often mixed with kibble
Humectants trap water to soften product and protect from bacteria
Advantages: palatable, convenient, and lack odor
Disadvantages: expensive, dry out quickly

Other types
Raw(Frozen, fresh, freeze dried)
Palatable, expensive, perishable
Risk of bacterial contamination
Typically high in fat
Cooked Fresh Or Frozen
Palatable, expensive, perishable
Typically high in fat

Answer 114

A

Engage the client in decision making and defining expectations
Expectations and goals should be specific and achievable
Include explicit follow-up:
Food intake and appetite
BCS and BW
Gastrointestinal signs, stool quality
Overall appearance and activity

Answer 115

A

organic compounds functioning as nutrients and required in tiny amounts in the diet
energy metabolism – coenzymes
regulation of mineral metabolism or cell growth and differentiation – hormones, antioxidants, etc.

Answer 116

A

Diverse structures and functions
Commonality = soluble in lipid solvents
Crosses cellular membranes:
Action in nucleus or within membrane
Similar in how digested, absorbed, transported with dietary lipid

Answer 117

A

A, D, E, and K
some body storage for A, D, and E A and D can be toxic
A and D can be toxic

Answer 118

A

A- Required, can be supplied as pro-vitamin in most species (not cats)
D- Conditionally essential (dogs & cats)
E- Requirement depends on diet
K- Conditionally essential if bacterial synthesis in gut not adequate

Answer 119

A

large group of chemically and functionally related compounds

Retinol (animal sources) and similar = retinoids = preformed vitamin A
Oxygen, heat, light, and moisture may damage vitamin A
Double bonds and reactive OH group
Stored as retinyl ester for stability
All trans retinol has the highest activity (i.e. is most potent; conversion to cis forms via damage reduces potency)
Retinal (aldehyde form; important for vision)
Retinoic acid (interacts with DNA)

Some carotenoids (plant sources) and similar = pro-vitamin A
Not all carotenoids can be converted to retinol
Pro-vit A carotenoids are converted to retinal by carotenoid-15,15’ dioxygenase
Very low activity in cats (pre-formed vit A required)

Answer 120

A

absorbed in the jejunum
70-90% efficacy for vitamin A
40-60% for carotenoids
incorporated into chylomicrons
transported via lymph to liver for storage in ester form
Some animals absorb carotenoids intact (can alter color of fat, skin, and yolk)

Answer 121

A

retinol binding proteins (RBP) for transport of retinol in the blood
Vitamin A interacts with several different cellular binding proteins that protect vit A, solubilize vit A, and transport vit A to cellular sites of action

Answer 122

A

Fish oils and liver
Milk fat and egg yolks
Reduced fat/skim milk must be fortified in US
Green leaves
Carrots, sweet potatoes, pumpkin, squash, yellow corn

Answer 123

A

Vision
Retinal is component of rhodopsin (retinal pigment in membrane of rod cell)
Photon energy → electrochemical signals
Cis-trans cycle

Growth, cell differentiation, and metabolism
Retinoic acid is a hormone
Acts through several specific nuclear receptors to influence gene transcription
Critical for growth, differentiation, metabolism
Induces differentiation of epithelial cells and production of some enzymes (e.g., PEPCK)
Required for normal lymphocyte proliferation
Regulates lipid and carbohydrate metabolism

Reproduction
Required for normal spermatogenesis
Required for maintenance of pregnancy

Bone formation
influences bone remodeling (acts on osteoclasts to increase resorption)
influences cartilage and collagen production

Answer 124

A

Def Commonly associated with:
corn silage fed with concentrates low in vitamin A
cut hay exposed to prolonged UV light
droughts or winter (summer) kill of green vegetation
consumption of grain diets with no vitamin A supplementation and no green vegetation
Captive chelonians with poor diet
Young animals nursing from animals consuming low vit A diets or young animals consuming relatively little milk

Basic symptoms of deficiency
Columnar mucus secreting cells (respiratory, GI, repro, ocular) → keratinized squamous
No normal cell division and growth
Leads to infectious disease, dry eye/poor vision, infertility/abortion, and anorexia/diarrhea
Leading cause of preventable blindness in people
Up to 1/2 million kids annually, half of those die w/in 12 months of losing sight
Common in developing countries
Congenital deficiency- Maternal deficiency → affected calves with malformed ocular structures (retinal dysplasia, occipital bone remodeling, etc.)
Ex. haired corneal dermoid, microphthalmia

Toxicity
Carotenoids vs performed vit A
Carotenoids considered non toxic
Not bioavailable
Conversion to vit A involves regulated steps
Over consumption of retinoids can cause toxicity
Food (liver or oils) or supplements
Major effects
Skeletal malformation and spontaneous bone fractures
Growth: premature growth plate closure
Adults: hyperplasia of cervical vertebrae
Birth defects (human and animal)- potent teratogen

Answer 125

A

used to describe one of several compounds
Tocopherols (& tocotrienols) with biological activity

Eight naturally occurring forms of vitamin E
Alpha, beta, gamma, & delta

Alpha tocopherol is the form with meaningful nutritional activity

D-alpha-tocopherol has the greatest activity

Synthetic vit E is racemic mixture
D and L alpha tocopherol

Expressing activity (concentration)
1 IU = 1 mg rac-alpha-tocopherol

Tocopherols unstable (reactive)

Must be stabilized for in vivo use
Ester forms to protect OH
Tocopherol acetate in supplements

In vitro activity complemented by other preservatives
Rosemary
Citric acid
Synthetic preservatives (most effective)

Role of oxidation
Loss of vitamin activity
Rancidity of fats
Toxic reaction products
Off flavors and odors
Extent of oxidation
Mineral content and form
Fat level and type

Answer 126

A

Absorbed with micelles in the small intestine
Transported in the lymph with chylomicrons
Released from liver with VLDL for transport to the tissues
Enter cells by receptor mediated endocytosis and incorporates into membranes
Stored in adipose
Found in all tissues (all cells have membranes!)

Answer 127

A

Increased with:
*polyunsaturated fats
trace minerals (Fe, Cu)

Spared by:
Selenium
Se and vit E capable of preventing same diseases and have similar functions
More than 30 selenoproteins have been identified
Most abundant is glutathione peroxidase (which is most abundant in RBC)- important antioxidant
Reduces lipid peroxidases to hydroxy fatty acids → metabolized
Antioxidants

Answer 128

A

Vegetable oils
eggs and liver
green forages (especially alfalfa)
Selenium- Forage, water, and cereal content depends on soil selenium content and plant species

Answer 129

A

Antioxidant
Used for both satisfying metabolic needs and as antioxidant in vitro
Antioxidant of foods/oils
Forms differ in activity in vitro vs. in vivo
Gamma and delta forms
Very little to no activity in vivo

Protect PUFA in all cell membranes

May also play a role in membrane structure

Answer 130

A

Vit E and Se Def Commonly associated with:
consumption of grains and forages deficient in Se or Vitamin E droughts and very dry pastures
diets that include unsaturated fatty acids (or other components that increase vitamin E requirements)
stress and high rates of production
Related to oxidation of cellular membranes
Damage to tissues
Oxidized fatty acids may react with divalent cations
Usually calcium
Leads to calcified areas in muscle (chalky deposits)
Clinical signs vary by species
Peroxidation: permeability → ischemia → necrosis
Hepatic necrosis (pigs- selenium)
Pancreatic dystrophy (chicks- selenium)
Infertility/embryonic death (many species- both)
Steatitis (cats- vit E only)

Conditions responsive to vit E and selenium
Nutritional muscular dystrophy (white muscle disease) in young animals
requires adequate selenium +/- vit E
Affects all muscles (cardiac, skeletal)
Stiff gait, ECG abnormalities (affects myocardium)

Toxicity of vit E
Relatively non toxic, but may antagonize other fat soluble vitamins at high levels
Compete for absorption
Supplementation considered safe

Toxicity of Se
Narrow margin of safety
Toxic to grazers in areas with high soil Se (3-4 ppm)
Symptoms (chronic) include: sloughed hooves, loss of mane or tail, rough coat
Iatrogenic (pharmacological overdose or feed formulation error):
Acute toxicity = sudden death (with dyspnea, sweating, pyrexia, tachycardia, ataxia, excitability)
Dog and cat data scarce
Anemia → liver necrosis/fibrosis
Unlikely to occur naturally

Answer 131

A

Gut and/or rumen microbes
Green leaves or dark green vegetables
Vegetable oils, liver, and fish meal
Absorption in distal small intestine in non ruminants
Chylomicrons → liver

Answer 132

A

Activates clotting factors II (prothrombin), VII, IX, and X
Key in formation of carboxyglutamic acid (calcium binding site)
Calcium binding → function

Carboxylates proteins including osteocalcin in bone (protein important for turnover)

No storage; turnover is hours to days

Answer 133

A

Def
Ingestion of antagonists: targets reductase- active K depleted
Moldy sweet clover hay (dicumarol)
Rat poison (warfarin)
Antibiotic treatment
Infants (lack gut microflora)
Lipid malabsorption
Biliary obstruction (must give parenterally)
Diagnosis
Measurement of clotting time
Measurement of P.I.V.K.A. (Proteins Induced by vit K Antagonism)
Inactive precursors of coagulation factors, need to be carboxylated by vit K
Various PIVKA test differ in accuracy, some have shortage of reagents
No test specific for vit K in vet med

Toxicity

Oral vs. parenteral (iatrogenic)
Oral vitamin K toxicity not seen clinically

Natural vs. synthetic form
Phylloquinone is safe even with massive doses but much more expensive than menadione

Injections of menadione not used but is also safe as food supplement

Answer 134

A

Macrominerals- Required in % (parts per 100) amounts
Ca, P etc.

Microminerals (trace minerals)
Required in parts per million (ppm) amounts
1 ppm = 0.0001% = 1 mg/kg
Cu, Zn, Fe, I, Se, Mn, Co, Mo etc.

Answer 135

A

Sources
Liver > shellfish > nuts > grains > fish > poultry > vegetables > meat
Little copper in drinking water

Organ conc. (per organ weight basis)- kidney > liver > brain > heart > bone

Answer 136

A

Low copper in the diet
Low copper bioavailability
Conditioned copper deficiency

Answer 137

A

High concentrations of molybdenum and sulfate in the diets or ruminants
Also referred to as “conditioned copper deficiency”

Conditioned def
Excess Mo → thiomolybdate formation
MoOnS4-n
Most common: MoO2S2 (sulfate) and MoO3S (Sulfite)
Prevents copper uptake in the gi tract
Enhance excretion in the urine and bile

Zinc excess
Induction of metallothionein in enterocytes
Binds to Cu and limits absorption
Zinc antagonizes copper by inducing production of intestinal cell metallothionein
Metallothionein has a higher affinity for copper than zinc and binds Cu in the GI tract

Answer 138

A

Anemia
When copper is deficient, the activities of cytosolic SOD and erythrocyte SOD decrease
The decline in activity of these enyzmes are postulated to contribute to neurological clinical signs
SOD = Superoxide Dismutase

Neonatal ataxia “swayback disease”
Deficiency of cytochrome oxidase
Deficiency of dopamine-b-hydroxylase
Demyelination and degeneration of motor neurons of the ventral horn of the spinal cord and red nucleus

Discoloration of hair and wool
“Hypochromotricia”
Deficiency of tyrosinase

Twisting or kinking of hair and wool
Keratinization defects of hair and wool
Fewer disulfide linkages and more free sulfhydryl groups

Defective collagen and elastin formation
Deficiency of lysyl oxidase
Converts soluble elastin and collagen to insoluble forms by cross linkage
Clinically manifested as twisted limbs, curly tails and aortic rupture

Oxidative damage
Cu/Zn Superoxide Dismutase
2 O2* - + 2 H+ SOD H2O2 + O2 * Protects against oxygen radicals

Cardiac hypertrophy/aortic rupture
Hypercholesterolemia
Hypertriacylglyceridemia
Reduced fertility
Diminished immune function

Answer 139

A

Diet history and analysis
Liver biopsy (gold standard)
Plasma or whole blood copper
Cu Zn SOD
Ceruloplasmin

Answer 140

A

Cu prevention and treatment
Small Animals - change to a complete and balanced diet
Food Animals - add copper sulfate or chloride to the ration (consider subsequent vitamin destruction)
Parenteral copper - copper glycinate
Salt block or fertilize pastures

Answer 141

A

Second most abundant trace element
Sources: red meat & shellfish > vegetable sources
Dogs and Cats: 50 ppm

Answer 142

A

Catalytic
>200 enzymes contain zinc

Structural
structural support in Cu,Zn SOD
zinc finger motif in proteins

Regulatory
stimulates factors regulating gene expression

Answer 143

A

Growth retardation
Impaired appetite and taste

Parakeratosis

Swine- Result of an absolute or conditioned Zn deficiency
Clinical signs: depressed growth and non-inflammatory proliferative epidermal lesions (parakeratosis)
Etiology:
Ca excess
Cu excess
Increased Phytate
Decreased linoleic acid
Treatment
Zinc supplementation
Reduce Ca or Cu concentrations
Linoleic acid supplementation

Dog- Parakeratosis in dogs consuming generic dog food
Siberian huskies and Alaskan malamutes
Malamutes - absorption defect
Huskies - hypothyroidism and ß Zn
Puppies on Zn deficient diets

Male reproductive failure
Delayed wound healing
Depressed immune function
Delayed dermal hypersensitivity and T lymphocyte function
Fetal resorption and congenital malformations
Developmental skeletal problems

Answer 144

A

Uncommon in cats
Cattle and sheep: decreased testicular size
Analysis: plasma

Answer 145

A

Most investigated trace mineral
Most common deficiency world-wide

Sources
Meat is best source
Dicalcium phosphate
Fiber – beet pulp and peanut hulls

Iron in food
Heme Iron- Present in hemoglobin and myoglobin
Nonheme Iron- Present in grains and plant sources

Answer 146

A

Available sources- Ferrous sulfate, ferric chloride

Iron oxide
Imparts the “meaty” color to pet foods
Biologically unavailable
Contributes to iron content of the diet

Answer 147

A

Iron Deficiency Anemia
Depleted or unavailable iron stores
Hypoproductive anemia
In most species classification is: Microcytic hypochromic

Answer 148

A

Possible ↓ serum iron
↓ serum ferritin (best diagnostic test)
↑ transferrin
↑ TIBC
Absence or ↓ in Fe on bone marrow stain

Answer 149

A

Uncommon in grazing animals
In healthy companion animals – uncommon
Occurs in growing animals
Hb ↓ around the 3rd week of lactation but increases at weaning

Answer 150

A

Microcytic hypochromic anemia
Piglets housed in stressed conditions
Not on solid food
Housed on concrete floors
Rare in modern husbandry conditions
Parenteral injection not given
Oral Fe not absorbed (diarrhea)
Usually develops ~ 3 weeks of age
Initially ↓ growth rates
Pallor, lethargy
Edematous head and forequarters
Diarrhea
Dyspnea, prominent heart beats (thumps)

Diagnosis
History
Site visit to assess husbandry conditions * Clinical signs
Low blood Hb concentrations
↑ TIBC (Total iron binding capacity), ↓ serum ferritin

Treatment
Supplementing the sow’s diet not effective
Iron Dextran injection IM at 3 days of age
Oral iron supplement
Do not use if diarrhea present – will not be absorbed
If no response, make sure that copper is not deficient

Answer 151

A

Derived from the Greek word for magic
Food sources: coffee, tea > nuts, cereals > vegetables > meat, dairy, poultry and fish

Answer 152

A

Limited number of metalloenzymes

Mn is an activator for many enzymes
MnSOD
Pyruvate carboxylase, glutamine synthetase

Can replace Mg2+ in many reactions

Answer 153

A

Neonatal ataxia
Reproductive problems
Altered lipid synthesis ( ̄ cholesterol syn)
Clotting abnormalities
Abnormal glycoprotein formation with vitamin K
Bone growth
Shortening and bowing of forelimbs
Lameness and enlarged joints in pigs
Locomotor abnormalities in cattle, sheep and goats
Perosis or “slipped tendon” in birds* enlarged tibiometatarsal joint

Answer 154

A

Mammals: 1 ppm, however 40 ppm is recommended for reproduction
Poultry: 50 ppm
Low absorption from the gut
Grains are low in Mn
Toxicity: rare

Answer 155

A

Mimics their natural environment
Eat all day→ chew and make saliva → buffers stomach acid

Answer 156

A

Typically meet the energy and protein needs for maintenance and light work by feeding 1.5-2% of BW as forage

Very likely also meet macro mineral requirements
However should provide sodium
Balance may not be great

Will exceed iron needs but be deficient in other trace minerals
Except possibly Se depending on location

Balance may be poor especially in trace minerals
If feeding hay or poor pasture will be low in vit E and omega-3 fatty acids

Answer 157

A

When work level increases
Biggest change is extra calories
Increase hay or feed more concentrate?
Pros and cons to each
Will depend on horse
Discipline used for
Personality
Management style
etc

As work level increases calorie needs increase
May be hard to meet requirement from forage alone
Need to find feed that provides calories in addition to micro nutrients
Feeding performance feeds at amounts less than manufacturer recommendations can result in deficient and poorly balanced diets
Different horses need different types of hay

Generally;
Alfalfa highest calorie, high protein, better protein quality (higher lysine), high calcium
Grass hay carb and protein fractions vary with maturity, calorie content about 0.8-1Mcal/lb
Grain hays low protein, can be high starch, may have low Ca:P

Performance horses, brood mares and youngstock should have forage with lower NDF and ADF
Easy keepers benefit from higher ADF and NDF
Horses with conditions requiring lower non- structural carb (NSC) levels (eg. insulin resistance, PSSM) need hay with NSC <12% on a DM basis
NSC = WSC + Starch
Compromised renal function need lower protein hays and lower Ca levels
HYPP horses need hay with <1% K
Basic Diet
Select the correct forage for the individual horse
Feed at least 1.5% of BW/d as forage
Provide 0.5oz (1tbsp) salt/500lb BW plus access to salt
At a minimum provide supplemental sources of copper and zinc
Ideally provide a product that will balance forage – Select appropriate feeds or supplements based on individual horse calorie needs – Feed per directions
Provide vitamin E and omega-3’s if on hay or poor pasture

Answer 158

A

Case factors to consider
Substance ingested
Inherent toxicity (ie. LD50)
Dose of toxicant given is based on animal weight
~1/10th of LD50 would not be considered a significant ingestion
Kinetics (if known)
ADME, physiochemical properties
Rapidity of onset of clinical signs
Duration of clinical signs
Target tissues

Amount ingested
Compare to measures of toxicity

Co-ingestants
Multiple active ingredients
Carriers – solvents such as mineral spirits

Time post-ingestion
< 1 hour or > 1 hour

Prior intervention
Induction of emesis at home?
Spontaneous emesis?

Species/Breed/Age of animal
Cats And Acetaminophen
Breed sensitivity to macrolide endectocides
Young animals absorb more lead

Past medical history and age
Underlying liver or renal disease
Altered ability to metabolize and/or eliminate toxicant

Answer 159

A

Absorption- emesis, lavage, activated charcoal (SDAC or MDAC), cathartic
Gets it out of the animal before it could be absorbed

Distribution- intravenous fat emulsions
Draw toxin away from the target site

Metabolism- Enzyme Induction for Detoxification, Enzyme Inhibition for Inhibiting Metabolism
Increases the metabolism because parent compound is toxic but the metabolite isn’t

Elimination- MDAC, Diuresis, urinary pH manipulation, dialysis
Want to increase elimination to get drug out of system

Answer 160

A

Emetics- cause vomiting
3% hydrogen peroxide (irritant)
3% formulation (do not use stronger formulations)
Readily available
Locally irritating
Administered orally at 1 to 2 ml/kg PO
can be repeated once

Good
Readily available
Safe

Bad
Not always efficacious
Not for use in cats

Answer 161

A

Not approved for use by FDA
Direct stimulation of CRTZ; dopamine agonist .
Available as tablet, capsule, or injection
Compounding pharmacies
Can be given IV, IM or via conjunctival sac
High doses are anti- emetic due to opioid receptor agonism

Good
Reliable in dogs
Quick emesis (mean time ~ 18 to 19 minutes)
Naloxone reverses some effects

Bad
Prolonged emesis
Respiratory and CNS depression (reversal with naloxone)
increases emetic effects via blockage of μ-receptors
Use in cats?

Answer 162

A

Newer drug; approved by FDA
Approved for use in dogs eye drop
Highly selective for D2-type (dopamine) receptors
Fewer adverse side effects
Easily administered, even in home environment
Fast onset of action (median time to first emesis = 10 min)
Efficacy shown by appropriate clinical study

Answer 163

A

Used in cats
Potent α2-adrenergic agonists
Injectable emetics of choice for cats

Good: generally reliable emesis within 3 to 5 minutes

Bad: CNS and cardiovascular depression (reversible with yohimbine or tolazoline), not as effective in dogs
Study shows that dex is most effective

Answer 164

A

Grapes, raisins
Chocolate
Xylitol gum
Bezoars
Massive ingestions
Drugs that decrease gastric emptying
Opioids
Salicylates
Anticholinergics
Tricyclic antidepressants

Answer 165

A

Used in ruminants and rabbits because they don’t vomit

Used when there is
Loss of consciousness or severe depression
Hypoxia
Loss of gag reflex
Significant prior vomiting
Seizures (or likely induction of seizures)
Species unable to vomit
Ingestion of corrosives
Ingestion of volatile petroleum products
May require tranquilization/ anesthesia
Airway protection mandatory
Use as large a gastric tube as possible

Make sure it is placed appropriately
Use tepid tap water or normal saline (5 to 10 ml/kg)
Introduce with minimal pressure
Withdraw by aspiration or gravity flow
Repeat until washing are clear

Answer 166

A

Pyrolysis of various carbonaceous materials such as wood, coconut or peat
Treatment with high temperatures and oxidizing agents to form a maze of pores to increase surface area
Adsorption is due to hydrogen bonding, ion-ion, dipole and van der Waals forces
Reversible binding of toxicant to activated charcoal
Less likely to be absorbed
strongly ionized and dissociated salts like sodium chloride and potassium nitrate
small, highly polar, hydrophilic substances
alcohols – ethylene glycol
strong acids
metals – iron, lithium, lead, etc.

Rapidity of adsorption is dependent on external surface area.
Capacity for adsorption is dependent on internal surface area.
AC can be given as a single dose (SDAC) or multiple doses (MDAC)
Effectiveness related to the ability of toxicant to be adsorbed by AC
Indication
large ingestions
sustained release toxicants or possibility of concretion formation
substances that delay gastrointestinal motility
enterohepatic recirculation of toxicant
high concentrations of “free” toxicant in circulation (“gut dialysis” effect)
low volume of distribution
not protein bound
MDAC- Dosages range from 0.5 to 1 g/kg every 6 to 8 hours for three to four doses
Aspiration (make sure airway protected)
Hypernatremia (serum sodium goes up)
Blockage – reported but very rare

Sooner you give AC, the better
Practically: for most ingestions, a dose of 0.5 to 1 g/kg is recommended. Larger doses (1.5 to 2.0 g/kg) recommended for massive ingestions of dangerous substances well adsorbed to AC.
Large animals- bio sponge

Answer 167

A

Laxatives
Emollient laxatives- mineral oil
Bulk laxatives: methylcellulose, psyllium

Osmotic
Saline: sodium or magnesium sulfate
Saccharide: sorbitol
Irritant: castor oil, phenophthalein
Neuromuscular: cholinergic agents

Contraindications
Absent bowel sounds, recent abdominal trauma or surgery, intestinal obstruction or perforation
Ingestion of a corrosive agent
Volume depletion, hypotension, or significant electrolyte imbalance
Magnesium cathartics should not be given to patients in renal failure, with renal insufficiency or heart block
Use caution if patient is very young or very old

Use of a cathartic alone has no role in the management of the poisoned patient.
There is a lack of data with regard to clinical efficacy of using a cathartic with AC.
Based upon available data, routine use of cathartic + AC is not endorsed.
If a cathartic is used, it should be limited to a single dose in order to minimize adverse effects.

Answer 168

A

MDAC*

Forced diuresis*
Primarily renal elimination
Low volume of distribution
low lipid solubility
Low protein binding
Low endogenous clearance
There must be a substantial reduction in total body burden as a result of the treatment and demonstrable clinical improvement.

Urinary pH manipulation*
Hemodialysis (e.g., EG)
Hemoperfusion
Exchange transfusion

Answer 169

A

Conium maculatum: Poison hemlock
(Also called European hemlock, spotted hemlock, California Fern

Lupinus spp.: Lupine

Nicotiana spp: tobacco

Cyanide containing plants
(Sorghum species- Sudan grass, Johnson grass, other forage sorghums; Prunus spp.: chocke cherries; Triglochin spp.: arrow grass; Malus spp: crab apple leaves; Eucalyptus cladocalyx: sugar gum; Amelanchier alnifolia: service berry)

Centaurea spp: Yellow star thistle

C. repens – Russian Knapweed

Answer 170

A

Widespread along roadsides, in fields and meadows
Erect, perennial or biennial, 4 to 6 ft tall
Hollow stems with purple spots
Root is a simple carrot-type tap root
Leaves are coarsely toothed with a fernlike appearance
Flowers in compound umbels, small and white
Strong pungent odor (like mouse urine)

Answer 171

A

200 to 300 species of lupine in the US
center
Wide spread from dry plains to mountain valleys
Perennial, up to 3 feet tall
Alternate, palmately compound leaves, each with 5 to 17 leaflets
Flowers arranged along the main axis (raceme), compact white, blue-purple, red, or yellow pea shaped flowers
Fruit is a multi seeded pod (legume family)

Answer 172

A

Predominantly found in the west and southwest
Evergreen shrub or small tree (6 to 20 feet)
Bluish green, alternate leaves
Leaves and stems have a covering of whitish powder that rubs off easily
Tubular, yellow flowers, about 2“ long
Other plants with similar alkaloids:
Lobelia spp.: found in the eastern US and Canada
N. attenuata – coyote tobacco; N. trigonophylla – desert tobacco; N. tabacum – cultivated tobacco

Answer 173

A

Cyanogenic glycosides found in leaves, fruit, seeds of mature fruit
Highest in newly developing leaves: called amygdalin, dhurrin, etc

Answer 174

A

Annual weed up to 12”
Leaves with cottony hair
Basal leaves are deeply lobed
Stem leaves are linear
Yellow ray flowers
Bracts have long yellow spines

Answer 175

A

Creeping perennial
Leaves covered with hair
Lower leaves alternate
Flower is lavender to whitish in color
Bracts have no spines

Answer 176

A

Alkaloids act on autonomic nervous system
Alkaloids mimic the action of Ach (nicotinic in nature)

Neurotoxic
Shaking, twitching
Staggering, paralysis
Convulsions
Heavy breathing
Coma, death

Teratogenic
Immobilization of fetal movement
Fetus remains in one position for extended period of time
Arthrogryposis, cleft palate
Carpal flexure, torticollis, scoliosis

Answer 177

A

No specific treatment exists

In acutely poisoned animals:
Activated charcoal and cathartics
Careful monitoring, avoid stress
If animals survive acute poisoning, full recovery is possible

Prevention:
remove plants from pasture
Work with farm advisors to identify where and when these plants grow in pastures

Answer 178

A

Hydrolysis by beta glucosidase yields hydrogen cyanide: occurs throughout the GI tract
Also can occur within the plant due to plant stress or trauma: frost, wilting, stunting, mastication
Free hydrogen cyanide is highly poisonous to all animals
Absorbed free cyanide binds to iron (Fe 3+) in cytochrome oxidase preventing normal enzymatic action → inactivation of cellular respiration
Oxygen saturation hemoglobin cannot release O2 → cherry red venous blood

Clinical signs and diagnosis
Animals often found dead
Death usually occurs within 1 – 2 hours after exposure to lethal amounts of cyanogenic plants
Animals die within minutes after onset of clinical signs
Labored breathing, frothing at the mouth, ataxia, muscle tremors, convulsions
Bright red mucous membranes initially; cyanosis of mucous membranes terminally

Answer 179

A

Check the color of blood: cherry red!
Live animal: Collect blood for cyanide testing
Liver and muscle ti-ssue for cyanide testing
Protect from heat; seal samples tight

Answer 180

A

Cyanide has high affinity to Fe3+→ create methemoglobinemia to allow binding of CN- to Methb →Formation of sodium thiocyanate (non-toxic) →Excretion via urine and bile
Dosage: 1 ml of 20% sodium nitrite IV
3 ml of 20% sodium thiosulfate IV

Answer 181

A

C. solstitialis (yellow star thistle) and C. repens (Russian knapweed) cause same disease
Only affects horses
Large intakes over weeks to months are needed to result in disease: ~80 to 200% of their bodyweight over several months
Fresh and dried plants are toxic
Toxins destroy dopaminergic neurons, particularly in the substanie nigra and globus pallidus (affecting cranial nerves V, VII, XII)
“Equine nigropallidal encephalomalacia” (ENE)

Clinical signs
“Chewing disease”: continuous chewing movements, frothing of saliva, difficulty prehending food
Frequent yawning
Open mouth, tongue protruding
Drinking: horses submerge their heads deeply into water buckets and then tip their heads back
Ulceration of tongue, lips, gingiva
Horses die of starvation

Diagnosis
MRI (antemortem)
Bilateral malacia of the substantia nigra or globus pallidus

Answer 182

A

Nerium oleander: Oleander
Rhododendron spp.: Azalea
Persea americana: Avocado
Taxus spp: Yews

Answer 183

A

Animals,humans and birds susceptible
All parts (dried and fresh) are toxic
Minimum lethal doses: ~ 5 leaves

Clinical Signs:within a few hours of exposure
Diarrhea, depression, anorexia, excess salivation
Cardiac signs: bradycardia, tachycardia, arrhythmias
Sudden deaths
Kidney failure

Treatment
No specific treatment available
Llamas,cattle,horses: act.charcoal(1-5g/kgbw)
Bradyarrhythmias:atropine sulfate
Tachyarrhythmias: propranolol, lidocaine, phenytoin, metoprolol
Digibind®: not fully evaluated in animals
Avoid Calcium-and potassium-containing fluids

Prognosis: Guarded!

Answer 184

A

Grayanotoxins- Highest Concentrations In The Leaves, but also in flowers, nectar and stems
Animals and humans susceptible
Most often reported in goats, but all animals are susceptible

Minimum lethal doses:
Goats: 0.1% of bodyweight

Clinical signs:
Vomiting, salivation, colic, depression
Tachycardia, tachypnea, recumbency, elevated body temperature, seizures.

Diagnostic testing:
Urine, serum, GI contents for grayanotoxins
Identify plant material in environment and/or rumen content

Treatment
No antidote available
Decontamination–activated charcoal, cathartics
Supportive Therapy With Fluids
Antibiotics In Animals That May Have Aspirated
Antiarrhythmics

Prognosis:Good With Supportive Care.Full Recovery May occur within 3 – 5 days of exposure.

Answer 185

A

Trees or shrubs
Widely cultivated
All above-ground parts are toxic
Especially leaves are toxic (toxic when dried)

Clinical signs highly variable
Acute deaths/cardiac signs: birds, rabbits, goats
Mastitis and agalactia: cattle, horses, goats, rabbits
Colic, diarrhea, neck edema: horses

toxin - persin
Mechanism is unknown

all plant parts are toxic
Diagnosis- Post mortem lesions
Treatment- supportive

Answer 186

A

Evergreen trees and shrubs (ornamentals)
Flat, needle-like leaves about 1 inch long
Leaves grow in opposite pairs along twigs
Characteristic red fleshy berry (when ripe) – not toxic!

Toxin- taxine alkaloids
Fatal conduction disturbance

6 – 8 oz. of yew→lethal for adult cow or horse
Toxic green & dry
Diagnosis- Taxine alkaloids in GI cont.
Treatment- Activated charcoal Atropine

Answer 187

A

Insoluble calcium oxalates
Grasses that cause Trauma
(Setaria spp. – Bristlegrass)
Lectins (toxalbumins)
Tropane alkaloid- containing plants

Answer 188

A

cause physical harm to oral cavity
All parts of the plants are toxic
Clinical signs:
Look terrible
Rapid, within 2 hours of ingestion
Hypersalivation, head shaking, chewing, pawing at mouth

Answer 189

A

Exposure to sharp grass awns and barbed bristles or prickly plant parts→ injury to the oral mucosa, ear canal or skin

Clinical signs:
Livestock and horses: mainly oral exposure; excessive salivation, ulceration, granulation tissue filling the ulcer, anorexia
Dogs: repetitive sneezing (nasal cavity); limping and continuous licking (interdigital); head shaking and ear scratching (ear); lacrimation (eye)

Treatment:
Remove foreign body/plant material (may have migrated)
General care for abscesses and infections

Answer 190

A

Toxin- lectins (toxalbumins)

Robinia pseudoacacia: Black locust
Small tree up to 70 ft
Common in the SW states
Leaves alternate, pinnately compound Flowers showy, white in clusters
Fruit: flat legume pod with many brown seeds
Bark and seeds have the highest concentrations of lectins→most toxic

Abrus precatorius: Rosary pea, precatory bean
Established in Florida
Twining, perennial vine, 10 - 20 ft long
Leaves alternate, opposite pinnately compound
Flowers in racemes, red to purple
Fruit: legume pod
Seeds: glossy red with jet black eye
Abrin is highly toxic: Lethal dose: 0.00015% of a person’sbw

Ricinus communis: Castor bean
Small tree in warmer areas Large, palmated leaves White flowers
Fruit: spiny capsule
Seeds: shiny with gray and brown mottling
60 seeds can kill a horse
3 to 4 seeds can kill a duck
2 to 20 seeds can kill a person
Toxic Principle
Toxalbumin / lectin
Proteins with affinity for sugar molecules
One of the most toxic compounds of plant origin.
Beans at 0.2% of BW may cause toxicosis. * Small animals are quite susceptible.
All parts of plant are toxic, but especially seeds. Seeds must be broken or crushed to release toxin
Castor oil does not contain ricin
Mechanism of action:
Two glycoprotein chains (A and B)
B chain- Binds to galactoside-containing proteins on cell surface facilitating internalization
A chain- Enters the ER and depurinates 28S rRNA
Result is inhibition of protein synthesis
Cellular death ensues
Clinical signs
Characteristic lag period- a few hours to days
Vomiting with blood
Diarrhea
Often bloody with tenesmus and abdominal pain
Lesions
Catarrhal to hemorrhagic gastroenteritis
Petechial hemorrhages on serosal surfaces
Necrotizing enteritis
Edematous mesenteric lymph nodes
Diagnosis
History of exposure
Presence of seeds in excreta
Leukocytosis
Increased ALT
Detection of alkaloids (ricinine) in gastric contents
LC/MS
Therapy
No specific antidote
Supportive as indicated
Poor prognosis if well-masticated / large quantity consumed
Prevention
Do not plant where animals (or children) may have access
Clip seed heads before maturity when used as an ornamental
Moist heat destroys ricin
Also, mistletoe
Mechanism
Toxins bind to certain cell receptor sites
Inhibition of cellular protein synthesis
Cell death (several days)
Clinical signs
GI irritation ~ hours to days after exposure
Colic
Increased heart rate
Hypovolemic shock

Treatment: supportive and symptomatic: GI decontamination, activated charcoal, fluids

Answer 191

A

Angel’s trumpet, thorn apple (Datura spp., Brugmansia spp)
Datura spp.: found in most of the continental US in overgrazed pastures and waste lands, major weed in soybeans
Brugmansia spp.: planted in gardens
3 to 5 ft tall
Leaves ovate, margins toothed or lobed Flowers trumpet-like, showy, short-lived Fruits: capsules with prickles
Seeds: flat, black or brown

Contain Tropane Alkaloids (hyoscine, hyoscyamine)
Highest Concentrations In Seeds And Leaves

Clinical Signs: anticholinergic toxidrome
Increased respiratory and heart rate, dry mouth, incoordination
Dilation of pupils, digestive tract motility
Positive drug testing result in race horses

Hay And Silage Remain Toxic

Answer 192

A

Senecio spp. (ragwort)
Crotalaria spp. (rattlepod)
Cynoglossum officinale (hound’s tongue)

Answer 193

A

Increased susceptibility of skin to damage caused by ultraviolet light.
Increase in sensitivity to UV radiation
Photodynamic agent in the bloodstream and its excitement by UV light
Reaction Most Severe Nonpigmented Skin
Nonpigmented skin: erythema and edema, pruritis
Clinical signs: Photophobia and hyperesthesia, exudation, ulceration, blindness

Types
Type I: Primary photosensitization
Plants Contain Photodynamic compounds
Hypericum perforatum– St.John’s wort

Type II: Congenital

Type III: Secondary (hepatogenous)
Hepatogenous Photosensitization
Liver Function Impairment
Phylloerythrin Is The Photosensitizing Compounds
Breakdown product of chlorophyll
Usually removed by the liver and excreted in the bile
Liver problem → accumulation in the circulation

Type IV: Idiopathic

Answer 194

A

Plants commonly associated:
Senecio spp. (ragwort)
Crotalaria spp. (rattlepod)
Cynoglossum officinale (hound’s tongue)

Species affected
Cattle, horses
Young more susceptible
Generally only consumed in drought conditions (unpalatable)
Sheep are more resistant
Sometimes used to control Senecio spp.

Answer 195

A

Liver activation of PAs to toxic pyrroles → hepatic disease
Susceptibility
pigs> poultry > cattle, horses&raquo_space;»> sheep, goats
Horses and cattle
5-10% of bw in a few days or weeks → acute liver disease
Most common: small amounts over several months to reach a total dosage of 25-50% of bw → chronic liver disease
Reluctant to eat plants, but do so if in hay
Unavoidable in pellets

Answer 196

A

Gross Lesions:
Acute:
Signs of liver failure
Icterus, edema
Chronic:
Firm nodular liver
Cirrhosis
Icterus
+/- photosensitivity

Microscopic lesions
Hepatocytomegaly
Atypical nuclei / karyomegaly
Bridging Periportal Fibrosis
Bile Duct Proliferation

Treatment: None specific
Supportive care for liver failure

Answer 197

A

Acer rubrum: Red maple

Allium spp.: onion and garlic
Allium cepa (Onion)
Allium sativum (Garlic)

Answer 198

A

Common in the Eastern US
Large tree (up to 100 ft)
Leaves: 3 – 5 lobes with palmately arranged veins.
The fruit is red in color and has 2 wings. The wings form a V and the two seeds lie at the bottom of the V.

Toxin Principle
Unidentified Toxin Wilted And Dried (for about 1
month) leaves
Green leaves Are Apparently Not Toxic
All Acer species should be considered toxic
Animals affected: horses, ponies, zebras, alpacas
Mechanism: Oxidant damage to the RBCs→hemolytic anemia
Ingestion of 1.5 g/kg bw→lethal in ponies

Clinical Signs:several days after exposure
Acute hemolytic anemia
Red-brown urine, oliguria, anuria
Weakness, tachypnea, depression
Cyanosis, icterus

Lab:
low PCV, Heinz bodies, hyperbilirubinemia
Hemoglobinuria, proteinuria

Lesions:
Generalized icterus, splenomegaly, severe diffuse congestion of kidneys

Treatment is symptomatic and supportive:
Activated charcoal
Dexamethasone
Ascorbic acid
Blood transfusion
Fluids to maintain kidney function
Hemoglobin glutamer (oxyglobin)

Prevention: Remove maple leaves and fallen branches; do not plant maple trees in horse or alpaca enclosures

Answer 199

A

Toxic principle
n-Propyl disulfides
Present in raw, cooked, and dried onions
Onion powder, some baby foods

Mechanism
Increased free radical formation→
Direct erythrocyte membrane damage and denatured hemoglobin→
Heinz body formation & acute hemolysis

Raw,dry and cooked onions are toxic
Most susceptible: dogs,cats and cattle
Dogs: 11-15 g/kg of raw onions are toxic

Clinical Signs:
Inappetence, lethargy, tachycardia, tachypnea
Onion odor to the breath, pale mucous membranes
Abortions possible

Treatment:
Avoid stress
Blood transfusions

Laboratory findings:
Hemolytic anemia
Heinz Body Formation
Readily evident when stained with new methylene blue (reticulocyte stain)
Eccentrocytes(*)
Ragged fringe of cytoplasm along one side of the cell
Occur secondary to oxidative stress

Answer 200

A

Amaranthus retroflexus – Pigweed
Oak – Quercus spp.

Most are soluble oxalates
Mainly a problem in cattle, sheep, and goats under grazing conditions without adaptation
Highest concentrations of soluble oxalates (sodium and potassium oxalate) are in leaves
If large quantities are ingested → rumen’s ability to detoxify oxalates is overwhelmed → absorption and formation of insoluble Ca and Mg oxalates
Leads to hypocalcemia and crystallization of Ca-oxalate in the kidneys

Answer 201

A

Affects pigs primarily
Cattle, sheep and goats also susceptible; horses rarely
Season of risk:
Mid June to late summer
Also toxic when dried

Toxic principle: Unknown
Causes acute renal tubular necrosis
Also accumulate nitrates and some soluble oxalates

Clinical signs:
Posterior weakness, incoordination, and sternal recumbency
Typically 5 – 10 days after ingesting large amounts of pigweed
Deaths may continue up to 10 days after removal from plants

Gross lesions:
Perirenal edema +/- hemorrhage
Ascites

Histologic lesions: Acute tubular necrosis affecting both proximal and distal tubules

Answer 202

A

Wide geographic distribution, > 60 spp. in US
Range in size from shrubs to tall trees
Leaves Have Irregular Rounded Lobes
Flowers appear in small clusters
Fruit is known as an acorn

Toxic principle
Hydrolyzable tannins = Polyphenolic complexes
Phenolic acids
Gallic acid, pyrogallol, resorcinol
Astringent effect on gut mucosa→GI irritation
React with cell proteins→denaturation→cell death
Tissue destruction: kidney (severe in cattle), liver
Tannin
Tannins found in leaves, bark and acorns
Young leaves and flower buds are especially toxic; Leaves become less toxic as they mature
Ripe acorns are less toxic than when green
Toxicity not diminished by freezing or drying
Conditions necessary to cause poisoning:
Large amounts (> 10 kg per day/cow)
Preceding period of feed restriction

Clinical signs
Cattle: typically affected
Abrupt Onset
Diarrhea Or Constipation With Bloody or Mucoid Feces
Anorexia, listlessness, rumen stasis
Oliguria (acute renal failure)
Weakness And Recumbency
If BUN highly elevated → guarded prognosis
Goats and Deer:
Can Browse Oak Effectively
Tannin-binding proteins in saliva and GI tract
Horses: Diarrhea,colic,tenesmus;fewer renal effects
Gross lesions:
Ascites, hydrothorax
Perirenal blood tinged edema
Hemorrhagic and ulcerative gastroenteritis
Acorns in rumen

Histologic lesions:
Coagulation necrosis of proximal convoluted tubules
Regeneration (if chronic)

Treatment/Prevention
Remove from access to oak
If unavoidable, grain mix containing 10% calcium hydroxide may be effective→binds tannins
Activated charcoal or mineral oil
Fluids to correct dehydration / acidosis

Answer 203

A

Veratrum californicum: skunk cabbage, corn lily
Pinus ponderosa: Ponderosa pine

Answer 204

A

Toxic principles
All parts of the plant are toxic, particularly roots
Over 50 complex steroidal alkaloids
Cevanine alkaloids: Neurotoxic effects
Bind open voltage-selective Na+ channels
Jervanine alkaloids:
Teratogenic effects: Cyclopamine, cycloposine and jervine
Cyclopamine is believed to be most important due to its greater concentration in plants
Interferes with intercellular signaling and patterning during embryogenesis and organogenesis

Corn lily
Teratogenic and neurotoxic
All species affected
Rarely enough ingested to cause neurotoxicity→ mostly teratogenic (mechanism unknown)
Frost results in loss of toxicity
Sheep: day of gestation
14th day: cyclops
19 – 21 days: embryonic death
28 – 32 days: limb defects
31 – 33 days: tracheal stenosis
Similar effects: cattle, goats, llamas, horses; but less common

Answer 205

A

Common in the Western US
Up to 100 ft tall
Dark green needles, 5 to 10 “ long in threes or twos
Flowers are small and in the leaf axil

Toxin: Isocupressic acid
Results in reduction in uterine blood flow
Subsequent reduction in nutrients and oxygen to the fetus stimulates release of fetal cortisol→abortion
In bark and needles. Needles present greatest risk

Abortion2–21daysafterexposure

Cattle:
Greatest risk in the last 3 months of pregnancy
2.2 to 2.7 kg pine needles per day for > 3 days→abortion

Answer 206

A

Juglans nigra: Black walnut

Answer 207

A

Species affected- Primarily Horses

Distribution
Hardwood timber and nut tree, eastern 1⁄2 USA
Popular in furniture industry
Generates a large amount of shavings/sawdust
Exposure of horses is due to walnut shavings or sawdust used as bedding
Walnut shavings are dark brown whereas cedar and pine shavings are pale

Clinical signs
May occur in ‘outbreaks’ as large groups of horses are exposed at once to new bedding
Reluctance to move within 24 hours of exposure
Depression
Increased
Temperature
Heart and respiration rate
Digital pulses
Hoof temperature
Lower limb edema
Severe laminitis with continued exposure
P3 rotation and separation

Diagnosis
History of recent exposure + acute clinical disease

Treatment
Nonfatal disease (if addressed early)
Essential to avoid long term sequelae Remove offensive bedding
Oral detoxification
Mineral oil
Activated charcoal
Cathartic
Treat limb edema and laminitis as indicated

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