Exam 1 Flashcards

Question

What data is plotted in a dose response curve?

Answer 1

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

Answer 2

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

Answer 3

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

Answer 4

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

Answer 5

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)

Answer 6

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

Answer 7

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

Answer 8

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)

Answer 9

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

Answer 10

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

Answer 11

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)

Answer 12

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

Answer 13

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

Answer 14

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

Answer 15

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

Answer 16

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

Answer 17

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

Answer 18

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

Answer 19

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

Answer 20

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

Answer 21

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

Answer 22

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

Answer 23

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

Answer 24

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

Answer 25

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

Answer 26

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

Answer 27

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

Answer 28

Local- close to/at site of action Systemic- drug administered at a convenient location and absorbed into the bloodstream for delivery

Answer 29

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

Answer 30

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

Answer 31

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

Answer 32

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

Answer 33

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

Answer 34

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

Answer 35

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

Answer 36

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

Answer 37

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

Answer 38

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

Answer 39

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

Answer 40

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 41

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

Answer 42

drug is chemically transformed into metabolites

Answer 43

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

Answer 44

Metabolism vs excretion predominant depends on ionization and lipophilicity

Answer 45

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 46

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 47

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 48

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 49

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 50

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 51

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 52

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 53

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 54

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 55

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 56

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 57

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 58

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 59

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 60

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 61

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

Answer 62

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 63

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 64

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 65

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 66

Can be synthesized from other amino acids

Answer 67

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

Answer 68

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 69

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 70

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 71

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 72

Maximum measured concentration

Answer 73

Time of maximum concentration

Answer 74

fraction of drug reaching the systemic circulation intact.

Answer 75

Measure of total systemic exposure.

Answer 76

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

Answer 77

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

Answer 78

fraction of a drug removed per unit time.

Answer 79

time for half of administered drug to be absorbed.

Answer 80

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 81

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

Answer 82

Five half lives for both instances

Answer 83

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 84

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 85

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 86

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 87

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 88

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 89

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 90

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 91

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 92

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 93

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 94

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 95

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 96

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 97

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 98

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 99

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 100

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 101

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 102

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 103

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 104

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

Answer 105

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 106

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 107

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 108

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 109

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 110

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 111

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 112

1. Low copper in the diet 2. Low copper bioavailability 3. Conditioned copper deficiency

Answer 113

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 114

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 115

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

Answer 116

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 117

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

Answer 118

Catalytic >200 enzymes contain zinc Structural structural support in Cu,Zn SOD zinc finger motif in proteins Regulatory stimulates factors regulating gene expression

Answer 119

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 120

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

Answer 121

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 122

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 123

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

Answer 124

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

Answer 125

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 126

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 127

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

Answer 128

Limited number of metalloenzymes Mn is an activator for many enzymes MnSOD Pyruvate carboxylase, glutamine synthetase Can replace Mg2+ in many reactions

Answer 129

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 130

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 131

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

Answer 132

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 133

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 134

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 135

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 136

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 137

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 138

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 139

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 140

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

Answer 141

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 142

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 143

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 144

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 145

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 146

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 147

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 148

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 149

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

Answer 150

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 151

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

Answer 152

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 153

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 154

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 155

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 156

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 157

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 158

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

Answer 159

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 160

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 161

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 162

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 163

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

Answer 164

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 165

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 166

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 167

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 168

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

Answer 169

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 170

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 171

Liver activation of PAs to toxic pyrroles → hepatic disease Susceptibility pigs> poultry > cattle, horses >>>>> 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 172

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 173

Acer rubrum: Red maple Allium spp.: onion and garlic Allium cepa (Onion) Allium sativum (Garlic)

Answer 174

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 175

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 176

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 177

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 178

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 179

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

Answer 180

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 181

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 182

Juglans nigra: Black walnut

Answer 183

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

Exam 1 Flashcards

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