1
Q
Nomenclature of Fatty Acids
A
“C-“: chain length (short 2-4, medium 6-12, long 14-18, 20 and greater)
Saturation: # of duble bonds (saturated = NO souble bonds)
2
Q
Conjugated Dienes
A
Conjugated fatty acids produced by rumen microbes, each double bond separated by a single bond (rather than a methylene group)
most common: cis-9, trans 11-18:2 (called Conjugated Linoleic acids)
3
Q
Nutrition chemical system of fatty acids
A
number of carbon:number of double bonds, number after the n/omega is location of double bonds counting from the methyl end (normally in other field, uses delta which counts from the carboxyl end)
e.g. C20:4 n6
4
Q
Unsaturated Fatty Acid Families and their n number (location of double bond)
A
- Palmitoleic: n-7
- Oleic: n-8
- Linoleic: n-6 or omega-6
- alpha-linoleic: n-3 or omega 3
5
Q
Essential Fatty Acids
A
- Linoleic Acids (C18:2 n-6)
- alpha-Linolenic Acids (C18:3 n-3)
- Arachidonic Acid (C20:4 n-6) **ssential in cats due to low Δ6 activity
- n-3 Long Chain Polyunsaturated Acids: eicosapentaenoic acid (EPA) and docosahexaenoic (DHA): required by AAFCO for inclusion in dogs and cats diet
6
Q
Linoleic Acid Deficiency
A
Linoleic Acid (omega 6): Required for normal growth, skin health, and cellular function
Essential for ceramide synthesis, which maintains the skin’s water barrier. Deficiency causes: Scaly skin, Poor wound healing, Increased water loss
7
Q
Functions of Essential Fatty Acids
A
- Cellular Membranes: components of phospholipids; modulare fluidity; bind to G-couples receptors (omega 3 has anti-inflammatory functions)
- Precursors of Eicosanoids
- Constituents of mylelin (neural func.), synaptosomal lipids, and the retina (n-3 fatty acids)
- Requires for reproduction (n-6)
- Regulators of gene transcriptino (n-3)
8
Q
Eicosanoids
A
Hormones that work on cells that produced them or cells closed to them (act locally, short half-life)
Derived from n-3 and n-6
Main: prostaglandins (PGE2)→ vasoldilation/inflammation thromboxanes (TXA2) → vasoconstrition/clotting, and leukotrienes (LTB4)
Precursors: n-6 (arachidonic acid) and n-3 (eicosapentaenoic acid) fatty acids
9
Q
Functions of n-6 vs n-3 derived Eicosanoids
A
n-6: pro-inflamatory → PGE2: increased vascular permeablity, increased COX 2/IL-6; TXA2: Vascontriction/clotting/platelets aggregation; LTB4: inflammation induction/ ROS/ neutrophils
n-3: generally anti-inflammatory → weak inducers **form protectins and resolvins: resolution of inflammation
10
Q
Reasons for adding fats to diet
A
- Energy
- Carrier of fat-soluble vitamins (A,D,E,K)
- Clinical: injury recovery, digestive disorders (MCT increases digestibility), joint health (n-3), skin conditions (n-6 linoleic acid and n-3 decrease inflammation), renal function, weight loss, aging (chronic inflammation)
- Palatability
- Coat condition
11
Q
Cellular Signal Transduction Pharmacodynamics equation for excitability proteins
A
[L]+[R] ↔ [LR] → [LR] excited →→→ reponsse
12
Q
Intrinsic efficacy
A
Drug’s ability to produce a response aka Degree of the excited state: α (alpha)
aka reflects the greatest clinical response attainable with a drug at any dose
[LR] → [LR] excited
13
Q
Kd
A
equilibrium dissasociation contant
Lower Kd= higher affinity/binding
**equals to when half of the receptors are occupied
14
Q
Potency vs Efficacy on graph
A
Potency: concentration needed to elicit a response → left shif on x-axis = more potent
Efficacy: maximal response → amplitude on y-axis
15
Q
ED50 and EC50
A
ED50:
- Drug Dose produces 50% of maximum effect in an individual (Graded relationship)
- Drug Does producing a given effect in 50% of the population (all or none response - Quantal relationship)
EC50:
- Drug concentration producing 50% of the maximum effect (in vitro)
16
Q
Agonist vs Partial Agonist vs Antagonist
A
Agonist: binds to active receptor and stimulates a maximal response characteristic of that receptor (promotes ongoing responses) 1.0>alpha>0.8
Partial Agonist: stimulates the receptor to produce a response, but not to the same extent as a full agonist (submaximal response) 0.8>alpha>0.2
Antagonist: Do not alter receptor activity on their own but can compete with agonists for receptor binding, thus competitively blocking the responses elicited by the agonist (inhibit responses)
17
Q
Graded vs Quantal Relationships
A
Graded: continuous scale; measured in a single biologic unit; relates does to intensity of effect (greater the dose, greater the intensity of the effect) → half the maximal response in an individual
Quantal: all-or-none pharmacologic effect; population studies; related dose to frequency of effect → half the maximal response in a population
18
Q
Therapeutic Index (TI)
A
TD50/ED50
High TI → wide safety margin → safer drug
Low TI → narrow safety margin → riskier drug
19
Q
Clinal potency
A
the amount of drug needed to produce a certain level of therapeutic response -aka- a drug’s affinity for its receptor
20
Q
what is magnitude if a response proportional to
A
proportional to the fraction of receptor sites (R) complexed with a reversible ligand (L)
21
Q
Inverse agonist
A
ligand that binds to the same receptor as the agonist and causes the opposite effect of the agonist ligand (efficacy is less than 0)
22
Q
Competitive antagonist
A
Antagonism can be overcome by increasing agonist concentration
** Right shift curve due to competitive antagonism (increase conc. & same efficacy) **
Schild plot slope= -1
Kb= disassociation constant of an antagonist
23
Q
Noncompetitve antagonism
A
Bind another site on same receptor (allosteric site) & reduce the magnitude of maximum response that can be attained by any amount of agonist → decrease efficacy (lower curve on y-axis)
**effects can’t be overcome with incrasing agonist concentration
24
Q
Drug-drug interactions effect
A
I. Increased effect: Increased therapeutic effect & increased toxic or adverse effect
- Additive: both drug actions together equals the sum of actions of each drug when administered alone
- Synergistic: promote an exaggerated effect out of proportion compared to each drug alone
II. Decreased effect: antagonistic effect (one drug inhibits action of another)
→ decreased therapeutic effect & decrease toxic effect
25
Tolerance
"safe concentration"
→ tissuse tolerances established in fat, milk, muscle, liver, kidney, or skin
aka highest concentration of a drug residue legally permitted in a specific edible tissue of a food animal
26
Withdrawal Time
- Time required for a drug to be depleted from the animal before the animal's meat can be marketed for human consumption
- Margin of safety: 95% confidence interval for 99% of the population to account for PK variability bt animals
** Only valid for the specified species, dose, route, and frequency of administration
→ time following the last administration of the drug before any particular portion of that animal can enter the food chain to allows for depletion of that drug to safe concentration (tolerance)
27
Characteristics of a ruminant
I. Four-compartment stomach:
Rumen – fermentation vat where microbes break down cellulose
Reticulum – traps foreign objects and helps form cud
Omasum – absorbs water and nutrients
Abomasum – the “true stomach,” similar to monogastric stomachs
II. Rumination (cud-chewing): regurgitate partially digested food (cud) and chew it again to further break it down for digestion.
spp. Cattle, sheep, goats, buffalo, deer, antelope, moose, elk, giraffe
28
Rumen
Microbial fermentation + produces VFAs
- No secretions; papillae vascularized for absorption of VFAs to portal vein; movement coordinated by vagus nerve; blood supply by celiac artery
Environment: higher temp due to fermentation generate heat, anaerobic bacteria, neutral pH, saliva, gas
29
Residues
parent compound or metabolite of the parent compound that accumulates, deposits, or stored within cells, tissues, organs or edible products → thing that shouldn't exceed the safe level
30
Detection Time (DT) vs Withdrawal Time in horse racing
DT: approximate period of time for which a drug or its metabolite remains in a horse's sytem such that it can be deteched by the lab
WDT: estimated time prior to competition that a medication should be withdrawn to avoid possible medication violation **longer than detection time
aka DT is how long a test can find the drug; WDT is how long before competition you should stop the drug
31
Ruminant Reticulum
Honeycombed; stimulation of rumination & eructation ("tickle factor")→ ruminants require hay fiber that causes the reticulum to contract and starts the whole path of contraction that occurs in the rumen
32
Reticular groove in calves
allows milk to bypass the rumen and directly from esophagus to the abomasum
Folds on the reticular groove is stimulated by suckling
33
Omasum (ruminants)
- Absorption of H2O & VFAs
- Folds act as filters to trap large particles → flushes large particles back to rumen for further fermentation
- Muscular action sucks digesta (partially digested food) through retic-omasumal orifice (opening bt reticulum and omasum)
34
Abomasum (ruminents)
acid or "true" stomach; covered by muscus to protect from HCl and pepsin
**first xtep of digestion of proteins
35
Rumenation & eructation
Rumens regurgitate and rechew cud to aid absorption
- Ruminate 9-10hrs/day on high forage; 5hrs on finely ground
Eructation: released gas through MOUTH produced during fermentation in the rumen (CO2 and methane CH4) "burbing"
36
Protozoa microflora in ruminants
Maintain stable fermentation & engulf starch
Types:
- Holostrichs: eat soluble sugars & microbes (cilia all over)
- Entodinomorphs: engulf starch → prevents acidosis (cilia at end)
Roles: not essential, produces VFA (energy), help recycle N when low, cannibalize other protozoa & microbes, tendency to lyse in rumen to feed microbe (not animal)
37
Fungi microflora in ruminants
Attach to feed particles (initiate microbial succession) & penetrate plant cell walls → increase SA for microbes
Produces Lactate & Acetate, H+, CO2, formate, ethanol from cellulose and sugars
High fiber diet = more fungi
38
Cellulolytics- bacteria microflora in ruminants
Produces Acetate, H+, ethanol, may require CO2; must attach to fiber, excrete cellulases
e.g. BF can produce butyrate (VFA)
39
Starch Digestors- bacteria microflora in ruminants
Ferment starch and soluble-sugars→ mainly propionate, acetate, and lactic acid
e.g. Streptococcuss gallolyticus (S. bovis) → rapidly degrade starch and grow with unlimited substrate → could lead to Acidosis; don't depend on redox to grow and produces lots of lactic acid
40
Organic Acid Ultilizers- bacteria microflora in ruminants
41
Methanogens- bacteria microflora in ruminants
Converts H2+CO2→ Methane (CH4)
Maintains fermentation
42
Feeds high in what can generate more of what volatile fatty acids? (ruminants)
Main VFAs in rumen: Acetate, Proprionate, Butyrate
Hay, Fiber feed → Acetate (abosrbed through rumen wall to supply energy) ** Primary Energy Source **
Grains, concentrate feeds (high starch) → Proprionate ** only VFA precursor to glucose **
43
Ruminant metabolism
Anerobic, no mitochondria
Substrate is limiting → more feed= more substrate for microbes = more VFA production to supply energy
Microbes need: Carbon and Nitrogen as subtrates
44
Most common metabolic Dz outcomes in ruminants
Sheep/goats: pregnancy toxemia
Cows; lactation-induced ketosis (post-parturition)
45
Rumen Acidosis
1. Rapid fermentation of starch and sugars by rumen bacteria → production of volatile fatty acids (VFAs) and lactic acid.
2. Excess acid accumulation → rumen pH drops →Acidic environment kills fiber-digesting bacteria, reducing fiber digestion.
3. Absorption of acids into bloodstream → metabolic acidosis. Severe cases → laminitis (weeks or months later), liver abscesses, or death.
** associated with overgrowth of Streph gallolyticus due to high starch
46
Monitoring animal nutritions
Monitoring nutrition = Animal Response
1. Intake → off-feed= not feeling well
2. Production (milk, meat, eggs, wool)
3. Body Condition Scoring
4. Excretion (feed) → feces (size), any non-food items
47
Modify ruminant diet in diseases: Negative energy balance
Negative energy balance
- Primary ketosis: low glucose & high E demand lead to high citculating ketone bodies → multiple fetus in sheeps/goats (pregnancy toxemia); parturition/lactation in cows
- Secondary ketosis: not eating or other Dz
TX: Get them eating! Increase Fiber in the diet, increase glucose
48
Modify ruminant diet in diseases: Positive energy balance
Obesity, pos. fat accumulation → leads to decreased intake, production/fertility, risk of fatty liver & compromised live func. → increaed risk of pregnancy toxemia/ketosis
TX: Increase Fiber in the diet!
49
What is nutrition assessment?
- Information collection: signalment, diet hx, environment, PE- visual and tactile/palpation (BCS- assesses and estimates body fat ONLY)
- Integration and evaluation of data: response to current diet? wt trends?
- Development of a feeding plan (diet/treats, amount- intake and wt trends, feeding method)
- Follow-up monitoring: fodo intake/appetite, BCS and BW, GI signs & stool quality, overall appearance & activity
50
Lean body mass loss (muscle and anything that's not fat, water, or bone) → MCS
- Cachexia: dz processes
- Sarcopenia: associated with aging
Muscle Condition Score: assessed by visualization and palpation of the spine, scapulae, skill, and wings of the ilia
→ can have normal/mild/moderate/severe muscle mass loss
→ include whether it's generalized or localized
51
Humectants in semi-moist pet foods
trap water to soften product and protect from bacteria
52
Jerky treats
We do not recommend dried meat or sweet potato treats → concern for kidney injury
53
Routes of exposure to toxins
- Dermal/ topical
- Mucosal
- Oral/GI
- Respiratory
- Parenteral
54
Decontaminating Sticky Substances: glues, tar, soap
- Avoid using irritant solvents (paint thinner, acetone)
- Use oils to dissolve or soften (mineral/vegetable oils, pb; pick out w/ combs/fingers)
- Additional: detergent baths, clip hair
55
Decontaminating Irritant Substances: fabric softener, liquid potpourri, detergents/pods
Flush with Copious water ~15-20', avoid traumatizing skin, DO NOT use acid/base to neutralize → generate heat, rinse bt toebeans
56
Decontaminating oily substances: petroleum, essential oils, pesticides
Use hand-dishwashing liquid, repeat bathing & rinse, keep the animal warm!
57
Mucosal decontamination (usually ocular)
Flush eyes 20-30 minutes w/ sterile saline, tepid (warm) water & take breaks
Ocular exam after (fluorescein)
Crazy glue → peel off when dry
58
Adverse Drug Events (ADE)
Any harm occur following administration of a drug product (from mild to life-threatening)
Includes: Toxicity, Ineffectiveness, Product defects, human safety associated with handling
Common reasons: drug-drug interactions, herbal, Dz, extra-label, genetics
59
Types of ADE
1. Medication Error: wrong dose, DI, route of admin
2. Adverse Drug Reaction (ADR):
- Toxicity of medication
- Type A "Augmented"
- Type B "Bizarre
60
Type A ADR
A = Augmented
Predictable but exaggerated response; Dose-dependent; Common
Related to drug’s pharmacology
Usually mild → can adjust dose
Well-perfused organs most susceptible due to greater amount of drug
e.g. Aminoglycoside antibiotics → risk of Nephrotoxicity increases with higher trough levels (dose-dependent) due to predictable drug accumulation in the kidneys
61
Type B ADR
B = Bizarre, unpredictable, rare
Not dose-dependent in the general population (Can be in susceptible population)
Immune or idiosyncratic, hypersensitivity rxns (requires prior exposure)
Often severe → discontinue drug permanently
- Often involves reactive metabolite (binding of hapten to epitope)
- Oxidative stressP
62
Primary targets of Type B Drug rxns
"Unexpected tissues" → immune-sensitive or genetically susceptible tissues e.g. Liver (perfusion, CYP450), Skin (SA, antigen presenting cells), Bone Maarow, Circulating Blood Cells (high mass of rapidly dividing cells), Tissue trap/filter immune complexes- glomerulus and joints
63
Primary targets of Type A Drug rxns
Tissues where drugs normally acts or build up e.g. well-perfused, kidney, liver, GI, CNS, blood
64
Example of Type B ADR: Sulfonamides antibiotics
Sulfonamides are metabolized in the liver to Hydroxylamine and Nitroso metabolites that are highly reactive → in susceptible individuals, they bind to proteins and form haptens → trigger immune system
** common in doberman pinscher
tx: d/c drug, supportive care
65
Pharmacogenetic Adverse Rxns: Transporters (Type B)
Changes in transporter functions or changes in enzymatic activity.
e.g. Certain dog breeds have mutation in MDR1 gene that encodes for P-glycoprotein (membrane transport proteins) making it nonfunctional→ drugs that normally pumped out of brain now accumulate
*Ivermectin is a substrate of P-gp→ dogs w/ MDR1 mutation: Ivermectin accumulates in the CNS → neurotoxicity
Breeds: Collies, australian sheperds, shetland sheepdogs, etc.
66
ABCG2 efflux transporters in Cats (Type B ADR)
ABCG2: efflux transporter for blood-retina-barrier
Enrofloxacin is substrate for ABCG2
MOA: generation of photoreactive compounds (ROS when exposed to light) → blindness
67
Pharmacovigilance
Detection, Investigation, assessment, and prevention of adverse effects or any other drug-related problems in veterinary productss → aimed at safety and effectiveness in animals and human exposed to products
**Include reports both when used according to or extra-label
68
FDA Black Box Warning
strictest warning the FDA can require on a prescription drug’s labeling → highlights serious or life-threatening risks associated with the drug
Indicates severe adverse effects.
Guides safe use and monitoring of the drug.
Aims to prevent serious harm or death.
69
Pioneer drug vs generic drug vs compounded drug
Pioneer (legend) drug: brand name; demonstrated safety/effiacy; manufature under GMP
Generic drug: bioequivalent to brand name drug → shown to reach same concentration as brand name drug when administered
Compounded drug: mixture of approved dosage forms or drugs formulated from bulk chemicals, not approved FDA for use as drugs
**on label "Approved by FDA": NADA#
70
Requirements for Extra-Label Drug Use
- Permitted only by or under supervision of a veterinarian
- FDA approved animal and human drugs
- Valid VCPR
- For therapeutuc purposed only (e.g. Not for production)
- ELDU must not result in violative drug residues in food animals
**compounding, NOT bulk chemicals
71
When Compounding is appropriate
Drug compounding: alteration of drugs with respect to dosage, form, and flavor to accomodate the needs of a particular patient
Appropriate when: modification of approved drug to sufficiently treat a patient, approved drug not commercially available
** Cost is NOT a valid reason for compounding **
Should NEVER compound copies of an available FDA approved drug
72
Expiration vs Beyond-use dates
Both indicates when a drug should no longer be used
Expiration dates: based on product-specific studies (formulation, container, conditions), FDA approved drugs
Beyond-use dates: full studies not performed, based on data for similar products → Applies after the product is opened, diluted, reconstituted, or compounded (Based on how long the drug is expected to remain stable)
Beyond use date should not exceed the expiration date of the active ingredient
73
Compounding from bulk (+office stock)
VCPR
Consider other FDA-approved options first
Distribute appropriately
Report adverse events & product defects
*Compounding office stock:
- patient is not food-producing animal
- bulk substance is on use in non-food producing animals
74
Venomous vs Poisonous
Venomous: produces a poison in higher developed secretory glands which can be Delivered during a stinging/biting act
Poisonous: creatures with tissues that are toxic (part or entire tissue); No deliver system → these animals are toxic when eaten
75
Types of biotoxins (Zootoxins)
1.. Hemotoxins: hemolysis, thrombosis, thrombolysis
e.g. Crotalid snakes (pit vipers), Viperid snakes
2. Neurotoxins: affects NS
e.g. black widow spiders, scorpions, jellyfish, elapid snakes
3. Cytotoxins: toxic at cellular levels, can be non-specific or only in certain cells
e.g. brown recluse spiders, blister beetles
76
Hymenoptera (bees, hornets, wasps) toxins and TX
Toxins:
- Bees: melittin, apamin, phopholipase A, mast cell degranulation peptides, hyaluronidase
- Wasps: mastropan (inflammation, allergic resp.) & bradykinin (pain & swelling)
TX: antihistamines, topical corticosteroids, treat anaphylaxis
77
Hyaluronidase acts as a venom
Hyaluronidase acts as a “spreading factor” in venom, helping toxins spread more efficiently through tissues
78
Epicauta species Blister Beetle (poisonous insect)
Toxin: Crystalline cantharidin
MOA: Irritate muscous membrane → epithelial damage → GI tract (anorexic, colic, dirrhea, bloody stool), Urinary tract (dysuria, hematuria), Respiratory Cardiac (tachypnea, tachycardia, slow CRT)
Pathology: oral ulceration, vasication (skin blisters), desquamation in GI (peeling outer layer); hyperemia & hemorrhages in urethra and bladder; necrosis & ulceration
TX: treat shock, correct acidosis, hypocalcemia, AC
79
Arachnids- Black Widow Spiders
Toxin: alpha-latrotoxin (neurotoxin) → Ionophore for Ca, Na, K → increases permeability and enhances neurotransmitters release → degeneration of nerve terminals (motor & sensory)
CS: severe muscle cramps, anxiety, pain → peak 6-12hrs
TX: pain control, muscle relaxant, calcium gluconate, Antivenin, treat shock
80
Brown Recluse Spider
Toxins: Hyaluronidase, Sphingomyelinase, Proteases, Hemolysins
MOA: Endothelial cell damage: cagulation, thrombus formation, tissue necrosis
Wound: Bite lead to chornic wound → grow large form center of bite and starts spreading
TX: wound care, antibiotic (2ndary infections), Daspone, no antivenin avail.
81
Crotalidae (pit vipers): Rattlesnakes, Water moccasins, copperheads
Localized tissue injuries → Bite wound = 2 fangs
Toxins: complex venoms → collagenase, hyaluronidase, phospholipase, ribonucleases, polypeptides, pro- and anti-coagulants
CS: rapid swelling, ecchymotic hemorrhages, salivation, hypernea, tachycardia, mydriasis
*Mojave rattle snakes causes neurotoxicity
TX:
SA: antivenom asap, shock tx, transfusions, diphenhydramine, pain meds, antibiotics
LA: maintain airway, anti-inflammatory, anti-tetanus, antivenom (risk for serum sickness → type III hypersensitivity)
82
Elapidae: Coral snakes & Cobras → neurotoxic effects
"Red Touch Yellow"
Toxin/MOA: blocks nerve-muscle communication
alpha-neurotoxin binds to nAchRs → prevents ACh at neuromuscular junction → paralysis
Local tissue rx, PLA2 enzymes (presynaptic neurotoxin), hemolytic anemias in dogs
CS: limb numbness, disorientation, paralysis, dyspnea; parasympathetic: salivation, emesis, diarrhea, small fang marks
TX: antivenin, resp. support, atropine
83
Venomous lizards: Gila Monster & Mexican beaded lizard
Toxin: Gilatoxin & Hyaluronidase → delivers venom form glands in lower jaw that flows by capillary action
CS: painful bite site (swell/bleed), hypotension and tachycardia, vomiting
TX: remove lizard (prying instrument/ heat source); Inpatient: treat hypotension w/ crystalloid fluis, flush bite site and check fragments of lizard teeth
84
Cane toad & Colorado river toad- poisonous Amphibians
Toxin: Bufotalin → inhibits Na/K ATPase → increase intracellular Na → marked effect on smooth muscle & heart (arrythmias: vasoconstriction, hypotension, hallucinations)
CS: Immediate salivation, emesis, head shake, apparent blindness, disorientation, seizures, V-fibirillation
TX: flush mouth, decontaminate w/ AC and carthartic, treat arrythmias (atropine, lidocaine, propranolol), control seizures
85
Melamine-Cyanuric Acid (feed toxicant)
Toxin: Combination of Melamine and Cyanuric acid *individually they are fairly safe
CS:Crystals in urine (feline) →Development of acute renal failure in cats when given melamine and cyanuric acid combined
TX: No specific antidote, Supportive therapy, Fluid therapy
86
Monensin- Ionophores (Feed additives)
Toxin
MOA: Excess Ca2+ uptake leading to mitochondrial damage, elevated cytoplasmic Ca2+ levels and muscle necrosis
CS:
1. Horse: Anorexia, uneasiness Sweating profuse to intermittent Abdominal pain Stiffness, progressive ataxia, posterior paresis, recumbency, tachycardia, hypotension. Death 24-72 hours
2. Cattle: Anorexia 6-12 hrs followed by 12-24 hrs with diarrhea, weakness, dyspnea. Death typically follows 5- 9 days after exposure
TX: Prevent further exposure; Activated charcoal +/- sorbitol cathartic; Fluids for shock and acidosis; Correct cardiac arrhythmias; Vit. E/Selenium; Long-term effects may persist for months and sporadic death may occur due to cardiac lesions
87
MOA and symptoms of Ionophores (feed additives)
Rapid absorption from the gut → minimal amounts reach systemic circulation
Rapid metabolism in the liver by P450 enzymes; Minimal urinary excretion; Minimal accumulation in tissues
Influx of Na+ , Efflux of K+ Increased Net Influx of Ca2+
Excess uptake of Ca2+ by mitochondria →Mitochondrial damage leading to a lack of energy elevated cytoplasmic Ca levels and muscle necrosis
Horses/cattle/camelids: Cardiac effects
Sheep/swine/dogs: Skeletal muscle effects (weakness)
Poultry: Cardiac and muscle effects
Cats: Polyneuropathy
Long-term effects: Possible cardiac fibrosis Sudden death
88
Cotton (feed toxicant)
Toxin: free Goosypol
MOA: Metabolites exert oxidative stress → Enzyme inhibition leading to Na/K dysregulation → Blockage of gap junction intercellular communication
CS: Cardiac failure, Reproductive effects, Malnutrition
TX: Symptomatic and supportive care; Alleviate edema; Provide nutrients (Vit. A)
89
Sodium Ion Poisoning and/or Water Deprivation
MOA: Initial brain dehydration → Fluid balance will lead to sodium shift across blood-brain-barrier→ Na+ rapidly absorbed, diffuses passively into CSF → High Na+ depresses glycolysis leading to decreased ATP and CNS signs Na+ trapped in CNS attracts water (osmotic) → Cerebral EDEMA
Swine CS: Dog sitting, knuckling of forelimbs, head tilt and bobbing swine; Eosinophilic meningoencephalitis and perivascular cuffing swine
Rehydrate SLOWLY
90
Urea (feed toxicant)
Toxin: urea (ruminants)
MOA: Rapidly hydrolyzed by urease in rumen to form ammonia
CS: Elevated blood ammonia accounts for signs; Frothy salivation, teeth grinding, abdominal pain, bloat, regurgitation; Polyuria; Muscle tremors, incoordination; Weakness, rapid breathing; Violent struggling and terminal tetanic spasms
TX: May not be effective because of rapid onset → Acute death within 24 hours
Vinegar orally to decrease rumen pH; Cold water to decrease rumen urease activity
91
Niacin (B3) function
Func: Coenzyme for oxidoreductase reactions; Substrate for ADPribosyl transferases catalyzing the transfer of ADP-ribose units to proteins; Tx of hyperlipidemia
Deficiency: pellagra in humans and black tounge in dogs (4 D's)
Many spp. can synthesize niacin from tryptophan
92
Riboflavin (B2) func., CS, and deficiency
Prosthetic group of flavoproteins and functions in oxidoreduction reactions
1. NADH Dehydrogenases
2. Oxidases
3. Dehydrogenases
In young birds: neuropathy, degenrating myelin of the sciatic and brachial nerves "Curly Toe"
93
Vitamin C & deficiency
Most spp. can synthesize vit C from glucose, spp. lack gulonolactone oxidase require dietary source → primates, guinea pigs, bats, some birds/fish
Function:
- Collagen synthesis -Required for production of hydroxylation of proline and lysine
- Water soluble antioxidant and regenerates reduced vitamin E
- Reduces metal ions and enhances Fe absorption
- Required for formation of epinephrine form tyrosine (hydroxylation reaction)
Deficiency: Scurvy
94
Thiamin (B1)
Most common water-soluble vit that causes single-vit deficiency
Functions: 1) Oxidative decarboxylation (CO2 exhale); 2) Transketolase reaction; 3)Nerve transmission
Reasons for low levels: Damaged by processing** in canned food!
Deficiency:
1) Wet beriberi: cardiovascular → tachycardia, enlarged heart, edema
2) Dry beriberi: NS disorders → muscle/mental, severe anorexia, opisthotonus (head contract backwards), *bilateral symmetrical lesions in distinct brain regions
95
Vitamin B6
Function:
1) AA metabolism: Transaminases; decarboxylation reactions; side chain cleavage
2) Glycogen metabolism: binds to lysine in glycogen phosphorylase to make the enzyme active
96
Pantothenic Acid
Function:
- Component of CoA required for fatty acid carbohydrate and protein metabolism.
- Component of acyl carrier protein required for fatty acid synthesis.
97
Biotin (Vit. H) function & deficiency
Coenzyme for carboxylase enzymes:
1) pyruvate carboxylase (gluconeogenesis) → making glucose
2) Propionyl CoA carboxylase (gluconeogenesis) → in ruminants
Deficiency signs:
- severe dermatitis & alopecia
- cracked hooves, dermal lesions on bottom of feet
98
Folate (folacin) func. & deficiency
Func: Methyl (met formation)
→ Methylene (DNA synthesis)
→ Formimino (Histidine metabolism)
**Requires B12 to convert to methionine (otherwise folate trap at Methyl H4 folate)
Deficiency: Megaloblastic anemia and leukopenia
99
Vitamin B12 (cobalamin)
**Only synthesize by microorganisms & requires Cobalt
Intrinsic factor is required for absorption in the ileum; Stomach, pancreas, and ileum are all required for absorption
Func: Methionine synthetase Methylmalonyl CoA mutase
Deficiency: Methylmalonic aciduria, hyperammonemia; Wasting syndrome; Megaloblastic anemia (humans) Normocytic, normochromic anemia (some animals) Neutropenia
100
Calcium- oxalate
Oxalates can be poisonous (ruminants) → Animals can develop tolerance for oxalate accumulating plants by building up the concentration of oxalate-degrading bacteria in the rumen (gradual exposure)
101
Calcium- parathyroid hormones functions
- PTH acts to increase Calcium concentration in the ECF back into the desired conc. (normal range)
- PTH promotes bone resorption (dissolution, demineralization) to provide Ca2+ to ECF
- Bone of young animals respond rapidly (12-24hrs); Bone of older animals respond more slowly (24-48hrs)
102
Calcium- Vit D roles
Absorption of vit D: skin, small intestine, liver, kidneys
Dogs & cats don't make much vitamin D in the skin
Low Vit D can cause reduced P and Ca absorption
103
Milk fever- characteristic
Low blood calcium levels around calving-> depleted serum calcium due to loss to colostrum and milk
- Older cows: bone and gut less responsive to PTH and 1,25(OH)2D than heifers
- Periparturient hypocalcemia is relatively rare in heifers
- Periparturient hypocalcemia also occurs in beef cows, ewes (sheep), and does (goat) → not as common as it is in dairy cattle (not making as much milk)
*higher demand during lactation may cause severe lethargy or milk fever
104
Milk Fever- treatment & prevention
Calcium salts: usually in the form of calcium borogluconate, administered IV slowly
** Caution:
- Rapid IV infusion of calcium solutions can lead to cardiac arrest (stone heart syndrome) → Cardiac auscultation (listen) is usually performed when ruminants are administered calcium-containing solutions
Prevention: make sure ration has adequate amount of Mg2+ -> a necessary cofactor of PTH release from parathyroid gland ** do not add calcium to diet hoping it will prevent milk fever
105
Phosphorous Metabolism
In excess P: Kidney reabsorption of P is inhibited by PTH, FGF-23 → reducing expression of Na/Pi cotransporters → increased urinary phosphorous (less urine reabsorption of phosphorous)
*FGF-23 is one of the most important regulator of certain phosphorous
106
Phosphorous in ruminants
- As an preventive measure, water intake can be maximized by adding salt to the ration (3-5% of dry mater as NaCl) → keeps urine dilute and prevents P and Mg from settling out (precipitating) in urine into solid form (uroliths)
- Water also has to taste good
- We don't want to much P →. risk of stones (struvite)
107
FGF-23 significance in P & vit D
increase kidney phosphate excretion, decrease calcitriol (↓GI phosphate reabsorption), decrease PTH secretion
108
Phosphorous in Pet food
2 forms:
I. Naturally occurring "organic" phosphorous (meat, dairy, plants)→ mostly water insoluble = less bioavailable
II. Added "inorganic" phosphoric salts and phosphoric acids → soluble (easier to be absorbed)/insoluble
109
Magnesium absorption in ruminants
- High nitrogen (protein) in a ruminant's diet, as well as high dietary K will reduce magnesium absorption from the rumen partly as the electric gradient would change
- Rapidly growing grasses have lots of nitrogen and potassium
110
Opisthotonus
severe backward head tilt *star gazing*
111
Milk fever prevention
- Do Not add calcium to the diet hoping it will prevent milk fever! → decreases response of the bone to PTH and vit D3
- Make sure ration has adequate amount of Magnesium → necessary cofactor for PTH release from parathyroid gland
*low calcium intake or supplement with acidifying anions
112
Calcium functions
physiological func. including neural and muscle function
113
Hypomagnesemia can cause
Hypomagnesemic tetany
114
Excess P in cats
Can cause kidney Dz
115
Potassium deficiency can cause
arrhythmia and severe weakness
116
U-shaped curve for essential nutrients
both too little AND too much of a nutrient can cause adverse effects
x-axis: increasing dose
y-axis: no effect→ adverse effect
117
Inorganic vs Organic metals
Inorganic → less bioavailable
Organic→ More bioavailable
**Excpetion: Inorganic Arsenics (As) are more toxic (found in wood preservative and fungiticidesN
118
Nonessential metals effects on essential minerals/metals
Nonessential metal typically decrease bioavailabily of essential minerals/metals → compete for the same transporters
119
Metals' Mechanisms of toxicity
2 ways:
I. Promote redox rxns → increase ROS → increase oxidative damage to critical macromolecules
II. Metals bind sulfhydryl groups → deplete glutathione (antioxidant) → promote oxidative stress
120
Chelation of metal
CaNa2EDTA → we want to use version with Calcium → capable of chelating many metals
can combine w/ Pb and eliminated via kidneys
Short term use only
Succimer- seletive → tx of lead, arsenic, and mercury poisoning; no side effects associated w/ EDTA
Does not chelate essential minerals like Zince; not nephrotoxic
121
Copper Toxicity (Cu)
Acute: GI tract → emesis, diarrhea, dehydration
*TX: supportive
Chronic: Liver (phase I), blood cells (phase II) → icterus, increase liver enzymes. hemoglobinemia, hemoglobiuria → spp. Sheep
*TX: Ammonium tetrathiomolybdate, IV fluid to flush kidneys
MOA: accumulation in hepatocytes → release from liver to blood → hemolytic crisis
**can also occur with deficiency in Molypdenum or sulfate not avail.; Sulfur also faciliates fecal excretion of Cu in bile (ruminants)
122
Selenium Toxicity clinical signs
Acute: NS, Resp. system, GI → incoordination, depressed, anorexia, cyanosis, labored breathing, colic, diarrhea
Garlic odor to breath
Subacute: NS → paralysis; in swine → focal symmetrical poliomyelolacia
Chronic: Dermal & reproductive → alopecia, rough coat, abnormal hooves/horns, infertility, abortions, teratogenic; e.g. chronic selenosis
123
Zinc toxicity
Acute: GI, kidney, pancreas, liver, blood cells, joints → anorexia, v, lethargy, icterus, acute renal failure, pancreatitis; Dogs → hemolytic anemia (Heinz bodies & nRBCs)
Chornic (foals): joints + hematopoietic system → enlargement, lameness, epiphyseal swelling
Chornic (livestock): GI + NS → lethargy, anorexia, decrease milk, seizures
124
Lead toxicity (Pb)
Among the most common poisoning in cattle; Absorption in duodenum and respiratory tract; bound to RBCs
MOA: binds to -SH groups; competes w/ Ca and Zn
Neuronal necrosis in CNA; demyelination in PNS; inhibits key enzyme in heme synthesis → basophilic stippling/erythrocyte fragility
CS: Subacute/chronic: NS, GI, hematopoietic → Encephalopathy, anorexia/colic, proteinuria
TX: Magnesium sulfate PO, Chelating agents → CaEDTA, DMSA
*Pb is excreted in milk
125
Chronic hepatic Cu Accumulations in Dogs
Inherites as autosomal recessive traits
breeds: bedlinton terriers, west highland terries, doberman, labs
126
Selenium Toxicity MOA & TX
Acute: oxidative damage
Chornic: replaceent of S in amino acids Selenium Toxicity affects function of essential proteins (hair, hooves)
Treatment:
Acute: Supportive tx to combat gastroenteritis & shock; N-acetylcysteine, a glutathione substiture
Chronic: prevention; dietary Cu; increasing sulfur-containing proteins (methionine, cysteine)
127
Zn salts characteristics
Have direct corrosive and cytotoxic effects → GI & pancreatic necrosis
128
Zinc toxicity treatment
- Removal of object
- GI protectants
- Supportive: bicarbonate for renal support, transfusion
- Supplement Cu in LA
- Chelation w/ calcium disodium EDTA
129
Absorbents
Binder
- AC +/- carthartics, mult. doses
- Cholestyramine: bile acid sorbent (vit D toxicosis)
Adverse: aspiration, hypernatremia, preclude endoscopy/sx
130
Exatracorporeal therapy
Hemoperfusion: cartridge filled w/ AC/resins
Hemodyalysis: fliter lipophilic compounds
131
Intravenous Lipid Emulsion (ILE) significance
permethrin tox. in cats & ivermectin tox. in certain dog breeds
adverse: Hyperlipidemia, Pancreatitis
132
Mycotoxin
metabolites of fungi
conditions favor production: humid/warm, nutrient-rich crops, storage quality, aerobic
133
Aflatoxin toxicosis
Chronic; all spp.
MOA: Biotransformation in the liver → liver damage (hepatic lipidosis & necrosis)
CS: liver Dz, Abnormal coagulation profile
134
Penitrem A toxicosis in dogs
Tremorgenic mycotoxin
CS: restless, pant, salivation → whole body tremors
Advances: like strychnine poisoning → tremors, seizures, hyperresponsiveness
TX: decontaminate, fluids, diazepam, methocarbamol, barbiturates
135
Fumonisin toxicosis in horses vs pigs
Infests corn; MOA: inhibits sphingolipid biosynthetic pathway (crucial for essential cell membrane components and signaling molecules)
Horses: CNS → Equine Leukoencephalomalacia (ELEM)→ neurotoxicosis
Swine: lungs (porcine pulmonary edema)→ respiratory syndrome
TX: remove feed, poor prognosis
136
Deocynivalenol (DON, Vomitoxin)
spp. Swine & dogs most susceptible
CS: Anorexia
TX: supportive, remove contaminated feed
137
Ergot alkaloids toxicosis & tx
MOA: Ergopeptine alkaloids → potent vasoconstriction → stimulates D2-dopamine receptor → decrease prolactin secretion → agalactia (decrease milk production)
Cutaneous form: "Fescue foot" (cattle/sheep)
TX: Horse → admin of D2-antagonist (domperidone)
138
Tall Fescue Toxicosis
“Summer slump” → hyperthermia (Cattle and sheep), Immunosuppression, Delayed shedding of the haircoat, Decreased feed intake, weight gain, milk production
Equine fescue toxicosis → mares during late gestation and
early post-partum period; Dystocia, abortion, retained placenta, increased fetus size at birth, neonatal septicemia, decreased viability
139
what mediates the degree of response between ligand and receptors?
Ligand's affinity for the receptor (potency) and the level of excited state of the receptor (efficacy)
140
When half the receptors ar occupied, this equals
Kd
141
Example of antagonism: Xylazine & Yohimbine
Xylazine: targets presynaptic alpha2-adenergic receptor → reduces neural transmission → sedation
Yohimbine: competitive antagonist by binding that receptor preventing xylazine effects → reversal effect → reversal of sedation
142
Isobologram plot showing prdicted drug effects when used togther
- Point on the line: Combined doses are additive (expected effect).
- Point below the line: Synergism → smaller doses than expected produce the effect.
- Point above the line: Antagonism → larger doses than expected are needed.
143
Agal Toxin
toxic metabolites of diatoms and cyanobacteria
144
V1
flashcards
Decks in class (15)
# Cards
-
VET401. Exam 3135
-
Anatomy Terminology6
-
VET401. Exam 432
-
VET402. Exam 1122
-
VET402. Exam 282
-
VET 402. Exam 3112
-
VET406. Midterm198
-
VET406. Finals144
-
VET403. Midterm - Musculoskeletal278
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VET403. MSK Finals130
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VET404. Neuro Exam 1135
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VET404. Exam 234
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VET404. Exam 33
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VET404. Final Exam110
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VET404. Behaviors8
