Cattle & Other

Food Animals
ELIZABETH YOUNG, PHARM.D., FSVHP
WASSON VETERINARY PHARMACY RESIDENT
PURDUE UNIVERSITY VETERINARY TEACHING HOSPITAL
APRIL 13, 2018
Objectives
• Introduce important features of bovine anatomy and physiology and how they
pertain to pharmacotherapy
• Discuss the anatomy of the ruminant GI tract and how it affects drug
pharmacokinetics
• Define “food animal”
• Summarize AMDUCA and its implications on ELDU and compounding in food
animals
• Discuss withdrawal times (WDT) and identify sources that can be used to
determine appropriate WDTs
History of the Cow
• Domesticated over 5000 years ago
◦ Almost exclusively to serve as a source of food
◦ For this reason the veterinary pharmacist must be extremely cognizant of
keeping drug residues out of this species.
◦ Food and drug law varies greatly between human and animal species
because unlike humans, animal patients can be eaten by humans.
History of the Cow
• Cattle are strict herd animals with complex social hierarchy
• ~1 bull : 30 females
• Do not include humans in hierarchy
◦ Unwilling to cooperate
• Do not function well as solitary members – results in stress
Bovine Nomenclature
• Male = Bull
◦ Castrated male = steer
• Mature Female = Cow
◦ 1 year old female non-gravid = heifer Non-gravid = not yet given birth
• Offspring = calves (singular calf)
• Gestation = 9 months
◦ Birthweight = 80 – 100 lbs
◦ Double birthweight in 60 days
• Average life span = 25 years (if not a food animal)
Vision
• More attention to motion than detail
• Wide field of vision with small blind spots
• Strong visual associate memory
• “Flight zone”
Olfactory
• Keenest sense
• Can detect odors 5 miles away
• Strong preference for sweet tastes
• Form strong olfactory associations with
positive and negative experiences
Bovine Anatomical Terminology
Bovine Vital Signs
• Body Temperature: Normal 100°F – 102.5°F
◦ Fever >103 °F
• Pulse: Normal: 60-70 bpm
◦ Bradycardia: <40 bpm
◦ Tachycardia: >80 bpm
• Respirations: Normal: 10-30 breaths/minute
Dietary Habits
• Herbivorous – no upper front teeth but have a dental pad that they use to rip
plant matter away from the roots.
• Ruminants: mammals that chew the cud regurgitated from their rumen
◦ cattle, sheep, antelopes, deer, giraffes, and their relatives
◦ Spend 6 hours eating daily & 8 hours chewing cud
◦ Each day cows ingests 95 lbs of food and ~30 gallons of water
◦ Typical GI pH is relatively alkaline compared to humans & carnivores
◦ Overall pH of 4 – 5
◦ Weak bases are ___________
more bioavailable compared to humans
◦ Weak acids are ____________
less bioavailable
However, their long, fluid filled gut decreases oral bioavailability of many drugs
Dietary Habits
• Cows have a 4 chambered stomach
◦ Rumen
◦ Reticulum
◦ Omasum
◦ Abomasum

• Food is ripped from roots  formed into a bolus  swallowed  enters the
rumen then the reticulum  regurgitated  chewed more --> swallowed
makes it’s way to the omasum  and finally the abomasum
The Rumen
• Largest compartment of the stomach
◦ Can hold up to 50 gallons of food
• Acts as a fermentation vat
◦ The fermentation process produces heat maintaining thermostasis
• Bacteria and protozoa supply enzymes to break down cellulose fiber as well as
assimilate proteins and manufacture all of the B vitamins needed by the cow
• Food then passes to the reticulum
The Reticulum
• Smallest compartment of the stomach
◦ Sometimes called the honeycomb or the hardware stomach
• This is where any foreign objects that may have been accidently swallowed
with the feed settle out
• Veterinarians may use magnets to collect all metallic objects to prevent
further movement through the GI tract and perforation.
◦ Which could lead to hardware disease
• Food also mixes with saliva here to produce cud
• The cud is regurgitated back into their mouths where they
chew the food completely.
The Omasum & Abomasum
• Omasum
◦ The food is further broken down and filtered
◦ All the water is also absorbed out of the food in the
compartment.
• Abomasum
◦ Also known as the True Stomach
◦ Responsible for true digestion by hydrochloric acid
◦ Remaining particles are passed on to the small intestine where
most of the nutrients are absorbed and made available
systemically
The Fistulated Cow
• Designated donor cows with a surgically installed port allow access to the
rumen from the outside.
• Transfaunation — the act of taking microbes from one source and putting
them in another.
• Rumen flora from a fistulated cow helps not only sick cows, but also sheep and
goats because they share similar digestive systems
• Remove a couple of gallons of rumen contents without any negative impact to
the donor cow.
• What you take is then kept warm and then run through a strainer and usually
diluted with water before administration through an orogastric tube to a
ruminant in need.
Bovine Physiology
• Glomerular filtration rate: 1.8 mL/min/kg
• Blood volume: 64 mL/kg
• Cannot vomit from the true stomach (____________)
abomasum or the omasum but can
regurgitate from the rumen & reticulum
◦ During acute poisonings, apomorphine and lithium chloride can be used to
induce regurgitation from the rumen
Bovine Metabolic Considerations
• Highly efficient hepatic biotransformation for elimination
◦ Lipophilic drugs have shorter half-lives in ruminants
• Rumen microflora degrade & metabolize many drugs
• Udder & milk act as a third compartment for some lipophilic drugs
Likely Toxicities in Cattle
• -agonist sedatives
◦ Xylazine, dexmedetomidine, detomidine
• Antibiotics which kill rumen microflora
• Seeds containing cyanogenetic glycosides (cyanide precursor)
◦ Results in prussic acid release in rumen
• Accidental poisonings from organophosphates & other chemical toxins
Food Animal
Considerations
What is a Food Animal?
• Cattle • Elk
• Pigs • Buffalo
• Poultry (chicken/turkey) • Deer
• Goats • Camelids (llama, alpaca)
• Sheep • Exotics (i.e. frogs, alligators)
• Fish • Bees

Not a comprehensive list

 What is a Food Animal?
• Any animal being used for milk, meat, organs, eggs, honey, or other
rendered products (leather, gelatin, bone meal, wool, glue,
collagen, soap, cosmetics, down feathers, etc.)

Intended use = determined by the human consumer

Any animal can be a food animal!*

*The only animals that can’t be food animals are endangered species and humans.
Food Animal Considerations
• Cattle are used for:
◦ Meat
◦ Milk
◦ Hides
◦ Hooves
◦ Bones
◦ Organs
• Harmful drug residues must NOT appear in any tissue that will be consumed by
humans
◦ Appropriate drug residue depletion times (withdrawal times – WDTs) should be
estimated prior to use.
Consequences of Drugs Used in Food
Animals
• Environmental contamination
• Cancer in humans from carcinogens
• Direct toxicity to humans from ingestion of animal meat
• Drug allergies in humans from constant exposure
• Development of bacterial resistance

Know this list!

Regulation of Drug Use in Food Animals
• Animal Medicinal Drug Use Clarification Act (AMDUCA)
◦ 1994 Amendment to the Food, Drug, and Cosmetic Act

• Made extra-label drug use (ELDU) legal

◦ Prior to it’s passage, all medications used in animals had to be labeled for
that species, indication, route of administration, dose, and frequency.

• In food animals ELDU is permitted only if:

◦ There are no inappropriate drug residues VCPR = Veterinarian Client Patient
◦ A valid VCPR exists Relationship
◦ Accurate WDTs are established
Regulation of Drug Use in Food Animals
• Animal Medicinal Drug Use Clarification Act (AMDUCA)
◦ Does not permit ELDU of medicated feeds
◦ Does not permit ELDU of certain drugs:
◦ Chloramphenicol
◦ Clenbuterol
What do all the highlighted medications
◦ Diethylstilbesterol (DES) have in common?
◦ Fluoroquinolones They are antibiotics
◦ Glycopeptides –vancomycin
◦ Nitroimidazoles –metronidazole
◦ Nitropurans – all agents, including furazolidine, nitrofurazone and others.
Regulation of Drug Use in Food Animals
• Animal Medicinal Drug Use Clarification Act (AMDUCA)
◦ Why does this matter for pharmacists?

All involved in the drug prescribing, dispensing, administration

chain will be prosecuted to the full extent of the law if residues of
prohibited drugs are detected in any food animal tissues or
byproducts.

Absolutely no compounding of these drugs is tolerated.

Withdrawal Time (WDT)
• The WDT is the estimated time that tissues can be safely consumed
following the last dose of drugs in 99% of animals treated.
• WDTs are expressed in days for meat and eggs, and hours for milk
◦ Meat: the animal cannot be slaughtered for food prior to that
time
◦ Milk: the milk taken from the lactating cow must be discarded for
that many hours after the last dose of drug is given
• Drugs approved for use in food animals must contain WDT
information on their labeling
What does this mean for pharmacists?
• Veterinarians are responsible for putting WDTs on prescriptions
◦ If you get a prescription for a food animal without a WDT, you
need to contact the veterinarian for one
• Prescription label MUST state all WDTs
• A pharmacist may NOT determine WDT but can assist the
veterinarian in finding or determining an appropriate WDT
• What Database provides drug and pesticide WDT’s
for producers, DVMs, and extension specialists? It’s
supported by the USDA.

• Food Animal Residue Avoidance Database (FARAD)

FARAD
• “The overarching goal of FARAD is to provide current and
accurate scientific information to veterinary practitioners
and thereby foster production of animal-derived human
foods that are devoid of unsafe chemical residues,
including drugs, pesticides, natural toxins and
environmental contaminants.”

• http://www.farad.org/
Participation
• Get on FARAD’s website and explore the site.
• Then determine the best WDT for the following prescription.
Purdue University Veterinary Teaching Hospital
625 Harrison St. West Lafayette, IN 47907
Small Animal Hospital: 765-494-1107 Meat Withdrawal: 10 days
DEA# AB1234567-Y56 Doctor’s Printed Name: Elizabeth Young
Milk Withdrawal: 120 hours
Name: “Blackie” Jane Doe (Bovine)__1300 lbs _2 yo cow__Date: 4/12/18
Address: 123 Cherry St. West Lafayette, IN 47907____________________
How would this be different if this was a 2 year
Xylazine 20 mg/mL old steer?
Give 9 mL IM once for sedation #9 mL Meat Withdrawal: 10 days
Refill NR 1 2 3 4 5 Void after_______________ Milk Withdrawal: N/A
___________________________ ___Elizabeth Young, DVM______
Dispense as Written May Substitute
Veterinary Feed Directive
Regulation of Drug Use in Food Animals
• Veterinary Feed Directive (VFD)
◦ Background
◦ Antimicrobial resistance linked to use of antibiotics in food animals
for production purposes
◦ Judicious Use Strategy
◦ Limit use of antimicrobials in food-producing animals to certain situations
◦ Health of animal is at risk
◦ Only under direction of a veterinarian
◦ Applies to medically important antimicrobials
◦ Necessary for treatment of certain human infections
Regulation of Drug Use in Food Animals
Medically Important Antimicrobials Disease in Humans
Natural penicillins (Penicillin G, V) Neurosyphillis
Other penicillins (oxacillin, nafcillin, dicloxacillin) Serious S. aureus infections
Antipseudomonal penicillins (piperacillin, ticarcillin) Serious P. aeruginosa infections
Aminopenicillins (amoxicillin, ampicillin) L. Monocytogenes
3rd generation cephalosporins (ceftriaxone) Necrotizing enterocolitis
Fluoroquinolones (ciprofloxacin, levofloxacin) MDR gram-negative rods
Aminoglycosides (amikacin, gentamicin) Enterococcal endocarditis
Macrolides (erythromycin, azithromycin) Legionnaire’s disease
Tetracyclines (doxycycline, minocycline) Anthrax treatment/prophylaxis
Glycopeptides (vancomycin) MRSA
Regulation of Drug Use in Food Animals
• Veterinary Feed Directive (VFD)
◦ Indications for “increased weight gain” or “improved feed
efficiency” no longer legal for these antimicrobials
◦ Use in feed = VFD required
◦ Use in water = prescription required
◦ Similar requirements to prescription writing
◦ Valid VCPR required
Medications used in
Food Animals
Medications used in Food Animals
• Topical antimicrobials
• Ionophores
• Anabolic Growth Promoters
• Antiparasitics
• Antibiotics
Medications Used in Food Animals
• Ionophores: transport ions across lipid membranes and
enhances rumen fermentation
◦ Increase feed efficiency and promote growth in food animals
(0.18-0.5 extra pounds/day)
◦ Decreases chance of bloat and acidosis in the rumen
◦ Available OTC!  No VFD required

Monensin (Rumensin®) Classified as antibiotics

Lasalocid (Bovatec®R) but have no therapeutic
antibiotic activity
Medications Used in Food Animals
• Antiparasitic Agents
◦ Internal parasites
◦ Antihelmintics (worms)
◦ Fenbendazole (Panacur)
◦ Antibiotics
◦ External parasites
◦ Pesticides
◦ Ivermectin, spectinomycin
Xylazine
• Alpha-2 adrenergic agonist used for its sedative & analgesic effects in a variety
of species
• Contraindications and Cautions:
◦ Those receiving epinephrine or having active ventricular arrhythmias.
◦ Generally should not be used in the last trimester of pregnancy, particularly
in cattle.
◦ Do not give to ruminants that are debilitated, dehydrated, or with urinary
tract obstruction.
• Dosages between species can be very different; be certain of product
concentration when drawing up into syringe, especially if treating ruminants.
Excede (Ceftiofur crystalline free acid)
• Time-dependent, bactericidal third-generation cephalosporin antibiotic active
against a variety of gram-positive and gram-negative bacteria and, like other
cephalosporins, inhibits bacteria cell wall synthesis.
◦ Ceftiofur is not active against Pseudomonas spp or enterococci.
• Administered SC at the posterior aspect of ear in cattle; administered IM in
swine.
• In beef and dairy cattle, ceftiofur is labeled for the treatment of bovine
respiratory disease (BRD, shipping fever, pneumonia) and for the treatment of
foot rot
• In swine, ceftiofur is labeled for the treatment of swine respiratory disease
(SRD)
Cephapirin
• First-generation cephalosporin indicated for Mastitis in lactating cows caused
by susceptible strains of Streptococcus agalactiae and Staphylococcus aureus
• Comes in 2 different salt forms
◦ Cephapirin sodium (ToDAY®)
◦ Used in lactating cows
◦ Cephapirin benzathine (ToMORROW®)
◦ Used in dry cows
Banamine (Flunixin) 50 mg/mL
• Cattle:
◦ Indication: Control of fever associated with respiratory disease or mastitis and fever and
inflammation associated with endotoxemia
◦ 1.1 – 2.2 mg/kg (1 – 2 mL per 100 lb) given slow IV either once daily or divided q12h for up to 3
days. Avoid rapid IV administration.
◦ One study suggested that the pharmacokinetics and elimination of flunixin in milk differed
between healthy cows and those with mastitis. The study also indicated that an extended
withdrawal time may be needed in cows with mastitis.

• Swine:
◦ Indication: Controlling pyrexia associated with swine respiratory disease
◦ 2.2 mg/kg IM once, only in the neck musculature with a maximum of 10 mL per site.
Key Points
• Any species can be a food animal (intended use determines)
• Drugs must be used as labeled in food animals to avoid drug
residues
• A valid VCPR is required for ELDU
• WDTs must be established by a veterinarian on the
prescription when using drugs in food animals
• Severe penalties for violations
References & Additional Readings
• Ruminants:
◦ Anderson DE & Rings DM. Current Veterinary Therapy: Food Animal Practice, Fifth Volume. 2009.
◦ http://www.vivo.colostate.edu/hbooks/pathphys/digestion/herbivores/rumen_anat.html
◦ http://www.merckvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-digestive-
system/the-ruminant-digestive-system

• AMDUCA: https://www.ecfr.gov/cgi-bin/text-
idx?SID=054808d261de27898e02fb175b7c9ff9&node=21:6.0.1.1.16&rgn=div5#sp21.6.530.a

• VFD: https://www.fda.gov/downloads/AnimalVeterinary/DevelopmentApprovalProcess/UCM455480.pdf

• https://www.fda.gov/animalveterinary/guidancecomplianceenforcement/actsrulesregulations/ucm08537
7.htm#limitations

• Plumb’s Veterinary Handbook: https://www.plumbsveterinarydrugs.com

Cattle & Other
Food Animals
ELIZABETH YOUNG, PHARM.D., FSVHP
WASSON VETERINARY PHARMACY RESIDENT
PURDUE UNIVERSITY VETERINARY TEACHING HOSPITAL
APRIL 13, 2018