Lecture 1: reproductive drugs and hormones

When is progesterone (P4) the most prominent hormone?

- diestrus

(steroid hormone of pregnancy)

What are 5 effects of progesterone on reproduction?

- decreases myometrial contractility = maintains preg

- suppresses estrus behavior = synchronization protocols

- lowers immune function within the uterus

- closes the cervix

- negative feedback to LH

What are the side effects of progesterones?

- skin absorption that can affect humans = wear gloves

- prolonged use can contribute to pyometra

- will decrease LH and alter male and female reproductive hormones

What are examples of oral progesterone?

- Altrenogest

- melengestrol acetate (MGA) (cattle in feed commonly)

What are examples of injectable progesterone?

- in oil

- altrenogest

- repository compounded formulations

what are examples of intravaginal progesterone?

- CIDR

What are the uses for progesterones in reproduction?

- synchronization protocols (intravaginal CIDR, MGA)

- maintenance of pregnancy (oral and injectable, for luteal insufficiency, need to keep the uterus quiet)

- estrus suppression

When is are estrogens (E2) the prominent hormone? What are they produced by?

- predominant steroid hormone during estrus

- produced by follicles

What are the effects of estrogens in reproduction?

- heightens immune function locally within uterus

- opens the cervix

- primes uterus for contractility (priming of oxytocin receptors)

- enhances estrus behavior

- negative feedback to FSH (stops follicle growth so 1 follicle is picked)

What are common types of estrogens?

- Estradiol 17beta (naturally occurring, unconjugated)

- esterified estrogens (more potent than above)

- estriol (incurin, treat urinary incontinence in dogs)

- estrone sulfate

- B ring unsaturated estrogens

What is estrone sulfate?

- a type of estrogen that can be given

- from fetus and placenta

- metabolite of estradiol

- major form in circulation

- somewhat good indicator of fetal viability

What are the following examples of:

Equilin

17 beta dihydroequilenin

17 alpha dihydroequilenin

- B ring unsaturated estrogens

When are B ring unsaturated estrogens produced and excreted?

- appears during pregnancy, produced by the placenta

- secreted in urine (Premarin used in dogs for urinary incontinence)

What is diethystilbestrol? When can and can't it be used?

- a estrogen like compound

- non-steroidal synthetic compound with estrogenic activity

- can't be used in food animals, but can be used in dogs

What are the side effects of estrogens?

- can lead to bone marrow suppression = fatal and irreversible

What are the uses of estrogens related to reproduction?

- synchronization protocols = neg feedback on FSH (illegal in cattle in the US)

- enhance effects of being in estrus = thickens vaginal wall in bitches

- induce behavioral aspects of estrus = jump wares

- interferes with unwanted breeding dogs (not recommended)

What drug should you give a dog to help with urinary incontinence?

- estriol (incurine)

What is the longest acting esterified estrogen?

- estradiol valerate

- estradiol cypionate

- estradiol benzoate

- estradiol valerate

Which esterified estrogen has a longer 1/2 life compared to estradiol 17B?

- estradiol valerate

- estradiol cypionate

- estradiol benzoate

- estradiol cypionate

What is testosterone? How does it impact the body?

- a steroid hormone

- negative feedback on LH = stops cyclicity bc no sign for ovulation

- muscle building

- appetite stimulant

What type of drug are these?

- Mibolerone (Cheque drops and Matenon)

- Stanozolol (Winstrol V)

- testosterone

What is gonadotropin releasing hormone (GnRH) released from and why?

- pulsatilly secreted by the hypothalamus to control FSH and LH release from the pituitary

What are examples of GnRH drugs, including their trade name and common names?

- Gondadorelin = cystorelin, factrel, fetagyl in cattle

- Desorelin =SucroMate, Ovuplant in horses

- Buserelin = suprelorin F implant in ferrets

What are the clinical uses for GnRH?

- exogenously to promote ovulation at large doses (part of synch programs)

- initiate cyclicity

- treat cystic ovarian syndrome

What medication can be given to promote ovulation?

- GnRH

What medication can be used to treat cystic ovarian syndrome?

- GnRH

What are the side effects of using GnRH long term?

- down regulate LH/FSH preventing cyclicity

What is follicle stimulating hormone (FSH)?

- a peptide and protein hormone

- secreted by the pituitary

- target is granulosa cells(female) or sertoli cells (male)

What are the reproductive effects of FSH?

- increase estrogen production (because growthing follicles)

- stimulate follicular growth and increase their number (initiate cyclicity)

What are examples of FSH?

- reFSH

- folltropin

What is luteinizing hormone (LH)?

- a peptide and protein hormone

- secreted by pituitary

- target is theca cells (female) or leydig cells (male)

(reLH is an example)

What effects does luteinizing hormone (LH) have on reproduction/why is it used?

- increase testosterone production in the male

- primarily used to stimulate ovulation in the female

What are drugs the mimic LH and FSH?

- human chorionic gonadotropin (hCG) = mimic LH to induce ovulation

- Equine chorionic gonadotropin (eCG) = mimics LH + FSH

- Chlorulon (hCG)

- Pg 600 = combination of eCG and hCG for inducing estrus in pigs and superovulation in SA

What are the uses for prostaglandin F2alpha (PGF2a) when related to reproduction?

- lyse luteal tissue =

- stimulate uterine contractions

What drug is used to "short cycle" the estrous cycle by shortening diestrus?

- PGF2a

What drug should you give an animal with a retained placenta?

- PGF2a

What are the side effects that can be seen when using PGF2a?

- careful handling in Ps asthma or are pregnant because induces smooth muscle contractions

- vomiting and urination in dogs

- sweating and colic in horses

What are examples of PGF2a that are used in practice?

- Dinoprost tromethamine = Lutalyse (quick but more side effects)

Cloprostenol sodium = estrumate (slow but less side effects)

A horse is sweating, not eating and seem to be colicy. What is the most likely drug that could cause this?

- PGF2a like lutalyse

What are prostaglandin E1 and E2's impacts on the reproductive tract?

- smooth muscle relaxant

- cervical relaxant

- oviductal relaxation

What drug do you want to give to encourage uterine evacuation? Why?

- misoprostol - PGE1

- due to its cervical relaxation effects

What drug do you want to give to encourage removal of oviductal blockages? why?

- PGE2s like Dinoprostone Gel (Primigyn or Prepidil)

- due to its oviductal relaxation effects

What are examples of drugs to increase dopamine? What are they used for?

- Pergolide (Prascend) for equine pituitary dysfunction

- Bromocriptine and Cabergoline (Dostinex) to induce canine abortion (decrease prolactin to lyse CL)

What dopamine receptor agonist (increase dopamine) is used to treat equine pituitary dysfunction?

- Pergolide (Prascend)

What dopamine receptor agonist (increase dopamine) is used to induce abortion in dogs by decreasing prolactin to lyse the CL and abort fetuses?

Bromocryptine and Cabergoline (Dostinex)

What hormones does domperidone (Equidone Gel q) impact and how?

What is domperidone (Equidone Gel q)?

- a hormone used stimulates lactogenesis mostly in fescue toxicosis mares

- decreases dopamine and increases prolactin

Oxytocin leads to the contraction of smooth muscle. What are its uses?

- used to initiate parturition due to uterine contractions

- milk let down due to alveoli contraction (must be primed first)

- down regulates oxytocin receptors = can prolong CL lifespan in horses

What does clenbuterol/terbutaline do to the body? What are some things to be aware of with it?

- a smooth muscle relaxant for the uterus

- illegal in food producing animals

- if used at a higher dose, may induce anxiety, increase heart rate, and sweating in the horse

What drug does the following

- control of abdominal pain associated with spasmodic colic, flatulent colic, and simple impactions in horses

- suppresses spasms in the GIT (antispasmodic + anticholinergic)

- decreases peristalsis for palpation per rectum, potential tocolytic for uterus

- buscopan (N-butylscopolammonium bromide)

What are 10 reasons why we manipulate the reproductive tract?

- induce luteolysis

- induce ovulation of a mature follicle

- suppress estrus

- induce cyclicity in anestrous animals

- terminate pregnancy

- manage dystocias

- treat uterine disease

- increase milk production

- superovulate cyclic animals

- grow promotant

What do we always want to do when using growth promotants?

- always check label to make sure growth promotes can be used in said species

What are examples of hormonal growth promotants?

- Estradiol (tablet or implant used in ruminants)

- Testosterone (used in combination with estradiol to slow the release rate of estradiol)

- Progesterone (used in combination with estradiol)

What are examples of synthetic growth hormones?

- trenbolone acetate (TBA; works like testosterone)

- Zeranol (analog of plant estrogen)

- Melengestrol acetate (MGA; works like progesterone)

What are examples of anabolic steroids, used as a growth promotant?

- Stanozolol

- Boldenone undecylenate

Intrauterine antibiotics are easy to use. What are they like?

- accepted treatment in horses

- direct treatment of organism

- can be irritating to the endometrium - may kill of normal bacterial flora (don't want to over do it)

When are intrauterine antibiotics chosen?

- first time infections

- no history of chronic infertility

- good biopsy scores

- antibiotic is not irritating to the endometrium

- don't require long term treatment

- owner compliance/budget

What are systemic antibiotics like when related to reproduction?

- increase dose and cost

- multiple day treatment

- route may limit usage (oral, IM, IV)

- no irritation to the uterus

- less introduction of infectious organisms into uterus

- better at treating deep seated infections (chronic)

- less effect of secretions on abx efficacy

- less effect on normal reproductive tract flora

- stable tissue concentration of abx

When would you choose systemic abx over intrauterine?

- chronicity of infection (repeated infections)

- bacterial susceptibility

- infections that change with treatment

- poor biopsy grade

- prior uterine fluid accumulation

- owner budget

- mare's who react to intrauterine treatment susceptible drug is irritating to endometrium

Reproductive antibiotics can be given systemically or intrauterine. What do you use them interuterine?

- post-partum

- usually during estrus

(should have good penetration into tissue and not be deactivated, expelled, or irritatin)

What does infusion mean in relation to reproduction?

- placement of liquid into uterus

What does lavage mean in relation to reproduction?

- placement and removal of a fluid into the uterus

A mare needs to be bred with cooled shipped semen. She must ovulate on the day she is inseminated. What drug should be used to cause ovulation?

- GnRH

A cow went through estrus 5 days ago. It was missed by the farmer. This cow needs to be bred ASAP. What would be the best drug therapy to get her bred quickly?

- Lutalyse (PGF2a) to shorten cycle

A dog presents for dystocia. On examination there is no obstruction of the pelvic canal. She has uterine inertia. What drug should be used to stimulate uterine contractions?

- oxytocin

the neighbors boar will be arriving at your boutique farm to breed your sow in a few weeks. You need to make sure she is in heat during the time he is at the farm. What drugs should you use to manipulate her cycle?

- eCG and hCG together

A mare just had a foal. She does not appear to have much milk for the foal in her udder. What two drugs might be effective in stimulating her milk production?

- Domperidone

- oxytocin