Lecture 1: Reproductive Drugs and Hormones

progesterone

• P4

• hormone of pregnancy (pro-gestational)

• predominant hormone during diestrus

• lowers immune function locally within uterus

• closes cervix

• decreases myometrial contractility

• suppresses estrus behavior

• negative feedback to LH

side effects of progesterone

• skin absorption that can affect human cyclicity

• prolonged use can contribute to pyometra

• will decrease LH and alter male and female reproductive hormones

oral progesterone

• altrenogest

• MGA → melengestrol acetate

injectable progesterone

• progesterone in oil

• altrenogest

• repository compounded formulations

intravaginal progesterone

CIDR → controlled internal release drug

uses for progesterone

• synchronization protocols (intravaginal CIDR, MGA, and others)

• maintenance of pregnancy (oral and injectable)

• estrus suppression (oral and injectable)

estrogens

• E2

• predominant hormone during estrus

• heightens immune function locally within uterus

• opens cervix

• primes uterus for contractility (estrogen priming of oxytocin receptors)

• enhances estrus behavior

• negative feedback to FSH

estradiol 17beta

• injectable estrogen

• naturally occurring, unconjugated

esterified estrogens

• injectable

• more potent than estradiol 17beta

• estradiol cypionate → has longer half-life than estradiol 17beta

• estradiol benzoate → has same half-life and closely related to estradiol 17beta

• estradiol valerate → longest acting

estriol

• incurin

• urinary incontinence in dogs

estrogen sulfate

• from fetus and placenta, also metabolite of estradiol → major form in circulation

• somewhat good indicator of fetal viability

B ring unsaturated estrogens

• conjugated estrogens

• equilin, 17beta dihydroequilenin, 17alpha dihydroequilenin

• appear during pregnancy, produced by placenta

• secreted in urine (premarin → estrone sulfate and equilin primarily)

estrogen-like compounds

• diethylstilbestrol

• non-steroidal synthetic compound

• estrogenic activity

• use is prohibited in food animals in the USA

• primarily used in dogs

side effects of estrogen

can lead to bone marrow suppression

uses of estrogens

• synchronization protocols → has negative feedback on FSH

• enhance effects of being in estrus → thickens vaginal wall in bitches

• induce behavioral aspects of estrus → jump mares

• interferes with unwanted breedings in dogs

• treatment for urinary incontinence

testosterone

• negative feedback on LH → stops cyclicity

• muscle building

• appetite stimulant

• mibolerone

• stanozolol

gonadotropin releasing hormone (GnRH)

• secreted by the hypothalamus

• 10 amino acids long (decapeptide)

• pulsatile release

• primary function is to regulate FSH and LH release from the pituitary

• synthetic GnRH → primarily causes release of LH

GnRH

• cystorelin, factrel, fetagyl → gonadorelin (bovine)

• sucromate, ovuplant → deslorelin (equine)

• suprelorin F implant → deslorelin (ferrets)

clinical uses for GnRH

• initiate cyclicity

• initiate ovulation → part of estrus synchronization program

• treat cystic ovarian syndrome

• long term use can down-regulate LH/FSH preventing cyclicity

follicle stimulating hormone (FSH)

• secreted by the pituitary

• target is granulosa cells or sertoli cells

• increases estrogen production

• stimulates follicular growth

• used to increase the number of follicles (superovulate)

• folltropin → porcine-derived for use in cattle

• reFSH → recombinant equine FSH

luteinizing hormone (LH)

• secreted by pituitary

• target area is theca cells or leydig cells

• increase testosterone production

• primarily used to stimulate ovulation

• reLH → recombinant equine LH

drugs that mimic LH and FSH

• human chorionic gonadotropin (hCG) → LH-like activity

• equine chorionic gonadotropin (eCG) → FSH and LH-like activity, primarily used for its FSH-like activity

• chlorulon → hCG

• Pg 600 → combination of eCG and hCG → induces estrus in pigs, induce superovulation in small ruminants

prostaglandin F2alpha

• lyses luteal tissue → short cycle in the estrous cycle

• stimulates uterine contractions → ecbolic

• side effects → vomiting and urination in dogs, sweating and colic in horses

• dinoprost tromethamine

• cloprostenol sodium

side effects in horses from PGF2a

sweating, colic, inappetence

prostaglandin E1 and E2

• smooth muscle relaxant

• cervical relaxation → used to encourage uterine evacuation

• oviductal relaxation → used to encourage removal of oviductal blockages

pergolide

• potent dopamine receptor agonist

• treatment for equine pituitary dysfunction

• may decrease milk production

bromocryptine and cabergoline

• dopamine receptor agonist

• induce abortion in dogs

• prolactin is luteotrophic in dogs

domperidone

• decreases dopamine

• increases prolactin

• primary use is for stimulating lactogenesis → primarily for fescue toxicosis in mares

• equidone gel

oxytocin

• contracts smooth muscle

• initiation of parturition

• alveoli contraction causing milk let down → receptors must be primed for this

• uterine contraction → induction of parturition or dystocia treatment, evacuation of uterus

• down regulates to prolong corpus luteum lifespan in horse

clenbuterol/terbutaline

• smooth muscle relaxant

• bronchodilator used for tx of COPD

• uterine relaxation

• if used at higher dose, may induce anxiety, increase HR and sweating in the horse

• some concern about cervical relaxation

• illegal in food producing animals

buscopan

• N-butylscopolammonium bromide

• indicated for the control of abdominal pain (colic) associated with spasmodic colic, flatulent colic, and simple impactions in horses

• antispasmodic and anticholinergic drug which suppresses spasms of the digestive system

• decreases peristalsis for palpation per rectum, potential tocolytic for uterus and may relax cervix with topical application

reasons for manipulation of 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

• growth promotant

growth promotants

• always check label to make sure growth promotants can be used in the species

• hormonal growth promotants

• synthetic hormones

• anabolic steroids

hormonal growth promotants

• estradiol → tablet or implant used in ruminants

• testosterone → used in combo with estradiol to slow the release rate of estradiol

• progesterone → used in combo with estradiol

synthetic hormones

• TBA → works like testosterone → trenbolone acetate

• MGA → works like progesterone → melengestrol acetate

• zeranol → analog of plant estrogen

anabolic steroids

• stanozolol

• boldenone undecyclenate

reproductive antibiotics

• may be given systemically or intrauterine

• intrauterine antibiotics given post-partum or usually during estrus

• systemic antibiotics should have good tissue concentrations into the uterus

• intrauterine antibiotics should have good penetration into tissue and not be deactivated, expelled, or irritating

infusion

placement of liquid into uterus

lavage

placement and removal of fluid into the uterus

intrauterine antibiotics

• easy to use

• accepted treatment (horses)

• direct treatment of organism

• irritating to endometrium

• may kill off normal bacterial flora

• in and out movement of contaminants with arm

when to choose intrauterine treatment

• 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

systemic antibiotics

• increased dose and cost

• multiple day treatment

• route may limit usage

• no irritation to uterus

• less introduction of infectious organisms into uterus

• better at deep seated infections

• less effect of secretions on antibiotic efficacy

• less effect on normal reproductive tract flora

• stable tissue concentrations of antibiotics

when to choose systemic treatment

• chronicity of infection

• bacterial susceptibility

• infections that change with treatment

• poor biopsy grade

• prior uterine fluid accumulation

• owner budget

• mare’s who react to intrauterine treatment

• susceptible drugs is irritating to endometrium

erring more on the use of systemic antibiotics for chronic infections if

• deep seated infections

• prevention of irritation of uterus/reproductive tissues

• longer treatment → more exposure for time-dependent antibiotics

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?

deslorelin or hCG

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?

PGF2a (dinoprost tromethamine or cloprostenol sodium)

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 neighbor’s 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?

• PG600 (combo of eCG and hCG)

• hCG

a mare just had a foal. she does not appear to have much milk for the foal in her udder. what 2 drugs might be effective in stimulating her milk production?

domperidone (equidone)