Pharmacotherapeutics of the Reproductive System Flashcards
What is the hypothalamic-pituitary-gonadal (HPG) axis?
- hypothalamus produces and releases gonadotropin-releasing hormone (GnRH)
- this stimulates the anterior pituitary to release LH and FSH
- LH stimulates the testes to produce testosterone
- FSH stimulates the ovaries to release estrogen and progesterone
- negative feedback controls the amount of hormones produced
What 5 drug classes typically act on the HPG axis? Which one is stored in the posterior pituitary gland?
- cabergoline
- prolactin
- oxytocin*
- prostaglandins
- hCG, eCG
What are the 4 main classifications of reproductive hormones based on biochemical structure?
- PEPTIDES: short chains of amino acids < 20
- GnRH, oxytocin - PROTEINS: longer chains of amino acids
- LH, FSH, prolactin - STEROIDS: core 4 carbon rings
- estrogens, androgens, progesterone - PROSTAGLANDINS: 20 carbon unsaturated fatty acids
- PGF2α, PGE
What is the function of gonadotropin-releasing hormone (GnRH)? What are the 2 main clinical uses?
stimulates the release of gonadotropins (LH, FSH) from the anterior pituitary
- induction of ovulation or follicular luteinization
- suppression of gonadotropin secretion (after a short period of stimulation)
GnRH has a very short half-life. How have synthetic analogs been produced to work around this?
substitution in amino acids at positions 6 and 10 at the site of cleavage
What are 5 common gonadotropin-releasing hormone analogs? How does their potency compare to GnRH?
- gonaorelin
- buserelin (20x)
- deslorelin (144x)
- triptorelin
- leuprolide
Where is oxytocin stored? What are 3 actions?
posterior pituitary
- mediates contractility of endometrium which has been pre-stimulated by estradiol
- stimulates contractility of the myoepithelial cells that surround mammary alveoli
- activate receptors in the brain to induce social maternity and bonding behavior
What are 5 clinical uses of oxytocin?
- uterine evacuation (powerful ecbolic action) of retained fluid during pregnancy
- assist in vaginal birth
- induce parturition in mares
- facilitates milk let-down without having galactopoietic ability
- prolog diestrus in mares by suppressing estrus
What 2 drugs act like oxytocin?
- mesotocin - functional homolog to oxytocin in birds
- carbetocin - synthetic analog with a longer half-life in horses
What is the structure of gonadotropins?
2 subunits - α and β (unique)
What are the 2 types of gonadotropins?
- PITUITARY - LH, FSH
- NON-PITUITARY - human chorionic gonadotropin (hCG), equine chorionic gonadotropin (eCG)
How do hCG and eCG behave?
hCG = LH-like > FSH-like
eCG = FSH-like > LH-like (more LH-like in equids to help maintain pregnancy by stimulating progesterone)
What are the 2 actions of gonadotropins?
- promote folliculogenesis, spermatogenesis, and steroidogenesis
- induce ovulation (LH, hCG)
What are the 3 clinical uses of gonadotropins?
- estrus induction (FSH stimulates follicle formation)
- luteinization of follicular cysts
- ovulation induction
What hormone is used to diagnose the presence of testicular/ovarian parenchyma? How does this work?
gonadotropins
if these structures remain, treatment will induce the release of testosterone or estrogen - if they are missing, no hormones will be produced
Where is prolactin produced?
lactotrophs of the adenohypophysis
What chemical controls prolactin secretion? How do agonists and antagonists affect prolactin?
hypothalamic dopamine has an inhibitory control on prolactin secretion by acting on D2 receptors of lactotrophs
- DOPAMINE AGONISTS inhibit prolactin secretion (bromocriptine, cabergoline, pergolide)
- DOPAMINE ANTAGONISTS increase prolactin secretion (metoclopramide, phenothiazines, domperidone, sulpiride)
How does serotonin affect prolactin secretion? What drug works this way?
inhibits dopamine secretion at the hypothalamus and indirectly stimulates prolactin secretion
metergoline
What is the clinical use of dopamine agonists in the reproductive system?
(decreases prolactin)
induces luteolysis during the second half of pregnancy to terminate pregnancies (pyometra, mismating)
What are the 2 clinical uses of dopamine antagonists in the reproductive system?
(increase prolactin)
- stimulate mammary gland development (especially in fescue toxicosis in horses)
- induction of cyclicity in deep anestrous mares
What are steroids synthesized from? How do they act upon target cells?
cholesterol (4 carbon rings)
bind to and penetrate cell membranes and bind to INTRACYTOPLASMIC receptors, inducing nuclear production of mRNA, which codes for new protein synthesis by the target cell
- high lipid solubility
What do progesterone and progestins do? Where are they produced?
mimic effects of the corpus luteum (CL)
PROGESTERONE = corpus luteum
PROGESTIN = synthetic (MPA, MA, delmadinone, altrenogest*)
What is the mechanism of action of progestins? What happens upon withdrawal?
act of progesterone receptors in the hypothalamus/pituitary, increasing negative feedback and decreasing FSH and LH* output
initiates new estrous cycle and ovulation
What are the 4 clinical applications of progesterone and progestin?
- supports pregnancy
- suppresses estrus
- suppresses libido in male dogs
- treats prostatic hyperplasia in dogs
