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Veterinary Pharmacology > Pharmacotherapeutics of the Reproductive System > Flashcards

Pharmacotherapeutics of the Reproductive System Flashcards

1
Q

What is the hypothalamic-pituitary-gonadal (HPG) axis?

A
  • 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
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2
Q

What 5 drug classes typically act on the HPG axis? Which one is stored in the posterior pituitary gland?

A
  1. cabergoline
  2. prolactin
  3. oxytocin*
  4. prostaglandins
  5. hCG, eCG
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3
Q

What are the 4 main classifications of reproductive hormones based on biochemical structure?

A
  1. PEPTIDES: short chains of amino acids < 20
    - GnRH, oxytocin
  2. PROTEINS: longer chains of amino acids
    - LH, FSH, prolactin
  3. STEROIDS: core 4 carbon rings
    - estrogens, androgens, progesterone
  4. PROSTAGLANDINS: 20 carbon unsaturated fatty acids
    - PGF2α, PGE
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4
Q

What is the function of gonadotropin-releasing hormone (GnRH)? What are the 2 main clinical uses?

A

stimulates the release of gonadotropins (LH, FSH) from the anterior pituitary

  1. induction of ovulation or follicular luteinization
  2. suppression of gonadotropin secretion (after a short period of stimulation)
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5
Q

GnRH has a very short half-life. How have synthetic analogs been produced to work around this?

A

substitution in amino acids at positions 6 and 10 at the site of cleavage

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6
Q

What are 5 common gonadotropin-releasing hormone analogs? How does their potency compare to GnRH?

A
  1. gonaorelin
  2. buserelin (20x)
  3. deslorelin (144x)
  4. triptorelin
  5. leuprolide
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7
Q

Where is oxytocin stored? What are 3 actions?

A

posterior pituitary

  1. mediates contractility of endometrium which has been pre-stimulated by estradiol
  2. stimulates contractility of the myoepithelial cells that surround mammary alveoli
  3. activate receptors in the brain to induce social maternity and bonding behavior
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8
Q

What are 5 clinical uses of oxytocin?

A
  1. uterine evacuation (powerful ecbolic action) of retained fluid during pregnancy
  2. assist in vaginal birth
  3. induce parturition in mares
  4. facilitates milk let-down without having galactopoietic ability
  5. prolog diestrus in mares by suppressing estrus
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9
Q

What 2 drugs act like oxytocin?

A
  1. mesotocin - functional homolog to oxytocin in birds
  2. carbetocin - synthetic analog with a longer half-life in horses
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10
Q

What is the structure of gonadotropins?

A

2 subunits - α and β (unique)

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11
Q

What are the 2 types of gonadotropins?

A
  1. PITUITARY - LH, FSH
  2. NON-PITUITARY - human chorionic gonadotropin (hCG), equine chorionic gonadotropin (eCG)
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12
Q

How do hCG and eCG behave?

A

hCG = LH-like > FSH-like

eCG = FSH-like > LH-like (more LH-like in equids to help maintain pregnancy by stimulating progesterone)

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13
Q

What are the 2 actions of gonadotropins?

A
  1. promote folliculogenesis, spermatogenesis, and steroidogenesis
  2. induce ovulation (LH, hCG)
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14
Q

What are the 3 clinical uses of gonadotropins?

A
  1. estrus induction (FSH stimulates follicle formation)
  2. luteinization of follicular cysts
  3. ovulation induction
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15
Q

What hormone is used to diagnose the presence of testicular/ovarian parenchyma? How does this work?

A

gonadotropins

if these structures remain, treatment will induce the release of testosterone or estrogen - if they are missing, no hormones will be produced

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16
Q

Where is prolactin produced?

A

lactotrophs of the adenohypophysis

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17
Q

What chemical controls prolactin secretion? How do agonists and antagonists affect prolactin?

A

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)
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18
Q

How does serotonin affect prolactin secretion? What drug works this way?

A

inhibits dopamine secretion at the hypothalamus and indirectly stimulates prolactin secretion

metergoline

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19
Q

What is the clinical use of dopamine agonists in the reproductive system?

A

(decreases prolactin)

induces luteolysis during the second half of pregnancy to terminate pregnancies (pyometra, mismating)

20
Q

What are the 2 clinical uses of dopamine antagonists in the reproductive system?

A

(increase prolactin)

  1. stimulate mammary gland development (especially in fescue toxicosis in horses)
  2. induction of cyclicity in deep anestrous mares
21
Q

What are steroids synthesized from? How do they act upon target cells?

A

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

22
Q

What do progesterone and progestins do? Where are they produced?

A

mimic effects of the corpus luteum (CL)

PROGESTERONE = corpus luteum
PROGESTIN = synthetic (MPA, MA, delmadinone, altrenogest*)

23
Q

What is the mechanism of action of progestins? What happens upon withdrawal?

A

act of progesterone receptors in the hypothalamus/pituitary, increasing negative feedback and decreasing FSH and LH* output

initiates new estrous cycle and ovulation

24
Q

What are the 4 clinical applications of progesterone and progestin?

A
  1. supports pregnancy
  2. suppresses estrus
  3. suppresses libido in male dogs
  4. treats prostatic hyperplasia in dogs
25
Q

What are the 2 important antiprogestins? What are their mechanisms of action?

A
  1. aglepristone*
  2. mifepristone
    - require FDA documentation

act as true receptor antagonists to prevent the uterine effects of progesterone without initially decreasing serum progesterone concentrations

26
Q

What are the 6 clinical applications of antiprogestins?

A
  1. pregnancy termination in bitches and queens
  2. medical treatment of pyometra
  3. induction of parturition
  4. planning elective cesarean section
  5. treatment of feline mammary fibroadenomatosis (decreases mammary sensitivity to progesterone and decreases development)
  6. treatment of hypersomatotropism (acromegaly) - decreased progesterone decreases growth hormone
27
Q

What formulations of testosterone are there? What derivative is most commonly used? How does it work?

A
  • testosterone cypionate
  • testosterone propionate
  • testosterone ethanate
    (no clinical use in animal reproduction)

mibolerone - blocks the release of LH from the anterior pituitary by negative feedback to prevent estrus in bitches

28
Q

What is finasteride? How does it work? What clinical application does it have?

A

antiandrogenic drug that inhibits 5α-reductase, which is responsible for the metabolism of testosterone to dihydrotestosterone in the prostate

treats prostatic disease in dogs, including canine benign prostatic hyperplasia (BPH)

29
Q

What is osaterone acetate (Ypozane)? What is it used for?

A

chemically related to progesterone, acting as an anti-androgen and progestagen

treatment of canine benign prostatic hyperplasia (BPH)

30
Q

What estradiol derivatives are commonly used?

A
  • 17β-estradiol
  • estradiol benzoate, cypionate, and valerate
  • diethylstilbestrol
  • zeranol
  • estriol
  • tamoxifen
  • clomifene
31
Q

What are the 4 actions of estradiol and its derivatives?

A
  1. stimulate sexual behavior and maintains the reproductive tract during estrus
  2. cause proliferation and cornification of the vaginal epithelium, endometrial proliferation, and increased uterine tone
  3. negative feedback effect of pituitary gonadotropin secretion
  4. affect oocyte transport in the oviduct
32
Q

How does estradiol work outside of the reproductive tract? What can toxicity cause?

A
  • calcium deposition
  • accelerated epiphyseal closure
  • anabolism

bone marrow aplasia

33
Q

What are 5 clinical applications of estradiol and its derivatives?

A
  1. estrus induction (diethylstilbestrol in dogs)
  2. mismating in dogs (not recommended)
  3. treatment of vaginitis in prepubertal or spayed bitches
  4. treat urinary incontinence after spaying in the bitch (estriol)
  5. estrus synchronization via negative feedback
34
Q

How does dexamethasone affect the reproductive system? How can it affect the fetus?

A

abortifacient agent at high doses

enhances maturation of fetal lungs just before parturition or before a cesarean section to increase survival

35
Q

Where were prostaglandins first discovered? How did this affect understanding of its origin?

A

seminal plasma

believed to be from the prostate

36
Q

What are prostaglandins considered with regard to biochemical structure? What are they synthesized from? What 2 are most important in reproduction?

A

eicosanoids, 20-carbon unsaturated fatty acids

from available arachidonic acid derived from cell membrane phospholipids

  1. PGE 1 & 2
  2. PGF2α
37
Q

How do Dexamethasone and NSAIDs affect the production of prostaglandins?

A

DEXAMETHASONE = blocks phospholipase A2, which is used. to synthesize arachidonic acid

NSAIDs = block COX, wihch converts arachidonic acid into prostaglandin H2

38
Q

What is the natural and synthetic analogs of PGF2α? What is important to note about administration?

A

NATURAL = dinoprost tromethamine
SYNTHETIC = cloprostenol

highly sensitive, DON’T administer IV —> will act fast and cause rapid smooth muscle contraction (trouble breathing, diarrhea)

39
Q

Where is PGF2α synthesized in farm animal species? When is it released?

A

uterine endometrium and released in late diestrus at parturition, causing luteolysis (CL regression, back into cycle)

40
Q

What are the 2 actions of PGF2α?

A
  1. luteolytic
  2. smoot muscle contraction
41
Q

What are 4 clinical uses of PGF2α?

A
  1. induce luteolysis/abortion, control estrus cycle
  2. ecbolic (uterus SM contraction)
  3. treat open pyometra
  4. facilitate semen collection (smooth muscle contraction of epididymis and vas deferens)
42
Q

What are the 2 analogs of PGE? What is its general action? What is its target tissue in males and females?

A
  1. misoprostol (PGE-1, $)
  2. dinoprostone (PGE-2, $$$)

vasodilation and relaxation

MALE = penile tissue (erection)
FEMALE = mature follicles and smooth muscle of uterine tubes, uterus, and cervix

43
Q

What 3 clinical aspects are relevant to PGE usage?

A
  1. cervical ripening
  2. myometrial contractions
  3. elective abortion
44
Q

PGF2α and oxytocin are both used as ecbolics. How are they chosen?

A

OXYTOCIN = most common, needs frequent administration due to low half-life

PGF2α = lasts longer, has more side effects

45
Q

What common cause of infertility in mares uses PGEs as a treatment? What 2 can be used?

A

unfertilized oocytes retained in the uterine tubes form oviductal masses that can obstruct the tube

  1. Misoprostol
  2. Dinoprostone

Veterinary Pharmacology (35 decks)

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