Reproductive Pharmacology (redue) Flashcards
What are the 3 sources of gonadotropins and which gonadotropins comes from which source?
Pituitary : FSH and LH
Pregnant women : HCG
Serum of pregnant mares : ECG
GnRH is a secretagogue for ____ and ____ release.
FSH and LH
From where is GnRH released?
Hypothalamus
What are the 2 uses of GnRH in the female?
- Increase conception (induces ovulation)
2. Tx follicular cysts
What is 1 use of GnRH in the male?
To increase libido
What are 3 GnRH preparations used in vet med?
- Gonadorelin
- Deslorelin
- Triptorelin
Which of the following is used in mares: Gonadorelin, Deslorelin, Triptorelin? How is it administered?
Deslorelin - SQ
Which of the following can be used in dogs: Gonadorelin, Deslorelin, Triptorelin? In which other species is it used? How is it administered?
Gonadorelin - SQ
Used in dogs, cats, and ruminants
Which of the following is used in sows: Gonadorelin, Deslorelin, Triptorelin? How is it administered?
Triptorelin - intravaginal
What is the common name of Gonadorelin?
Ovacyst
What is the common name of Deslorelin?
SucroMate
What is the common name of Triptorelin?
OvuGel
For what is Leuprolide acetate used?
For the control of adrenocortical disease in ferrets neutered too young
Adrenocortical disease in ferrets is the overproduction of sex steroids by the adrenal gland. What are the clinical signs of this?
Males - aggressive sexual behavior
Females - constant estrus
Alopecia
Pruritus
What is the mechanism of action for Leuprolide acetate?
(GnRH receptor agonist)
Disrupts pulsatile GnRH secretion, causing a down-regulation of GnRH receptors.
What are GnRH vaccines used for?
GnRH vaccines are an excellent way to control population in dogs and wild horses - they serve as a form of chemical sterilization (neuter)
How does FSH stimulate the development of follicles in the female?
FSH increases the production of estrogen in granulosa cells, then estrogen increases the FSH receptors in follicles, increasing follicular development.
What is the function of aromatase?
Converts testosterone to estradiol
FSH has 2 important actions in the male, what are they?
- Increase diameter of seminiferous tubules
2. Increase development of spermatozoa
What 5 main effects does LH have on a female?
- Induce ovulation
- Induce luteinization
- Increase progesterone production
- Increase estrogen production
- Increase testosterone production in theca cells
What effect does LH have on a male?
Increases testosterone levels by proliferation of leydig cells
Where does testosterone come from in the female?
Theca cells
Where does testosterone come from in the male?
Leydig cells
What is the mechanism of action of FSH and LH?
Activate Gs-adenylyl cyclase system –> increase cAMP –> activate PKA –> activate enzymes of sex steroid synthesis
What does PKA activate in order to increase mRNA for proteins for the proliferation of enzymes for sex steroid synthesis?
CREB (cAMP response element binding protein)
Where is HCG synthesized in a pregnant women?
Placenta
When are HCG levels the highest in a pregnant women?
First 2 months of the pregnancy
What are the 4 clinical uses of LH/HCG?
- Induce ovulation
- Treat follicular cysts
- Treat persistent infertility in the female
- Treat cryptorchidism
What are the 3 clinical uses of FSH/ECG?
- Breeding control
- Induce superovulation
- Treat infertility in the male
Repeated interspecies use of ECG and HCG may cause __?__ in animals.
Anaphylaxis
Which of the following has the LONGEST T1/2 in the human: LH, FSH, HCG, or ECG?
ECG
In the human, how long are the half lives of the following: LH, FSH, HCG, ECG?
LH = 30 minutes
FSH = 60 minutes
HCG = 8 hours
ECG = 24 hours
Why does ECG have the longest half life?
ECG has the greatest carbohydrate content
Carbohydrates account for ____% of FSH, LH, TSH, ____% of HCG and ____% of ECG.
Carbohydrates account for 13-16% of FSH, LH, TSH, 31% of HCG, and 47% of ECG.
Removal of ____ ____ from one of these glycoprotein hormones (FSH, LH, HCG, ECG) greatly decreases the T1/2.
Sialic acid
HCG is found in the urine of _____women.
Pregnant
FSH is found in the urine of _____ women.
Postmenopausal
What are the 4 natural sources of estrogen?
- Ovary
- Testicle
- Adrenal gland
- Placenta
____% of estrogens are bound to plasma proteins.
90%
Concerning estrogens, which of the following has a high affinity and low capacity: albumin OR sex-steroid binding globulin?
Sex-steroid binding globulin
What is the plasma T1/2 of estradiol?
30 minutes
What is the most potent form of estrogen?
Estradiol
What are the roles of estrogen in the body?
- Increase sexual receptivity
- Increase repro tract growth
- Increase oxytocin receptor expression
- Dilate the cervix
- Increase mammary growth
What effect does estrogen have in the ruminant?
Luteolysis
What effect does estrogen have in the pig?
CL retention
What effects do estrogens have on the bone?
Decrease IL-6 and IL-11 –> decreases osteoclastic vitality –> increases bone mass
Ossification of epiphyseal plate –> decreases bone growth
Which of the following contain testosterone and which contain progesterone: Synovex-C, -S, -H?
Synovex-C = Progesterone
Synovex-S = Progesterone
Synovex-H = Testosterone
Other than estradiol benzoate, what does Synovex-Plus contain?
Trenbolone acetate
In which animals can Synovex-Plus be used?
Steers OR heifers
What is the name of the only non-steroidal estrogen available in the U.S. for use in beef cattle and sheep as an ear implant?
Zeranol
True or False: Estradiol preparations require pre-slaughter withdrawal.
FALSE
True or False: Zeranol requires pre-slaughter withdrawal.
FALSE - not in cattle, 40 days in sheep
What are the 6 mechanisms of estrogen-induced anabolism?
- Increased GH secretion
- Increased GH receptor expression
- Increased IGF-1 secretion
- Increased IGF-1 receptor expression
- Increased IGF-1 binding proteins
- Increased mRNA for muscle protein
What is the main (recommended) indication for the use of estrogens clinically?
- To treat problems associated with spaying: incontinence, vaginitis, dermatitis.
What is the name of the drug used to treat urinary incontinence in the spayed dog?
Estriol (Incurin)
What is the name of the alpha-AR agonist used to contract the bladder sphincter muscle in incontinent dogs?
Phenylpropanolamine
What are the 2 approved treatment methods for prostatic hyperplasia?
- Finasteride (Proscar)
2. Castration
What is the MOA of Finasteride (Proscar)?
Inhibits 5-alpha reductase, the enzyme used to convert testosterone to dihydrotestosterone
What are the 6 side effects associated with estrogen use?
- Abortion
- Prolapsed vagina or rectum
- Aplastic anemia
- Pyometritis
- Follicular cysts
- Bone fracture
What are the 3 natural sources of progestins?
- Adrenal gland
- Ovary
- Placenta
What is the plasma half life of progestins?
30 minutes
What are the 5 clinical uses of progestins?
- Synchronization of estrus
- Treatment of implant failure
- Contraception in the bitch
- Control of aggressiveness
- Control of inappropriate urination
What are the 2 side effects associated with the use of progestins?
- Endometrium hyperplasia
2. Glucocorticoid effects (diabetes, inhibition of the adrenal cortex)
What is RU 486?
Progestin receptor antagonist - very efficient abortifacient and parturition-inducing agent
What are the 3 natural sources of androgens?
- Ovary
- Testicle
- Adrenal gland
____% of circulating testosterone is bound by plasma proteins.
90%
What is the plasma T1/2 of testosterone?
20 minutes
What are the 4 actions of androgens?
- Increase spermatogenesis
- Increase growth of accessory organs
- Increase bone growth
- Increase EPO synthesis
What are the 4 clinical uses of androgens?
- Treat cryptorchidism
- Treat mammary gland tumors
- Treat infertility
- Induction of teaser cows
- Growth promotion (as well as reversal of tissue depletion)
- Treat anemia
DHEA does NOT increase plasma _____ levels, but increases _____ level and decreases _____.
DHEA does NOT increase plasma TESTOSTERONE levels, but increases ESTRADIOL levels and decreases HDL.
What are the 4 side effects associated with androgen use?
- Infertility
- Water retention
- Masculinization of females
- Liver disorders
What are the 4 anti-androgens available?
- Finasteride
- Cimetidine
- Ketoconazole
- Trilostane
What is the main use for anti-androgens in vet med?
Prostatic hyperplasia
What are the 5 indications for inducing uterine contractions?
- Induce labor
- Abortion
- Expel uterine contents
- Post-partum hemorrhage
- Treat uterine inertia
Which substances have oxytocic activity?
- Muscle stimulants
- Poisons (lead)
- PGE2, PGF2-alpha
- Glucocorticoids
- Ergot alkaloid
- Oxytocin, vasopressin
What is Domperidone?
D2 receptor antagonist
What effect does Domperidone have on prolactin?
Increases prolactin secretion
What effect does Domperidone have on milk production?
Increases milk production
Does Domperidone cross the BBB?
NO
Use Domperidone to treat ____ ____ in prepartum mares.
Fescue toxicosis
The primary source of PGF2alpha is _____ in species other than primates and rodents.
Endometrium
Vasopressin increases the contractions of what 3 structures?
- Blood vessels
- Uterus
- GI
_____ enhance the effects of oxytocin.
Estrogen
_____ reduce the effects of oxytocin.
Progesterone
What are the 4 clinical uses for oxytocin?
- Induce labor (only in mares and humans)
- Treat placental retention
- Milk letdown
- Treat dystocia
What are the 2 main uses of ergot alkaloids?
- Post-partum hemorrhage
2. Uterine involution
What is the MOA of ergot alkaloids?
Activate alpha-1 adrenergic receptors and 5-HT2 receptors, increasing smooth muscle contraction
What are the 3 effects of ergot alkaloid overdose?
- Vomiting
- Gangrene
- Excitation
What are carbachol and bethanechol?
Potent uterine contractors
Which is more specific, carbachol or bethanechol?
Bethanechol is specific to muscarinic receptors, whereas carbachol is non-specific, for muscarinic and nicotinic receptors
When should Carbachol or Bethanechol be used?
As a last resort - only in large animals that are refractory to other oxytocic agents
What are the following: Dinoprost tromethamine and Cloprostenol?
PGF2-alpha analogs
Which is more potent, Dinoprost tromethamine or Cloprostenol?
Cloprstenol
PGF2-alpha analogs cause potent ______.
Vasoconstriction
What effect does PGF2-alpha have on the corpus luteum?
Cuts off its blood supply, leading to luteolysis (apoptosis of the CL)
What effect does PGF2-alpha have on progesterone levels?
Decrease
PGF2alpha analogs can be used in estrus synchronization, except in which species?
Swine
How long after PGF2-alpha induction will a cow or sow go into labor?
1 - 8 days (mean 3 days)
How long after PGF2-alpha induction with a mare go into labor?
1 - 2 days (unless milk is present - labor can then occur within 30 minutes of induction)
What would you use to treat pyometra in the dog?
PGF2-alpha analog
What would you use to induce expulsion of mummified fetuses?
PGF-2 alpha analog
What would you use instead to synchronize estrous cycle in the pig?
Matrix
How would you administer PGF2-alpha to induce luteolysis?
IM - small repeated doses
What is the mechanism of action of long-acting glucocorticoids in induction of labor?
Increase PGF2-alpha secretion from the endometrium
Why is Dexamethasone (long-acting corticosteroid) not recommended for pregnancy termination in the dog?
Have to give large doses, 2x/day for 10 days