Reproductive Pharmacotherapeutics - 2

Question 1

1. Explain the dangers with extra label drug usage.
2. What written law do you refer to in regards to extra-label drug use?

Answer 1

1. E.g. Human Chorionic Gonadotropin (hCG): for inducing ovulation in mares. We do not have a drug approved for this use, so we can use a drug that is used in cows. This drug was used for treating cystic ovaries. If your patient is a companion animal you can choose both but you ideally use the one of the animal because usually it is cheaper and it was tested on another animal. In summary: always choose drug approved in animals over one for humans.
2. Refer to the Animal Medicinal Drug Use Clarification Act (AMDUCA)

Question 2

Why should you read the label when looking at drugs to dispense?

Answer 2

Question 3

What is the main function of Superovulation?
What is its purpose?

Answer 3

1. The main function of superovulation is to induce the ovulation of multiple follicles so that embryos can be transferred to multiple recipient animals to increase the number of progeny.
2. The main purpose is to maximize available genetics from female animals without spending too much time.
   e.g. cattle: 10-12 ovulations, compared to the normal, single ovulation

Question 4

What options in terms of drugs can you use to induce superovulation?
What is the half life for each of these drugs?

Answer 4

Options:
1.l Follicle-Stimulating Hormone (FSH)
* e.g. pFSH (FOLLTROPIN®-V) p stands for porcine, pituitary extract
* short half life: < five hours in cows
2. eCG/Pregnant Mare Serum Gonadotropin (PMSG)
* long half life, e.g. 40 hours in cows
* prolonged ovarian stimulation and reduced embryo quality
3. P.G. 600®: 400 IU of eCG + 200 IU of hCG

Question 5

What it the purpose of inducing ovulation?

Answer 5

By inducing ovulation you are controlling the time period (especially beneficial for artificial insemination). You can even induce ovulation without detecting estrus.

Question 6

In order to induce ovulation, the animal needs to have?

Answer 6

A pre-ovulatory follicle, which also needs to reach a certain size
e.g. cow: >12mm; mare: >30mm

Question 7

If you want to trigger ovulation you need a surge in?

Answer 7

LH

Question 8

What drugs can you use to induce ovulation?

How long after inducing ovulation will cows ovulate? What about mares?

Answer 8

1. GnRH analogs:
   * e.g. Cows ovulate 28 (24 - 30) hrs after injection
2. hCG:
   * LH-like property
   * e.g. mares ovulate 36 (24-48) hrs after injection

Question 9

What is the clinical application of inducing and suppressing estrus/libido?

Answer 9

Synchronization - synchronize the group of animals so that they can all come into heat at the same time to be bred at the same time.

“Short-cycling” will induce luteolysis early. The entire cycle will become shorter to be able to breed the animal again. Do this by operating on diestrus.

suppression of estrous behavior: suppress for shows, etc.

Question 10

In order to induce polyestrous in cows, horses, etc, what drugs would you use and at what phase in their estrus cycle?

Answer 10

Induction (Polyestrous species: cows, horses…) via
1. Terminate the luteal phase
* Prostaglandin F2alpha (PGF2α)
* e.g. mare: return to estrus on average 2-5 days after PGF
administration
* insensitivity of single administration during early
diestrus (mare: <5 days; sows: < 12 days)
2. Withdrawal of progestagens:
* e.g. controlled internal drug release (CIDR) devices

Question 11

1. Define monoestrus.
2. What drugs can be used to induce monoestrus in dogs?

Answer 11

1. experiencing estrus once each year or breeding season.
2. • Dopamine agonist: e.g. cabergoline; sid, PO, 16-19 days; Dopamine agonists decrease PRL and speed up anestrus
   • Others: estrogen (e.g. diethylstilbestrol); gonadotropins; GnRH analog

Question 12

What drugs can be used to suppress estrus/libido?
What drugs are only reliable in mares?

Answer 12

1. By prolonging the luteal phase:
   A. Exogenously: progesterone/progestin
   - Controlled internal drug release (CIDR) devices, oral, injection
   - Only progesterone and altrenogest are reliable in mares
   B. Endogenously (prolong the luteal phase):
   - Oxytocin during mid-diestrus (down-regulate the oxytocin receptor in the endometrium → prevent the release of PGF2α)
   
   • Mare: twice a day on days seven to 14 after ovulation
     
     • Induce diestral ovulation; if there is a dominant follicle during diestrus
2. Prolong the anestrus (female dogs):
   A. Androgens: Mibolerone and others
   B. Progestin
   
   • e.g. megestrol acetate: FDA approved but beware of the side effects

Question 13

How to induce parturition in the sow?

Answer 13

PGF2α ± oxytocin: after 112 days of gestation

Question 14

1. Before you induce parturition in a mare, what must you do?
2. What drugs can be administered to induce parturition in a mare?
3. What drug has been used to induce fetal maturation?
4. What is prostaglandin E (PGE) used for?

Answer 14

1. Check for signs of readiness FIRST!
2. Oxytocin, low doses (2.5–3.5 IU)
3. Fetal maturation has been successfully induced using dexamethasone
   (100 mg q 24 h for 3 days)
4. PGE: cervical dilation

Question 15

What drugs can be used to induce parturition in cattle?

Answer 15

• Dexamethasone (20-30 mg) or flumethasone (8-10 mg) IM; 24–72 hours
• PGF2α: Dinoprost (25-30 mg) or cloprostenol (500 μg) IM; 24–72 hours

Question 16

How to induce parturition in the dog?

Answer 16

Aglepristone (progesterone antagonist); not commonly done

Question 17

How do you induce an abortion?

Answer 17

Abortion: induce luteolysis + promote uterine contraction
* PGF2α: only when the pregnancy is maintained by the progesterone secreted by the corpus luteum

Question 18

Induction of Abortion, Mismating, Treatment of Mummification
Clinical example: Mismated dog
1. What medication would you give?
2. Higher doses of prostaglandins are associated with?
3. Estrogens can be given during?

Answer 18

1. Multiple doses of natural prostaglandin F2α (dinoprost, 25–250 μg/kg) or synthetic PGF2α (cloprostenol, 1–5 μg/kg)
   * Dopamine agonist: e.g. cabergoline, ↓ prolactin (it is luteotropic in the 2nd half of gestation)
   * Progesterone antagonist: aglepristone
2. substantial clinical side effects, including vomiting, diarrhea, lethargy
3. estrus to prevent pregnancy (not recommended)

Question 19

How does Fetal mummification occur?
What can happen to the conceptus in this case?
What drug do you use to treat fetal mummification?

Answer 19

1. Fetal death in utero + luteolysis does not occur + retained fetus is not contaminated by bacteria + the cervix remains closed
2. → the conceptus can undergo an aseptic process of partial desiccation and absorption of much of the fetal and placental fluids
3. Treatment: PGF2α

Question 20

How do you diagnose Crypytorchidism/Ovarian Remnant?

Answer 20

• GnRH- or hCG-Response Test: Testosterone
  for Males
• Pre- and post-injection paired samples
• Diagnostic tests:
• Anti-Müllerian Hormone (AMH) assay
• Witness LH Test
• Progesterone Test: after induction of
  ovulation

Question 21

1. If you are presented with a dog or cat suffering from pyometra, what would be two major components of your treatment plan?
2. Other than surgical treatment, what other forms of medical treatment are used for pyometras?

Answer 21

1. Clinically ill patients will benefit from intravenous (IV) fluid therapy and the administration of parenteral antibiotics
2. Medical treatment use the sames drugs used to induce an abortion –> PGF2α, cabergoline, aglepristone

Question 22

1. Mammary Fibroadenomatous Hyperplasia (cat) are associated with high amounts of what reproductive hormone?
2. How is this condition treated?

Answer 22

1. prolonged progesterone (endogenous or
   exogenous sources)
2. Medical treatment: cabergoline, aglepristone, PGF2α

Question 23

1. Benign Prostatic Hypertrophy (BPH) occurs in what species? What is prevalence amongst this species?
2. What is this condition linked to?
3. How is this condition treated?

Answer 23

1. Ooccurs in more than 80% intact male dogs over 5 years of age
2. Linked to the androgenic activity of dihydrotestosterone, metabolized locally from testosterone, by 5α-reductase
3. (A) Castration
   (B) 5α-reductase inhibitor: finasteride, flutamide
   (C) Androgen receptor antagonist: osaterone acetate, flutamide
   (D) By inhibiting the hypothalamic-pituitary-gonadal axis:
   - GnRH analog: e.g. deslorelin (flare-up effect and affect libido)
   - Progestins (side effects)
   - Estrogens (side effects)

Question 24

1. Describe the condition Overt Pseudopregnancy.
2. What are the treatment options?

Answer 24

1. Canine condition, rarely cats: nesting behavior, mammary gland development (can even secrete milk). Happens when the progesterone levels begin to fall –> increase in prolactin
2. Usually do not require treatment: do not massage the glands, Subside in 2-3 weeks, Remove the toys
   Dopamine agonist: e.g. cabergoline (5 μg/kg, PO, SID, for 5-10 days)
   * Generic 0.5 mg tablet
   * How about a 3 kg Chihuahua?
   → Compounding pharmacy: as low as 12.5 μg/mL and
   3.7 μg/capsule
   * Side effect: usually safe, may cause vomiting