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Year 2 Pharmacology > Reproductive pharmacology > Flashcards

Reproductive pharmacology Flashcards

1
Q

A mare is brought to stud. She has been cleared of veneral disease and you need to induce luteolysis. What drug class would you use?

A
  1. Prostaglandin F2a receptor agonist
  2. causes CL regression and luteolysis.
  3. This is given to synchronise oestrus.
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2
Q

Which of these drugs is the most appropriate to inject to induce ovulation in mares?
GnRH, eCG, hCG, LH

A

All these drugs would potentially induce ovulation, but hCG is the most appropriate

  1. GnRH is not the most appropriate as in mares the GnRH surge lasts for several days, so a GnRH implant would be required, not an injection
  2. eCG is not the most appropriate as it results in a higher FSH release than LH release
  3. hCG is the most appropriate as it results in the highest LH release, longer t1/2 than LH and cheaper
  4. LH is not the most appropriate as it has a very short half-life (0.5 hrs) and is expensive
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3
Q

Mechanism of action of GnRH agonist. Both naturally and pharmacologically

A
  1. Endrogenous GnRH released in PULSES from hypothalamus.
  2. Binds to specific receptors on anterior pit, releasing LH and FSH
  3. Pharmacologically given in pulsatile injections
  4. Continuous will cause downregulation and inhibit LH and FSH!
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4
Q

How do we administer GnRH agonist?

A

injectible continuous release implants

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5
Q

When would you use GnRH agonist

A
  1. To improve conception rates and improve synchronisation of oestrus/ ovulation
  2. To suppress repro function e.g. used in sexually mature male dogs and ferrets: deslorelin implant
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6
Q

Main effect of GnRH agonist pulsitile

A

• Stimulate short surge in FSH & LH and thus ovulation if there is a pre-ovulatory follicle. In mares the gonadotropin surge lasts for several days so use implants rather than single injection

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7
Q

warning when using GnRH and why

A

Pregnant women should not administer GnRH agonists. They can be absorbed through the skin

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8
Q

You are trying to synchronize a 3 year old dairy cow ready for AI using PGF2 alpha and GnRH. What is the correct order for the Ovsynch programme?

  1. 2nd dose of GnRH
  2. 1st GnRH dose
  3. AI
  4. Prostaglandins
  5. progesterone
A

2, 4, 1, 3

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9
Q 
You are trying to synchronize a 3 year old dairy cow ready for AI using PGF2 alpha and GnRH. What happens on:
Day 0
Day 7
Day 9
Day 10
for the Ovsynch programme?
A

On day zero = GnRH will be given to start off the development of a new follicular wave
Day 7 = Prostaglandins (PGF2 alpha) will cause the luteolysis of a CL
Day 9 = GnRH second dose to cause ovulation of the tertiary follicles
Day 10 = AI will be done once they have ovulated

Progesterone would not be used in Ovsynch but may be used to help synchronize a group of animals so they come into heat at the same time- this may be used in sheep flocks such as a progesterone sponge to prolong the current cycle and prevent ovulation temporarily

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10
Q

GnRH Vaccines Mechanism of action

A
  1. 2 doses of GnRH analogue protien conjugate (vaccine) given 2 weeks apart
  2. Induces antibodies against GnRH
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11
Q

Route of GnRH vaccine administration

A

Injectible

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12
Q

Main effects and example of use of GnRH vaccine

A
  1. Induces antibodies against GnRH and can thus be used to chemically castrate pigs (prevent boar taint)
    WARNING: self-injection can disrupt reproductive function. Should not be administered by pregnant women
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13
Q

What are gonadotropins?

How do we administer

A

Anterior Pituitary Hormones
1. Glycoproteins = peptide and CHOs
Administer: Injection
2. They are LH/ FSH receptor agonists - stimulating the release of sex steroid hormones from the testis adn ovary

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14
Q

How resistant to breakdown are gonodotropins? and what are the half lives of the respective hormones?

A
  1. More resistant to breakdown than peptides/proteins
  2. The more CHO in the structure, the more resistant to breakdown by proteases and thus longer
    Half life:
    (LH - 0.5 hrs)
    (FSH - 1 hr)
    hCG = 8 hrs
    eCG = 25 hrs
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15
Q

List the gonadotropings

A

PMSG, eCG, hCG

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16
Q

Main effects of eCG/ PMSG

Where produced

A
  1. Produced from the endometrial cups of pregnant mare 40 – 120d pregnancy. 2. Mostly FSH activity but some LH. Longer T1/2 than FSH and cheaper.
  2. promote recruitment of follicles and can be used for superovulation programmes
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17
Q

HCG main effects in males and females

A
  1. HCG in the female can be used to promote maturation of the follicle, ovulation & the formation of the CL.
  2. In the male it stimulates the production of testosterone. And can therefore be used to determine whether testicular tissue is present e.g. in cryptorchid animals (rig test).
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18
Q

WARNINGS og HCG and eCG

A

eCG have teratogenic effects – should NOT be handled by women who could be pregnant and are exogenous proteins for species other than humans or horses and can therefore promote an antigen – antibody reaction

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19
Q

List the Gonadal steroid receptor agonists and antagonists

A
  1. Oestrogen receptor agonist estriol
  2. Progestogen receptor agonist and antagonist (Aglepristone )
  3. Androgens & anti-androgens
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20
Q

Name the only licenced oestrogen receptor agonist

A

ESTRIOL

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21
Q

Where is endrogenous oestrogen released. Where does it bind

A

Endogenous hormone is released from the ovarian follicular cells, the placenta and to a lesser degree the adrenal cortex. It binds to specific receptors which are largely found in the brain, uterus & mammary gland.

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22
Q

MEchanism of action, route of administration of oestrogen receptor agonist (Estriol)

A

Mechanisms of action
Oestrogen receptor agonist.

Route of administration
Oral administration

23
Q

Main effects and examples of use.

Adverse effects

A
  1. Estriol is a synthetic short-acting oestrogen that is licensed to treat urethral sphincter incompetence. Its oestrogenic effects on the female reproductive tract & mammary gland are unwantedIn 5 – 9% bitches due to oestrogenic effects on female reproductive tract and mammary glands. This product should not be used in entire females.
    2.
24
Q

What are progestogens and what do they do?

A

Progesterone receptor agonist

  1. Inhibits GnRH
  2. Prolongs luteal phase
  3. Inhibits repro behaviour.
25
Q

Where is endrogenous progesterone released adn what binds to

A

Endogenous hormone is released from the corpus luteum, the placenta and to a lesser degree the adrenal cortex. It binds to specific receptors which are largely found in the brain, uterus & mammary gland.

26
Q

Route ofadministration of progesterone receptor agonists/ progesterones

A

Widely used in vet
RoA = Injectable
Implants
Oral preparations

27
Q

When are preparations of progesteroens sued?

A
  1. used in oestrus synchronisation programmes (e.g. cattle pigs),
  2. to supress oestrus (small animals)
  3. chemically castrate dogs (Delmadinone acetate which also has anti-androgen properties).
28
Q

Adverse effects of progesterone receptor agonists

A

Endometrial hyperplasia

Endometritis

Pyometra

Diabetes mellitus ( increased glucocorticoid activity)

Acromegaly

29
Q

Progesterone receptor antagonists/blockers

  1. mechanism of action
  2. Route of administration
A
  1. Aglepristone is only product available and is licensed in dogs
  2. MoA = competetive progesterone antagonist
  3. RoA = Injection
30
Q

Progesterone receptor antagonist/ blockers main effects adn example of use. Adverse affects and warning

A

Main effects and examples of use
a) Misalliance and induction of abortion

Main adverse effects
After 20d gestation abortion is accompanied by physiological signs of parturition

WARNING
Should not be administered by pregnant women as accidental self- injection can result in abortion

31
Q

When to use weak androgen receptor agonist and what is its name

A

Called nandrolone

a) excessive tissue breakdown has occurred
b) excessive tissue repair needed
c) anaemia associated with renal disease

32
Q

about endrogenous hormone androgen

A

Endogenous hormone is released from the Leydig cells of the testis and to a lesser degree the adrenal cortex. It binds to specific receptors which are largely found in the brain, accessory sex glands, testis and skeletal muscle.
The effects of endogenous androgens are masculinising, increasing spermatogenesis and libido and secondary sex characteristics. They also have anabolic effects such as increasing protein synthesis particularly in skeletal muscle, increasing the growth of bone & cartilage and increasing erythropoiesis

33
Q

Route of administration of androgen receptor agonists

A
  1. injection
34
Q

Adverse effects of androgen receptor agonists

A
  1. Due to androgen effects
  2. Should not be used on immature animals as may cause premature closure of growth plates
  3. Sex steroids have cause negative feedback on hypothalamus and inhibit normal secretion of GnRH
  4. Infertility or oligospermia
  5. Masculinisation of females
35
Q

Androgen receptor antagonist

A

BLOCKERS e.g. osaterone and delmadinone acetate

36
Q

Mechanism of action of androgen receptor antagonists adn administration

A
  1. competitive androgen receptor blocker

2. ORal

37
Q

Main effects, examples of use and general adverse affects of androgen receptor antagonists

A

Main effects and examples of use
Used to treat prostatic hyperplasia and male hypersexual behaviour

General adverse effects
Similar structure to progesterone so adverse effects due to progestogen & glucocorticoid effects
Reduced ACTH stimulation test
Increased appetite
PUPD
Feminisation
38
Q

Prolactin inhibitors (antagonists)
RoA
Main effects and e.g. of use
Adverse efffects

A

Route of administration
Oral (licensed in dogs)

Main effects and examples of use
Inhibits lactation – Can be used to treat false pregnancy in bitches - dopamine receptor agonist

Main adverse effects
Can induce luteolysis as prolactin is a luteotrophic hormone in dogs and cats therefore can cause abortion.
Contra-indicated in pregnancy. Shouldn’t be used with dopamine-receptor antagonists.

39
Q

Role of endrogenous prolactin

A

Endogenous prolactin is a peptide secreted from the anterior pituitary gland in response to both stimulating and inhibitory neuro-hormones from the hypothalamus of which dopamine (inhibitory) is the most important. Prolactin receptors are largely found in the mammary gland and endogenous hormone stimulates the growth and differentiation of mammary tissues and initiates milk secretion. Cabergoline is a dopamine receptor agonist and inhibitor of native prolactin secretion

40
Q

Oxytocin receptor agonists main effects and e.g. of use

A

Stimulation of uterine contraction to facilitate parturition in the presence of a fully dilated cervix
Promote involution of the post-parturient uterus and thus aid the passage of retained placenta
Aid in the control of post-partum haemorrhage
Promotion of milk let-down' in cases of agalactia and to facilitate stripping out’ of infected quarters in the treatment of mastitis in cows.

41
Q

Endrogenous oxytocin

A

Endogenous oxytocin is a peptide hypothalamic hormone that is stored & released from posterior pituitary. It is structurally very similar to ADH, is water soluble and has a short plasma half- life.
It binds to specific receptors on the myoepithelial cells of the mammary gland, the uterus and in the brain. Oxytocin receptor expression is affected by gonadal steroids (increased by oestrogen)

42
Q

Route of administration of oxytocin

A 
Parenteral administration (peptides are broken down in the GI tract)
Synthetic preparations preferable avoid contamination with vasopressin (ADH)
43
Q

Main adverse affects adn warnings of oxytocin

A

Main adverse effects
May cause/complicate uterine dystocia

WARNINGS
Should not be used by pregnant, postpartum or breastfeeding women

44
Q

Prostaglandin receptor agonist

A

PGF2α receptor agonists

  1. RoA parenteral
  2. main effects and e.g of use - to synchronise oestrus adn induce abortion and parturition
45
Q

Endrogenous prostaglandin

A

Endogenous prostaglandins are local hormones. They are synthesised and released locally and nor stored. They are rapidly catabolised by degrading enzymes in the lung, kidney, spleen, adipose tissue, and intestine and have a very short half- life.
Lung tissue is particularly effective and can remove about 90% of PGE2 or PGF2α from blood in one passage through the lungs.

46
Q

Main adverse effects of prostaglandin F 2 alpha

A

Induction of abortion or parturition by using exogenous substances may increase the risk for dystocia, foetal mortality retention of the placenta and/or metritis.

47
Q

Warnings of using prostaglandin receptor agonist

A

Prostaglandins of the PGF2α type can be absorbed through the skin and may cause bronchospasm or miscarriage.
Care should be taken when handling the product to avoid self-injection or skin contact. Pregnant women, women of childbearing age, asthmatics and persons with other respiratory tract diseases should exercise caution when handling

48
Q

Melatonin
RoA
Main effects and adverse effects

A
  1. Route of administration
    Implant – slow release
  2. Main effects and examples of use:
    Increased melatonin increases GnRH pulsatility and a return to seasonal oestrus cycling in sexually mature sheep. Melatonin can therefore be used to advance the breeding season.
    Only overcomes the effects of seasonality. If there are any other adverse influences on reproduction present within a flock, the full benefit of melatonin treatment may be reduced or even eliminated.

Main adverse effects
These are due to the use of implants – should not be used if sheep are excessively dirty or wet

49
Q

B 2 adrenergic agonists RoA,

A

Route of administration

Parenteral

50
Q

B2 adrenergic agonists main effects adn examples of use

A

To relax the uterus in cattle, usually at the time of parturition. In particular:
In heifers to delay delivery to allow full preparation of the soft birth canal.
As an aid to obstetrical manoeuvres in dystocia e.g. malpresentation and malposture.
To relax the uterus for caesarean section.
To delay and therefore programme delivery to permit observation of parturition e.g. avoidance of night time delivery.
To facilitate the replacement of prolapsed uterus.
During embryo transfer to ensure less traumatic manipulation of the uterus.

51
Q

B2 adrenergic agonists main adverse affects adn warning

A

Main adverse effects
Tachycardia and tremor (can treat effects with beta blockers)
Don’t use with atropine

WARNING
Should not be administered by pregnant women

52
Q

Glucocorticoid receptor agonists.

  1. RoA
  2. main effects and e.g of use
A

Route of administration
Administered by injection to induce parturition/abortion

Main effects and examples of use
In pregnant animals, these agents can mimic the effects of foetal cortisol surge, thereby inducing parturition or abortion.

53
Q

ADverse effects of glucocorticoid receptor agonists MANY

A

Decreases milk yield
High incidence of retained placentae may be experienced and possible subsequent metritis and/or subfertility
Low-dose glucocorticoid replacement therapy is usually without problems but serious unwanted effects occur in some animals from large doses or prolonged administration of glucocorticoids. Cats, are less prone to these adverse effects than dogs. The major adverse effects are as follows:-
Suppression of the response to infection or injury
Wound healing is impaired and opportunistic infections can occur
Cushing’s syndrome
Iatrogenic hypoadrenocorticism on withdrawal of exogenous glucocorticoids due to prior suppression of the HPA axis
Osteoporosis
Hyperglycaemia. Exogenous glucocorticoids cause insulin resistance and can cause hyperglycaemia and diabetes mellitus
Muscle wasting
Fluids & electrolyte imbalances
Oedema
GI ulceration
Abortion in late pregnancy
Laminitis

Year 2 Pharmacology (21 decks)

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