Pharmacology of the Reproductive Tract 1 Flashcards
What are the main drugs used to control female reproduction cycles?
- Gonadotrophins/Gonadotrophin releasing hormone (GnRH)
- Prostaglandin F2a
- Progestins
- Other: Progesterone receptor antagonist, anti-prolactins
Is it necessary or women of reproductive age to take care handling drugs that control repro cycles?
Women of reproductive age should take care in handling GnRH, prostaglandin F2a, and progesterone receptors antagonists (progestins may be a risk) as they are all very lipophilic and can penetrate the skin, with long withholding periods
How many times a year would a bitch cycle?
twice per yeah with an inter-oestrus interval (anoestrus) of at least 4 months
What are some reasons we may want to use drugs in reproductive scenarios in the bitch?
- Induction of oestrus and/or ovulation: Postpone oestrus or suppress oestrus (requires contraception)
- Terminating pregnancy (requires contraception)
Draw out the bitch hormonal reproduction pathway. Are there any special features in the bitch?
The hypothalamus -> GnRH -> Pituitary -> produces FSH and LH.
FSH is important for the development of the ovarian follicles -> oestrogen rises and stimulates LH -> that LH on a mature follicle causes ovulation -> formation of CL (everytime she has a cycle)
How is the bitch different to other species?
- In the formation of the CL (produces P4)
- Long P4 phase
- Prolactin maintains the CL (luteotophic) ** important
- Unlike other domestic species, there is no production of prostaglandin F2a from endometrium to cause luteolysis
The bitch is unique as prolactin maintains the corpus luteum (luteotrophic). What factors can change this process? (ie. what can we do to get rid of the CL?)
Inhibition of prolactin is luteolytic
Dopamine is also known as prolactin inhibitory hormone
Dopamine D2 receptor agonists and serotonin receptor antagonists inhibit prolactin secretion
The bitch has a long P4 phase which can cause problem sometimes. What is this problem?
Long P4 phase leads to cyctic endometrial hyperplasia which will result in pyometra
What is a false pregnancy in the bitch and do you have to do anything about it?
It is when the bitch isnt prenant but goes into metoestrus/dioestrus, generally dont have to do anything about it
If the false pregancy is severe, what drug would you give? What effect does this have on her cycle?
Antiprolactins
- Dopamine receptor agonists (cabergoline, bromocriptine)
- After antiprolactin treatment, the bitch will go into anestrus or prooestrus
Why would you use antiprolactins with PGF2a?
To synchonise pigs
In what instance would gonadotropins be used in the bitch? What are they?
To mimic FSH and LH
o Equine chorionic gonadotrophin (eCG) has mainly FSH activity
Also called pregnant mare serum gonadotrophin (PMSG)
Also porcine FSH formulation
Injection of eCG (folligon = FSH, LH + oestradiol analogue) causes induction of oestrus
Possible side effects include immune mediated and anaphylactic reactions
o Human chorionic gonadotrophin (hCG) has mainly LH activity
Collected from urine of pregnant women
Chorulon by intramuscular injection on the first day of oestrus induces ovulation in the bitch
What would gonadotropin-releasing hormone be used for in the bitch?
Gonadotrophin-releasing hormone (GnRH) e.g. gonadorelin or deslorelin
o GnRH is released in pulses from hypothalamus, both gonadotrophins (LH and FSH) and gonadal steroids regulate GnRH production in a negative feedback manner
o Two principal uses
Stimulate ova development and ovulation e.g. injection of GnRH causes maturation and ovulation in horses
Implants: Long term suppression of FSH/LH leading to medical castration
What would you give to induce ovulation in the bitch during oestrus?
hCG by IM on the first day of oestrus
What is the issue with using a GnRH implant?
- You get a build up of GnRH
- Due to neg feedback, you lose the receptors on the pituitary
- So GnRH cant lock onto any receptor to secrete the FSH and LH
- When used in a patient, it is actually a contraceptive. BUT ovulation may be induced in the short time after implantation so you have to be careful.
How would you induce oestrus in the bitch? Are there any side effects of inducing oestrus with this drug?
- Injections of ECG (Folligon = FSH, LH + oestradiol analouge)
- Side effects: possible immune mediated/anaphylactic reactions
What drugs would you use to suppress or postpone oestrus?
Progesterone alalogues - progestins
- Proligesterone (covinan) - drug of choice for an unexpected oestrus NOTE that it is not advised for the first oestrus
- Implant called levonorgetrel (norplant) - note will get a surge and possible ovulation shortly after implantation.
- Megastrol acetate (ovarid) tablets
- Medroxyprogeterone acetate (MPA) - long acting injection
How do progestins work? Draw out the reproduction pathway and highlight where progestins impact the pathway.
Neg feedback on the pituitary. Stops the stimulation of LH and FSH which in turn cuts out all activity beneath it in the pathway
Are progestins more or less reliable when administered in anoestrus?
More reliable, they are less reliable if administered in pro-oestrus
What are some adverse effects associated with repeated administation of progestins in the bitch?
- Cyctic endometrial hyperplasia -> pyometra
- mammary hyperplasia
- progestins are GCS like -> they are not a long term solution. Can lead to hyperadrenocorticism, secondary DM, acromegaly.
What drug would be used for sychronisation, suppression, postponement of oestrus in livestock?
- Progestins
- GnRH agonist (deslorelin) - implant
What drug can be used for pregnancy termination (abortifacients) in the bitch and queen? Are there any side effects associated with this medicaiton?
- Anti-progestin – aglepristone -> Alizin Anti-progesterone injection
- Also known as anti-progestin
- Induces abortion 0-45 days after mating
- 2 SC injections given 24h apart
- Caution to women handling drug -> equivalent to the morning after pill
- Side effects: more likely when used 25-40d, foetal expulsion, vaginal discharge, anorexia and mammary congestion
What is PGF2A used for in horses and livestock species?
- For break down of the corpus luteum (i.e. luteolysis)
- Corpus luteum must be > 5 days old to break down under the influence of PGF2 α
- Used in horses, livestock species (not used in pigs)
- Used alone or in combination with progestogens for the synchronisation of oestrus in groups / herds of female animals
Are there any side effects associated with administation of PGF2A?
- Results in contraction in smooth muscle
- Dinoprost may result in lowered body temperature, increased heart and respiratory rates, sweating, muscle cramping, colic, ataxia, and weakness.
- Signs are seen within 15 min and usually subside within 1 hr
- Synthetic preparations e.g. cloprostenol have fewer adverse effects
Oestrus behaviour may be undesirable in some performance mares. How would you postpone oestrus in the mare?
- Administer progestogens: either progesteronein oil or altrenogest.
Suggest 3 method of oestrus synchronisation in cows.
- Method 1: Controlled internal drug release (CIDR) of progesterone inserted into vagina for 7 days, injection of PGF2α on day 6, withdrawal of CIDR on day 7, return to oestrus within 3 days after withdrawal
- Method 2: Two dose prostaglandin (PGF2α) treatment: two prostaglandin injections given 12 – 14 days apart to all cows – cows will return to oestrus within 3 days of last injection
- Method 3: GNRH/prostaglandin injections, GNRH injection day 0, PGF2α injection alpha day 7, GNRH injection day 9, Cows should be inseminated 0 – 20 hrs after second GNRH treatment
What are some of the reproductive problems in the male dog?
- Benign prostatic hyperplasia
- Prostatitis
- Excessive libido
- Aggression
How can benign prostatic hyperplasia be treated?
- Surgery - castration
- Can use a GnRH implant (decreases testosterone)
- Can also use anti-androgens or delmadinone acetate
What drug reduces a male dogs libido?
- Deslorelin implant
- finasteride
Are there any drugs that can be used to deal with aggression in male dogs?
- Progestins (decrease testosterone): MPA, megastrol acetate, TCAs, SSRIs
