Reproductive pharmacology Flashcards
What are gonadotropins?
Pituitary (FSH, LH) or chorionic (CGs). Different isoforms exist for each gonadotropin during different reproductive staes. Sugar composition determines the half life of a particular isoform i.e isoforms containing more sialic acid residues are more slowly degraded and therefore have longed half lifes. CGs are more heavily sialylated than FSH or LH and therefore have much longer half lives. CGs are more readily available (from urine) than pituitary gonadotropins. They also high higher bio potency.
What are the clinical uses of GnRH?
Induction of follicular growth and ovulation - treatment of post partum anoestrus in cows. Induction of ovulation - timing of ovulation in mares, follicular cysts in cattle. Synchronisation of oestrus in cattle, protocol: GnRH>8days> PGF2a>2days>GnRH>2days>Artificial insemination. Stimulation of luteal function - improvement of pregnancy rates in cattle.
What are the clinical uses of gonadotropins?
Human CG has LH like bioactivity in all species. Equine CG and LH act like LH in the horse but have strong FSH activity when administered to other species. hCG is used for induction of ovulation - timing of ovulation in mares and cows, follicular cysts in cows. Induction of follicular growth during Anoestrus - eCG - in combination with progesterone implants to advance breeding season in sheep and goats and in combination with progesterone implants in anoestrus cows and in combination with hCG to advance puberty in gilts.
How are gonadotropins used for the induction of superovulation in cattle?
eCG given on day 12 of the oestrus cycle followed by PGF2a within 2-3 days and AI 60-72 hours later. eCG allows multiple follicles to be selected within the second follicular wave of the oestrus cycle. PGF2a lyses the CL therefore decreasing circulating progesterone which results in an LH surge. eCG often results in an excessive super ovulatory response, therefore use of purified or recombinant FSH may be preferred. If FSH is chosen, twice daily administration over 4-5 days is required.
What are the indications for use of oxytocin?
Dystocia due to uterine inertia, to promote uterine invoution and/or expulsion of retained foetal membranes, uterine prolapse (oxytocin reduces size of uterus), to facilitate clearance of uterine discharge in mares, induction of parturition in mares, agalactia due to failure of milk ejection (does not promote lactogenesis)
What are the possible adverse effects of oxytocin?
Onset of action after secretion or exogenous administration is very quick and duration of action is relatively short. Uterine rupture may occur - oxytocin is contra indicated in cases of abnormal fetal position, insufficient cervical dilatation, closed Pyometra, previous uterine surgery, uterine tetany, anti diuretic effects (similar to vasopressin structurally), vasodilation and hypotension.
Describe the binding proteins of steroids.
Steroids circulate mostly bound to specific blood proteins. Sex hormone binding globulin binds testosterone and Oestradiol. Corticosteroid binding globulin binds cortisol and progesterone. Binding proteins are synthesised in the liver, binding proteins regulate steroid activity by regulating steroid metabolism and regulating steroid access to target cells.
How are steroids metabolised?
Steroids undergo oxidative processing in the liver and are then excreted in urine or faeces as sulfate or glucuronide compounds. Clinical steroid formulations are often available as oily solutions that slow down absorption increasing duration of action. Withdrawal periods usually exist for administration of steroids for food producing animals.
What are the Progestagens and why are they used?
Progesterone and several synthetic derivatives are used very extensively in large animals, mostly for synchronisation or induction of oestrus - based on ability of exogenous Progestagens to induce artificial luteal phase and temporarily inhibit LH secretion followed by massive LH release and ovulation when progestagen treatment is discontinued. Used as intravaginal sponges/ear implants/ feed supplements.
Describe how progestagens are used to synchronise oestrus in cattle.
Intravaginal progesterone implant > 8 days> PGF2a > 2 days> implant removal > oestrus detection + AI. Ovulation occurs 2-5 days after implant removal. Progesterone can be combined with oestradiol (enhances progesterone action) and/or GnRH or ECG (Stimulates follicular growht.)
How are progestagens used for the indution of oestrus in anoestrus animals?
Advancement of the breeding season in ewes and mares - altrenogest (feed supplement) very popular in mares but efficacy not proven. Effective at suppressing irregular oestrus periods at the end of non breeding season. Also progestagens used for the initiation of puberty in heifers in combination with eCG.
What are the adverse effects of prostagestens?
Uterine disorders - endometrial hyperplasia, pyometra, since they stimulate cell proliferation and glad secretion in the endometrium and reduce uterine immunity. They should not be given to animals with uterine disorders or immature animals. When used for long term suppression of oestrus animals should be allowed to have a normal cycle every 18-24 hours (small animals). They may have adrenal cortical suppression because of their glucocorticoid like effects. Some progestagens may cause mammary tumours, pseudopregnancy or exacerbate diabetes.
What is Prostaglandin F2a used for?
Induction of luteolysis, stimulation of myometrial contraction, several synthetic forms of PGF2a or analogs are available. Most have relatively short half lives in blood from a few minutes to a few hours since they are rapidly metabolised.
When would PGF2a be used as a luteolytic agent?
Persistent CL in mares, luteal cysts in cattle, termination of pregnancy. In species that do not maintain CL throughout pregnancy, PGF2a needs to be administered before placental progesterone comes into play e.g before day 150 in cattle and before day 50 in sheep. In horses - need to administer before day 35 of pregnancy i.e before endometrial cups begin to secrete luteotropic eCG to avoid pseudopregnancy. Synchronisation of oestrus - PGF2a shortens dioestrus phase resulting in early oestrus and ovulation. Interval from treatment to ovulation is variable since it depends on level of follicular development at time of treatment. 2-5 days in cattle 2-12 days in mares. PGF2a does not work in anoestrus animals.
How is oestrus synchronisation in cattle managed with PGF2a?
At any given time not all animals within a herd will be responsive to PGF2a, two separate PGF2a injections 11 days apart will be necessary to synchronise the entire herd. First PGF2a injection is given. Group 1: animals on days 5 to 16 of the oestrus cycle will ovulate within 2 to 5 days. Group 2: animals between days 1-4 or 17-21 of the cycle will not respond. Group 1 animals will be on days 6–9 of the cycle at second PGF2a injection 11 days later. Group 2 animals will be on days 7 to 15 of the cycle. All animals will then ovulate within 2-5 days. To better time ovulation GnRH can be given 48 hours after second PGF2a injection.
