Drugs Acting On The Reproductive System

Many drugs are used at different stages of the oestrous cycle to manage the response of the reproductive system; these are summarised in Table Drags affecting the reproductive system.

Table Drags affecting the reproductive system

Indications Species Drug
Synchronisation and regulation of the oestrous cycle and ovulation Horses Altrenogest, Buserelin, Cloprostenol, Dinoprost, Luprostiol
Cattle Buserelin, Cloprostenol, Dinoprost, Etiproston, Gonadorelin, Luprostiol, Progesterone (Eazi-Breed CIDR), Progesterone + estradiol benzoate (Prid)
Sheep, Goats Flugestone acetate, Medroxyprogesterone acetate
Pigs Altrenogest
Stimulation of the onset of cyclical ovarian activity Horses Altrenogest, Buserelin, Chorionic gonadotrophin, Cloprostenol, Deslorelin, Dinoprost, Luprostiol, Serum gonadotrophin
Cattle Buserelin, Chorionic gonadotrophin, Cloprostenol, Dinoprost, Etiproston, Gonadorelin, Luprostiol, Progesterone, Progesterone + estradiol benzoate (Prid), Serum gonadotrophin
Sheep, Goats Flugestone acetate, Medroxyprogesterone acetate, Melatonin, Serum gonadotrophin
Pigs Altrenogest, Chorionic gonadotrophin + serum gonadotrophin (PG600)
Dogs Chorionic gonadotrophin, Serum gonadotrophin
Rabbits Buserelin
Superovulation Cattle Chorionic gonadotrophin, Menotrophin, Serum gonadotrophin, Follicle stimulating hormone (porcine, ovine, recombinant)
Misalliance and pregnancy termination Horses Cloprostenol, Dinoprost, Luprostiol
Cattle Cloprostenol, Dinoprost, Etiproston, Luprostiol
Dogs Aglepristone, Cabergoline, Estradiol benzoate
Induction of parturition Horses Cloprostenol, Dinoprost, Luprostiol
Cattle Cloprostenol, Dexamethasone, Dinoprost, Etiproston, Luprostiol
Sheep Dexamethasone
Pigs Cloprostenol, Dinoprost, Luprostiol
Overt pseudopregnancy Horses (type 1 only) Cloprostenol, Dinoprost
Goats Cloprostenol, Dinoprost
Dogs Cabergoline, Methyltestosterone, Proligestone, Testosterone esters (Durateston)
Suppression of ovarian activity Dogs Medroxyprogesterone acetate, Megestrol acetate, Methyltestosterone, Proligesterone, Testosterone esters (Durateston)
Cats Megestrol acetate, Proligesterone

 

Drugs used to promote gonadal function

Gonadotrophins

Gonadotrophin-releasing hormones

Melatonin

Melatonin advances the time of onset of cyclical ovarian activity in the ewe and doe goat by mimicking the natural production of melatonin by the pineal gland. This gives improved reproductive performance in sheep flocks mated early in the season. A single dose of 18 mg, in a modified-release formulation, is implanted behind the ear. This is carried out 30 to 40 days before the introduction of the ram. It is important that ewes are kept completely separate from rams and also male goats for no less than 30 days after implantation.

In the UK, for Suffolk and Suffolk cross-breeds, the drug should be administered from mid-May to late June, for ram introduction in late June and July. For Mule and Half-bred flocks, melatonin should be administered from early June to late July, for ram introduction from mid-July to late August.

MELATONIN

Indications. Induction of ovulation

Contra-indications. Sexually immature animals

Warnings. Use of drug in ewes suckling lambs at foot may not give optimum results. The drug should not be used at times other than recommended, see notes above

Dose:

Sheep: by subcutaneous administration, 1 implant

PML Regulin (Ceva) UK Implant, m/r, melatonin 18 mg, for sheep

Withdrawal Periods.

Sheep: slaughter withdrawal period nil, milk withdrawal period nil

Sex hormones

Prostaglandins

Myometrial stimulants

Myometrial relaxants

Prolactin antagonists

Pregnancy in bitches is maintained by the presence of corpora lutea; if they regress, pregnancy will be terminated. The presence of corpora lutea is probably dependent upon the luteotrophic support of pituitary-derived prolactin during the second half of the luteal phase of metoestrus and pregnancy.

The prolactin inhibitor cabergoline exerts its effect by inhibiting prolactin release by direct stimulation of dopamine receptors in prolactin-releasing cells in the anterior pituitary. As a consequence, the corpora lutea regress. Towards the end of metoestrus, as the corpora lutea start to regress, there is a concomitant rise in prolactin which is responsible for the overt signs of pseudopregnancy such as behavioural signs and mammary development and lactation. Cabergoline reduces prolactin release and is used for the treatment of overt pseudopregnancy in the bitch. Bromocriptine is a potent dopamine receptor agonist (dopamine receptor stimulant), which inhibits prolactin release from the anterior pituitary gland. Bromocriptine commonly causes side-effects such as vomiting, anorexia, and behavioural changes, which may be severe. Metergoline is a serotonin agonist with actions similar to bromocriptine; it is used to suppress lactation.

CABERGOLINE

Indications. Pseudopregnancy; suppression of lactation; termination of pregnancy ; behavioural modification

Contra-indications. Pregnant animals unless pregnancy termination required; lactating animals unless suppression of lactation required; use directly after surgery while animal still recovering from anesthesia

Side-effects. Transient hypotension, occasionally vomiting or anorexia, transient drowsiness

Warnings. Drug Interactions.

Dose: Doe goats, to suppress lactation, by mouth, 5 micrograms/kg

Dogs: by mouth, 5 micrograms/kg once daily for 4-6 days.

May be mixed with food

Prescription-only medicine: Galastop (Ceva) UK

Oral solution, cabergoline 50 micrograms/mL, for dogs (3 drops = cabergoline 5 micrograms)

Non-hormonal abortificants

Lotrifen is a phenyltriazole isoquinoline which causes embryopathy and abortion in many species such as rats, hamsters, guinea pigs, and dogs. It is most effective in dogs when administered around 20 days of gestation and it is used in dogs for pregnancy termination. The mode of action is unclear: the drug may be embryotoxic, it may reduce blood supply to the gravid uterus, or modify the animal’s immune response.

Drugs for uterine infections

Bacteria will contaminate the uterus of most individuals after normal parturition. However these micro-organisms will soon be eliminated by natural defence mechanisms. The bacteria may originate from the environment and are opportunist pathogens or may be specific venereal pathogens; failure to eliminate them due to impaired defence mechanisms will result in infection. In addition, trauma associated with dystocia and heavy bacterial contamination are also likely to predispose to infection. Uterine infection may be acute, frequently involving all layers of the uterine wall (metritis) or chronic, usually involving the endometrium (endometritis). The former may be fatal. Treatment of metritis includes the use of systemic antimicrobials such as potentiated sulphonamides, oxytetracycline, or semisynthetic penicillins, NSAIDs, and supportive therapy. Chronic infection involving the endometrium can be treated by the intra-uterine infusion of broad-spectrum antimicrobials, administered at the usual therapeutic dosage. In the cow, if a corpus luteum is present, endometritis is best treated by administration of prostaglandin F2alpha or an analogue. In bitches, cystic endometrial hyperplasia and pyometra most commonly occur in the luteal phase of the oestrous cycle (metoestrus). In animals with ‘open’ pyometra with dilated cervix and vaginal discharge, dinoprost is administered at a dose of 250 micrograms/kg for at least 5 days. It is contra-indicated in bitches with very enlarged uteri, animals with heart conditions, and patients with ‘closed’ pyometra. Side-effects occur within 15 minutes of administration and include panting, salivation, vomiting, and whimpering. These symptoms are transient and cease within one hour.

In the UK, the Horserace Betting Levy Board publishes Codes of Practice on contagious equine metritis (CEM) Klebsiella pneumoniae, Pseudomonas aeruginosa; equine viral arteritis (EVA); and equid herpesvirus-1 (EHV-1), which include recommendations for disease prevention and control in breeding horses.

Prescription-only medicine: Metricure (Intervet) UK

Intra-uterine suspension, cephapirin (as cephapirin benzathine) 500 mg, for cattle; dose applicator

Withdrawal Periods.

Cattle: slaughter 2 days, milk withdrawal period nil

Dose:

Cattle: by intra-uterine administration, contents of one applicator. May be repeated after 7-14 days

Prescription-only medicine: Utocyl (Novartis) UK

Pessaries, benzylpenicillin 62.7 mg, formosulphathiazole 1.75 g, streptomycin (as sulfate) 50 mg, for cattle

Withdrawal Periods.

Cattle: slaughter 2 days, milk withdrawal period nil

Dose:

Cattle: by intra-uterine administration, 6 pessaries for prophylaxis only