Parturition Pharmacological Manipulation - Anatomy & Physiology

()Map REPRODUCTIVE SYSTEM (Map) PARTURITION

Summary of Treatments,Copyright RVC 2008

Why Control Timing of Parturition?

Herds

• Improves supervision to ensure the farmer can be around at the time of parturition.
• Reduces the incidence of parturition at night/weekends which is socially undesirable.
• Aids cross fostering between litters.
• Tightens the calving interval in cattle.

Individuals

• Maternal emergency such as abnormal foetal position, bone fracture of the pelvis etc.
• Foetal abnormality, or an oversized foetus.

Disadvantages of Parturition Induction

• Timing may not be absolutely perfect, there is considerable variation in the timing of drug action and effect.
• Premature delivery of small, immature offspring.
• Increased incidence of retained placenta.
• Pharmacological induction can only be used commercially in cattle and pigs. Induction in other species is used only to overcome birth associated problems.
• Increased dystocia in cattle
• Increased incidence of clinical post-parturient uterine infections.

Requirements for Parturition Induction

You must ensure the foetus is appropriately developed before inducing parturition. The lungs must be mature to enable survival. Naturally maturation of the lungs is induced by foetal cortisol, so it may be useful to administer glucocorticoids to artificially mature the lungs.

  Prostaglandin F2α: Cervical dilation
  Prostaglandin F2α and Oxytocin: Uterine contractions
  Oxytocin: delivery of the Placenta

• Oxytocin and Prostaglandin F2α both signal by the Gαq -> IP3 + DAG pathway to raise intracellular calcium , so are able to effect each other in the Fergusson reflex.
• COX II increases during labour, so prostaglandins will form as long as arachidonic acid is available.

Drugs Influencing Uterine Activity

Ecbolic Drugs

• Induce parturition by uterine activation.

Ergot Alkaloids

• Induce contraction
• Vasoconstrictors
• Not used in the UK
• Ergonavine taken off the market, Methergine is the only derivative in use.

PGF2α Analogues

• Dinoprost
• Clonprosterol
• Exert action over a long period of time.

Oxytocin

• Used in conjuction with Oestradiol Benzoate
  • Oestradiol induces oxytocin receoptor upregulation on the endometrium.
  • Inhibits uterine activity, but sensitizes the uterus to oxytocin.

Tocolytic Drugs

• Delay parturition by relaxation of the uterine myometrium.

Progesterone

• Slow acting steroid through nuclear receptors.
• Not useful in emergency situations.

Relaxin

• Rapidly acting peptide hormone
• Essential in farrowing sows

Myometrial Innervation and Manipulation

The autonomic nervous system is not important in normal labour, since uterine contractions are controlled by the neuroendocrine release of oxytocin. However, the autonomic nervous system can be used to control parturition pharmacologically by changing cAMP levels which effects the myometrium.

Sympathetic

α Adrenoceptors

• Induce contractions
• Agonists induce parturition
• Antagonists delay parturition

β Adrenoceptors

• Progesterone increases the number of β Adrenoceptors
• Inhibit contractions
• Agonists delay parturition e.g. Clenbuterol
• Antagonists induce parturition e.g. Carazolol

Parasympathetic

• Acetylcholine inhibits contractions

Induction of Parturition

Cow

To Induce Parturition

Corticosteroids

• Mimic foetal cortisol to remove the progesterone block by upregulating enzymes that will increase the oestrogen:progesterone ratio (for more information see endocrinology of parturition).
• Short Acting: apply 2-3 days before the due date (270+ days gestation). Complications include retained placenta and stillbirth.
• Medium-Long Acting: apply 2-3 weeks before the due date. Administration after 260 days will cause no advance of the calving date. Administration before 260 days will cause neonatal mortality. Thus use of these corticosteroids is reliant upon accurate record keeping by the farmer so that exact dates are known.

Corticosteroid & PGF2α Analogue

• Has the additional benefit of acting to dilate and soften the cervix to facillitate delivery.

PGF2α Analogue Alone

• Causes luteolysis to remove the progesterone block.
• Triggers delivery in 48 hours.
• However, it risks inadequate foetal maturation upon delivery.

To Delay Parturition

• Useful in valuable cows coming in to calf too early.
• Administer a β Adrenoceptor agonist such as Clenbuterol.

Sow

• Widespread use

PGF2α Analogue

• Administer 2 days before the mean gestation of the herd.
• Causes luteolysis to remove the progesterone block keeping the uterus quiescent.
• 97% will farrow within 36 hours
• Used to ensure tight farrowing

PGF2α Analogue + Oxytocin

• Favoured method
• Tightens the delivery pattern
• The oxytocin increases milk production and ensures delivery of the placenta.

β Adrenergic Antagonist

• Administer in the first stage of labour.
• Decreases the duration of parturition.
• Decreases the incidence of stillbirths

Progesterone

• Delays parturition by 1.5-3 days

Oxytocin

• Administer postpartum to increase uterine involution and milk production.

Mare

Drugs are used in individuals with a history of difficult birth and in emergency situations, The mare must be 320-330 days pregnant to ensure adequate maturity of the foetus. Also, the mammary gland must be developed and contain colostrum. The mammary gland is a good indicator of foetal maturity. Mammary secretion of calcium carbonate increases 24 hours before foaling. So, calcium carbonate levels can be used to assess foetal maturity prior to induction. Mammary secretions are generally tested using a titret kit. A disadvantage of this is that essential immunoglobulins can be lost by this pre-parturient release of colostrum, resulting in the foal receiving less colostrum on its first suckle.

• Corticosteroids are NOT effective and prostaglandin results in abdominal pain.

Low dose Oxytocin

• Induces foaling in ~90 minutes.

Ewe

• Prostaglandin analogues are NOT active. They cause luteolysis, but do not remove the progesterone block due to placental progesterone production.

Short Acting Corticosteroids

• Administer on day 144 of gestation.
• Induces lambing in ~48 hours.
• Risks delivery of low weight lambs.

Bitch and Queen

• Induction is rare
• Caesarian more commonly implicated

Low Dose Oxytocin

• Initiates myometrial contractions.