Drugs affecting Uterine Motility Flashcards
What are the main objectives of drugs affecting uterine motility?
- To induce & augment labour
- To control post partum haemorrhage (PPH)
- To induce pathological abortion
- To arrest premature labour
What are the 3 clinical uses of uterine stimulants?
- To induce abortion in the first half of pregnancy
- To induce or augment labour in late gestation
- To prevent or arrest PPH- Common cause of maternal death
How do uterine motility drugs help with postpartum haemorrhage?
through stimulation of tonic contractions that constrict uterine blood vessels
- necessary to prevent excessive blood loss
Name the drugs that stimulate uterine contractility?
- Oxytocin - Syntocinon ®
- Ergot alkaloids - Ergometrine
- Prostaglandins - Misoprostol, Gameprost, PGE, PGF2 α
- Miscellaneous - Quinine, Emetine, Alcohol
Name the drugs that relax uterine muscles?
- β2 Selective stimulants - Ritodrine, Salbutamol
- Oxytocic antagonist - Atosiban
- COX inhibitors - Celecoxib, Aspirin,
Indomethacin, Ibuprofen
Describe oxytocin and its effect?
- Has short half life
- contractions lasting a few minutes therefore has to be infused
In what case is oxytocin the least effective?
in early pregnancy
- due to low density of oxytocin receptors
When can oxytocin be used?
- Induction of labour for medical reasons
- Augmentation of labour in hypotonic uterine inertia
- Can also be used following incomplete abortion after 20 weeks (prostaglandins a preferred choice)
- In high doses used to induce abortion
- May be used after full-term delivery to prevent and treat PPH
Describe the mode of administering
oxytocin in different cases?
- Given by IV infusion for labour induction
- Careful monitoring of fetal heart rate and
uterine motility essential for dose titration
- Discontinue immediately in uterine
hyperactivity or fetal distress - may be given IM in PPH
- as a nasal spray to promote milk ejection
What is the function of prostaglandins?
induce uterine contractions with varying degrees of pain according to the strength of contractions induced
What medication cocktail is used in early pregnancy to induce abortion?
Mifepristone + prostaglandins
Which prostaglandin is preferred for the medical use of induction of late therapeutic abortion and how is it administered?
Gemeprost
- administered vaginally as pessaries
- It ripens the cervix before surgical abortion, particularly in primigravidas
Describe the use of Misoprostol?
- to induce labour or medical abortion
- given by mouth or by vaginal administration
- Intravaginal use ripens the cervix before
surgical abortion - alternative in postpartum haemorrhage if
unresponsive to ergometrine, oxytocin and
carboprost
What are the uses of Ergot alkaloids?
They cause intense tonic myometrial contractions
- Prevention and treatment of haemorrhage
- Active management of the third stage of labour
- reduces the risk of postpartum haemorrhage
Which ergot alkaloid can cause intense tonic myometrial contractions?
ergometrine
Describe the prevention and treatment of haemorrhage by ergot alkaloids?
ergometrine + oxytocin
- Bleeding due to incomplete abortion can be controlled
- given intramuscularly
- the dose is adjusted according to the patient’s condition and blood loss
- combined are more effective in early pregnancy than either drug alone.
What dosages of ergot alkaloids manage the third stage of labour?
Ergometrine 500mcg with oxytocin 5units is given by IM on delivery of the anterior shoulder or, at the latest immediately after the baby is delivered
Describe the dosage of ergot alkaloids used to treat postpartum haemorrhage caused by uterine atony?
Ergometrine 250–500micrograms by IV
- use with caution because there is a risk of hypertension
What is the most widely used progesterone receptor anatgonists?
mifepristone
What is mifepristone?
an anti-progestogenic steroid, sensitises the myometrium to prostaglandin-induced contractions and ripens the cervix
Describe the use of mifepristone?
Useful for termination of early pregnancy, when uterine quiescence is dependent principally on progesterone
What are the 2 phases of the onset of labour?
- activation phase
2. stimulation phase
Describe the activation phase of the onset of labour?
- The uterus acquires an increased number of receptors for stimulants, particularly oxytocin
- an increased number of ion channels are formed,
- an increased number of gap junctions are formed for cell to cell signal transmission
Describe the stimulation phase?
The myometrium is more responsive and is stimulated by both oxytocin and prostaglandins (produced locally within the uterine muscles)
Describe the side effects of oxytocin?
Hyper- stimulation caused by Oxytocin
- can be reversed by reducing or discontinuing infusion since oxytocin has short half life or administering beta2 agonists
Side effects of oxytocin and prostaglandins?
Anaemia, uterine rupture, tachychardia, abdominal pain, vomiting, dyspnoea
- Medical supervision needed
Describe the side effects of prostaglandins?
Hyperstimulation by PG gel
- insertion into cervix or vagina can cause more problems, saline can be used to wash out the PG
Describe the side effects of ergot alkaloids?
stroke, hypertension myocardial infarction, palpitations, dyspnoea, abdominal pains
What do uterine relaxants do?
Postpone premature labour and they are used with the aim of reducing harm to the child.
- there is no satisfactory evidence that the use of these drugs reduce mortality
Describe the safe use of uterine relaxants?
Prolonged therapy should be avoided since risk to the mother increases after 48 hours and there is a lack of evidence of benefit from further treatment;
- maintenance treatment is therefore not recommended
What is atosiban?
oxytocin receptor antagonist
What is Atosiban used for?
the inhibition of uncomplicated premature labour between 24 and 33 weeks of gestation
Name the uterine relaxants?
- beta2 –adrenergic receptor agonist
- NSAIDs
- magnesium sulphate
- calcium channel blockers
How do beta 2 agonists work?
Uterus is made of smooth muscles therefore beta2 –adrenergic receptor stimulation causes relaxation
How do NSAIDs work?
inhibit PG synthesis by inhibiting both COX-1 and COX-2 enzymes
Why might magnesium sulphate not be favourable in use as a uterine relaxant?
mechanism of action is assumed to compete with Ca++ in myometrial cells.
How is magnesium sulphate administered?
It is given by IV
Give an example of a calcium channel blocker used as a uterine relaxant?
nicardipine
- by oral route
Why is atosiban favoured over beta 2 agonists?
has fewer side effects
Name beta 2 agonists?
ritodrine, salbutamol or terbutaline
Describe the use of beta 2 agonists?
- is used for inhibiting uncomplicated premature labour between 24 and 33 weeks of gestation as Atobisan
- may permit a delay in delivery of at least 48 hours
Describe the use of COX inhibitors?
Indomethacin also inhibits labour and it can be useful in situations where a beta2 agonist is not appropriate
What are the 4 clinical uses of uterine relxants?
- To prevent or arrest preterm labour.
- To reverse inadvertent overstimulation.
- To facilitate intrauterine manipulations, such as conversion of a foetus from a breech to a cephalic presentation, surgical procedures, or postpartum replacement of an inverted uterus.
- To relieve painful contractions during menstruation - Dysmenorrhea
Describe the side effects of beta 2 agonists?
- Beta2-adrenergic receptor agonists have generalised effects
- Beta2 agonists should also be used with caution in diabetes—monitor blood glucose (risk of hyperglycaemia and ketoacidosis, especially with intravenous beta2 agonists)
Describe the side effects of COX inhibitors?
neonatal complications such as transient impairment of renal function and premature closure of ductus arteriosus
Describe the complications of magnesium sulphate?
can lead to loss of deep tendon reflexes, respiratory depression and myocardial depression
Describe the side effects of calcium channel blockers?
generalised fall in blood pressure
Describe the dosages of salbutamol?
By intravenous infusion, initially 10mcg/ min, rate increased gradually according to response at 10-minute intervals until contractions diminish then increase rate slowly until contractions cease (max. rate 45micrograms/minute)
Maintain rate for 1hour after contractions have stopped, then gradually reduce by 50% every 6hours; then by mouth 4mg every 6–8hours
Describe the dosages of atosiban?
By IV, initially 6.75mg over 1 minute, then by intravenous infusion 18mg/hour for 3 hours, then 6mg/hour for up to 45 hours; max. duration of treatment 48 hours
Describe the dosages of nifedipine?
Given initially in a dose of 20mg followed by 10– 20mg ,3–4 times daily adjusted according to uterine activity
