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Many conditions in pregnancy require prescribed medication and increasing numbers of women are on regular drugs for pre-existing medical conditions. This chapter reviews the common drugs used in obstetric patients and looks at their mechanisms of action, side effects and evidence of efficacy.
Drugs in common use in pregnancy
Anti-hypertensives
Hypertension and pre-eclampsia (PET) affect approximately 10% and 3% of all pregnancies respectively and are amongst the commonest medical problems in pregnancy. Whilst the benefits of treatment are clear for a minority with severe hypertension, much controversy exists over the benefit of treatment in mild and moderate hypertension. The purpose of treatment is to reduce the risk of acute intra-cerebral events in the mother.
The only clear indications for treatment are:
Persistent BP >/= 160/100
Acute severe hypertension
Fulminating PET
Eclampsia
Treatment from 140/90 – 160/110 is debatable but most obstetricians pragmatically medicate from 150/100 upwards.
β blocker labetolol is considered safe and has been used extensively in human pregnancy – it is generally considered as first line treatment
It has non-specific α + β blockade
It may be also be used for acute hypertension as a first line IV infusion
Side effects:
It may cause IUGR (even after controlling for BP) with prolonged use
Neonatal hypoglycaemia + bradycardia have rarely been reported
The safety of other β-blockers, atenolol in particular, in the early and late stages of pregnancy is unresolved; their use is therefore generally contraindicated according to several guidelines [1].
Methyldopa is considered safe and has been used extensively in human pregnancy – it is now generally considered as second line treatment as an add on to labetolol but may be used first line instead
It is centrally acting and is metabolised to α-methylnoradrenaline (it’s active component)
It works as a post-synaptic α2 agonist reducing central sympathetic outflow
Side effects include:
Rebound hypertension
Depressed mood (with long term use)
Flattened CTG variability
Autoimmune haemolytic anaemia (rare)
Raised prolactin (outside of pregnancy)
Hepatitis
Nifedipine – nifedipine is not licensed in pregnancy but is a commonly used second line treatment – a modified release (MR) preparation is recommended due to the potential acute hypotensive effect it can have [2].
It is a member of the dihydropyridine group and blocks inward flux of calcium through voltage gated calcium channels
It has a preferential effect on vessels as a vasodilator rather than the myocardium
It can also be used for acute hypertension
It has no anti-arrhythmic activity
It also has a known effect on the myometrium – it may inhibit premature labour (unlicensed use) and has been used as a tocolytic agent
Side effects include:
Acute hypotension if given sub-lingually
Peripheral oedema
Headache + flushing
Hydralazine IV is used for acute hypertension
It needs to be given slowly over a minimum of 5 minutes IV
It can be repeated IV every 15 minutes if needed
It is a potent vasodilator with a poorly understood mechanism of action
It is metabolised by acetylation in the liver (fast and slow acetylators are genetically determined)
Side effects include:
Acute hypotension if given too fast or too often
There is a recognised idiosyncratic adverse event (AE) of a lupus like syndrome rarely in slow acetylators
MgSO4 is proven to be the best prevention and best treatment of fits in severe PET / Eclampsia. The landmark MAGPIE trial showed that it halved the risk of eclampsia and probably reduced the risk of maternal death. There did not appear to be any substantive harmful effects to mother or baby in the short term [3]. It’s mechanism of action:
It acts as a membrane stabiliser
It has a rapid onset of action – maintained for 24 hours post delivery / fit
It does require Mg level monitoring only usually if the patient is oliguric
Side effects in toxicity:
Hyporeflexia presents in advance of more serious effects
Respiratory depression
Cardio-respiratory arrest
Drugs to avoid for hypertension
ACE-Inhibitors are contra-indicated in pregnancy. They are associated with:
Congenital malformations – especially CVS
Skull defects
Oligohydramnios + impaired fetal renal function
Thiazides diuretics – diuretic-associated harmful effects on maternal and fetal outcomes are controversial: their use is discouraged in pregnancy1.
neonatal thrombocytopaenia has been reported with bendromethafluazide
Tocolytic agents
Tocolytic agents are used to abolish unwanted uterine activity most commonly for preterm labour (PTL) but also for acute hyperstimualtion and external cephalic version.
Preterm labour (PTL)
There is little evidence of benefit to overall outcome for the fetus with blanket tocolysis for PTL and not using it is reasonable. Currently the two clinical uses are:
To achieve 24 hour steroid latency < 34 weeks
Where in-utero transfer is necessary for neonatal care
The following drugs have been and are used. The recent NICE guidelines [4] recommend nifedipine as first line if used reserving Atosiban if there is a contra-indication to nifedipine:
Nifedipine (unlicensed use) – it is at least comparable with the below agents and appears to have a better side effect profile
Atosiban (oxytocin antagonist) – has less side effects than most other tocolytics but the Cochrane review suggests no overall benefit.
Side effects: nausea, tachycardia, hypotension. Appears to cause no fetal/neonatal harm
Beta-sympathomimetics (salbutamol, ritodrine, terbutaline). These are historically the most used tocolytic agents, however their use is limited by significant side effects: tachycardia, hypotension, pulmonary oedema, hypokalaemia, hyperglycaemia. Current NICE guidelines advise avoiding using them
Mg SO4 – more commonly used in USA. This now recommended for neuroprotection from 24–30 weeks gestation and possibly 30–34 weeks.
GTN patches – no evidence of benefit over ritodrine, but side effects are relatively reduced.
Side effects: headache, rarely hypotension
NSAIDS have been used historically but are currently not recommended
External cephalic version
Terbutaline s/c prior to ECV has some evidence of increased procedural success in primigravidae and should only be used for this group. It is a one off dose so the only common side effect is usually a transient maternal tachycardia and tremor.
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