Non-Hormonal Therapy in obstetrics and gynaecology

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Chapter 27 Non-Hormonal Therapy in obstetrics and gynaecology


Kevin Hayes


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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Jan 29, 2017 | Posted by in GYNECOLOGY | Comments Off on Non-Hormonal Therapy in obstetrics and gynaecology

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