Antenatal Care: Medications in Pregnancy Flashcards
Mechanism of NSAIDs?
1) Inhibits synthesis of prostaglandin from arachidonic acid by inhibiting cyclo-oxygenase (COX)
2) COX-1 –> stimulates prostaglandin synthesis that is essential to preserve integrity of gastric mucosa, maintains renal perfusion & inhibits thrombus formation at vascular endothelium (i.e. inhibition of COX-1 increases risk of bleeding, can cause AKI, and increases risk of peptic ulcers).
3) o COX-2 –> expressed in response to inflammatory stimuli and stimulates production of prostaglandins that cause inflammation and pain (i.e. inhibition of COX-2 reduces pain and inflammation)
The therapeutic benefits of NSAIDs are principally mediated by COX-2 inhibition and adverse effects by COX-1 inhibition
Side effects of NSAIDs?
- GI toxicity e.g. peptic ulcer disease, GI bleeding
- Renal impairment
- Increased risk of CVS events e.g. MI, stroke
Contraindications of NSAIDs?
- Severe renal impairment
- Heart failure
- Liver failure
- NSAID hypersensitivity
- Peptic ulcer disease
- GI bleeding
What drugs can increase the risk of peptic ulceration when given alongside NSAIDs?
1) corticosteroids
2) aspirin
What drugs can increase the risk of GI bleeding when given alongside NSAIDs?
1) Anticoagulants e.g. warfarin, DOACs
2) SSRIs
3) Venlafaxine
What drugs can increase the risk of renal impairment when given alongside NSAIDs?
1) ACEi
2) Diuretics
How do NSAIDs impact other antihypertensives ?
NSAIDs reduce therapeutic effects of other antihypertensives
In pregnancy, what are prostaglandins important for?
1) Maintain the ductus arteriosus in the fetus and neonate
2) Soften the cervix and stimulate uterine contractions at the time of delivery.
Are NSAIDs safe in pregnancy?
NSAIDs are generally avoided in pregnancy unless really necessary (e.g. in rheumatoid arthritis).
In what trimester are NSAIDs particularly avoided? Why?
3rd trimester:
1) can cause premature closure of the ductus arteriosus in the fetus.
2) can also delay labour
What is the most frequently used beta-blocker in pregnancy?
Labetalol
1st line management of HTN caused by pre-eclampsia?
Labetalol
3 adverse effects of beta blockers in pregnancy?
1) Fetal growth restriction
2) Hypoglycaemia in the neonate
3) Bradycardia in the neonate
How can medications that block the renin-angiotensin system (ACE inhibitors and ARBs) affect pregnancy?
Can cross the placenta and enter the fetus.
1) In the fetus, they mainly affect the kidneys, and reduce the production of urine (and therefore amniotic fluid).
2) The other notable effect is hypocalvaria, which is an incomplete formation of the skull bones.
2 main adverse effects of ACEi and ARBs in pregnancy?
1) affect kidneys of foetus and reduce production of urine (and theremore amniotic fluid)
2) hypocalvaria
What is hypocalvaria?
An incomplete formation of the skull bones.
What adverse effects can ACEi and ARBs cause when used in pregnancy?
1) Oligohydramnios (reduced amniotic fluid)
2) Miscarriage or fetal death
3) Hypocalvaria (incomplete formation of the skull bones)
4) Renal failure in the neonate
5) Hypotension in the neonate
Adverse effects of use of opioids during pregnancy?
Withdrawal symptoms in the neonate after birth –> neonatal abstinence syndrome (NAS).
How does neonatal abstinence syndrome (NAS) present?
NAS presents between 3 – 72 hours after birth with:
a) irritability
b) tachypnoea
c) high temperatures
d) poor feeding.
Is warfarin safe during pregnancy?
No - teratogenic
Adverse effects of using warfarin in pregnancy?
1) foetal loss
2) congenital malformations, particularly craniofacial problems
3) bleeding during pregnancy, postpartum haemorrhage, fetal haemorrhage and intracranial bleeding
Adverse effects of sodium valproate in pregnancy?
neural tube defects and developmental delay.
Rules around sodium valproate in women?
There are strict rules for AVOIDING sodium valproate in girls or women unless there are no suitable alternatives and strict criteria are met to ensure they do not get pregnant. There is a specific program called Prevent (valproate pregnancy prevention programme) to ensure this happens.
Adverse effects of lithium in pregnancy?
Risks and benefits carefully weighed up by psychiatrist.
1st trimester –> linked with congenital cardiac abnormalities e.g. Ebstein’s anomaly
What is Ebstein’s anomaly?
where the tricuspid valve is set lower on the right side of the heart (towards the apex), causing a bigger right atrium and a smaller right ventricle.
Can lithium be used in breastfeeding?
No - enters breast milk and is toxic to the infant, so should be avoided in breastfeeding.
What are the most common antidepressants used in pregnancy?
SSRIs
There are potential adverse effects of SSRIs in pregnancy.
The risks and benefits are weighed up.
What are some potential risks of SSRIs in pregnancy?
1st trimester:
- link with congenital heart defects
- paroxetine has a stronger link with congenital malformations in 1st trimester
3rd trimester: risk of persistent pulmonary hypertension in the neonate
Neonates can experience withdrawal symptoms, usually only mild and not requiring medical management
What are risks of SSRIs in the 1st trimester?
Congenital heart defects (paroxetine has strongest link)
What SSRI has strongest link of congenital malformations?
Paroxetine
What are risks of SSRIs in the 3rd trimester?
persistent pulmonary hypertension in the neonate
What is Isotretinoin?
Isotretinoin is a retinoid medication (relating to vitamin A) that is used to treat severe acne.
Also known as roaccutane.
Can isotretinoin be used in pregnancy?
Isotretinoin is highly teratogenic, causing miscarriage and congenital defects.
Need to use very reliable contraception before, during and for one month after taking isotretinoin.
name as many drugs as you can that may harm a developing fetus
- ACEi/ARBs
- Alcohol
- Aminoglycosides
- Carbamazepine
- Chloramphenicol
- Cocaine
- Diethylstilbesterol
- Lithium
- Smoking
- Tetracyclines
- Thalidomide
- Valproate
- Warfarin
What are 2 possible effects of ACEi during pregnancy?
1) Renal dysgenesis
2) Craniofacial abnormalities
Impact of alcohol during pregnancy?
- Craniofacial abnormalities
- Fetal alcohol syndrome
Impact of aminoglycosides during pregnancy?
Aminoglycoside Abx cross the placenta –> can cause ototoxicity e.g. irreversible bilateral congenital deafness.
What is an adverse effect of taking chloramphenicol in pregnancy?
‘Grey baby’ syndrome
What is chloramphenicol used for?
For treatment of superficial eye infections such as bacterial conjunctivitis, and otitis externa.
What is grey baby syndrome?
An adverse reaction to chloramphenicol that is characterised by abdominal distention, hemodynamic collapse, and ashen-grey skin discoloration in neonates.
Give 2 effects of cocaine use during pregnancy
1) Intrauterine growth retardation
2) Preterm labour
What is Diethylstilbesterol?
A synthetic form of oestrogen prescribed to pregnant women between 1940 and 1971 to prevent miscarriage, premature labor, and related complications of pregnancy.
Banned as strong association with vaginal clear cell adenocarcinoma.
What impact can lithium have during pregnancy?
Ebstein’s anomaly (atrialised right ventricle)
What are some impacts of maternal diabetes mellitus?
- Macrosomia
- Neural tube defects
- Polyhydramnios
- Preterm labour
- Caudal regression syndrome
What are 2 effects of smoking during pregnancy?
1) preterm labour
2) intrauterine growth retardation
What is the impact of tetracyclines in pregnancy?
Discoloured teeth
What is the impact of thalidomide in pregnancy?
Limb reduction defects
What are 2 impacts of sodium valproate in pregnancy?
1) Neural tube defects
2) Craniofacial abnormalities
What is an impact of warfarin during pregnancy?
- Stillbirth
- Prematurity
- Haemorrhage
- Ocular defects
- Foetal warfarin syndrome: nasal hypoplasia, hypoplasia of the extremities, and developmental delay.
When is organ formation completed during development?
12 weeks (end of 1st trimester)
Which anticoagulants are safe in pregnancy?
UH & LMWH
Clotbusters e.g. alteplase can be given in life-threatening situations.
What is the only exception for use of warfarin in pregnancy?
In women with mechanical prosthetic heart valves who have a high risk of valve thromboses.
Warfarin is used in SOME of these women between 12-36 weeks.
What is the main cause of haemorrhage in pregnancy?
Uterine atony
What is Syntocinon?
Synthetic version of oxytocin
Indications for syntocinon?
1) active management of 3rd stage of labour
2) induce labour
Role of syntocinon in 3rd stage of labour?
Stimulates the contraction of the uterus (uterotonic), reducing risk of PPH.
What is Ergometrine?
An ergot alkaloid
Indication for ergometrine?
used as an alternative to oxytocin in the active management of third stage of labour.
Role of ergometrine in 3rd stage of labour?
By constricting vascular smooth muscle of the uterus it can decrease blood loss.
Mechanism - stimulates alpha-adrenergic, dopaminergic and serotonergic receptors
What is a key adverse effect of ergometrine?
Coronary artery spasm
What is misoprostol?
Prostaglandin (E1) analogue
Indication for misoprostol?
1) Termination of pregnancy (TOP) following mifepristone
2) Miscarriage management
3) Induction of labour (cervical softener)
What 2 medications are used in the TOP?
Misoprostol & mifepristone
Mifepristone (an anti-progestogen) followed 48 hours later by prostaglandins (e.g. misoprostol) to stimulate uterine contractions.
What is mifepristone?
An anti-progestogen
Mechanism of Mifepristone?
competitive progesterone receptor antagonist
When is ergometrine NOT used?
HTN
What is a key adverse effect of mifepristone?
Menorrhagia
What can be used for the medical management of ectopic pregnancies?
Methotrexate
What class of drug is tranexamic acid?
Antifibrinolytic (indicated for menorrhagia without pain)
What class of drug is mefenamic acid?
NSAID (menorrhagia + pain)
Is paracetamol safe during pregnancy?
Yes
Can opioids be used during pregnancy?
Relatively safe
Can cross placenta and cause neonatal respiratory depression
What is entonox?
Gas and air - 50% nitrous oxide and 50% oxygen
Are NSAIDs safe in pregnancy?
Typically avoided
1st trimester: miscarriage and malformation
3rd trimester: premature closure of the ductus arteriosus
Abx management of UTIs in pregnancy?
-Trimethoprim (anti folate drug) DO NOT use in 1st trimester (teratogenic)
-Nitrofurantoin DO NOT USE in 3rd trimester (neonatal haemolysis)
- Cephalosporins and penicillins safe but avoid co-amoxiclav in pregnancy due to risk of necrotising enterocolitis (NEC) in baby.
What can co-amoxiclav in pregnancy cause?
Risk of necrotising enterocolitis (NEC)
Abx management of RTIs in pregnancy?
Penicillins and Macrolides are safe.
What Abx is given in Preterm Prelabour Rupture of Membranes (PPROM)? Why?
Erythromycin 250mg qds to prevent chorioamnionitis
Abx management of chorioamnionitis?
Cefuroxime + metronidazole
Abx management of endometritis?
Co-amoxiclav
or Clindamycin + Metronidazole (if penicillin allergic)
What is endometritis?
Infection of uterus AFTER pregnancy
2 key antihypertensives used in pregnancy?
1) Labetalol (beta blocker)
2) Nifedipine (CCB)
Contraindication of labetalol?
Asthma
What antihypertensive is indicated in pregnant African / Caribbean patients?
Nifedipine
What 2 key antihypertensives are contraindicated in pregnancy?
ACEi & ARBs
1st line anticonvulsant in eclampsia?
IV magnesium sulphate
What are 2 antiepileptics indicated in pregnancy?
Lamotrigine & leviteracetam
What folic acid dose is indicated in epilpetic pregnant women?
Remember high dose 5mg folic acid for epileptic women (neural tube defect reduction)
