PPT Flashcards
When is the period of organogenesis in pregnancy?
Between 3-12 weeks
Important prescribing considerations during pregnancy and breastfeeding?
Changes to the mother’s physiology
Drugs passing through placenta to foetus
Drugs passing through breast milk to baby
Less available licensed medications
Minimal evidence base
Patient/healthcare professional anxiety surrounding prescribing in pregnancy
Dose alterations required in pregnanc
Physiological changes occurring in pregnancy: cardiovascular system
Increases in plasma volume, CO, stroke volume and HR
Decreases in serum albumin concentration and serum colloid osmotic pressure
Increases in coagulation factors and fibrinogen
Compression of IVC by uterus
Physiological changes occurring in pregnancy: kidneys
Increases in renal blood flow and GFR
Physiological changes occurring in pregnancy: liver
Changes in oxidative liver enzymes e.g. CYP450
Can alter oral bioavailability
E.g. CYP1A2 is responsible or caffeine metabolism and during pregnancy the activity is reduced which can cause caffeine plasma concentrations to double
Physiological changes occurring in pregnancy: lungs
Increases in tidal volume and minute ventilation
Physiological changes occurring in pregnancy: stomach and intestines
N+V more common
Delayed gastric emptying
Prolonged small bowel transit time
GI reflux
How can the physiological changes occurring in pregnancy affect the absorption of a drug?
Nausea and vomiting can affect the ability to administer medication
Delayed gastric emptying and prolonged transit time can extend the time it takes to reach peak concentration, decreases the maximum concentration of the drug and more absorb more of the drug than normal
How can the physiological changes occurring in pregnancy affect the distribution of a drug?
Increases in plasma volume increases the volume of distribution so higher drug doses are required
Reduction in plasma protein levels decreases protein binding which increases the free fraction of the drug
How can the physiological changes occurring in pregnancy affect the metabolism of a drug?
Altered liver enzymes e.g. CYP450 = increases, decreases or remains unchanged
This can alter the oral bioavailability
How can the physiological changes occurring in pregnancy affect the elimination of a drug?
Increased renal blood flow and GFR increases renal clearance so there are shorter half lives
E.g. clearance of lithium is doubled in the third trimester = sub-therapeutic drug concentrations
Background risk of birth defects?
2-3% of the general population will have a baby with a major malformation
Risk of birth defects in those who have epilepsy and take anti-epileptic drugs vs those who dont take anti-epileptic drugs?
Epilepsy and dont take AEDs = 3% will have a baby with a major malformation
Epilepsy and do take an AED = up to 10% will have a baby with a major malformation
What are the potential problems and risks of using medications during pregnancy?
Teratogneesis
Effects on growth and development even post-delivery
Effects on neonate during delivery
Passage of drug through breast milk
Long term effects on IQ or behavioural problems
Prescribing principles in pregnancy?
Pre-pregnancy counselling involving:
- Risks vs benefit discussion
- minimise drug use in first trimester
- smallest effective dose
- opt for well-known meds for which we have historical data
- mono therapy wherever possible
- consider non-drug options wherever possible
Carefully monitor meds and their effects
No drug is safe beyond all doubt: absence of evidence is not evidence of absence!!
Exposure to potential teratogens often precedes conception and first contact with a HCP so if exposure has already occurred it may not convey any added benefit to stop Tx
Which women are at higher risk of having a baby with neural tube defects and therefore should recieve 5mg of folic acid to 12 weeks gestation?
either partner has a NTD, they have had a previous pregnancy affected by a NTD, or they have a family history of a NTD
the woman is taking antiepileptic drugs or has coeliac disease, diabetes, SCD or thalassaemia trait.
the woman is obese (defined as a body mass index [BMI] of 30 kg/m2 or more).
Sources of information for the prescriber for prescribing in pregnancy?
National teratology advisory service
UKTIS
TOXBASE
BNF
NICE/RCOG guidelines
Local guidelines
Which anti-epileptics are options in pregnancy?
Lamotrigine, levetiracetam, carbamazepine - lower risk of malformations (2-5%)
Sodium valproate has a higher risk of malformation (up to 10%) and 40% of these children’s have developmental problems
What factors affect the rate of placental transfer of drugs?
Physical:
- placental SA
- placental thickness
- pH of maternal and foetal blood
- Placental metabolism
- uteroplacental blood flow
- presence of drug transporters
Pharmacological:
- molecular weight of drug (e.g. heparin is much larger than warfarin so can be used in pregnancy)
- lipid solubility
- protein binding
- concentration gradient
Which drugs can pass freely through the placenta?
Only drugs with a molecular weight of >1kDa
Risk of metoclopramide in women under 20?
Risk of acute dystonia
What is thalidomide? What did it cause?
An immunomodulator - initially marketed as a sedative as it was used to Tx pregnancy-related nausea
Found to cause phocomelia, + deformities of ears heart and kidneys
Mortality rate of 40%
Common teratogenic drugs
ACEi
Anti-thyroid drugs
BB
Lithium
Methotrexate
NSAIDs
Phenytoin
Retinoids
Sodium valproate
Tetracyclines
Thiazide diuretics
Warfarin
Effects of ACEi in pregnancy and when is effect greatest?
Renal abnormalities, PDA, oligohydramnios
2nd+3rd trimester
