B42 - drugs in pregnancy Flashcards
7 important prescribing considerations during pregnancy/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 pregnancy
What is the effect of pregnancy on inhaled medications?
More readily absorbed due to physiological changes
How do the physiological changes of pregnancy affect oral drug absorption?
Delayed gastric emptying and prolonged transit time alters drug bioavailability, with prolonged time to reach peak levels after oral administration and an overall decrease in maximum concentration achieved. Factors such as nausea and vomiting can also affect absorption.
How do the physiological changes of pregnancy affect drug distribution?
Maternal intravascular fluid volume begins to increase in the first trimester of pregnancy as a result of increased production of renin–angiotensin–aldosterone, which promotes sodium absorption and water retention.
Increased total body water/extracellular fluid increases the volume of distribution of water-soluble drugs. Lipid-soluble drugs are also affected due to increased fat compartment stores, with an increased volume of distribution.
What are the clinical implications of the changes to drug distribution in pregnancy?
Clinically, this could necessitate a higher initial and maintenance dose of drugs to obtain therapeutic plasma concentrations.
How do the physiological changes in pregnancy affect drug metabolism?
Cytochrome P450 is a family of liver enzymes and a major route of drug metabolism. Altered cytochrome P450 activity in pregnancy (unchanged/increased/decreased), alters oral bioavailability and hepatic elimination.
How do the physiological changes in pregnancy affect drug elimination?
Increased renal blood flow and glomerular filtration rate, increases renal clearance. The increase in renal clearance can have significant increase in the elimination rates of renally cleared medications leadings to shorter half-lives, requiring higher doses of medications. Important for drugs such as penicillin antibiotics, digoxin and lithium.
5 potential risks of medications during pregnancy
Teratogenesis Effects on growth and development Effects on the neonate during delivery Passage of drug through breast milk Long term effects on IQ or behavioural problems
7 prescribing principles to reduce the risks of medication during pregnancy
Pre-pregnancy counselling:
- Risk vs. benefits decision
- Minimise drug use in first trimester
- Small effective dose
- Opt for ‘well-known’ medications
- Monotherapy where possible
- Consider non-drug options
Carefully monitor medications and their effects
4 conditions where increased dose of folic acid indicated
Anti-epileptic medication
Diabetes
Family history of NTD
Sickle cell
6 sources of information about drugs in pregnancy for the prescriber
National Teratology Advisory Service UKTIS TOXBASE BNF NICE/RCOG guidelines Local guidelines
3 anti-epileptic drugs with lower risk of teratogenicity (2-5%)
Lamotrigine
Levetiracetam (Keppra)
Carbamazepine
What type of drugs can cross the placenta from maternal circulation to foetal?
lipid-soluble drugs
Three mechanisms of placental transfer:
Complete transfer with drugs rapidly crossing the placenta and equilibrating in maternal and fetal blood
Exceeding transfer with drugs crossing the placenta to reach greater concentrations in fetal compared with maternal blood
Incomplete transfer with drugs incompletely crossing the placenta resulting in higher concentrations in maternal compared with fetal blood
6 physical factors affecting placental transfer
Placental surface area Placental thickness pH of maternal/fetal blood Placental metabolism Uteroplacental blood flow Presence of drug transporters
4 pharmacological factors which affect placental transfer
Molecular weight of drug
Lipid solubility
Protein binding
Concentration gradient
What are the first-line ant-emetics in pregnancy which have safety and efficacy data
cyclizine
prochlorperazine
promethazine
chlorpromazine
Additional treatments which may be indicated alongside anti-emetics in pregnancy (4)
IV fluid rehydration with potassium supplementation
Pabrinex/Thiamine if prolonged vomiting
Severe cases:
Enteral/parenteral feeding
Termination of pregnancy as last resort
12 common drugs which are teratogenic
ACE inhibitors Anti-thyroid drugs (e.g. carbamazole) B-blockers Lithium Methotrexate NSAIDs Phenytoin Retinoids Sodium Valproate Tetracyclines Thiazines Warfarin
Teratogenic effects of ACE inhibitors
Renal abnormalities, patent ductus arteriosus (PDA), oligohydramnios
2nd/3rd trimester
Teratogenic effects of anti-thyroid medication
Neonatal hypothyroidism
after w10
Teratogenic effects of B-blockers
IUGR, neonatal hypoglycaemia and bradycardya
throughout pregnancy
Teratogenic effects of Lithium
Cardiac defects (Ebsteins anomaly)
1st trimester
teratogenic effects of methotrexate (4)
Medical termination
craniofacial defects
ear/kidney/lung defects
cardiac abnormalities
