3. Drugs in Pregnancy Flashcards
These points should be kept in mind as regards the diagnosis of pregnancy?
Assume all women of reproductive age potentially pregnant since…
• At least 50% of pregnancies are unplanned.
• Not all pregnant women know they are pregnant.
Describe the transplacental passage of drugs?
By passive diffusion only
Rate of transfer depends on drug chemistry
In practice, virtually all drugs cross the placenta
The placenta acts like a filter, what is the range of drugs which can pass through?
Pores allow drugs of a certain molecular mass to pass through:
• < 600 Daltons if lipid, or partially lipid, soluble
• < 200 Daltons if water soluble
The extent to which a drug passes freely through the placenta is determined by what factors?
- Molecular weight
- Protein binding
- Lipid solubility
- Electric charge
- Duration maternal Rx
Give some examples of differing maternal drug levels?
Atenolol/Diazepam 100% Vancomycin 100% Nevirapine 60% Prednisolone 20% Macrolides 3% Heparin Minimal
What principle overarches the prescribing of drugs in pregnancy?
If you give a drug to an expectant mother, you give it to the fetus
How might drugs be beneficial to the fetus? Examples?
Give drugs to the fetus via the mother
• Dexa/Betamethasone (To accelerate lung maturity)
- Magnesium Sulphate (To protect against Cerebral Palsy in pre-term birth
- Anti-arrhythmics (To treat fetal heart rhythm disturbances)
- Antibiotics (To treat fetal infections)
Causing of a congenital abnormality by drugs?
Teratogenicity
What are the potential harmful effects of drugs on the fetus?
- Teratogenic = Cause a congenital abnormality.
- Unwanted therapeutic effect e.g. fetal anticoagulation with Warfarin
- Side effects e.g. Sulphomanides in late pregnancy
- Withdrawl effects e.g. Opiates, Benzodiazepines, Anti-psychotics
When are adverse drug affect most likely to harm the fetus?
Harm is most likely in early pregnancy
However defects may be gestation specific
Not all fetuses might be affected (20%), some may have genetic suseptibility.
In what percentage of congenital abnormalities is the cause/moa apparent?
<30%
25% are due to genetic/chromosomal factors
10 - 15% due to environmental factors, including drugs
How does the FDA categories drug risk in pregnancy?
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk
B: May be acceptable. Animal studies show no risk and human studies are not available or animal studies showed minor risks and the human studies that are available show no risk
C: Use with caution if benefits outweigh risks
Animal studies show risk/human studies not available or no human or animal studies done
D: Use in life-threatening emergencies when no safer drug is available. Positive evidence of human fetal risk.
X: Do not use in pregnancy, safer alternatives
What were the consequences of Diethylstilbestrol?
Found to be teratogenic to both female and male offspring
Mean age at diagnosis 18.9 years
Female offspring
• Adenosis/Clear Cell Ca of cervix/vagina
• Structural genital tract anomalies
Male offspring • Hypogonadism • Hypospadias • Epididymal cysts • Varicocoele • Meatal stenosis
What were the consequences of Thalidomide?
10,000 children in 46 countries were born with deformities such as phocomelia as a consequence of thalidomide use.
Which disease pose a greater risk to pregnancy than there potentially teratogenic treatments?
- Epilepsy
- Asthma
- Diabetes
- Chronic hypertension
- Cancer
- Most infections
What is correlation between anti-epileptic drugs and the risk of congenital malformation?
Risk increases with the number of medications One 3% Two 5% Three 10% Four 20%
What impact does pregnancy have on drug dosing?
Physiological changes in pregnancy may affect drug absorption, metabolism, binding, excretion and bio-availability.
Drug dosage usually the same as for the non-pregnant patient
In the case of some drugs, may need to measure blood levels
o Anti epileptic drugs
o Lithium
o Gentamycin
Which categories of vaccine should be given to pregnant women? Which should be avoided? Others?
Influenza Vaccine in Pregnancy is GOOD
• Influenza is 5 times more likely to cause severe illness in pregnant women compared to women who are not pregnant.
• All pregnant women advised to get vaccinated against influenza (TIV not LAIV)
BAD = Live-virus vaccines should be avoided in women who are, or are suspected to be, pregnant.
i.e. Measles, Mumps, Rubella, Varicella, BCG, Vaccinia, Zoster,
MAYBE =Vaccinations for cholera, hepatitis A and B, plague, polio, rabies, tetanus-diphtheria*, typhoid and yellow fever may be given during pregnancy if a substantial risk of infection exists.
Which anti-biotics should be avoided in pregnancy and why?
DONT USE
- Tetracyclines
Staining of teeth
Impaired bone growth - Aminoglycosides
Ototoxic - Cloramphenicol
‘Grey Syndrome’
DON’T USE NEAR TERM
- Nitrofurantoin
Haemolytic anemia - Sulphonamides
Neonatal jaundice
Name common drugs that are C/I while breast feeding?
o Iodides o Indomethacin o Lithium o Oestrogens o Pethidine o Doxepin
How can harmful fetal drug effects be predicted?
- Animal studies have a limited ability to predict adverse fetal effects in humans.
- Drug trials do not include pregnant women.
- Most studies have insufficient numbers to detect differences in the incidence of birth defects
- Many fetal effects are only discovered by post-marketing surveillance (yellow forms in Ireland)
How can the risk of Rx complications be mitigated in pregnancy?
1. Pre-conception counselling (about Rx) • Review medications • Simplify treatment • Discuss risk • Contraceptive advice
- Take no drugs (including OTC* self medication) in the 1st trimester.
Take home messages…
- Assume all female patients pregnant, or potentially so.
- Remember, if you give a drug to the mother, you give it to the fetus
- Do not prescribe drugs in the 1st trimester unless absolutely necessary
• Know where to get information regarding potential drug effects in pregnancy (don’t trust blurb, probably out of date)
o Pharmacy
o On-line
- Motherisk (Hospital for Sick Kids, Toronto)
- CDC
