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Reproductive > 3. Drugs in Pregnancy > Flashcards

3. Drugs in Pregnancy Flashcards

1
Q

These points should be kept in mind as regards the diagnosis of pregnancy?

A

Assume all women of reproductive age potentially pregnant since…
• At least 50% of pregnancies are unplanned.
• Not all pregnant women know they are pregnant.

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2
Q

Describe the transplacental passage of drugs?

A

By passive diffusion only
Rate of transfer depends on drug chemistry
In practice, virtually all drugs cross the placenta

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3
Q

The placenta acts like a filter, what is the range of drugs which can pass through?

A

Pores allow drugs of a certain molecular mass to pass through:
• < 600 Daltons if lipid, or partially lipid, soluble
• < 200 Daltons if water soluble

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4
Q

The extent to which a drug passes freely through the placenta is determined by what factors?

A
  1. Molecular weight
  2. Protein binding
  3. Lipid solubility
  4. Electric charge
  5. Duration maternal Rx
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5
Q

Give some examples of differing maternal drug levels?

A 
Atenolol/Diazepam	100%
Vancomycin			100%
Nevirapine			60%
Prednisolone			20%
Macrolides			3%
Heparin				Minimal
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6
Q

What principle overarches the prescribing of drugs in pregnancy?

A

If you give a drug to an expectant mother, you give it to the fetus

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7
Q

How might drugs be beneficial to the fetus? Examples?

A

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)
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8
Q

Causing of a congenital abnormality by drugs?

A

Teratogenicity

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9
Q

What are the potential harmful effects of drugs on the fetus?

A
  • 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
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10
Q

When are adverse drug affect most likely to harm the fetus?

A

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.

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11
Q

In what percentage of congenital abnormalities is the cause/moa apparent?

A

<30%

25% are due to genetic/chromosomal factors
10 - 15% due to environmental factors, including drugs

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12
Q

How does the FDA categories drug risk in pregnancy?

A

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

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13
Q

What were the consequences of Diethylstilbestrol?

A

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
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14
Q

What were the consequences of Thalidomide?

A

10,000 children in 46 countries were born with deformities such as phocomelia as a consequence of thalidomide use.

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15
Q

Which disease pose a greater risk to pregnancy than there potentially teratogenic treatments?

A
  • Epilepsy
  • Asthma
  • Diabetes
  • Chronic hypertension
  • Cancer
  • Most infections
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16
Q

What is correlation between anti-epileptic drugs and the risk of congenital malformation?

A 
Risk increases with the number of medications
One 	3%
Two       5%
Three    10%
Four	20%
17
Q

What impact does pregnancy have on drug dosing?

A

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

18
Q

Which categories of vaccine should be given to pregnant women? Which should be avoided? Others?

A

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.

19
Q

Which anti-biotics should be avoided in pregnancy and why?

A

DONT USE

  1. Tetracyclines
    Staining of teeth
    Impaired bone growth
  2. Aminoglycosides
    Ototoxic
  3. Cloramphenicol
    ‘Grey Syndrome’

DON’T USE NEAR TERM

  1. Nitrofurantoin
    Haemolytic anemia
  2. Sulphonamides
    Neonatal jaundice
20
Q

Name common drugs that are C/I while breast feeding?

A 
o	Iodides
o	Indomethacin
o	Lithium
o	Oestrogens
o	Pethidine
o	Doxepin
21
Q

How can harmful fetal drug effects be predicted?

A
  • 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)
22
Q

How can the risk of Rx complications be mitigated in pregnancy?

A 
1. Pre-conception counselling (about Rx)
•	Review medications
•	Simplify treatment
•	Discuss risk
•	Contraceptive advice
  1. Take no drugs (including OTC* self medication) in the 1st trimester.
23
Q

Take home messages…

A
  • 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

Reproductive (6 decks)

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