Drugs in Pregnancy
Drugs in pregnancy: what do we need to think about?
- Changes in maternal pharmacokinetics
- Placental transfer and teratogenicity
- Pre-existing medical conditions
- Pregnancy-associated medical conditions
- Prescribing in pregnancy
Maternal Pharmacokinetics
- pharmacokinetics is about what the body does to the drug
- Absorption
- Distribution
- Metabolism
- Excretion
Changes in maternal pharmacokinetics: Absorption when pregnant
- Absorption – when pregnant
- decreased intestinal motility
o → Increased transit time, results in increased absorption of drugs
- decreased gastric emptying
o → Results in delayed absorption
- Emesis (morning sickness)
o → Results in decreased absorption
- increased cardiac output and increased tidal volume
o → Results in increased absorption of inhaled drugs
Changes in Maternal Pharmacokinetics: Distribution when pregnant
- Distribution – when pregnant
- Increased total body fat → adipose tissues acts as a storage of fat-soluble drugs
o This will increase half life and volume of distribution
- Increased plasma volume; by 45% at 32 weeks
- Decreased concentration of plasma proteins (e.g. albumin)
- Increased Vd of certain drugs
- BUT some drug-binding proteins may be dramatically INCREASED – e.g. thyroid and cortisol-
binding globulins
Changes in Maternal Pharmacokinetics: Metabolism when pregnant
- Metabolism – when pregnant
- Changes in drug metabolising enzyme activity
- Can or
- Changes in metabolism driven by elevated female hormones
, Changes in Maternal Pharmacokinetics: Excretion when pregnant
- Excretion – when pregnant
- 50% increase in glomerular filtration rate by mid-term
o Caused by increase in plasma volume
- Increased excretion of renally excreted drugs
- Can potentially have a drug that has an increased metabolism – but would be more readily
excreted due to increased glomerular filtration rate (GFR)
- May need to increase dose to achieve same effect
Placental Transfer
- Drugs given to treat the mother almost always cross the placenta and enter fetal circulation
- Placental transfer influenced by physicochemical properties of the drug
- Effects on fetus depends on many factors and changes throughout the pregnancy
- Most drugs can cross placenta
- Rate of diffusion depends on:
o Molecular weight
o Lipid solubility
o Degree of ionisation
o Extent of plasma protein binding
- BUT most drugs will achieve equal concentrations in maternal and fetal circulation
eventually
- EXCEPT large molecules such as heparin
Teratogenicity
- A teratogen is an agent that, when given to a pregnant woman, causes or contributes to
structural malformation, abnormal physiological function or abnormal mental development
of the fetus (or in the child, after birth)
- Malformations – usually happen when exposure to teratogen in early pregnancy (embryonic
development), e.g. thalidomide
Thalidomide
- Probably the most notorious human teratogen
- Originally marketed as a sedative in 1950s
- Prescribed for morning sickness (which is usually worst in the first trimester)
- Withdrawn in 1962
- 20% of pregnant women who took thalidomide gave birth to babies with abnormalities
- Associated with ~12,000 birth defects
- Mostly phocomelia
- Other abnormalities included:
o Gut atresia
o Cardiac defects
o Renal agenesis
o Deformed external ear
- Different birth defects associated with different time periods. Thalidomide taken on:
o Day 35-37 → absence of ears & deafness
o Day 39-41 → absence of arms
o Day 43 -44 → phocomelia
Drugs in pregnancy: what do we need to think about?
- Changes in maternal pharmacokinetics
- Placental transfer and teratogenicity
- Pre-existing medical conditions
- Pregnancy-associated medical conditions
- Prescribing in pregnancy
Maternal Pharmacokinetics
- pharmacokinetics is about what the body does to the drug
- Absorption
- Distribution
- Metabolism
- Excretion
Changes in maternal pharmacokinetics: Absorption when pregnant
- Absorption – when pregnant
- decreased intestinal motility
o → Increased transit time, results in increased absorption of drugs
- decreased gastric emptying
o → Results in delayed absorption
- Emesis (morning sickness)
o → Results in decreased absorption
- increased cardiac output and increased tidal volume
o → Results in increased absorption of inhaled drugs
Changes in Maternal Pharmacokinetics: Distribution when pregnant
- Distribution – when pregnant
- Increased total body fat → adipose tissues acts as a storage of fat-soluble drugs
o This will increase half life and volume of distribution
- Increased plasma volume; by 45% at 32 weeks
- Decreased concentration of plasma proteins (e.g. albumin)
- Increased Vd of certain drugs
- BUT some drug-binding proteins may be dramatically INCREASED – e.g. thyroid and cortisol-
binding globulins
Changes in Maternal Pharmacokinetics: Metabolism when pregnant
- Metabolism – when pregnant
- Changes in drug metabolising enzyme activity
- Can or
- Changes in metabolism driven by elevated female hormones
, Changes in Maternal Pharmacokinetics: Excretion when pregnant
- Excretion – when pregnant
- 50% increase in glomerular filtration rate by mid-term
o Caused by increase in plasma volume
- Increased excretion of renally excreted drugs
- Can potentially have a drug that has an increased metabolism – but would be more readily
excreted due to increased glomerular filtration rate (GFR)
- May need to increase dose to achieve same effect
Placental Transfer
- Drugs given to treat the mother almost always cross the placenta and enter fetal circulation
- Placental transfer influenced by physicochemical properties of the drug
- Effects on fetus depends on many factors and changes throughout the pregnancy
- Most drugs can cross placenta
- Rate of diffusion depends on:
o Molecular weight
o Lipid solubility
o Degree of ionisation
o Extent of plasma protein binding
- BUT most drugs will achieve equal concentrations in maternal and fetal circulation
eventually
- EXCEPT large molecules such as heparin
Teratogenicity
- A teratogen is an agent that, when given to a pregnant woman, causes or contributes to
structural malformation, abnormal physiological function or abnormal mental development
of the fetus (or in the child, after birth)
- Malformations – usually happen when exposure to teratogen in early pregnancy (embryonic
development), e.g. thalidomide
Thalidomide
- Probably the most notorious human teratogen
- Originally marketed as a sedative in 1950s
- Prescribed for morning sickness (which is usually worst in the first trimester)
- Withdrawn in 1962
- 20% of pregnant women who took thalidomide gave birth to babies with abnormalities
- Associated with ~12,000 birth defects
- Mostly phocomelia
- Other abnormalities included:
o Gut atresia
o Cardiac defects
o Renal agenesis
o Deformed external ear
- Different birth defects associated with different time periods. Thalidomide taken on:
o Day 35-37 → absence of ears & deafness
o Day 39-41 → absence of arms
o Day 43 -44 → phocomelia
