Pharmacology in pregnancy and breastfeeding

Question 1

Pharmacokinetics

Answer 1

• Absorption:
o Oral route
♣ May be more difficult due to “morning sickness”
♣ Increase in gastric emptying and gut motility - unlikely to be a problem with regular dosing, but may affect single doses
o Intramuscular route
♣ Blood flow may be increased, so absorption may also increase using this route
o Inhalation
♣ Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs
• Distribution:
o Increase in plasma volume and fat will increase volume of distribution of drugs.
o Greater dilution of plasma will decrease relative amount of plasma proteins increased fraction of free drug
•

Excretion:
o GFR is increased in pregnancy by 50% leading to increased excretion of many drugs.
o This can necessitate an increase in dose of renally cleared drugs.
•

Question 2

Placental transfer

Answer 2

factors
size MW>1000 cannot cross
electric charge
non ionized drugs crossed easier
protein binding
High lipophilicity will increase placental transfer

Question 3

foetal pharmacokinetics

Answer 3

o Foetus has 50% less protein than mother Less protein binding & therefore more “free” drug
o Little fat, so distribution different
o Relatively more blood flow to brain

Question 4

teratogenicity

Answer 4

• Mechanisms:
o Folate Antagonism
♣ A key process in DNA formation and new cell production
♣ Two groups of drugs:
1. Block the conversion of folate to THF by binding irreversibly to the enzyme
(e.g. methotrexate, trimethoprim)
2. Block other enzymes in the pathway
(e.g. phenytoin, carbamazepine, valproate)
♣ Tend to result in neural tube, oro-facial or limb defects

o	Neural Crest Cell Disruption
♣	Retinoid drugs (e.g. isotretinoin)
♣	Problems: 
1.	1.	aortic arch anomalies 
2.	ventricular septal defects
3.	craniofacial malformations
4.	oesophageal atresia 
5.	pharyngeal gland abnormalities

o Endocrine Disruption: Sex Hormones
o Oxidative Stress
o Vascular Disruption
o Specific Receptor or enzyme-mediated teratogenesis
♣ Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes, damaging foetal development.
♣ E.g. NSAIDs causing orofacial clefts and cardiac septal defects

Question 5

fetotoxicity

Answer 5

o	Growth retardation
o	Structural malformations
o	Fetal death
o	Functional impairment
o	Carcinogenesis

o ACE inhibitors/ARBs renal dysfunction and growth retardation

Question 6

FDA classification

Answer 6

• A: Controlled human studies show no fetal risks; these drugsare the safest.
• B: Animal studies show no risk to the fetus but no controlled human studies have been
conducted, or animal studies show a risk to the fetus but well-controlled human studies don’t
• C: No adequate animal or human studies have been conducted, or adverse fetal effects have been
shown in animals but no human data are available
• D: Evidence of human fetal risk exists, but benefits may outweigh risks in certain situations (e.g.,
life-threatening disorders, serious disorders for which saferdrugscannot be used)
• X: Proven fetal risks outweigh any possible benefit.

Question 7

known teratogens

Answer 7

anticonvulsants
anticoagulants
antihypertensives
NSAIDS
alcohol
retinoids

Question 8

drugs breastfeeding

Answer 8

o	Cytotoxics
o	Immunosuppressants
o	Anti-convulsants (not all)
o	Drugs of abuse
o	Amiodarone
o	Lithium
o	Radio-iodine

Question 9

principles of prescribing in pregnancy

Answer 9

• If possible, try non-pharmacological treatment first
• Use the drug with the best safety record (avoid new drugs unless proven safe)
• Check the SPC for the most up to date information
• Use the lowest effective dose
• Use the drug for the shortest possible time, intermittently if possible
• Avoid the first 10 weeks of pregnancy if possible
• Consider stopping or reducing dose before delivery
Don’t under treat disease which may be harmful to the foetus