Pharmacology in Pregnancy and Breast Feeding

Question 1

What absorption changes may occur in pregnancy?

Answer 1

• Oral route: increased nausea/vomiting and an increase in gastric emptying and gut motility
• IM: increased blood flow
• Inhalation: increased cardiac output and decreased tidal volume (increased absorption)

Question 2

What distribution changes may occur during pregnancy?

Answer 2

• Increase in plasma volume and fat changes distribution

- Greater dilution of plasma will decrease the relative amount of plasma proteins

Question 3

What metabolic changes can occur during pregnancy?

Answer 3

-Oestrogen and progestogens can induce or inhibit P450 enzymes, increasing or reducing metabolism

Question 4

What changes happen to the excretion of drugs during pregnancy?

Answer 4

• GFR is increased by 50% leading to increased excretion of many drugs
• Reduces plasma conc. and can necessitate an increase in dose of renally cleared drugs

Question 5

What pharmacodynamic changes may happen during pregnancy?

Answer 5

• Pregnancy may affect the site of action and receptor response to drugs
• Efficacy may be different
• Adverse effects may be different

Question 6

What are the functions of the placenta?

Answer 6

Attaches the fetus to the uterine wall, provides nutrients to the fetus and allow the fetus to transfer waste products to the mother’s blood

Question 7

Which materials are exchanged across the placenta from mother to fetus?

Answer 7

Oxygen, glucose, amino acids, lipids, FAs, glycerol, vitamins, ions, alcohol, nicotine, drugs, viruses and antibodies

Question 8

Which materials are exchanged across the placenta from fetus to mother?

Answer 8

Carbon dioxide, urea and other waste products

Question 9

What factors determine whether drugs will transfer across the placenter?

Answer 9

Molecular weight (smaller crosses easier), polarity (non-polar is easier) and lipid solubility (lipid soluble will cross)

Question 10

What is different about drug distribution in a fetus?

Answer 10

• Circulation different
• Less protein binding than in adults (more free drug available)
• Little fat so distribution is different
• More blood flow to the brain

Question 11

What is different about drug metabolism in a fetus?

Answer 11

• Less enzyme activity (increases with gestation)

- Different isoenzymes than adults

Question 12

What is different about drug excretion in a fetus?

Answer 12

• NB excretion into amniotic fluid
• Drugs and metabolites can accumulate in amniotic fluid
• Placenta not functioning at delivery so can be issues with excretory function

Question 13

What are the two concerns with regard to the safety of drugs in pregnancy?

Answer 13

Teratogenicity (1st trimester)

Fetotoxicity (2nd and 3rd trimester)

Question 14

What are the mechanisms in which drugs can be teratogenic?

Answer 14

Folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption and specific receptor/ enzyme mediated teratogenesis

Question 15

Which drugs can cause folate antagonism and what is the consequence?

Answer 15

• Methotrexate, trimethropin, phenytoin, carbamazepine and valproate
• Neural tube, oro-facial and limb defects

Question 16

Which drugs can cause neural crest cell disruption and what is the consequence?

Answer 16

• Retinoid drugs
• Aortic arch anomalies, ventricular septal defects, craniofacial malformations, oesophageal atresia and pharyngeal gland abnormalities

Question 17

Which drugs cause enzyme mediated teratogenesis and what are the consequences?

Answer 17

• NSAIDs

- Orofacial clefts and cardiac septal defects

Question 18

What are the possible issues of fetotoxicity?

Answer 18

Growth retardation, structural malformations, fetal death, functional impairment and carcinogenesis

Question 19

What effect can ACE inhibitors or ARBs have on the fetus?

Answer 19

Renal dysfunction and growth retardation

Question 20

Which drugs are to be avoided in breast feeding?

Answer 20

Cytotoxics, immunosuppressants, anti-convulsants (not all), drugs of abuse, amiodarone, lithium and radio-iodine

Question 21

What are the main principles of prescribing for women of child-bearing age?

Answer 21

• Always consider possibility of pregnancy
• Warn of possible risks
• Advise to attend before getting pregnant
• Discuss contraception (if necessary do not prescribe without contraception)

Question 22

What are the main principles of prescribing in pregnancy?

Answer 22

• Try non-pharmacological management first if possible
• Use drugs with best safety record (avoid new drugs unless proven safe)
• Check SPC for most up to date info
• Use lowest effective dose
• Use for shortest possible time
• Avoid first ten weeks if possible
• Consider stopping or reducing dose before delivery
• Don’t under treat the disease (may be harmful to the fetus)

Question 23

What are the principles of prescribing in breast feeding?

Answer 23

• Avoid uneccessary drug use
• Check up to date info
• If licensed and safe in paediatrics it is likely to be safe in breast feeding
• Choose drugs with pharmacokinetic properties that reduce infant exposure