Pharmacology in Pregnancy and Breast Feeding

Question 1

Absorption changes in pregnancy

Answer 1

Oral route
- morning sickness
- increase in gastric emptying and gut motility
IM route
- blood flow increased so absorption may increase also
Inhalation
- CO increased and TV decreases which may cause increased absorption of inhaled drugs

Question 2

Distribution changes in pregnancy

Answer 2

Increased plasma volume and fat will change distribution of drugs and increase vD
Greater distribution of plasma will decrease the relative amount of plasma proteins and increase the fraction of free drug

Question 3

Metabolism changes in pregnancy

Answer 3

Oestrogens and progesterones can induce or inhibit P450 enzymes, increase or decrease metabolism

Question 4

Excretion changes in pregnancy

Answer 4

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

Question 5

Pharmacodynamic changes in pregnancy

Answer 5

May affect site of action and receptor response to drugs
Efficacy may be different
Adverse effects may be different

Question 6

Functions of the placenta

Answer 6

Attach foetus to uterine wall
Provide nutrients to foetus
Allows foetus to transfer waste products to mothers blood

Question 7

What materials are exchanged from foetus to the mother?

Answer 7

Carbon dioxide
urea
other waste products

Question 8

What materials are exchanged from mother to foetus?

Answer 8

Oxygen
glucose
amino acids
lipids, fatty acids and glycerol 
Vitamins
Ions; Na, Cl, Ca, Fe
Alcohol, nicotine and drugs
Viruses 
Antibodies

Question 9

Placental transfer depends on

Answer 9

Molecular weight (smaller sizes will cross more easily)
Polarity (non-polar cross more easily)
Lipid solubility (lipid soluble drugs will cross)

Question 10

Foetal distribution features

Answer 10

Circulation different (e.g. umbilical vein to liver)
Less protein binding than adults so more free drug available
Little fat so distribution is different
Relatively more blood flow to the brain

Question 11

Metabolism of the foetus features

Answer 11

Less enzyme activity, though increases with gestation

Different izoenzymes to adults

Question 12

Foetal excretion features

Answer 12

Excretion is in amniotic fluid - this can be swallowed and allow recirculation
Drugs and metabolites can accumulate in amniotic fluid
Placenta not functioning at delivery so can be issues with excretory function

Question 13

Which trimester does teratogenicity affect?

Answer 13

First trimester

Question 14

Which trimester does fetotoxicity affect?

Answer 14

Second and third trimester

Question 15

What time is the biggest risk of teratogenicity?

Answer 15

During organogenesis (weeks 3-8)

Question 16

Mechanisms of teratogenicity

Answer 16

Folate antagonism 
neural crest cell disruption 
endocrine disruption; sex hormones
oxidative stress
vascular disruption 
specific receptor or enzyme mediated teratogenesis

Question 17

Folate antagonism drugs

Answer 17

Methotrexate 
Trimethoprim 
Phenytoin 
Carbamazepine 
Valproate

Question 18

Folate antagonism drugs tend to result in

Answer 18

Neural tube defects
Oro-facial defects
Limb defects

Question 19

Neural crest cell disruption is caused by

Answer 19

Retinoid drugs (e.g. isotretinoin)

Question 20

Drugs causing neural crest cell disruption result in….

Answer 20

Aortic arch anomalies
Ventricular septal defects
Craniofacial malformations
Oesophageal atresia
Pharyngeal gland abnormalities

Question 21

Enzyme mediated teratogenesis is caused by

Answer 21

NSAIDs

Question 22

Enzyme mediated teratogenesis results in…

Answer 22

Orofacial clefts

Cardiac septal defects

Question 23

Possible issues caused by fetotoxicity

Answer 23

Growth retardation 
Structural malformations
Foetal death 
Functional impairment 
Carcinogenesis

Question 24

ACEIs and ARBs result in

Answer 24

Renal dysfunction

Growth retardation

Question 25

Drugs to avoid in breast feeding

Answer 25

cytotoxics 
immunosuppressants 
anti-convulsants (not all)
drugs of abuse 
amiodarone 
lithium 
radioiodine

Question 26

Principles of prescribing in breast feeding

Answer 26

Avoid unnecessary drug use
Check on up to date drug info
If licensed and safe in paediatric use (esp < 2 years) a drug is likely to be safe in breast feeding
Choose drugs with pharmacokinetic properties that reduce infant exposure (e.g. highly protein bound)

Question 27

Which cancers is the COCP protective against?

Answer 27

Ovarian

Endometrial

Question 28

Which cancers does the COCP increase the risk of?

Answer 28

Breast

Cervical