Pharmacology in Pregnancy and Breast feeding

Question 1

Introduction

Answer 1

• Majority of women take medication during pregnancy
• Many pregnancies will be unplanned
• Must consider effect of pregnancy when prescribing to any women of childbearing age

Question 2

Why are medications used during pregnancies

Answer 2

• Hypertension
• Asthma
• Epilespy
• Mental health issue
• Migraines
• Long-term anticoagulant therapy

Question 3

Why is pharmacology during pregnancy so complex

Answer 3

• Very little pharmacokinetic studies of medicaitons during pregnancy
• Datae is limited

Question 4

Absorption changes during pregnancy

Answer 4

• Oral route
  
  • Morning sickness causing nausea/ vomitting
  • Decreased gastric emptying and gut motility (more likely to affect single dose medications)
• IM and SC route -> increased blood flow, increased absorption of medications
• Inhalation -> increased cardiac output and tidal volume, increased absoprtion of medications

Question 5

Distribution changes during pregnancy

Answer 5

• Increased volume of distribution due to:
  
  • Increased plasma volume
  • Increased fat composition
• Increased fraction of unbound drugs in plasma
  
  • Greater proportion of plasma to plasma protein
  • More dilution

Question 6

Metabolism changes in pregancy

Answer 6

• Oestrogen and progestrogen can alter P450 liver enzme
• Causes changes in metabolism
• E.g
  
  • Phenytoin levels reduced, metabolism increases
  • Theophylline levels increase, metabolism decreases

Question 7

Excretory changes

Answer 7

• Increased GFR by 50% during pregnancy
  
  • Increased excretion of medications
  • Reduced plasma concentration of medications
  • Therapeutic levels of medications require an increased dose

Question 8

Pharmacokinetics vs pharmacodynamics

Answer 8

• Pharmacokinetics (what the body does to the drug)
• Pharmacodynamics (what the drug does to the body)

Question 9

Pharmacodynamic changes in prgenancy

Answer 9

• Affects site of action and response of receptor to drug
  
  • Concentration of the drug
  • Presence of metabolites at site
  • Changes to the receptor
• Changes in efficacy
• Less understood and can have different adverse reactions

Question 10

Factors affecting drug tranfer across placenta

Answer 10

• Properties of the drug
• Rate of drug tranfer across placenta and amount reaching fetus
• Duration of exposure
• Distribution in fetal tissue
• Stage of placental and fetal development
• Combination effects of drugs

Question 11

Factors affecting placental transfer of medications

Answer 11

• Molecular weight og medicaitons
• Polarity
• Lipid solubility
• Placental metabolism of medication
• Assume all medications can cross placenta**​

Question 12

Distribution of medications in fetus

Answer 12

• Different circulatory system (umbilical vein -> liver)
• Less plasma protein to adults (more free drug available)
• Little fat (less lipid distribution of medications)
• More bloodflow to brain

Question 13

Metabolism of medications in fetus

Answer 13

• Different P450 enzyme to adults (isoenzyme)
• Reduce enzyme activity (increases with gestation)

Question 14

• Excretion of medicaitons in fetus

Answer 14

• Fetal excretion into amniotic fluid -> swallowed then recirculated
• Drugs/ metabolites accummulate in amniotic fluid
• Non-functioning placenta during delivery (causes

Question 15

Teratotoxicity vs fetotoxicity

Answer 15

• Teratotoxicity (fiest trimester)
• Fetotoxicity (second and third trinemester)

Question 16

Principles of prescribing when planning on conceiving

Answer 16

• Consider effects of any medication on women of childbearing age
• Warn them of the risk
• Optimise treatment of medical condiiton prior to planning to conceive
• Discuss contraception in those taking teratogenic medications
• Do not prescribe without contraception

Question 17

Principles of prescribing during pregnancy

Answer 17

• Try non-pharmacological treatment prior
• Medication with best safety record
• Use lowest effect dose
• Use for shortest time possible
• Avoid in first 10 weeks of pregnancy
• Consider stopping, redcuing dose before delivery
• Never undertreat disease (harmful to baby and mother)

Question 18

Highest risk period of teratotoxicity

Answer 18

• Organogensis (weeks 3-8)

Question 19

Mechanisms of teratotoxicity

Answer 19

• Folate antagonism
• Neural crest disruption
• Endocrine dysruption (sex hormones)
• Oxidative stress
• Vascular disruption
• Specific receptor dysruptions/ enzyme-mediated teratogenesis

Question 20

Folate antagonism

Answer 20

• Folate function: DNA formation and cell cycle
• Antagnistic drugs
  
  • Blocks folate -> THF conversion (methotrexate, trimethaprim)
  • Blocks other enzymes in folate pathway (phenytoin, carbamazepine, sodium valoproate)
• Effects: neural tube, oro-facial, limb defects

Question 21

Neural crest cell dysruption

Answer 21

• Drugs: retinoid drugs (isotretinoin)
• Effects
  
  • Aortic arch defects
  • Ventricular septal defect
  • Craniofascial malformations
  • Oesophageal atresia
  • Pharyngeal gland abnormalities
    *

Question 22

Enzyme-mediated teratogenesis

Answer 22

• Any drugs inhibiting/ stimulating enzymes to cause therapeutic effect
• E.g -> NSAIDS (orofacial clefts, cardiac septal defects)

Question 23

Consequences of fetotoxicity

Answer 23

• Growth retardation
• Structural malformations
• Fetal death
• Functional impairment
• Carcinogensis

ACEI/ARB (renal dysfunction and growth retardation)

Question 24

Effect of anticonvulsants during pregnancy

Answer 24

• Neural tuve defects
• Sodium valoproae, carbamazepine, phenytoin
  *

Question 25

Effects of anticoagulants during pregnancy

Answer 25

• Fetal haemorrhage
• Multiple CNS and skeletal maformations
• Warfarin, heparin, aspirin

Question 26

Antihypertensive agents

Answer 26

• Renal damage
• Restricted growth patterns
• ACEI/ARB

Question 27

Effect of NSAIDS on pregnancy

Answer 27

• Premature closure of ductus arteriosus

Question 28

Effects of retinoids on pregnancy

Answer 28

• Ear, CNS, cardiovascular and skeletal disorders

Question 29

Issues associated with drugs and lactation

Answer 29

• All drugs taken by mother present in breast milk
• Must minimise exposure of drug to neonate/ infant
• Monitor infant blood levels of drug
• Remember herbal mediations

Question 30

Drugs to avoid during breastfeeding

Answer 30

• Cytotoxins
• Immunosupressants
• Anticonvulsants
• Drugs of absue
• Amiodarone
• Lithium
• Radio-iodine

Question 31

Possible effects of medications during lactation

Answer 31

• Tetracycline -> permanent tooth decay
• Isoniazid -> pyroxidine deficiency
• Barbiturates -> lethargy, sedation, poor suckling
• Chloral hydrates -> drowsniness
• Diazepam -> drug accumulation and sedation
• Methadone -> withdrawal if breastfeeding stops
• Iodine -> thyroid suppression, risk of cancer
• Propylthiouracil -> thyroid function suppression

Question 32

Principles of prescribing in breast feeding

Answer 32

• Avoid unecessary use
• Safe if licenced in paediatric use
• Choose drug with exposure reducing pharmacokinetics (highly protein bound)