Foetal dev

Question 1

Core concept of prescribing in pregnancy

Answer 1

• Drug given to mother can reach foetus or breastfed infant
• Must consider two pharmacology systems: mother + baby
• Pregnancy alters physiology, pharmacokinetics and pharmacodynamics

Question 2

Key hormonal changes in pregnancy

Answer 2

• Prolactin ↑ (lactation preparation)
• Oxytocin ↑ near delivery (labour + milk let-down)
• Placental GH → insulin resistance → more glucose to foetus
• Cortisol ↑ (2–3×): lipolysis, insulin resistance, immune adaptation
• Aldosterone ↑: Na⁺/water retention → blood volume expansion

Question 3

Thyroid changes & relevance

Answer 3

• Oestrogen ↑ → TBG ↑ → total T3/T4 ↑
• hCG suppresses TSH early pregnancy
• Maternal thyroid hormones crucial for early foetal brain development

Question 4

GI & protein binding changes

Answer 4

• Gastric pH ↑, gastric emptying ↓, intestinal transit ↓
• Weak bases absorbed less; weak acids more
• Albumin ↓ → more free (active) drug
• Higher toxicity risk for narrow therapeutic index drugs

Question 5

Body composition & nutrition

Answer 5

• Total body water ↑ ~6 L; plasma volume ↑ 40–50%; fat ↑ ~4 kg
• Hydrophilic drugs diluted; lipophilic stored in fat
• Iron for maternal RBCs & foetal Hb
• Folic acid for DNA & neural tube (prevents spina bifida)
• Vitamin K for clotting

Question 6

Cardiopulmonary changes

Answer 6

• Renal blood flow ↑, sodium/water retention ↑
• Tidal volume ↑; CO₂ sensitivity ↑ → better O₂ delivery to foetus
• Lung absorption of inhaled drugs ↑

Question 7

Placental drug transfer factors

Answer 7

• Mainly passive diffusion
• <500 Da crosses easily
• Only free drug crosses (protein binding limits transfer)
• Lipophilic drugs cross easier

Question 8

Ion trapping & transporters

Answer 8

• Foetal blood more acidic → basic drugs ionised and trapped in foetus
• Acidic drugs remain ionised in mother
• Active transporters: P-gp, MRP families

Question 9

Maternal pharmacokinetics — absorption & distribution

Answer 9

• Nausea/vomiting affects adherence
• ↑ skin, nasal, vaginal & lung absorption
• ↑ Vd hydrophilic & lipophilic drugs due to water & fat expansion

Question 10

Protein binding & metabolism

Answer 10

• Albumin ↓ ~10 g/L → ↑ free drug
• Free fatty acids compete for binding near term
• Increased metabolism: methadone, metoprolol, sotalol
• No major change: labetalol, atenolol
• Decreased metabolism: caffeine, theophylline

Question 11

Renal elimination

Answer 11

• Renal blood flow ↑ ~100%
• GFR ↑ ~170 mL/min → faster clearance of renally excreted drugs
• Pre‑eclampsia → ↓ clearance → ↑ toxicity

Question 12

Teratogenicity timing

Answer 12

• 0–2 weeks: miscarriage or none
• 3–8 weeks: major malformations
• > 8 weeks: growth & functional defects

Question 13

General prescribing rules

Answer 13

• Avoid drugs if possible, especially 1st trimester
• Lowest effective dose, shortest duration
• Avoid polypharmacy
• Prefer drugs with known safety
• Check BNF/SPC/Toxbase

Question 14

Epilepsy drugs in pregnancy

Answer 14

• Seizures harm foetus but AEDs may be teratogenic
• Phenytoin: malformations + neurodevelopmental issues
• Valproate: ~11% birth defects (spina bifida, facial, limb, cardiac, renal) + 30–40% developmental delay → contraindicated unless PPP
• Carbamazepine: malformations
• Lamotrigine: relatively safer

Question 15

Antibiotics safety

Answer 15

• Safe: penicillins, cephalosporins
• Avoid unless severe: quinolones, aminoglycosides, tetracyclines
• Tetracyclines: skeletal effects, tooth discoloration, maternal hepatotoxicity
• Sulphonamides near delivery → kernicterus
• Trimethoprim avoid 1st trimester (folate antagonist)
• Nitrofurantoin avoid at term (haemolysis)
• Streptomycin → auditory nerve damage

Question 16

Antifungals & antiemetics

Answer 16

• Topical azoles safe; high-dose systemic azoles teratogenic
• Fluconazole low dose likely OK but avoid if possible
• Safe antiemetics: cyclizine, promethazine, metoclopramide (EPSE risk)
• Domperidone only if benefits outweigh risks

Question 17

Hypertension & indigestion treatment

Answer 17

• Safe antihypertensives: labetalol, methyldopa, nifedipine
• Avoid ACE inhibitors/ARBs (renal malformations)
• Antacids/alginates (separate from iron/folate 2 h), omeprazole safe
• Lifestyle: small meals, upright posture, left-side sleeping

Question 18

Analgesics in pregnancy

Answer 18

• Paracetamol first line
• Codeine relatively safe (caution near term)
• NSAIDs late pregnancy → ductus arteriosus closure & neonatal complications

Question 19

Breastfeeding drug transfer

Answer 19

• Similar factors to placenta
• Drugs enter milk if low MW, lipophilic, weak base, low protein binding
• Milk more acidic → ion trapping of basic drugs

Question 20

Milk/plasma ratio & neonatal PK

Answer 20

• Higher M/P ratio: basic, lipophilic, low protein-bound drugs
• Infants have immature liver & kidneys → drug accumulation risk
• Highest risk: neonates, premature infants, multiple drugs

Question 21

Safe prescribing during breastfeeding

Answer 21

• Avoid long half-life drugs
• Prefer well-studied or infant‑licensed medicines
• Consider alternative routes

Question 22

Timing & monitoring

Answer 22

• Breastfeed just before maternal dose
• Monitor infant: sleepiness, poor feeding, irritability, poor weight gain, developmental delay
• May need clinical monitoring (e.g., BP)