Prescribing in special groups 1

• Definition: a substance, physical agents or deficiency state capable of induicing abnormal structure of function such as:
  • gross structural abnormalities
  • functional deficiencies
  • IUGR
  • behavioural aberrations
  • demise
• drugs cause 2-3% of all congenital malformations (0.15% of all pregnancies)
• susceptibilty depends on genotype of mother/baby and on developmental stage of foetus
• 1st trimester
  • drugs can cause congenital malformations
  • 3rd to 8th week is period of highest risk as organ systems are formed
  • pre-embryonic phase (0-14 days post-conception) is "all or nothing" i.e. completely healthy or spontabneois abortion
• 2nd and 3rd trimester
  • drugs can cause IUGR or functional development or have toxic effects on tissues
  • a/e on neonate if given shortly before or during labour e.g. diazepam or pethidine

• Pregnancy category A
  • adequate and well controlled studies have failed to demonstrate risk to foetus in 1st T.
• Pregnancy category B
  • animal reproduction studies failed to show risk if no adequate studies in pregnant women OR animal studies show adverse effect but adequate, well controlled human studies do not
• Pregnanacy category C
  • animal reproduction studies have shown adverse effect and there are no adequate, well controlloed human studies but potential benefits may warrant use
• Pregnancy category D
  • positive evidence of human foetal risk based on adverse reaction dta from investigational or marketing experience or human studies but potential benefits may warrant use
• Pregnancy category E
  • studies in humans or animals have dmeonstrated foetal abnormalities and/or there is positive evidence of human foetal risk and the risks involved clearly outweigh any potential benefits

• ACE inhibitors: impaired neonatal BP control and renal function
• Aminoglycosides: eighth nerve damage
• Androgens: virilisation, multiple congenital defects
• Opiates: perinatal respiratory depression
• Quinolone antibiotics: skeletal abnormalities
• Sodium valproate: neural tube defects
• Tetracyclines: yelolow discolouration of teeth, inhibtis bone growth
• Warfarin: multiple congential defects

• assume all drugs will cross the placenta unless they have high molecular weight
• avoid drugs in 1st trimester if possible
• only prescribe if benefit to mother outweighs risk to foetus
• check all drugs in BNF
• check UK Teratology Informatrion Service

NB on dosing:

• maternal drug concentration is often lower than in non-preganant women (incr vol of distribution)
• renal elimination may incr thus higher dose needed (enoxaparin)
• lamotrigine metabolism enhanced so need higher dose (antiepileptic)

• avoiding breatsfeeding to take drugs is NOT a no harm option
• most drugs are passed in small qunatities so are not a concern
• neonates and prem babies are at greater risk due to poor excretion and thus accumulation
• risk depends on:
  • passage of drug to milk
    • reduced passage= good
      • HMW (e.g. insulin, heparins)
      • high protein binding (e.g. warfarin, NSAIDS)
      • low lipid solubility (e.g. loratidine)
      • lower pH (e.g. amoxacillin) because pH of breat milk lower than plasma (6.9 vs 7.4)
  • amount of active drug delivered to infant
  • infant pharmacokinetics
    • absorption, distributioni, elimination
  • adverse reaction profile
  • infant age
  • infant co-morbidities

• Amiodarone
  • present in milk in significant amounts
  • risk from release of iodine
• Antithyroid drugs
  • neonatal goitre and hypothyroidism
• Benzodiazepines
  • presentin breast milk
• Lithium salts
  • present in milk and risk of toxicity
• Radioactive iodine
  • breastfeeding contraindicated
• Statins
  • high conc in breast milk
• Sulphonamides
  • risk of kemicterus (bilirubin-induced brain dysfunction) in jaundiced infants

• drugs which affect dopamine activity will cause changes in lactation b/c dopamine inhibits release of prolactin from ant pituitary
  • dopamine agonists (e.g. cabergoline) reduce milk production
  • dopamine antagonists (e.g. domperidone) promote lactation
• early postpartum use of oestrogen reduces milk volume
  • therefore use POP as contraception postpartum
• some drugs (e.g. phenobarbital) inhibit the infant's suckling reflex