lactation Flashcards
composition of breast milk
Milk consists of simple sugars (carbs), lipids, proteins, vitamins and minerals dissolved in water
Water accounts for >80% of its volume
Changes from colostrum to mature milk
describe the drug transfer into breast milk
Most drugs pass into breast milk to some extent – although transfer usually low
Amount of drug ingested by infant rarely causes adverse effects
Almost all drugs enter milk by passive diffusion of unionised, unbound drug through the lipid membranes of the alveolar cells of the breast
Although early on, drugs may pass between the alveolar cells (first 72 hours postpartum)
Babies most vulnerable to the effects of drugs in the first few days after delivery as intercellular gaps in the milk ducts
This allows large molecules such as antibodies (Igs) to pass through into the breast milk
Antibodies important to protect baby from infection (passive immunity)
However, this is also when the most medication is given to lactating women
Over 50% of women given medication in first few days after birth (mainly painkillers and antibiotics)
drug factors that affect infant exposure to maternal drug therapy
MW
The lower the molecular weight of a medication, the more likely it is to penetrate into human milk – as diffusion through the alveolar epithelial cell is much easier
Plasma protein binding – the more highly bound the drug, the less that can transfer into milk ( e.g. ibuprofen >99% bound)
Lipophilicity – alveolar epithelium of breast is a lipid barrier, so lipid soluble drugs pass more freely into breast milk than water-soluble drugs/ ions (e.g. CNS drugs)
pKa
drugs with lower pKa are preferable for breastfeeding, - less penetration into milk compartment
Oral bioavailability to infant
drugs with low oral bioavailability are poorly absorbed from infant’s GI tract
Half life
short half life preferable as less likelihood of the drug accumulating
drug factors that affect infant exposure to maternal drug therapy
MW
The lower the molecular weight of a medication, the more likely it is to penetrate into human milk – as diffusion through the alveolar epithelial cell is much easier
Plasma protein binding – the more highly bound the drug, the less that can transfer into milk ( e.g. ibuprofen >99% bound)
Lipophilicity – alveolar epithelium of breast is a lipid barrier, so lipid soluble drugs pass more freely into breast milk than water-soluble drugs/ ions (e.g. CNS drugs)
pKa
drugs with lower pKa are preferable for breastfeeding, - less penetration into milk compartment
Oral bioavailability to infant
drugs with low oral bioavailability are poorly absorbed from infant’s GI tract
Half life
short half life preferable as less likelihood of the drug accumulating
Active metabolites
presence may prolong infant drug exposure and lead to drug accumulation (esp. in neonatal period)
Therapeutic index
some drugs have very narrow ranges and need monitoring (e.g. digoxin, lithium and warfarin)
maternal factors
Maternal drug regimen – single doses/short courses rarely cause problems, but chronic therapy can be problematic. Multiple medications increase risk, as well as higher doses. Topical/inhalation routes preferred
Maternal plasma concentration - usually, the most important determinant of drug penetration into milk is the mother’s plasma level
As the level of the medication in the mother’s plasma begins its rise, the concentration in milk begins its rise as well. Drugs both enter milk, and in most cases, exit milk as a function of the mother’s plasma level
As soon as the maternal plasma level of a medication has fallen, the milk level soon follows
Pharmacogenetics – sedation and one death occurred in infants of mothers with rare genotypes of the cytochrome P450 enzyme CYP2D6, leading to ultrarapid metabolism of codeine to morphine
Timing of feed – often impractical, especially if infants are feeding frequently, also not useful if drug has long half life or when drug has reached steady state. This technique should be selectively for drugs with short half lives and predictable peaks/troughs
infant factors
The age and maturity of the baby – liver and kidney systems do not work fully for some time after birth. Premature babies may show higher than expected drug levels.
Pharmacogenetics - Infants with certain enzyme deficiencies (e.g. G6PD) deficiency may experience adverse effects with even small amounts of certain drugs
Allergies - Possibility of allergic reaction in infant exposed to drug in breast milk, even minimal exposure could cause this response; rare in practice
Volume of breast milk ingested – higher volume = higher drug exposure. Volume may depend on child age
Relative infant dose - a level <10% is probably safe but inherent toxicity/ adverse effect profile of drug needs to be taken into account
relevant infant dose?
Infant plasma levels are most accurate indicator of drug exposure but are seldom available
The Relative Infant Dose (RID) estimates infant drug exposure via breast milk
The daily dose received via breast milk is compared to the dose used therapeutically for an infant of the same age
When the medication is not used in infants or does not have an accepted infant dosage, a weight-adjusted maternal dose is used
ideal drug for breast feeding
Licensed for use in children
Wide therapeutic index
Highly plasma protein bound (<90%)
Low milk:plasma ration (<1)
Low pKa
Poor oral bioavailability
Large molecular weight
Half life < 24 hrs
Low relevant infant dose (RID)
commonly recommended OTC medicines for breastfeeding
Many OTC medicines are compatible with breastfeeding (e.g. paracetamol, oral/topical NSAIDs, bulk and osmotic laxatives, loperamide)
OTCS to avoid whilst breastfeeding
Codeine should NOT be recommended as metabolism varies between individuals and some breastfeeding mothers may concentrate the drugs into milk
Aspirin as a painkiller (high dose) - aspirin is associated with Reye’s syndrome in children under 16 yrs
Medicines that have the potential to cause drowsiness (e.g. diphenhydramine) should be avoided - they can pass the blood-brain barrier, causing sedation in the child.
These medicines may also have the potential to reduce milk supply
Herbal remedies are best avoided during breastfeeding, due to lack of data
prescribed medicines compatible with breastfeeding?
antibiotics, Antidepressants
contraindicated medicines in breastfeeding?
Amiodarone
Lithium
Isotretinoin
These are medicines with inherent toxicity or high infant exposure and therefore potential for significant toxicity
Radiopharmaceutical administration also requires temporary cessation of breastfeeding
alcohol and breastfeeding
Chronic or heavy users of alcohol should not breastfeed
High intake of alcohol:
decreases milk let down and disrupts feeding
cause sedation, fluid retention and hormonal imbalances in breastfed infants
vaccines and breastfeeding
Neither inactivated nor live vaccines affect the safety of breast feeding for women or their infants
Breast feeding does not adversely affect immunization and is not a contraindication for any UK-licensed vaccine
Breast-fed infants should be vaccinated according to recommended schedules
considerations for the prescriber
No baby should be exposed to risk by the mother taking a drug which is contra-indicated in breastfeeding
Breast feeding should be suspended/stopped as a last option
