Drugs in Pg and Lactation Flashcards
Placental Transfer
Transplacental Drug Transfer
• Transfer across placenta is bidirectional and usually occurs by simple diffusion
• The placenta is thick early and has decreased permeability
• It becomes thin in late pregnancy and has greater surface area easier passage of drug
Characteristics that ↑ Transfer • High lipiphilicity • Low ionization • Low maternal protein binding • Low molecular weight
Drugs with Teratogenic Effects
- Chemotherapeutic agents (e.g. methotrexate, cyclophosphamide): fetal death or teratogenic effects
- Anticonvulsants (CBZ, PHT, VPA): CBZ: spina bifida, PHT : cardiac defects, fetal hydantoin syndrome ; VPA : neural tube, cardiac and facial defects
- Sex hormones (androgens, DES, Danazol) : genital track ambiguity in female fetus ; DES also associated with cervical or vaginal adenocarcinoma (incidence < 1.4/1000 exposures)
- Warfarin: fetal abnormalities
- ACEIs/ARBs: renal failure in neonate, pulmonary hypoplasia, limb contracture
- Anticholinergic drugs: meconium ileus
- Oral hypoglycemics: neonatal hypoglycemia
- Antithyroid drugs: fetal hypothyroidism
- Lithium (D): cardiac malformations (1st trimester); use lowest dose possible, fetal cardiac US and echo to screen for abnormalities between 16 & 20 weeks
- Misoprostol: abortifacient
- NSAIDs: constriction of ductus arteriosus
- Psychoactive drugs: withdrawal symptoms
- Retinoids (isotretinoin, etretinate): major fetal abnormalities, spontaneous abortion, premature births, low IQ
- Tetracyclines: permanent tooth discoloration
- Thalidomide: limb defects
- Systemic corticosteroids: oral cleft (risk of 3-4/1000 versus 1/1000 in general population)
- Fluconazole: skeletal and craniofacial malformations, cleft palate (with chronic dose > 400 mg/day)
- Trimethoprim: cardiac and urogenital malformations, neural tube defects, oral cleft
Recommendations for Drug Selection in Pg
Choose meds with a long hx of safety
Avoid self-medicating
Use doses at lower end of range
Preconception planning
0.4-0.8mg folic acid qd or 4mg qd if high risk
Limit alcohol and drugs
Optimize control of chronic illness
SSRIs during Pg
Most issues with paroxetine
Congenital malformations - MC if used in first trimester; cardiac malformations
Neonatal behavioral syndrome - from use during 3rd trimester; causes tremors, agitation, irritability; can taper dose 2 weeks prior to due date to try to avoid and restart after delivery
Persistent pulmonary HTN
Potential risks of untreated depression: preterm labor and low birth weight infants
Weight risks and benefits
Strategies to minimize drug exposure while lactating
- Maternal dose immediately after nursing
- Use of short-acting medication forms
- If medication is lipophilic, terminate nursing sessions prior to ingestion of hind-milk; supplemental feeding prn
- Choose drugs that pass poorly into breast milk (e.g. acidic drugs)
- Use alternative routes (inhalation, topical)
- Avoid nursing at peak serum concentrations
- Use drug before infant’s longest sleep period
- Withhold breastfeeding temporarily
Drugs of concern during breastfeeding
Drug or Class Comments
Acebutolol, atenolol Neonatal beta blockade reported
Amiodarone May accumulate because of long half-life; possible neonatal thyroid and cardiovascular toxicity
Antineoplastics Neonatal myelosuppression possible
Ertotamine Symptoms of ergotism (vomiting and diarrhea) reported; inhibition of prolactin secretion possible
Illicit drugs Unknown contents and effects
Lamotrigine A breast-fed infant will receive a dose estimated between 10% and 50% of the lowest pediatric dose; serum concentrations reported in breast-fed infants were between 3% and 50% of maternal levels; potential for rash and CNS side effects
Lithium Up to 50% of maternal serum levels have been measured in infants; cases of infant toxicity have been reported
Radioactive iodine-131 Long radioactive half-life (21-42 days)
Tetracyclines Chronic use may lead to dental staining or decreased epiphyseal bone growth
