Pharmacology in pregnancy, breastfeeding and the neonate Flashcards
What are the four main components of pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
How is absorption of drugs affected in pregnancy?
Gastric emptying is delayed for oral preparations
How is distribution of drugs impacted by pregnancy?
- Total body water and fat are increased - lower conc of water and lipid-soluble drugs
- Protein binding reduced, increased free drug conc
How is metabolism of drugs affected in pregnancy?
Increased clearance of drugs which depend on liver enzyme activity
How is elimination affected in pregnancy?
Increased renal plasma flow, doubling elimination of renally-cleared drugs
What are the factors affecting placental transfer of drugs?
- lipid/water solubility
- molecular size
- protein binding
- metabolism
small, lipid-sol, unbound, uncharged molecules cross most easily, but most drugs cross the placenta
In which period of pregnancy will most known teratogens have the worst effect?
First trimester (organogenesis day 17-60)
List 8 drug classes that should be avoided as best as possible or completely avoided in pregnancy.
- ACEi/ARBs
- Anticonvulsants
- Antibiotics
- Antipsychotics
- Antithyroid
- Anticoagulant
- Abuse of alcohol, cigs, opioids, bzds
- DMARDs/cytotoxics
What are the things to consider when prescribing in pregnancy?
- All drugs cross placenta but amount depends on their properties
- Drugs which are safe in adults can cause serious effects in fetus
- Half-life may be shorter as absorption takes longer and elimination is quicker (change freq. of delivery/change dose )
- Few drugs are clearly teratogenic, most increase background risk
- Administration during first trimester has greatest risk - avoid
- If possible, use drug with proven safety record
- Must always be sound reasons for prescribing during pregnancy
What are the common drug issues in pregnancy?
- Nausea and vomiting
If mild, nothing or vitamin/electrolyte support
1st - promethazine, cyclizine
2nd - metoclopamide, ondansetron - Asthma
Maintain good control with inhalers, prednisolone if needed - Hypertension
Labetalol/methyldopa/nifedipine - UTI (even asymptomatic)
Antibiotic - nitrofurantoin (look at previous urine cultures and antibiotic use) - Anticoagulation
Heparin/LMWH, AVOID warfarin + DOAC - Anticonvulsants
Seizure more risk than drug, refer to specialist
Which drugs should be cautioned in a nursing mother?
Most drugs detectable in breast milk at low conc. Diazepam Alcohol Lithium Iodine Opioids Tetracyclines Corticosteroids
How is absorption of drugs different in a neonate?
Skin - SA/BW greater, absorption of topical agents increased e.g. steroids
Intramuscular - absorption impaired due to reduced mass
Rectal absorption relatively efficient e.g. diazepam, theophyllines
How is distribution of a drug different in a neonate?
- Body water as % is greater than in older children - loading dose is greater for aminoglycosides, digoxin and aminophylline
- Albumin binding is decreased, increasing free conc. of highly bound drugs and increasing risk of drug/bilirubin interaction (bilirubin displaced + jaundice)
How is metabolism of drugs diff in neonates?
- Impaired oxidation, increasing conc of drugs such as warfarin, diazepam, theophylline
- Impaired glucuronidation, increased risk of toxicity of drugs metabolized by this metabolism e.g. chloramphenicol
How is elimination of drugs diff in a neonate?
- Glomerular filtration/tubular secretion and reabsorption in kidneys all impaired
Requires dose reduction for renally- cleared drugs (aminoglycosides, digoxin, penicillin) - Standard dose can be used by 6 months
