Pharmacology in Pregnancy and Breast Feeding Flashcards
What reasons are there for women to be on medicines during pregnancy and breast feeding?
- Hypertension
- Asthma
- Epilepsy
- Migraine
- Mental health disorders
- Long term anticoagulant therapy
How does pregnancy affect the absorption of a drug?
- Oral route may be more difficult due to morning sickness, increase in gastric emptying and motility
- Intramuscular route may be difficult due to increased blood flow meaning that absorption increases
- Inhalation route may be difficult due to increased cardiac output and decreased tidal volume causing increased absorption of inhaled medicine
How does pregnancy affect the distribution of a drug?
Distribution changes occur due to an increase in fat and plasma volume. Greater volume will also cause a decrease in relative amounts of plasma proteins so fraction of free drug increases.
How does pregnancy affect the metabolism of a drug?
Metabolism changes can occur due to oestrogen and progesterone inducing or inhibiting liver enzymes or increasing or reducing metabolism
How does pregnancy affect the excretion of a drug?
Excretion changes occur due to increase of GFR, which can increase excretion of drugs, reduce plasma concentration and an increase in dose of renally cleared drugs.
What are the functions of the placenta?
- Attach the fetus to the uterine wall
- Provide nutrients to the fetus
- Allow the fetus to transfer waste products to the mother’s blood
What drugs cross the placenta most easily?
Low molecular weight, non-polar and lipid soluble materials
What factors affect placental drug transfer?
- Drug physiochemical properties
- Rate at which drug crosses placenta
- Duration of drug exposure
- Distribution in different fetal tissue
- Stage of placental and fetal development
- Effects of drugs uses in combination
How do fetal pharmacokinetics differ to adult?
- Distribution- circulation different, less protein available, little fat, relatively more blood flow to brain
- Metabolism- less enzyme activity and different isozymes
- Excretion- excreted into amniotic fluid which can be swallowed and reabsorbed, drugs and metabolites can accumulate in the amniotic fluid and placenta is non-functional at delivery so can be issue with excretory function
What is the difference between teratogenicity and fetotoxicity?
Teratogenicity occurs in the first trimester, whereas fetotoxicity occurs in the second and third trimesters.
What is the implication of avoiding medications to avoid damage to the baby?
Chronic conditions tend to be under-treated in pregnancy due to fear of damaging the baby but this may cause greater foetal risk due to effects of illness
When is the developing foetus at most risk of teratogenicity?
During organogenesis in weeks 3-8
What are the possible mechanisms for teratogenicity?
- Folate Antagonism
- Neural Crest Cell Disruption
- Endocrine Disruption: Sex Hormones
- Oxidative Stress
- Vascular Disruption
- Specific Receptor- or Enzyme-mediated Teratogenesis
What is folate antagonism?
The blocking of a key process in DNA formation and new cell production. It can occur by blocking the conversion of folate to THF by binding irreversibly to the enzyme or by blocking other enzymes in the pathway
What are the possible results of folate antagonism?
Neural tube, oro-facial or limb defects.