Pharmacology in Pregnancy and Breastfeeding Flashcards
What percentage of pregnant women will take a drug during pregnancy?
Around 50-90%
Why is it important to be careful of medication given for all women of child bearing age?
Many pregnancies are unplanned so the fetus could be affected by drugs before the woman knows she is pregnant
Why may a woman be on medication during pregnancy?
Hypertension Asthma Epilepsy Migraine Mental health disorders Long term anticoagulant therapy
What are the 4 basic pharmacokinetic processes?
Absorption
Distribution
Metabolism
Excretion
Why is data limited for pharmacokinetics in pregnancy?
There have been very few studies
How may absorption change in drugs taken orally?
Morning sickness causing nausea and vomiting may reduce absorption
Decrease in gastric emptying and motility may affect single dosage drugs
How may absorption be affected in drugs taken intramuscularly?
Blood flow may increase so absorption may also increase
How may absorption be changed in inhaled drugs?
Increased cardiac output and tidal volume may cause increased absorption
How is distribution affected in pregnancy?
Plasma volume increases while protein volume stays the same, leading to dilution of proteins meaning the fraction of free drug increases
How does metabolism change in pregnancy?
Oestrogen and progestogens can induce or inhibit liver enzymes leading to increased or reduced metabolism
How is excretion of drugs affected in pregnancy?
GFR is massively increased by around 50%, leading to increased excretion
How may pharmacodynamics be changed in pregnancy?
Site of action and receptor
Concentration of drug and metabolites at site of action
Efficacy may change
Adverse effects may be different
What does the mother give to the fetus across the placenta?
Oxygen Glucose Amino acids Lipids Vitamins Ions Alcohol, nicotine, etc Viruses Antibodies
What does the fetus give to the mother across the placenta?
CO2
Urea
Other waste products
What does placental transfer depend on?
Molecular weight - small sizes cross more easily
Polarity/lipid solubility - non-polar cross more readily
Some drugs may be metabolised by placenta
What causes drug distribution in the fetus to be different to the mother?
Circulation is different
Less protein binding so more free drug
Little fat so distributed differently
Relatively more blood flow to the brain
What is different about drug metabolism in the fetus?
Enzyme activity is decreased but increases with gestation
Different isoenzymes to adults
How is fetal drug excretion different to an adults?
Excretion is into amniotic fluid which is swallowed again allowing recirculation
Drugs and metabolites can accumulate in amniotic fluid
What drug groups have data for use in pregnancy?
Anti-convulsants
Anti-hypertensives
Analgesics
Antibacterials
When is teratogenicity an issue?
First trimester
When is fetotoxicity an issue?
Second and third trimester
When in the first trimester is the biggest risk of teratogenicity?
Organogenesis - 3-8 weeks
What are mechanisms of teratogenicity?
Folate antagonism Neural Crest Cell Disruption Endocrine disruption of sex hormones Oxidative Stress Vascular Disruption Specific Receptor or Enzyme-mediated Teratogenesis
What happens as a result of folate antagonism?
Neural tube defect
Oro-facial defect
Limb defect
What are mechanisms of folate antagonism?
Block conversion of folate to THF by irreversibly binding to the enzyme
Or Block other enzymes in the pathway
What drugs are folate antagonists by blocking conversion of folate to THF?
Methotrexate
Trimethoprim
What drugs cause Neural crest cell disruption?
Retinoids
What problems can be caused by neural crest cell disruption?
Aortic Arch Anomalies Ventricular septal defects Craniofacial malformations Oesophogeal atresia Pharyngeal gland abnormalities
What drugs cause enzyme-mediated teratogenesis?
NSAIDs
What is fetotoxicity?
Toxic effect on the fetus later in pregnancy
What are possible issues caused by fetotoxicity?
Growth retardation Structural malformations Fetal death Functional impairment Carcinogenesis
What are issues with drugs with lactation?
Most drugs will be present but will be at lower doses than in utero
Important to know what concentration will be present in breast milk
Pharmacokinetics are different to the fetus
What drugs need to be avoided completely in breast feeding
Cytotoxics Immunosuppressants Most anti-convulsants Drugs of abuse Amiodarone Lithium Radio-iodine
