19. Pharmacology in Pregnancy / Breast Feeding Flashcards
What are common medications a woman may be on during Pregnancy / Childbirth / Lactation?
- Hypertension
- Asthma
- Epilepsy
- Migraine
- Mental Health Disorder - Depression / Anxiety
- Long-Term Anticoagulant Therapy - e.g. A. Fib.
What are the 4 basic Kinetic Processes, which can change during pregnancy?
- Absorption (Administration)
- Distribution
- Metabilism (and Elimination)
- Excretion
What Absorption Changes occur in Pregnancy, at:
- Oral Route?
- Intramuscular Route?
- Inhalation Route?
- Increase in Gastric Emptying and Gut Motility / May be more difficult due to Morning Sickness
- Blood flow may be Increased, so absorption may also increase using this route
- Increased Cardiac Output and Decreased Tidal Volume may cause an Increased Absorption using this Route
What Distribution Changes occur in Pregnancy?
- Increased in Plasma Volume and Fat - Increased Vd
2. Greater Dilution of Plasma, decreasing relative amount of Plasma Protein - Increased Fraction of Free Drug
What Metabolism Changes occur in Pregnancy?
Oestorgen and Progestogens can Induce / Inhibit Liver P450 Enzymes - Increasing / Reducing Metabolism
What Excretion Changes occur in Pregnancy?
Glomerular Filtration Rate is increased by 50% - Increased Excretion of Many Drugs
This can reduce the plasma concentration, and necessitate an increase in dose of Renally Cleared Drugs
What are the Pharmacodynamic Changes which occur in Pregnancy?
Pregnancy may affect the Drugs Site of Action / Receptor:
- Concentration of Drugs / Metabolites at Sites of Biological Action (Changes in Blood Flow)
- Mechanism of Action (Changes in Receptors)
- Efficacy may be different
- Adverse effects may be different
What are the functions of the Placenta?
- Attach the Foetus to the Uterine Wall
- Provide nutrients to the Foetus - O2 / Glucose / Amino Acids / Vitamins / Ions / Lipids, Fatty Acids and Glycerol
- Allow the Foetus to transfer Waste Product to the Mothers Blood - CO2 / Urea
What does Placenta Transfer depend on?
- Molecular Weight - Smaller Sizes will cross more easily
- Polarity - Non-Polar Cross more Readily
- Lipid Solubility - Lipid Soluble Drugs will Cross
- Placenta may metabolise some drugs
Note - Safest to assume all drugs will cross the Placenta
What differs in the Foetal Pharmacokinetics?
- Distribution - Circulation is different / Less Protein binding / Little Fat / Relatively more Blood Flow to Brain
- Metabolism - Less Enzyme Activity (increase with Gestation) / Different Isoenzymes to Adults
- Excretion - Into Amniotic Fluid where they can accumulate (Swallowed and can allow recirculation)
What is the difference between:
- Teratogenic?
- Fetotoxicity?
- Teratogenic is in the First Trimester
2. Fetotoxicity is in the Second / Third Trimester
By what Methods does Teratogenicity work?
- Folate Antagonism - DNA Formation / Cell Production
- Neural Crest Cell Disruption - Retinoid Drugs
- Endocrine Disruption - Sex Hormones
- Oxidative Stress
- Vascular Disruption
- Specific Receptor (or Enzyme) Mediated Teratogenesis - NSAID’s
Note - Biggest Risk is Organogenesis
What are the possible issues of Fetotoxicity?
- Growth Retardation
- Structural Malformations
- Foetal Death
- Functional Impairment
- Carcinogenesis
E.g. ACE Inhinhibitors / ARB’s
What are the Common Teratogens to avoid during Pregnancy?
- Anticonvulsants - Valproate / Carbamazepine / Phenytoin
- Anticoagulants - Warfarin
- Antihypertensives - ACE Inhibitors / ARB’s
- NSAID’s
- Alcohol
- Retinoids
What are Drugs to avoid in Breastfeeding?
- Cytotoxics
- Immunosuppressants
- Anti-Convulsants (Not all)
- Drugs of Abuse
- Amiodarone
- Lithium
- Radio-Iodine
