Pharmacology in Pregnancy Flashcards
Which Pharmacological factors change in pregnancy?
Absorption
Distribution
Metabolism + elimination
Excretion
What are the absorption changes in pregnancy?
Oral route
Intramuscular route
Inhalation
Why does the oral route of absorption change in pregnancy?
Morning sickness
Increased gastric motility and emptying
(may affect single doses)
Why does the intramuscular route of absorption change in pregnancy?
Blood flow may be increased
Why does the inhalation route of absorption change in pregnancy?
Increased cardiac output and decreased tidal volume
What are the distribution changes in pregnancy?
Increased plasma volume and fat
Greater dilution of plasma (increased fraction of free drug)
What are the metabolism changes in pregnancy?
Ostrogens and progestogens can induce/inhibit liver P450 enzymes
How does Phenytoin change in pregnancy?
Decreased (induction of metabolism)
How does theophylline change in pregnancy?
Increased (induction of metabolism)
What excretion changes are seen in pregnancy?
GFR increased
Reduced plasma concentration (might need to increase dose of renally cleared drugs)
Placental transfer depends on what?
Molecular weight (smaller crosses more easily) Polarity Lipid solubility Protein binding Placenta may metabolise some drugs
What are the changes in distribution in fetal pharmacodynamics?
Circulation different
Less protein binding = more free drug
Little fat
Relatively more blood flow to brain
What are the changes in metabolism in fetal pharmacodynamics?
Less enzyme activity, increases with gestation
Different isoenzymes to adults
What are the changes in excretion in fetal pharmacodynamics?
Drugs/metabolites can accumulate in amniotic fluid
Which groups of drugs are high risk in pregnancy?
Anti-convulsants Anti-hypertensives Analgesics Antibacterials NSAIDs Alcohol retinoids
When is teratogenicity at highest risk?
3-8 weeks gestation
What are the mechanisms of teratogenicity?
Folate antagonism Neural crest cell disruption Endocrine disruption Oxidative stress Vascular disruption
What is folate antagonism?
Methotrexate/trimethoprim
Phenytoin, carbamazepine, valproate
Results in neural tube, facial, limb defects
Which drugs cause Neural Crest Cell disruption?
Retinoid drugs (isotretinoin)
Neural Crest Cell disruption causes what?
Aortic arch anomalies Ventricular septal defects Craniofacial malformations Oesophageal atresia Pharyngeal gland abnormalities
What is enzyme mediated teratogenesis?
Drugs which inhibit/stimulate enzymes to produce therapeutic effects, may also interact with specific receptors
Which drugs can cause teratogenic effects by Enzyme mediated teratogensis?
NSAIDs
orofacial clefts, septal defects
Which drugs are fetotoxic?
ACEI
ARBs
What effect do ACEI/ARBs have on the baby?
Fetotoxic
Renal dysfunction
Growth retardation
Which drugs should be avoided in breast feeding?
Cytotoxics Immunosuppressants Anti-convulsants Drugs of abuse Amiodarone Lithium Radio-iodine
What are the principles of prescribing women of child-bearing age?
Always consider possibility of pregnancy Try non-pharmacological first Use lowest effective dose, for as little time as possible Avoid in first 10 weeks Warn of risks Discuss contraception
What are the principles of prescribing breastfeeding women?
Avoid unnecessary drug use
Check if safe in paediatric use
Highly protein bound drugs better
