Pharmacology in Pregnancy Flashcards
What pharmacokinetic processes are affected in pregnancy?
- Administration
- Distribution
- Metabolism
- Excretion
What changes in absorption occur in pregnancy?
Oral; may be more difficult due to morning sickness, increase in gastric emptying and gut motility
IM; blood flow may be increased so absorption may increase using this route
Inhalation; raised CO and TV may increase absorption
What changes in distribution occur in pregnancy?
Increase in plasma vol and fat will change distribution
Greater dilution of plasma will decrease relative amount of plasma proteins
Describe placental transfer of drugs
Depends on molecular weight, polarity and lipid solubility
Placenta may metabolise some drugs
ALL drugs will cross the placenta
Describe foetal distribution of drugs
Circulation is different; umbilical vein to lbier
Less protein binding than adults therefore more “free” drug available
Little fat so distribution different
Relatively more blood flow to brain
Why are there issues with dosing in pregnancy?
Pregnancy and foetal pharmacokinetics are different but little data for most drugs
Describe the problems with drugs in pregnancy at the different trimesters
Teratogenicity; first trimester weeks 3-8
Fetotoxicity; second and third trimester
Describe drug teratogenicity in pregnancy
Drugs responsible for ~2% of foetal abnormalities
Biggest risk during 3-8 weeks
Mechanisms
- folate antagonism
- neural crest cell disruption
- endocrine disruption
- oxidative stress
- vascular disruption
- specific receptor (or enzyme) mediated teratogenisis
What is folate antagonism and how can drugs affect it in pregnancy?
Key process in DNA formation and new cell production
Two groups of drugs affect this in pregnancy
- block conversion of folate to THF by binding irreversibly to enzyme i.e. methotrexate, trimethoprim
- block other enzymes in pathway i.e. phenytoin, carbamazepine
Tend to result in neural tube, oro-facial or limb defects
Describe neural crest cell disruption in pregnancy due to drugs
Retinoid drugs i.e. isotretinoin
Problems
- aortic arch anomalies
- ventricular septal defects
- craniofacial malformations
- oesophageal atresia
- pharyngeal gland abnormalities
Describe enzyme-mediated teratogenesis
Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging foetal development
Eg. NSAIDs causing orofacial clefts and cardiac septal defects
Describe fetotoxicity
Toxic effect on foetus later in pregnancy
Possible issues
- growth retardation
- structural malformations
- foetal death
- functional impairment
- carcinogenesis
Eg. ACE inhibitors/ARBs; renal dysfunction and growth retardation
Describe issues with drugs and lactation
Most drugs the mother takes will be present in breast milk
Important to know what concentration will be in breast milk
What drugs should be avoided in breast feeding?
Cytotoxics Immunosuppressants Anti-convulsants (not all) Drugs of abuse Amiodarone Lithium Radio-iodine
Describe the principles of prescribing in pregnancy
If possible try non-pharmacological first
Use drug with best safety record
Check SPC for most up to date info
Use lowest effective dose
Use drug for shortest possible time, intermittently if possible
Avoid first 10 weeks of pregnancy if possible
Consider stopping or reducing dose before delivery
Don’t UNDER TREAT disease which may be harmful to foetus
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