Pharmacology in pregnancy and breastfeeding part 2 Flashcards
What is really important regarding safety of drugs in pregnancy?
Management of maternal chronic illness is paramount
- Undertreatment of maternal illness due to fear of using medicines during pregnancy may cause greater fetal risk!
What % of abnormalties are drugs responsible for?
2%
Where does the highest risk of fetal abnormalities occur?
organogenesis (3-8 weeks)
Variety of Mechanisms for fetal abnormalties? (6)
- Folate Antagonism
- Neural Crest Cell Disruption
- Endocrine Disruption: Sex Hormones
- Oxidative Stress
- Vascular Disruption
- Specific Receptor- or Enzyme-mediated teratogenesis
Folate antagonism is a key process in?
DNA formation and new cell production
What 2 groups of drugs affect folate metabolism and how do they do it?
- Block the conversion of folate to THF by binding irreversibly to the enzyme (eg methotrexate, trimethoprim)
- Block other enzymes in the folate pathway (e.g. phenytoin, carbamazepine, valproate)
drugs which block folate metabolism tend to result in what defects? (3)
neural tube, oro-facial or limb defects
Neural crest cell disruption is associated with what drugs?
Retinoid drugs (eg isotretinoin ) used in treatment for severe acne
Problems caused by isotretinoins (5)
aortic arch anomalies ventricular septal defects craniofacial malformations oesophageal atresia pharyngeal gland abnormalities
isotretinoins cant be used unless the patient is in?
contraception
Enzyme-mediated teratogenesis - what may drugs that stimulate or inhibit enzymes to produce therapeutic effects interact with?
- give an example and what defects
specific receptors and enzymes damaging fetal development.
- NSAIDs causing orofacial clefts and cardiac septal defects
When does Fetotoxicity occur?
when therapeutic agent produces toxic affect on fetus later in pregnancy - 3rd trimester
possible issues of fetotoxicity
Growth retardation Structural malformations Fetal death Functional impairment Carcinogenesis
Give an example of drugs causing fetotoxicity - what would this drug cause?
ACE inhibitors/ARBs – renal dysfunction and growth retardation
Examples of known teratogens to avoid during pregnancy - anticonvulsant example
Anticonvulsants - valporate - neural tube defects, as is carbamazepine and phenytoin
What can the anticoagulant warfarin cause?
haemorrhage in the fetus, as well as multiple malformations in the central nervous system and skeletal system.
Antihypertensive agents - examples
ACE inhibitors cause renal damage and may restrict normal growth patterns in the unborn child.
fetotoxic and teratotgenic
Non-steroidal anti-inflammatory drugs can cause?
Premature closure of the ductus arteriosus.
Alcohol should be avoided due to ?
Fetal alcohol syndrome/effects
Retinoids should be avoided as they can affect what? (4)
Ear, CNS, cardiovascular, and skeletal disorders
- teratogens
Issues with drugs and lactation - all drugs will be?
present in breast milk- important to know the concentration of the drug
pharmacokinetics are different in ?
neonate compared to the fetus
Minimal Exposure - questions to ask? (4)
Is maternal drug therapy necessary?
If yes. What is the safest option for the infant?
If there is the possibility of harm, monitor infant blood levels of the drug
Minimize infant exposure
Treating a lactating woman? - things you try to do and avoid (7)
- If possible postpone drug treatment until the baby is weaned
- Use non-pharmacological strategies when possible.
- If a drug needs to be used, then the mother should take the medication immediately after feeding the baby
- Avoid breast-feeding during peak drug effect
- Avoid drugs with long half-life or active metabolites
- Drugs that are highly protein-bound are preferred (less likely to dissolve in lipid component)
- Extra caution if baby is severely ill or preterm.
