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.
Drugs to avoid in breast feeding (7)
)balancing it for mother and child)
- Cytotoxics
- Immunosuppressants
- Anti-convulsants (not all)
- Drugs of abuse
- Amiodarone
- Lithium
- Radio-iodine
Teeth staining in infant caused by?
Tetracycline
Risk of pyridoxine deficiency in the infant caused by?
Isoniazid
Lethargy, sedation and poor suck reflexes caused by?
Barbiturates
Drowsiness if infant fed at peak caused by?
Chloral hydrate
What can diazepam cause?
Drug accumulation and sedation
What can Methadone cause?
Risk of withdrawal if breast feeding stops
Effect of iodine?
Thyroid suppression and risk of cancer
Propylthiouracil can cause?
suppressed thyroid function in infant
half of pregnant women will use
herbal medicines.
Two popular herbal galactagogues for nursing mothers pose a health risk to their infants. - what are they called?
Fenugreek
Comfrey.
Herbal medicines and pregnancy advice? - why?
should avoid herbal medicines.
- This is is due to the lack of information of scientific safety data.
- Contamination of herbal products with conventional medicines, pesticides or heavy metals.
What can be hepatotoxic?
Herbs containing pyrrolizidine alkaloids (PAs)
Effects of hormonal medicines?
- hormonal effects.
- Some herbal medicines contain constituents with sedative properties
new diagnosis of hypertension in patient who wants to become pregnant- what are the options? (NA, patient is overweight)
- Discuss alternative anti-hypertensive therapy, look at weight loss,
- Ensure good blood pressure control pre-pregnancy
17 y.o patient - severe acne, resistant to other treatment - what do you have to be sure of before starting them on isotretinoin
BNF states she must have monthly pregnancy checks and use at least one (preferably two) methods of contraception
Principles of prescribing in pregnancy? (8)
- try non-pharmacological treatment first
- Use the drug with the best safety record (avoid new drugs unless proven safe).
- Check the SPC for the most up to date information
- Use the lowest effective dose.
- Use the drug for the shortest possible time, intermittently if possible.
- Avoid the first 10 weeks of pregnancy if possible.
- Consider stopping or reducing dose before delivery.
- Never under a treat disease which may be harmful to the fetus
33 y.o patient, 26 weeks pregnant - suffering from:
Vomiting, dysuria, abdominal pain
Urinary tract infection
Positive MSSU
- Gp recommended Trimethoprim 200mg bd for 7 days - opinion?
first trimester it has its teratogenic effects
- avoid throughout pregnancy but may be necessary to use in the later stages of pregnancy , use a safer antibiotic alternative
What is important for chronic diseases?
- what must you do?
Good disease control is important
- specialist input
Principles of prescribing in breast feeding (4)
- Again avoid unnecessary drug use.
- Check on up to date drug information.
May be a lack of information. - If licensed and safe in paediatric use (esp under 2 years), a drug is likely to be safe in breast feeding.
- Choose drugs with pharmacokinetic properties that reduce infant exposure (e.g. highly protein bound). - short half life, low lipid solubility
patient, 3 week old baby, currently breastfeeding - has low back pain
what can she safely take?
GO TO THE BNF!!
- Paracetamol, ibuprofen – BNF notes amounts too small to be harmful in breast milk though some manufactures will state avoid ibuprofen
codeine is?
- use in pregnancy
converted to morphine by liver enzymes
- concentration usually too low to be harmful, but maternal metabolism very variable so risk of morphine OD in baby - morphine can reach the baby and cause sedation
