Pharmacology in Pregnancy and Breast Feeding Flashcards
Aprox 50-90% of pregnant women take a medicine during pregnancy
Many pregnancies are unplanned (80% of women of child-bearing age take medication)
Should consider the effect on _________ when prescribing for any women of childbearing age
pregnancy
Why may a women be on medicine during pregnancy, childbirth and lactation?
Hypertension
Asthma
Epilepsy
Migraine
Mental health disorders
Long term anticoagulant therapy use
Physiological changes during pregnancy have implications for drug therapy and may affect any of the four basic kinetic processes namely:
absorption, distribution, metabolism and elimination, excretion
Pharmacokinetic in pregnancy – processes of _________, ________, ________ and _______ – very few pharmacokinetic studies in pregnancy so data is very limited
absorption
distribution
metabolism
excretion
what absorption changes happen during pregnancy through the oral route?
May be more difficult “morning sickness” nausea/vomiting
Decrease in gastric emptying and gut motility – this is unlikely to be a problem with regular dosing, but may affect single doses
what absorption changes happen during pregnancy through the intramuscular route?
blood flow may be increase, so absorption may also increase using this route
what absorption changes happen during pregnancy through the inhalation?
increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs
how may distribution change in pregnancy?
Increase in plasma volume and fat will change distribution of drugs – increase Vd (volume of distribution)
Greater dilution of plasma will decrease relative amount of plasma proteins – increase fraction of free drug (Free drug which is pharmacodynamically active)
what metabolism changes happen in pregnancy?
Oestrogen and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing (drug) metabolism
Examples – phenytoin levels reduced (due to induction of metabolism), theophylline levels increased (due to inhibition of metabolism)
what excretion changes happen in pregnancy?
GFR is increased in pregnancy by 50% leading to increased excretion of many drugs. (and reduction in circulating drug levels so may need increase in dose)
This can reduce the plasma concentration, and can necessitate an increase in dose of medicine cleared by the kidney
Summary picture showing how absorption, distribution, metabolism and excretion are effected in pregnancy
Pharmacodynamics describe what……
the drug does to the body
Pharmacokinetics describes what………..
body does to the drug
what pharmacodynamic changes happen in pregnancy?
Less well understood
Pregnancy may affect the site of drug action and the receptor response to drug:
- Concentration of drug, 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
During pregnancy most drugs can cross the placenta. Factors affecting placental drug transfer and drug effects on the featus include what?
Drug physiochemical properties
Rate at which drug crosses placenta and amount reaching fetus
Duration of drug exposure
Distribution of drug exposure
Distribution in different foetal tissues
Stage of placental and foetal development
Effects of drugs when used in combination
placental transfer of drugs depend on what?
molecular weight (smaller sizes will cross more easily)
polarity (unionised molecules cross more readily)
lipid solubility (lipid soluble drugs will cross)
Placenta may also _______ some drugs
Safest to assume all drugs will _____ placenta
metabolise
cross
Foetal Pharmacokinetics
how is distribution different in the foetus?
Circulation is different (e.g. umbilical vein to liver)
Less protein binding than adults therefore more “free” drug available
Little fat, so distribution different
Relatively more blood flow to brain
Foetal Pharmacokinetics
how is metabolism different in the foetus?
Reduced enzyme activity, although this increases with gestation
Fetus exhibits different P450 isoenzymes to adults
Foetal Pharmacokinetics
how is excretion different in the foetus?
Excretion is into amniotic fluid – which the foetus swallow leading to recirculation
Drugs and metabolites can accumulate in amniotic fluid (can cause toxicity to the foetus)
Placenta not functioning at delivery so can be issues with excretory function
Teratogenicity (____ trimester) – an agent that can disturb the development of the embryo or fetus
Fetotoxicity (________ and _____ trimester)
first
second
third
Don’t ________ a chronic illness due to fear of using drugs during pregnancy that may cause _______ foetal risk
undertreat
greater
What are the principles of prescribing for women of child-bearing age (not always pregnant)
Always consider possibility of pregnancy (planned or not!)
Warn women of possible risk
When treating medical conditions, advise women to attend before getting pregnant if planning to (optimise treatment)
Discuss contraception
If necessary, do not prescribe without contraception
whata re the Principles of prescribing in pregnancy?
If you can, try non-pharmacological treatment first
Use the drug with the best safety record (avoid new unless proven safe)
Check the SPC (Summary product characteristics) for the most upto date information
Use lowest effective dose
Use the drug for the shortest time possible, intermittently if possible
Avoid in the first 10 weeks of pregnancy if possible
Consider stopping or reducing dose before delivery
Never under treat a disease which may be harmful to the mother or foetus
Teratogenicity:
- Drugs responsible for 2% of foetal abnormalities
- Highest risk is during organogenesis (3-8 weeks)
what different mechanisms of harm may there be?
Folate antagonism
Neural crest cell disruption
Endocrine disruption: sex hormones
Oxidative stress
Vascular disruption
Specific receptor or enzyme mediated teratogenesis
what is Folate antagonism?
Key process in DNA formation and new cell production
Two groups of drugs affect folate metabolism:
- 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)
Tend to result in neural tube, oro-facial or limb defects
What may cause Neural Crest Cell Disruption and what problems may there be?
- Retinoid drugs (e.g. isotretinoin – cant be used unless patient is on contraception)
- Problems – aortic arch abnormalities, ventricular septal defects, craniofacial malformation, oesophageal atresia, pharyngeal gland abnormalities
what is Enzyme-mediated teratogenesis?
- Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging foetal development
- Example – NSAIDS causing orofacial clefts and cardiac septal defects
what is fetotoxicity?
- Toxic effects on the foetus later in pregnancy
- Possible issues: growth retardation, structural malformations, foetal death, functional impairment, carcinogenesis
- Example – ACE inhibitors/ARBS cause renal dysfunction and growth retardation
what are the issues with drugs and lactation?
- Almost all drugs the mother takes will be present in breast milk
- Important to know what concentration will be in breast milk
- Remember pharmacokinetics are different in neonate compared to the foetus
How do you ensure minimal exposure to the neonate to drugs form breast milk?
- Is maternal drug necessary? If yes, then 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
- If possible minimise drug treatment until the baby in weaned
- Une non-pharmacological treatments when possible
- If it needs be used then it should be taken right after feeding the baby
- Avoid breast feeding during peak drug effect – avoid drugs with long half life, drugs that are highly protein bound are preferred as less likely to dissolve in the lipid component of breast milk, caution if baby severely ill or preterm as full metabolism excretion wont be established
are herbal medicines safe in pregnancy and breast feeding?
Herbal medicine can cause harm and almost half of pregnant women use herbal medicines
Breast feeding mothers should avoid herbal medicines due to the lack of information and contamination of herbal products with conventional medicines, pesticides or heavy metals
Some herbal medicines also have hormonal effects and some may contain constituents with sedative properties
what are the principles for prescribing in breast feeding?
- Again avoid unnecessary drug use
- Check on up to date drug information – may be lack of information
- In 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)
