Pregnancy and breastfeeding Flashcards
Describe the significant factors affecting the pharmacokinetics and pharmacodynamics of drugs in pregnancy and breastfeeding
Recognise the importance of providing effective advice to women pre-conception, during pregnancy and whilst breast-feeding
Know where to find information to inform your discussions regarding the safety of taking medicines whilst pregnant / breast feeding
whats the high risk time for fetus?
first trimester- where women also enter well before realising pregnant
drugs pregnant women in Europe often may take? epidemiology
legal: POM, P, GSL
also illicit drugs, alcohol, smoke
what types of drugs prescribed in pregnancy to treat problems
minor ailments:
- analgesics
- antibiotics
- for migraine
pregnancy induced disorders
chronic problems:
- asthma
- epilepsy
- depression/psychiatric
- HIV
what to consider regarding drugs for chronic disorders in pregnancy? Examples
dont stop them as disease itself may adversely affect pregnancy/ become worse
(epilepsy,diabetes,hypertension)
e.g. epilepsy=fit, fetus damaged
what proportion of med molecules are genuine human teratogens?
< 30 med molecules = genuine human teratogens
important to counsel patient as could = excess harm
3 specific OTC meds that may be taken in pregnancy?
paracetamol, alginates, osmotic laxatives (lactulose)
what OTC meds to AVOID in pregnancy?
ibuprofen, cough and cold formulations, antihistamines, nasal decongestants
reasons meds adherance may decrease in pregnancy?
doubt about drug use, side effects, complaints for drugs prescribed disappear- sometimes imporve
importance of pre-conception counselling and what to address?
biomedical/behavioural issues posing a risk to the health of woman or foetus
‘window of oppurtunity’ before pregnancy confirmed- discuss risks/benefits of drug therapy and begin prophylaxic (folic acid) and immunisations where req.
type of pharmaceutical interventions to make in pre-conception counselling
- prophylactic drugs (can prevent adverse consequences during pregnancy)
- appropriate immunisation
- ensure can make informed decisions about therapeutic drugs too
reason for prescribing folic acid
needed for proper haematopoeisis, lowers risk of fetus having neural tube defect
what to consider and advise regarding other vitamin supplements in pregnancy?
some may cause ADRs in pregnancy e.g. high dose Vit A = teratogenic.
give appr advice
when folic acid prescribed and why then?
first trimester (until wk 12) as when neural tube and CNS developing in fetus
what can increase risk of NTD (neural tube defects) based on? (3)
- partner w/ NTD, previous child w/ NTD, family history of NTD
- anti-epileptic drugs or diabetic
- BMI >30kg/m2 obese
folic acid dose prescribed for
a) normal risk NTD
b) high risk NTD
a) Folic acid 400mg daily until trim 1/wk12
b) folic acid 5mg daily
What should women seeking emergency contraception, who have used cytochrome P450 3A4 (CYP3A4) enzyme inducers within the last 4 weeks use ?
- preferably non‐hormonal emergency contraceptive (a copper IUD)
- if this is not an option, double the usual dose of levonorgestrel from 1.5 milligrams to 3 milligrams (i.e. 2 packs)
5 enzyme inducer drugs? that hence reduce plasma levonorgestrol (emergency contraception) conc?
- Antiepileptics (e.g. barbiturates, primidone, phenytoin, carbamazepine)
- Anti‐tuberculosis (e.g. rifampicin, rifabutin)
- HIV medicines (e.g. ritonavir, rifabutin)
- Antifungals (e.g. griseofulvin)
- Herbal remedies that contain St John’s Wort
pregnancy affect of absorption of drug (3)
affect of nausea+vomiting
Nausea and vomiting:
- ↑ gastric pH
- ↑ gut transit time
- ↓ gastric emptying
Increased absorption from IM injections + inhalation
Change in bioavailability
pregnancy affect on metabolism of drug
- hepatic blood flow
- P450 (increased/decreased)
- UGT (enzymes - increased)
- P glycoprotein
- N-demethylation
overall change in drug metabolism
pregnancy affect on distribution of drug
Increased:
- ECF
- plasma volume
- pH
- fat
- volume of distribution
Decreased:
- albumin
- concentration
Change in drug protein binding
pregnancy affect on elimination of drug 2
- renal blood flow & GFR
- hepatic blood flow & cholestasis
overall change in drug elimination
changes not clinically significant for most drugs BUT what drugs to carefully monitor?
drugs w narrow therapeutic index:
e.g. antiepileptics, enoxaparin
- may alter dosing
- monitor drug conc/clinical effects
- effect may be delayed after oral dose/ enhanced after IM
Critical periods in human development
- Important during first 12 weeks during embryogenesis
- may even be potential harm pre-implantation
What is a teratogen?
substance, organism, physical agents/ deficiency state capable of inducing abnormal structure or function:
- Gross structural abnormalities
- Functional deficiencies
- Intrauterine Growth Restriction (IUGR)
- Behavioural aberrations
- Demise
some seen later in life
In the context of pharmacodynamics & teratology, how does the predictability of maternal and foetal effects compare?
- Maternal effects are largely predictable
- Foetal effects are less predictable
What percentage of congenital malformations do drugs account for?
2-3%
difficult to separate effect of condition form that of drug
In the context of pharmacodynamics & teratology, what does susceptibility depend on? (2)
- genotype of mum and baby
- developmental stage
partly environmental?
What are the US FDA pharmaceutical pregnancy categories?
Category A, B, C, D , X
What is teratogenicity?
the potential for a drug to cause foetal malformations and affects the embryo 3‐8 weeks after conception
drugs can cause congenital malformations
During which weeks of the 1st trimester is the highest risk and why?
3rd to 8th - organ systems are formed
What is meant by the ‘all-or-nothing effect’ in the context of teratogenicity? And when
this is the pre-embryonic phase (days 0‐14 after conception) which can lead to recovery or spontaneous loss (abortion)
What is fetotoxicity?
And when does it happen
when drugs can affect growth and functional development or have toxic effects on tissues
2nd and 3rd trim-where organs formed
How can drugs adversely affect the foetus in the 2nd and 3rd trimester? (3)
- cause fetotoxicity
- some functional effects (some reversible) may extend into neonatal period
- adverse effects on neonate if given shortly before or during labour e.g. diazepam or pethidine may affect the neonate
What should we assume about all drugs when prescribing in pregnancy?
all drugs will be able to cross the placenta unless they have a high MW
What do we avoid when prescribing in pregnancy?
- prescribing in 1st trimester if possible
- medicines known to be harmful
- prescribing unless the benefit to mother outweighs risk to foetus e.g. antiepileptics for management of epilepsy
What drugs/ classes should be avoided in the 1st trimester of pregnancy? 8
- Androgens
- cytotoxic drugs
- lithium
- quinolone antibiotics
- retinoids
- sodium valproate
- thalidomide
- warfarin
What drug classes should be avoided in the 2nd & 3rd trimester of pregnancy?
- ACEi and ARBs (Angiotensin receptor blockers)
- aminoglycosides
- NSAIDs, aspririn
- opiates, benzodiazepines
- sulphonamides
- tetracyclines
Why do doses need to be adjusted in pregnancy? (2)
- physiological changes of pregnancy = maternal
drug conc is lower than non‐pregnant women taking
the same dose - foetal and placental metabolism affects drug conc
Explain how enoxaparin and lamotrigine need to be adjusted during pregnancy
- Renal elimination of enoxaparin requires ↑ dose
- Lamotrigine metabolism significantly enhanced requires ↑↑dose
careful:conc of bound and free drug may vary
Pregnancy Prevention program (PREVENT) example of Valproate
- New guidance (2018): valproate medicines (Epilim®, Depakote®) must no longer be used in women or girls of childbearing potential unless a Pregnancy Prevention Programme is in place
- Annual risk assessment MUST take place for all premenopausal
women
What 3 recommendations have been made based on sodium valproate’s discovered risk?
- Communicate risks- are aware prior to family planning decisions
- Establishing specialist centres for families affected by teratogenic medication.
- Measures to reduce and monitor effects of other medications which are regularly taken during pregnancy, and considered to have teratogenic potential, or known risk above that of the general population.
What will the BNF typically say about all drugs when prescribing while pregnant?
- Drugs can have harmful effects on the fetus at any time…
- Drugs can produce congenital malformations (teratogenesis)
- ….only if expected benefit to the mother > risk to the foetus
What are 4 good info sources when looking at drugs and pregnancy?
- BNF (absence of info doesn’t mean safe)
- Summary of Product
Characteristics (medico‐legal statements about
pregnancy and breastfeeding) - consult TOXBASE (www.toxbase.org)
- UK teratology information service (www.uktis.org)
What is the recommended length of exclusive breastfeeding?
until 6 months
Why is avoiding breastfeeding to take prescribed drugs not a no harm option?
benefits of breastfeeding will be lost (immunity, reduced risk of allergy in infant)
What does the safety of drug use whilst breastfeeding depend on? (6)
- the passage of a drug into breast milk
- subsequent absorption in the infant
- the adverse drug reaction profile
- infant age
- infant co‐morbidities
- effective clearance of the drug
How do drugs interact with breast milk?
- they can be excreted into it
- most drugs pass in small quantities and are not a concern
What age group of infants are at a greater risk from exposure to drugs via breast milk and why?
- neonates (and particularly premature infants)
- immature excretory functions and the consequent risk of drug accumulation
When prescribing in breastfeeding, what can we infer the potential of harm to the infant from?
– the amount of active drug delivered to infant in breast milk
– efficiency of absorption, distribution and elimination of drug by infant (infant pharmacokinetics)
– the effect of the drug on infant (infant pharmacodynamics)
Why is timing of med important when prescribing in breastfeeding? (2)
- related to feeding
- mother may express milk prior to taking drug so can feed infant while conc of drug is highest to avoid peak levels in milk
Which drugs are considered to be compatible with breastfeeding and why?
drugs associated with reduced passage into breast milk as:
- High MW (e.g. insulin, heparins)
- High protein binding (e.g. warfarin, NSAIDs)
- Low lipid solubility (e.g. loratadine)
- Lower pH (e.g. amoxicillin; as pH of plasma is about 7.4 and that of breast milk is 6.9 the conc of acidic drugs in breast milk will be low)
What should be avoided when prescribing in breastfeeding?
- unnecessary drug use (including OTC meds)
- the use of drugs known to cause toxicity in adults or children
When prescribing in breastfeeding, you should choose a regimen + route which presents the XXX amount of drug.
When prescribing in breastfeeding, you should choose a regimen + route which presents the minimum amount of drug
multidose regimens and MR preps may have increased risk
What drugs should be avoided in breastfeeding (and what are their adverse effects)?
- Amiodarone
- Antithyroid drugs
- Benzodiazepines
- Li salts
- radioactive iodine
- Statins
- Sulphonamides
Special case of codeine/tramadol in breastfeeding
potentially serious ADR
- some breastfeeding women can ultrarapid CYP2D6 metabolisers
- can = ultra-rapid conversion of codeine to morphine and tramadol to M1 leading to high/unsafe levels in breast milk
- can = serious ADRs in infants (excess sleepiness, difficulty breastfeeding, serious breathing problems →death)
- contraindicated in breastfeeding therefore
How do dopamine affecting drugs affect breastfeeding?
- affect lactation by changing plactin
- dopamine agonists (e.g. cabergoline) decrease milk production
- dopamine antagonists (e.g. domperidone) may promote lactation when inadequate
- some drugs can also inhibit infant’s suckling reflex (e.g phenobarbital)
why progesterone recommended over oestrogen as initial contracetption
early postpartum use of oestrogen may reduce milk volume- progesterone rec as initial contraception
What are 4 good sources to check for drugs and breastfeeding?
- BNF
- UK Drugs in Lactation Advisory
Service (UKDILAS - general guidance and drug
monographs) - United States National Library of Medicine Lactmed database (http://toxnet.nlm.nih.gov/cgi‐ bin/sis/htmlgen?LACT)
- Specialist Pharmacy Service
Statement concerning the safety of drug use in pregnancy and breastfeeding
A drug that is safe to use during pregnancy does not necessarily mean that it is safe to use in breastfeeding (and Vice Versa)
Is flucloxacillin excreted in breast milk likely to be harmful to the baby
Babies can be prescribed flucloxacillin
Flucloxacillin changes gut microbiota which will cause runny nappies at most and might make the breastmilk taste off
For flucloxacillin excreted in small amounts the risk is acceptable to continue breast feeding
consider that the small amount present could affect frequency of babies stools
Is co-codamol advised in breastfeeding women?
Codeine gets metabolised to morphine – different people metabolise it at different rates
Paracetamol or ibuprofen is used instead
