Pharmacology in Pregnancy and Breast Feeding Flashcards
4 basic kinetic processes
- Absorption
- Distribution
- Metabolism and Elimination
- Excretion
Why may the oral route of administration be affected during pregnancy
- Morning sickness => vomiting
- Increased gastric emptying and motility (unlikely to be a problem with regular dosing but may affect single doses
Why would the IM route be affected during pregnancy
Blood flow is increased, so absorption from this route increases
Why would the inhalation route be affected during pregnancy
- Increased cardiac output
- Decreased tidal volume
- Both lead to increased absorption of inhaled drugs
What effect does the greater dilution of plasma, and therefore the decreased relative amount of plasma proteins, have on the distribution of drugs during pregnancy
Increased fraction of free drug
The effect of oestrogen and progestogens of P450 enzymes
Can inhibit or induce
In what way and why is excretion changed in pregnancy
What should be done to deal with this
- Increased
- GFR increased by 50%
- Increase the dosages of renally excreted drugs
Effect on absorption via oral route in pregnancy and why
- Reduced
- Increased vomiting, gastric emptying and gut motility
What 3 factors determine placental transfer of a drug
- Molecular weight (smaller crosses better)
- Polarity (non-polar crosses better)
- Lipid solubility (Lipid soluble drugs will cross)
At what molecular weight will drugs cross the placenta
MW < 500 Da (Dalton)
At what molecular weight will drugs NOT cross the placenta
MW > 1000 Da (Dalton)
Difference in foetal drug-protein binding vs adults and the result of this
- Less protein binding vs adults
- More “free” drug available
Foetal blood flow to brain vs adult
Relatively more blood flow to brain vs adult
Foetal enzyme activity (metabolism) vs adults
Less enzyme activity vs adults (increases with gestation)
Describe foetal excretion of drugs
- Excretion is into amniotic fluid
- Amniotic fluid is then swallowed, allowing for recirculation
- Drugs and metabolites and accumulate in the amniotic fluid
When does Teratogenicity refer to
When does Fetotoxicity refer to
- First trimester
- Second and third trimester
What period of gestation is the risk of teratogenicity at its highest
During organogenesis (3-8 weeks)
6 mechanisms of Teratogenicity
- Folate antagonism
- Neural crest disruption
- Endocrine disruption (sex hormones)
- Vascular disruption
- Oxidative stress
- Specific rector or enzyme mediate teratogenesis
5 Drugs that can cause folate antagonism and the result of it
- Methotrexate
- Trimethoprim (antibiotic for bladder infections)
- Phenytoin
- Carbamazepine
- Valproate
Tends to result in neural tube, oro-facial or limb defects
Drug that causes neural crest disruption
-Retinoid drugs (isotretinoin, used to treat severe acne or occasionally prevent skin cancers)
5 problems that result from neural crest disruption
- Aortic arch abnormalities
- Craniofacial malformations
- Oesophageal atresia (oesophagus ends in blind-ended pouch)
- Pharyngeal gland abnormalities
- Ventricular septal defects
Type of drug that causes enzyme-mediated teratogenesis and what that leads to
- NSAIDs
- Orofacial clefts and Cardiac septal defects
Define Fetotoxicity
Toxic effect on the foetus later in pregnancy (second and third trimester)
2 types of drugs that cause Fetotoxicity and what that leads to
- ACE inhibitors
- ARBs (Angiotensin II receptor blocker)
- Renal dysfunction and growth retardation
Scoring system for how safe a drug is during pregnancy
- A, Controlled human studies show no foetal risk
- B, Animal studies show no risk but no human studies have been conducted OR animal studies show risk to foetus but well controlled human studies don’t
- C, No adequate human or animal studies have been conducted OR risks shown in animals but no human data available
- D, Human foetal risk evident but benefits may outweigh the risk
- X, Proven foetal risk outweigh any possible benefit
3 anticonvulsants that are teratogens and their effects
- Valproate
- Phenytoin
- Carbamazepine
Neural tube defects
Anticoagulant that is a teratogen and its effect
Warfarin
Haemorrhage of foetus + multiple malformations of CNS and skeletal system
Antihypertensive drugs that are teratogens and their effect
ACE inhibitors + ARB’s
Renal damage + growth retardation
Effect of NSAIDs on foetus
-Premature closure of the ductus arteriosus
Retinoid that is a teratogen and its effect on the foetus
Isotretinoin
Neural crest disruption
6 drugs to avoid during breast feeding
- Cytotoxics (chemo)
- Immunosuppressants
- Anticonvulsants (not all)
- Amiodarone
- Lithium
- Radio-iodine
If prescribing Isotretinoin, to a woman of child bearing age, what 2 things must also be done with regards to the patient, according to the BNF
- Monthly pregnancy checks
- Use at least one (preferably 2) methods of contraception
When should you avoid using Trimethoprim for a UTI
BNF says avoid during 1st trimester
6 principles of prescribing in pregnancy
- Try non-pharmacological treatment first (if possible)
- 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
- Use drug with best safety record, avoid new drugs unless proven safe
Principles of prescribing in breast feeding
- Check on up to date info
- If licensed and safe in paediatric use (esp. under 2yrs) a drug is likely to be safe in breast feeding
- Choose drugs with pharmacokinetic properties that reduce infant exposure (e.g. highly protein bound)
Baby JR
- 3 weeks old
- Breast feeding
- Mother has lower back pain
What can she safely take
- Paracetamol + Ibuprofen, BNF notes amounts too small to be harmful in breast milk (though some manufacturers state avoid ibuprofen)
- Codeine USUALLY too small to be harmful, but maternal metabolism very variable so risk of morphine OD in baby
