Pharmacology in Pregnancy Flashcards
What ‘high risk’ woman should be put on aspirin during pregnancy?
Elderly, HTN, high BMI, prev pregnancy problems
How will absorption via oral route change in pregnancy?
May decrease due to nausea and vomiting but unlikely to affect continuous therapy
How will IM absorption change in pregnancy?
BF increases so likely to increase
How will inhalatory absorption change in pregnancy?
Increases as CO increased and TV decreased so drug sits in lungs for longer
How is the Vd affected in pregnancy?
Increases (increase in fat and plasma volume)
What is the volume of distribution?
Volume of water that would contain the total amount of the substance in the same concentration as it is in the plasma
How do you work out Vd?
Total volume of drug/concentration in plasma
Greater dilution of plasma in pregnancy results in what?
Relatively less plasma proteins –> increased free drug
What plasma protein is often reduced in pregnancy?
Albumin
How does metabolism change in pregnancy?
Oestrogen/progesterone tend to induce P450 enzymes –> increased metabolism
How is excretion changed in pregnancy?
Increased GFR (by 50%) leads to increased excretion of some drugs
What are the pharmacodynamic changes in pregnancy?
Receptor/action of drug can change –> different efficacies and different ADRs
What are the functions of the placenta?
Attach foetus to uterine wall
Provide nutrients to foetus (e.g. lipids, oxygen, glucose, viruses, antibodies etc..)
Take waste away from foetus (e.g. urea, CO2)
What features of a drug would increase its chances of crossing the placenta?
Small size (MW <500Da), lipophilic, non-polar Doesn't matter if protein bound or not (will set up equilibrium)
What can the placenta do to drugs?
Allow their transfer or not
May also metabolise them
How does the foetal distribution of drugs differ to ours?
Different circulation (umbilical vein to liver)
Less plasma proteins –> increased free drugs
Less fat –> different distribution
More BF to brain
Inefficient BBB
How does foetal metabolism differ?
Different isoenzymes
Less enzymes
So less metabolic activity
How does foetal excretion differ?
Excretion into amniotic fluid which leads to accumulation/recirculation of the drug
Define teratogenicity
An agent that disturbs development of the foetus/embryo in the first trimester
What are the key ways that teratogens can affect development?
Folate antagonism Neural crest cell disruption Endocrine disruption Oxidative stress Vascular disruption Specific receptor/enzyme effect
Why are trimethoprim and methotrexate teratogenic?
Block enzyme converting folate into tetrahydrofolate
What other drugs block enzymes in the folate metabolism pathway?
Phenytoin, carbamazepine, Na valproate
What is the action of folate?
Involved in new DNA formation
What does folate antagonism lead to?
Neural tube defects, orofacial/limb defects
What drugs cause neural crest cell disruption?
Retinoids
What is the result of disruption of crest cells?
Aortic arch anomalies, VSDs, pharyngeal gland abnormalities, oesophageal atresia, cranio-facial malformations
Define fetotoxicity
Toxicity to the foetus in the 2nd/3rd trimester
Describe the classification of safety of drugs on foetuses
A - safe as shown by human studies
B - safe as shown by animal studies
C - no studies
D - unsafe, but benefits may outweight risks of use in certain scenarios
X - benefits won’t outweight risks, e.g. Na valproate
What are the effects of anticonvulsants?
Neural tube defects
What are the effects of warfarin?
Haemorrhaging foetus, CNS/skeletal malformatiosn
What are the effects of ACEi/ARBs?
Renal damage and IUGR
What are the effects of NSAIDs?
Premature closing of AD
What are the effects of alcohol?
Foetal alcohol syndrome
What are the effects of retinoids?
Ear, CNS, CV and skeletal disorders
What drugs should you avoid in breast feeding?
Cytotoxics Lithium Amiodarone Drugs of Abuse Anti-convulsants Immunosupressants Radio-iodine
What are the key things to remember when prescribing to pregnant woman?
Use safest drug, for shortest time/intermittently, try avoid 1st 10wks or consider stopping/reducing before birth, don’t under Rx (esp in asthma, epilepsy etc.)
What are the key things to remember when prescribing to a breast feeding woman?
Try use highly protein bound drugs and those safe in <2y
Possibly avoid herbals
