Pharmacology in pregnancy Flashcards
When should you think about pregnancy?
In any woman of child bearing age - regardless if she is thinking she will get pregnant or not
Why should you also think about men whilst prescribing for pregnancy?
Certain medications can damage sperm
Can lead to foetal abnormalities
Why is untreated hypertension dangerous in all women of child bearing age?
As going in to pregnancy hypertensive increases risk massively of pre-eclampsia
Which of the ADME are affected in pregnancy?
All four Absorption Distribution Metabolism And excretion
How is the oral absorption route changed?
May be more difficult due to nausea/vomitting
Increased gastric emptying and gut motility
–(more of a problem with single doses than multi-treatment)
How is the intramuscular route changed in pregnancy?
Blood flow could be increased
Could lead to increased absorption
How is inhalation route changed in pregnancy?
Increased cardiac output and decreased tidal volume
Leads to drugs staying in lungs longer, increases absorption
Why does distribution change in pregnancy?
Increase in plasma volume and fat
Greater diltion of plasma protein relatively
How do the changes in pregnancy affect distribution?
Increased plasma volume/fat changes the volume of distribution
Dilution of plasma proteins results in a greater fraction of free drug (more active drug)
How does metabolism change during pregnancy
Oestrogen and progesterone induce (most) liver enzymes
This increases metabolism
(note some are also reduced)
Results in changes being needed to prescription levels
Need to monitor and alter doses on a case by case basis
How does excretion change during pregnancy?
Increased GFR leads to increased excretion
Can necessitate an increased in drug dose
What are the pharmacodynamic drug changes in pregnancy?
May affect site of action and receptor response to drugs
MOA may change (receptor change)
Concentrations/metablites of drugs may change (blood flow)
Effiacy may be different
Adverse affects (like in pregnancy) may be different
What does placenta transfer depend on?
Molecular weight (smaller better) Polarity (non-polar better) Lipid solubility (lipid soluble better)
Which drugs should you assume the placenta will transfer?
Assume all
May also metabolise some
How is distribution different in foetal pharmacokinetics?
Circulation different
Less protein, therefore more free drug available
Little fat, differnet distribution
Relatively more blood flow to brain (and not fully formed BBB)
How does metabolism differ in foetal pharmacokinetics?
Less enzyme activity (although increases with gestation)
Different isoenzymes to adults
How does excretion differ in foetal pharmacokinetics?
Excretion is into amniotic fluid which is then reabsorbed
Can lead to a build up of drugs in amniotic fluid
As placenta not working at delivery, can be issues with this
What are the two classes of adverse effects in pregnancy?
Teratogenicity
Foetotoxicity
Should you treat long term conditions in a pregnant woman?
Yes - lowers overall risk to child
If condition unmanaged and harm is doen to mother, harm will be done to child
What are the mechanisms of teratogenicity?
Folate antagonism Neural crest cell disruption Endocrine Disruption: Sex Hormones Oxidative Stress Vascular Disruption Specific Receptor- or Enzyme-mediated Teratogenesis
When is the biggest risk for teratogenicity?
During organgensis - weeks 3-8 (sometimes 12)
What are the mechanisms of folate antagonism?
Block conversion of folate into THF (irreversibly)
Block other enzymes in pathway
What defects come from folate anatagonism?
Neural tube defects
Oro-facial
Limb defects
What drugs disrupt folate?
Directly - methotrexate, trimetroprin
Other enzymes - pheyntoin, carbamazepine, valproate
What drugs disrupt neural cell development?
Retinoids
What are the potential presentations of neural crest cell disruption?
aortic arch anomalies ventricular septal defects craniofacial malformations oesophageal atresia pharyngeal gland abnormalities
What is enzyme mediated teratogenesis?
Where drugs interact with specific receptors and enzymes damaging fetal development.
Should women take NSAIDs when pregnnat? Why?
No - they cause enzyme mediated teratogenesis
Cause septal heart defects
Orofacial clefts
What are some potential issues resulting from foetotoxicity?
Growth retardation Structural malformations Fetal death Functional impairment Carcinogenesis
Why are ACEI no longer first line hypertensives in pregnant women?
Result in renal dysfunction and
growth retardation in foetuses
What are some known tetragenic drugs to avoid in pregnancy?
Anticonvulsants (neural tube defects)
Anticoagulants (although wafarin still sometimes used)
Antihypertensives (beta blockers first line)
NSAIDs
Alcohol
Retinoids
What drugs should be avoided when lactating?
Cytotoxics Immunosuppressants Anti-convulsants (not all) Drugs of abuse Amiodarone Lithium Radio-iodine
What are the principles of prescribing to women of childbearing age?
Always think pregnancy as a possibility
Warn women of possible risks
Advise women to attend doctor before getting pregnant
Discuss contraception - potentially do not prescribe until on at least one contraceptive (preferably 2)
What are the principles of prescribing in pregnancy?
No-pharmacological treatments first if possible
Use drug with best safety record (not new drugs)
Lowest effective dose
Avoid first 10 weeks if possible
Consider stopping/reducing before delivery
Don’t under-treat potentialy dangerous diseases
Use for shortest period possible
Chec with specialist if unsure
What are the principles of prescribing in breast feeding?
Avoid unessecary drug use (again)
Check information is up to date
Likely to be safe if liscensed in paedeatric use (especially under 2s)
Choose drugs that reduce pharmacokinetic properties that reduce infant exposure
