Pharmacology in Pregnancy and Breast Feeding Flashcards
What are the different aspects of pharmacokinetics?
- Absorption
- Distribution
- Metabolism
- Excretion
What are some common reasons for prescribing during pregnancy?
- Hypertension
- Asthma
- Epilepsy
- Migraine
- Mental health disorders
- Long term anticoagulant use
What are some absorption changes during pregnancy?
Oral route:
- Morning sickness
- Decrease in gastric emptying and gut motility
Intramuscular route (IM):
- Blood flow increase, so absorption enhanced
Inhalation:
- Increased cardiac output and decreased tidal volume may increase absorption
What are some distribution changes during pregnancy?
- Increase in plasma volume and fat
- Increases volume of distribution
- Greater dilution of plasma
- Decrease relative amount of plasma proteins so increase fraction of free drug
What are some metabolism changes during pregnancy?
Oestrogen and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing metabolism
What are some excretion changes during pregnancy?
GFR increased in pregnancy by 50%, causing increased excretion of many drugs:
- Can reduce plasma concentration and necessitate an increase in dose
What is pharmacodynamics?
Drug effect on body
What is pharmacokinetics?
Bodies effect on drugs
What pharmacodynamic changes can occur during pregnancy?
- Site of drug action
- Receptor response to drugs
- Efficacy may be difference
- Adverse effects may be different
What do drugs need to cross before reaching the foetus?
The placenta, which most drugs can
What are some factors affecting placental drug transfer and drug effect on the foetus?
- Drug physiochemical properties
- Rate at which drug crosses placenta and amount reaching foetus
- Duration of drug exposure
- Distribution in different foetal tissues
- Stage of placental and foetal development
- Effect of drugs when used in combination
What does placental transfer depend on?
- Molecular weight
- Smaller sizes cross more easily
- Polarity
- Unionised molecules cross more readily
- Lipid solubility
- Lipid soluble drugs will cross
How is distribution different in a foetus?
- Circulation is different
- Such as 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
How is metabolism different in a foetus?
- Reduced enzyme activity, although increases with gestation
- Different P450 isoenzymes to adults
How is excretion different in a foetus?
- Excretion is into amniotic fluid, which foetus then swallows leading to recirculation
- Drugs and metabolites can accumulate in amniotic fluid
- Placenta not functioning at delivery so can be issues with excretory function
Is there a lot of guidance about prescribing during pregnancy?
Due to lack of research there is uncertainty around dosing, some information is available for some drug groups:
- Anti-convulsants
- Anti-hypertensives
- Analgesics
- Antibacterials
What are the principles for prescribing for woman of child bearing age?
- Always consider possibility of pregnancy
- Warn of possible risks
- When treating conditions, advise woman to attend before getting pregnant
- Discuss contraception
What are the principles of prescribing during pregnancy?
- Try non-pharmacological measures first
- Use safest drug, avoiding new drugs unless proven safe
- Use lowest effective dose
- Avoid in first 10 weeks of pregnancy
- Consider stopping or reducing drug before delivery
What are the two major risks of taking drugs during pregnancy?
- Teratogenicity (mostly occurs during first trimester)
- Fetotoxicity (most occurs during second and third trimester)
When does teratogenecity and fetotoxicity mostly occur?
Teratogenecity - first trimester
Fetotoxicity - second and third trimester
What are teratogenic drugs?
Teratogen is an agent that can disturb the development of the embryo or foetus
When is the highest risk of teratogenecity?
During organogenesis (weeks 3-8)
Through what mechanisms do teratogenic drugs act?
- Folate antagonism
- Key process in DNA formation
- 2 groups of drugs affect folate metabolism
- Block conversion of folate to THF by binding irreversibly to the enzyme
- Block other enzymes in folate pathway
- Tends to result in neural tube, oro-facial or limb defects
- Neural crest cell disruption
- Associated with retinoid drugs
- Problems includes aortic arch anomalies, ventricular septal defects, craniofacial malformations, oesophageal atresia, pharyngeal gland abnormalities
- Endocrine disruption
- Oxidative stress
- Vascular disruption
- Specific receptor or enzyme mediated teratogenesis
What is folate key for?
DNA formation
How do the 2 groups of drugs that block folate metabolism work?
- Block conversion of folate to THF by binding irreversibly to the enzyme
- Block other enzymes in folate pathway
What kind of defects does folate metabolism tend to cause?
- Tends to result in neural tube, oro-facial or limb defects
What drug is neural crest disruption associated with?
- Associated with retinoid drugs
What kinds of problems does neural crest disruption cause?
- Problems includes aortic arch anomalies, ventricular septal defects, craniofacial malformations, oesophageal atresia, pharyngeal gland abnormalities
What are some examples of known teratogens?
- Anticonvulsants
- Neural tube defects
- Anticoagulants
- Haemorrhage
- Antihypertensive agents
- Renal damage and restrict normal growth
- NSAIDs
- Premature closure of ductus arteriosus
- Alcohol
- Foetal alcohol syndrome
- Retinoids
- Ear, CNS, cardiovascular and skeletal disorders
What are some possible issues due to fetotoxicity?
- Growth retardation
- Structural malformation
- Foetal death
- Functional impairment
- Carcinonogenesis
Why is taking drugs during lactation an issue?
Almost all drugs mother takes will be present in breast milk
Describe the strategy of drug prescription during breast feeding?
- Is drug necessary
- If yes, is it safest option
- Non-pharmacological strategies
- Avoid drugs with long half life
- Use drugs that are highly protein bound
What are some examples of drugs that should be avoided in breastfeeding?
- Cytotoxics
- Immunosuppresants
- Anti-convulsants
- Drugs of abuse
- Amiodarone
- Lithium
- Radio-iodine
