Pharmacology in Pregnancy Flashcards
Why may a woman be on medications in pregnancy?
Hypertension Asthma Epilepsy Migraine Mental health disorders Long-term anticoagulant therapy.
How may absorption of a drug change during pregnancy?
Oral route - morning sickness and general nausea and vomiting makes it more difficult. Increase in gastric emptying/ gut motility may affect single doses.
Intramuscular route - Blood flow may be increased so absorption may also increase.
Inhalation - increased cardiac output and decreased tidal volume may cause increased absorption.
How may distribution of a drug be affected in pregnancy?
Increase in plasma volume and fat changes distribution of drugs.
Greater dilution of plasma will decrease relative amount of plasma proteins increasing the fraction of free drug.
How may drug metabolism be affected in pregnancy?
Oestrogen and Progesterone can induce or inhibit liver P450 enzymes, increasing or reducing metabolism.
e.g phenytoin level reduced due to induction of metabolism.
theophylline levels increased due to inhibition in metabolism.
How may drug excretion be affected during pregnancy?
GFR increased by 50% in pregnancy leading to increased excretion.
This can reduce plasma conc. and necessitate an increase in dose of renally cleared drugs.
What are some pharmacodynamic changes that occur during pregnancy?
Less well understood as little data on pregnant women.
May affect site of action and receptor response.
Efficacy and adverse affects may be different.
What materials are exchanged from mother to foetus across the placenta?
Oxygen Glucose Amino acids Lipids, fatty acids, glycerol Vitamins Ions Alcohol, nicotine, other drugs Viruses Antibodies
What materials are exchanged from foetus to mother across the placenta?
Carbon dioxide
Urea
Waste products
What does placental transfer depend on?
Molecular weight - smaller sizes cross more easily.
Polarity - non polar cross more readily.
Lipid solubility - lipid soluble drugs can cross.
Protein binding - both bound and unbound can cross.
How does foetal pharmacokinetics affect distribution?
Circulation is different as umbilical vein goes straight to foetal liver.
Less protein bounding than in adults so more free drug available.
Little fat
Relatively more blood flow to brain.
How does foetal pharmacokinetics affect metabolism?
Less enzyme activity, though this increases with gestation.
Different isoenzymes than in adults.
How does foetal pharmacokinetics affect excretion?
Excrete into amniotic fluid which is swallowed and lead to recirculation.
Drugs and metabolites may accumulate in amniotic fluid.
Placenta does not function at delivery so can be issues with excretory function.
What is teratogenicity?
The capability to cause congenital abnormalities following foetal exposure during pregnancy.
When does teratogenicity occur?
First trimester
What is fetotoxicity?
Toxic effects on the foetus by a substance that crosses the placental barrier.
When does fetotoxicity occur?
Second and Third trimester
What are some mechanisms of action of teratogens?
Folate antagonism Neural breast cell disruption Endocrine disruption to sex hormones Oxidative stress Vascular disruption Specific receptor/enzyme mediated teratogenesis.
What is folate?
Essential amino acid that is key in the process of DNA, RNA and new cell production.
How may drugs antagonise folate production?
Block the conversion of folate to THF by binding irreversibly to the enzyme. e.g methotrexate, trimethoprim.
Block other enzymes in the pathway e.g phenytoin, carbamazepine, valproate.
What does folate antagonism tend to result in?
Neural tube defects
Oro-facial defects
Limb defects
Which group of drugs disrupt neural crest cells?
Retinoid drugs e.g Isotretinoin for acne.
What abnormalities can neural crest cell disruption result in ?
Aortic arch anomalies Ventricular septal defects Craniofacial malformations Oesophageal atresia Pharyngeal Gland abnormalities.
What is Enzyme mediated teratogenesis?
Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes, damaging foetal development.
e.g NSAIDs causing orofacial clefts and cardiac septal defects.
What are some possible issues of fetotoxicity?
Growth retardation Structural malformations Foetal death Functional impairment Carcinogenesis
e.g ACE inhibitors/ARBs causing renal dysfunction and growth retardation.
What is a category A drug?
Controlled human studies show no foetal risks, safest.
What is a category B drug?
Animal studies show no risk to foetus but no controlled human studies have been conducted.
or
Animal studies show a risk to the foetus but well-controlled human studies do not.
What is a category C drug?
No adequate human or animal studies have been conducted or adverse foetal effects have been shown in animals but no human data was available.
What is a category D drug?
Evidence of human foetal risk exists but benefits may outweigh risks in certain situations.
What is a category X drug?
Proven foetal risks outweigh any possible benefit.
What are some examples of known teratogens to avoid during pregnancy?
Anticonvulsants - e.g valproate, phenytoin, carbamezapine.
Anticoagulants - e.g warfarin
Antihypertensives - e.g ACE Inhibitors
Non-Steroidal Anti-Inflammatory Drugs
Alcohol
Retinoids
What are some examples of drugs to avoid during breastfeeding?
Cytotoxics Immunosuppressants Anti-convulsants Drugs of abuse Amiodarone Lithium Radio-iodine
What are the principles of prescribing for women of child bearing age?
- Always consider possibility of pregnancy (planned or not).
- Warm women of possible risks
- Advise women to attend before getting pregnant to treat medical conditions
- Discuss contraception
- if necessary do not prescribe without contraception.
What are the principles of prescribing in Pregnancy?
- Try using non-pharmacological treatment first
- Use drug with best safety record
- Check summary of product characteristics for up to date info
- Use lowest effective dose
- Use drug for shortest time possible and intermittently if you can
- Avoid first 10weeks of pregnancy if possible
- Consider stopping or reducing before delivery
- Don’t under treat disease which may be harmful to foetus.
