Pharmacology in Pregnancy Flashcards
What percentage of pregnant women will take a drug during pregnancy?
50-90%
List some absorption changes in pregnancy?
- Oral route changes due to ‘morning sickness’/Increase in gastric emptying and gut motility
- Intramuscular (Blood flow may be increased -^absorption)
- Inhalation (Increased CO, decreased tidal volume - can increase absorption)
List some distribution changes in pregnancy?
- Increases in plasma volume and fat
- Greater dilution of plasma will decrease relative amount of plasma proteins ^fraction of free drug
List some metabolism changes in pregnancy?
-Oestrogen/Progestogens can induce/inhibit P450 enzymes, increase/reduce metabolism.
(Eg Phenytoin reduced/Tehophylline increased)
List some excretion changes in pregnancy?
- GFR ^ - ^Excretion
- Can reduce plasma conc, so need to increase dose of renally cleared drugs
What are the pharmacodynamic changes in pregnancy?
- May affect site of action and receptor response to drugs
- Efficacy/adverse effects may be different
Do most drugs cross the placenta?
Yes
What does placental transfer depend on?
- Molecular weight
- Polarity (non-polar crosses easier)
- Lipid solubility
- Charge
What are the distribution differences in fetal pharmacokinetics?
- Circulation different
- Less protein binding - more ‘free drug’ available
- Little fat, different distribution
- Relatively more blood flow to brain
What are the metabolism differences in fetal pharmacokinetics?
- Less enzyme activity (increases with gestation)
- Different isoenzymes to adults
What are the excretion differences in fetal pharmacokinetics?
- Excretion into amniotic fluid, swallowed and can allow recirculation
- Drugs and metabolites can accumulate in amniotic fluid
- Placenta not functioning at delivery - can be issues with excretory function
What issues are there with sodium valproate (anti-convulsant) in pregnancy?
Teratogenicity
Neural tube defects
What trimester does teratogenic drugs affect?
First trimester
What trimesters do fetotoxic drugs affect?
Second and Third timester
List some mechanisms of teratogenicity
- Folate Antagonism
- Neural Crest Cell Disruption
- Endocrine Disruption: Sex Hormones
- Oxidative Stress
- Vascular Disruption
- Specific Receptor- or Enzyme-mediated Teratogenesis
What defects are usually seen in folate antagonism?
Neural tube defects
Oro-facial defects
Limb defects
List some drugs involved in folate antagonism
Methotrexate, Trimethprim (Block coversion of Folate to THF)
Phenytoin, Carbazepine, Valproate (Block other enzymes in pathway)
What defects may arise from neural crest cell disruption?
Aortic arch anomalies Ventricular septal defects Craniofacial malformations Oesophageal atresia Pharyngeal gland abnormalities
What class of drugs may be involved in neural crest cell disruption?
Retinoids (eg isotretinonin)
Give an example of drugs involved in enzyme-mediated teratogenesis?
NSAIDs causing orofacial clefts and cardiac septal defects
List some possible issues from fetotoxicity?
- Growth retardation
- Structural malformations
- Fetal death
- Functional impairment
- Carcinogenesis
Give an example of a fetotoxic drug?
ACE inhibitors/ARBs - renal dysfunction and growth retardation
List some examples of known teratogens to avoid in pregnancy?
Anticonvulsants (Valproate) Anticoagulants (Warfarin) Antihypertensive agents (ACE inhibitors) NSAIDs Alcohol Retinoids
List some drugs to avoid in lactation
- Cytotoxics
- Immunosuppressants
- Anti-convulsants (not all)
- Drugs of abuse
- Amiodarone
- Lithium
- Radio-iodine
- Also avoidance of some herbal remedies (Fenugreek, comfrey)
