Pharmacology Flashcards
Common reasons pregnant women are on medication?
- Hypertension
- Migraine
- Asthma
- Epilepsy
- Long term anticoagulant therapy
- Mental health disorders
What are the four basic kinetic processes?
- Absorption
- Distribution
- Metabolism and elimination
- Excretion
Absorption changes: Oral? intramuscular route? Inhalation?
Oral:
- Morning sickness causes difficulties (nausea/vomming)
- Increased gastric emptying and gut motility: may affect single doses
Intramuscular:
- Blood flow may be increased, so absorption may also increase using this route
Inhalation:
- Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs
Distribution changes in pregnancy?
- Increased plasma volume and fat will effect distribution [increased volume of distribution]
- Greater dilution of plasma will decrease relative amount of plasma proteins [greater fraction of free drug]
What are the metabolism changes during pregnancy?
- Oestrogen and progesterones can induce or inhibit liver P450 enzymes, increasing or reducing metabolism
What is the effect on the excretion during pregnancy?
- GFR is increased in pregnancy meaning there is an increased excretion of drugs
- This can reduce the plasma concentration, and can necessitate an increase in dose of renally cleared drugs
What does the placental transfer of medication depend upon?
- Molecular weight (smaller sizes will cross more easily)
- Polarity (non-polar cross more readily)
- Lipid solubility (lipid soluble drugs will cross)
- Placenta may also metabolise some drugs
- Safest to assume all drugs will cross placenta
Fetal pharmacokinetics: how does distribution differ?
- Circulation is different
- Less protein binding than adults therefore more ‘free’ drug is available
- Little fat so this effects distribution
- Relatively more blood flow to the brain
Fetal pharmacokinetics: how does metabolism differ?
- Less enzyme activity, though increases with gestation
- Different isoenzymes to adults
Fetal pharmacokinetics: hows does excretion differ?
- Excretion is into amniotic fluid – this is swallowed and can allow recirculation
- Drugs and metabolites can accumulate in amniotic fluid
- Placenta not functioning at delivery so can be issues with excretory function
What trimester does teratogenicity have importance?
First trimester
At which trimester(s) does Fetotoxicity have effect?
2nd and 3rd
What are 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 is folate antagonism and what are the effects on the fetus?
- Key process in DNA formation and new cell production
- The drugs will either block the conversion of folate to THF by binding irreversibly to the enzyme or block other enzymes in the pathway
- This results in neural tube defects, oro-facial or limb defects
Which drugs can cause neural crest cell distribution issues? and effect on fetus?
- Retinoid drugs (isotretinoin)
Problems:
- Aortic arch anomilies
- Ventricular septal defects
- Craniofacial abnormalities
- Oesophageal atresia
- Pharyngeal gland abnormalities
