Pharmacology in Pregnancy and Breast Feeding Flashcards
1
Q
What are the four basic pharmacokinetic processes?
A
- absorption
- distribution
- metabolism and elimination
- excretion
2
Q
Absorption changes during pregnancy
A
- Oral route
- May be more difficult “morning sickness” nausea/vomiting
- Decrease in gastric emptying and gut motility
- This is unlikely to be a problem with regular dosing, but may affect single doses
- Intramuscular route
- Blood flow may be increased, so absorption may also increase using this route
- Inhalation
- Increased cardiac output and increased tidal volume may cause increased absorption of inhaled drugs
3
Q
Distribution changes during pregnancy
A
- Increase in plasma volume and fat will change distribution of drugs
- Greater dilution of plasma will decrease relative amount of plasma proteins
- Increased Fraction of Free Drug
4
Q
Metabolism changes during pregnancy
A
Oestrogen and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing metabolism.
5
Q
Excretion changes during pregnancy
A
- GFR is increased in pregnancy by 50% leading to increased excretion of many drugs.
- This can reduce the plasma concentration, and can necessitate an increase in dose of renally cleared drugs.
6
Q
Pharmacodynamic changes during pregnancy
A
- Pregnancy may affect site of action & receptor response to drugs
- Concentration of drug and metabolites at sites of biological action (changes in blood flow)
- Mechanism of action (changes in receptors)
- Efficacy may be different
- Adverse effects may be different
7
Q
What does placental transfer of drugs depend on?
A
- Molecular weight (smaller sizes will cross more easily)
- Polarity (non-polar cross more readily)
- Lipid solubility (lipid soluble drugs will cross)
8
Q
Foetal pharmacokinetics distribution
A
- Circulation different (e.g. 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
9
Q
Foetal pharmacokinetics metabolism
A
- Less enzyme activity, though increases with gestation
- Different isoenzymes to adults
10
Q
Foetal pharmacokinetics excretion
A
- NB excretion is into amniotic fluid - this is swallowed and can allow recirculation
- Drugs and metabolites can accumulate in amniotic fluid
11
Q
What causes drugs to be unsafe during pregnancy?
A
- Teratogenicity (first trimester)
- Fetotoxicity (second and third trimester)
- NB Under treatment of chronic illnesses due to fear of using drugs during pregnancy may cause greater fetal risk!
12
Q
When is the biggest risk of teratogenicity?
A
During organogenesis - weeks 3-8
13
Q
What are some mechanisms of teratogenicity?
A
- Folate Antagonism
- Neural Crest Cell Disruption
- Specific Receptor or Enzyme-mediated Teratogenesis
14
Q
Folate antagonism result
A
- Key process in DNA formation and new cell production
- Tend to result in neural tube, oro-facial or limb defects
15
Q
Which groups of drugs cause folate antagonism?
A
Two groups of drugs
- Block the conversion of folate to THF by binding irreversibly to the enzyme (eg methotrexate, trimethoprim)
- Block other enzymes in the pathway (eg phenytoin, carbamazepine, valproate)
