Pharmacology in pregnancy and breast feeding

Question 1

what are the changes in Absorption of drugs throughout pregnancy?

Answer 1

IM- blood flow may be increased so absorption may be too

Inhaled- may be increased

Oral- may be more difficult due to morning sickness

Question 2

what are the changes in Distribution of drugs throughout pregnancy?

Answer 2

increased plasma volume, therefore plasma proteins are diluted. This means the fraction of free drug will increase, as less proteins to bind to

Question 3

what are the changes in Metabolism of drugs throughout pregnancy?

Answer 3

oestrogen and progesterone can induce OR inhibit liver p450 enzymes - this will either increase or reduce metabolism

Question 4

what are the changes in Excretion of drugs throughout pregnancy?

Answer 4

GFR increases by 50% in pregnancy therefore increased excretion of drug

Question 5

what are the pharmaco dynamic effects of pregnancy?

Answer 5

pregnancy may affect:

• site of action
• mechanism of action ie receptor response to drug

Question 6

what are the properties that allow a molecule to cross the placenta

Answer 6

• lipid-soluble
• non-polar
• low molecular weight

Question 7

foetal pharmacokinetics

describe the distribution of drugs in the foetus

Answer 7

less plasma protein binding and therefore increased fraction of free drug present

Question 8

foetal pharmacokinetics

describe the metabolism of drugs in the foetus

Answer 8

less enzymes so less metabolism, although this increases with gestation

Question 9

foetal pharmacokinetics

describe the excretion of drugs in the foetus

Answer 9

• excretion is into the amniotic fluid, which is then swallowed again & allowed recirculation
• drugs and metabolites can accumulate in amniotic fluid

Question 10

what are the risks of drugs in pregnancy

Answer 10

• teratogenicity –> in 1st trimester
• foetotoxicity–> in 2nd + 3rd trimester

Question 11

when is the biggest risk of teratogenicity?

Answer 11

during organogenesis (weeks 3-8)

Question 12

name 2 mechanisms by which teratogenicity can occur

Answer 12

• neural crest cell disruption
• folate antagonism

Question 13

what may folate antagonism cause?

Answer 13

• oro-facial
• limb
• neural tube defects

Question 14

what may neural crest cell disruption cause?

Answer 14

• aortic arch abnormalities
• ventricular septal defects
• oesophageal atresia

Question 15

list some known teratogenic drugs

Answer 15

• valproate
• NSAIDs
• alcohol
• ACEI/ARB
• Retinoids
  
  • these cause neural crest disruption
• Warfarin

Question 16

what can foetotoxicity result in?

Answer 16

• growth retardation
• structural abnormalities
• foetal death

Question 17

what about drugs and lactation?

Answer 17

most drugs are present in breast milk, but at a lower dose than in utero