Pharmacology in pregnancy and breastfeeding

Question 1

What percent of women will use prescribed meds and also OTC meds during pregnancy?

Answer 1

60%

90%

Question 2

Why may a woman be on medicines during pregnancy, childbirth and lactation?- what conditions? (6)

Answer 2

Hypertension 
Asthma 
Migraines 
Epilepsy 
Mental health disorders - chronic therapy 
long-term anticoagulant therapy use - AF

Question 3

Physiological changes and drug toxicity - what are the 4 basic kinetic processes?

Answer 3

absorption
distribution
metabolism and elimination
excretion

Question 4

How does absorption change? - oral route (2)

Answer 4

May be more difficult “morning sickness” nausea/vomiting - often first 3 months

Decrease in gastric emptying and gut motility
This is unlikely to be a problem with regular dosing, but may affect single doses

Question 5

How does absorption change? - IM route

Answer 5

Blood flow may be increased, so absorption may also increase using this route

Question 6

How does absorption change? - inhalation

Answer 6

Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs

Question 7

Distribution changes - what will an increase in plasma volume and fat do to drug distribution?

Answer 7

Increase Vd

Question 8

A greater dilution of plasma will?

Answer 8

decrease relative amount of plasma proteins.

- increase the fraction of free drug

Question 9

free drug is?

Answer 9

pharmodyamically active

Question 10

Metabolism changes - what can Oestrogen and progestogens do?

Answer 10

induce or inhibit liver P450 enzymes, increasing or reducing metabolism.

Question 11

Phenytoin levels in pregnancy?

Answer 11

reduced (due to induction of metabolism)

Question 12

Theophylline levels in pregnancy?

Answer 12

increased (due to inhibition of metabolism)

Question 13

How is GFR affected with excretion changes?

Answer 13

GFR is increased in pregnancy by 50% leading to increased excretion of many drugs - reduction in circulating drug level

Question 14

What can Excretion reduce?

Answer 14

plasma concentration, and can necessitate an increase in dose of medicines cleared by the kidney.

Question 15

Pharmacodynamic means

pharmokinetic means?

Answer 15

what the drug does to the body

what the body does to the drug

Question 16

Pharmacodynamic changes may affect what?

- what sites can be affected

Answer 16

site of drug action & the receptor response to drugs
- Concentration of drug, metabolites at sites of biological action (changes in blood flow)
Mechanism of action (changes in receptors

Question 17

What may be different in pregnancy?

Answer 17

Efficacy

- adverse effects may be different

Question 18

What factors affect placental drug transfer and drug effects on the fetus? (6)

Answer 18

• Drug physiochemical properties
• Rate at which drug crosses placenta and amount reaching the fetus
• Duration of drug exposure
• Distribution in different fetal tissues
• Stage of placental and fetal development
• Effects of drugs when used in combination

Question 19

Placental Transfer depends on? (3)

Answer 19

• Molecular weight (smaller sizes will cross more easily)
• Polarity (unionised molecules cross more readily)
• Lipid solubility (lipid soluble drugs will cross the centre more easily)

Question 20

What can the placenta do?

Answer 20

metabolise some drugs

Safest to assume all drugs will cross placenta

Question 21

What type of drug crosses the placenta more easily?

Answer 21

Non-ionized drugs cross the placenta more easily than ionized drugs

Question 22

can protein-bound drugs cross the placenta?

Answer 22

yes, for non-bound versions this is not true

Question 23

Lipophilicity affect on placental transfer?

Answer 23

transfer

Question 24

Fetal pharmacokinetics - Distribution - why is this different compared to an adult (4)

Answer 24

Circulation is 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 , less well developed blood brain barrier

Question 25

Fetal Pharmacokinetics - how is the metabolism different (2)

Answer 25

Reduced enzyme activity, although this increases with gestation.
Fetus exhibits different P450 isoenzymes to adults.

Question 26

When does enzyme activity increase?

Answer 26

with gestation

Question 27

Fetal Pharmacokinetics - excretion - where does this happen (role of amniotic fluid) (3)

Answer 27

• Excretion is into amniotic fluid – which the fetus swallows leading to recirculation.
• Drugs and metabolites can accumulate in amniotic fluid. - TOXICITY
• Placenta not functioning at delivery so can be issues with excretory function,

Question 28

Issues with PK and PD?

- info is available for what 4 drug groups?

Answer 28

uncertainty around dosing

• Anti-convulsants
• Anti-hypertensives
• Analgesics
• Antibacterials

Question 29

Safety of drugs in pregnancy - what are the 2 areas

Answer 29

Teratogenicity (first trimester)

Fetotoxicity (second and third trimester)

Question 30

Principles of prescribing for women of child-bearing age (5)

Answer 30

• Always consider possibility of pregnancy (planned or not!)
• Warn women of possible risks
• When treating chronic medical conditions, advise women to attend before getting pregnant if planning to (optimise treatment)
• Discuss contraception
• If necessary, do not prescribe without contraception

Question 31

Principles of prescribing in pregnancy

Answer 31

• try non-pharmacological treatment first
• Use the drug with the best safety record (avoid new drugs unless proven safe).
• Check the SPC (summary product characteristics) for the most up to date information
• Use the lowest effective dose.
• Use the drug for the shortest possible time, intermittently if possible.
• Avoid the first 10 weeks of pregnancy if possible.
• Consider stopping or reducing dose before delivery.
• Never under a treat disease which may be harmful to the mother or fetus