Pharmacology in pregnancy

Question 1

When should you think about pregnancy?

Answer 1

In any woman of child bearing age - regardless if she is thinking she will get pregnant or not

Question 2

Why should you also think about men whilst prescribing for pregnancy?

Answer 2

Certain medications can damage sperm

Can lead to foetal abnormalities

Question 3

Why is untreated hypertension dangerous in all women of child bearing age?

Answer 3

As going in to pregnancy hypertensive increases risk massively of pre-eclampsia

Question 4

Which of the ADME are affected in pregnancy?

Answer 4

All four
Absorption
Distribution
Metabolism
And excretion

Question 5

How is the oral absorption route changed?

Answer 5

May be more difficult due to nausea/vomitting
Increased gastric emptying and gut motility
–(more of a problem with single doses than multi-treatment)

Question 6

How is the intramuscular route changed in pregnancy?

Answer 6

Blood flow could be increased

Could lead to increased absorption

Question 7

How is inhalation route changed in pregnancy?

Answer 7

Increased cardiac output and decreased tidal volume

Leads to drugs staying in lungs longer, increases absorption

Question 8

Why does distribution change in pregnancy?

Answer 8

Increase in plasma volume and fat

Greater diltion of plasma protein relatively

Question 9

How do the changes in pregnancy affect distribution?

Answer 9

Increased plasma volume/fat changes the volume of distribution
Dilution of plasma proteins results in a greater fraction of free drug (more active drug)

Question 10

How does metabolism change during pregnancy

Answer 10

Oestrogen and progesterone induce (most) liver enzymes
This increases metabolism
(note some are also reduced)
Results in changes being needed to prescription levels
Need to monitor and alter doses on a case by case basis

Question 11

How does excretion change during pregnancy?

Answer 11

Increased GFR leads to increased excretion

Can necessitate an increased in drug dose

Question 12

What are the pharmacodynamic drug changes in pregnancy?

Answer 12

May affect site of action and receptor response to drugs
MOA may change (receptor change)
Concentrations/metablites of drugs may change (blood flow)
Effiacy may be different
Adverse affects (like in pregnancy) may be different

Question 13

What does placenta transfer depend on?

Answer 13

Molecular weight (smaller better)
Polarity (non-polar better)
Lipid solubility (lipid soluble better)

Question 14

Which drugs should you assume the placenta will transfer?

Answer 14

Assume all

May also metabolise some

Question 15

How is distribution different in foetal pharmacokinetics?

Answer 15

Circulation different
Less protein, therefore more free drug available
Little fat, differnet distribution
Relatively more blood flow to brain (and not fully formed BBB)

Question 16

How does metabolism differ in foetal pharmacokinetics?

Answer 16

Less enzyme activity (although increases with gestation)

Different isoenzymes to adults

Question 17

How does excretion differ in foetal pharmacokinetics?

Answer 17

Excretion is into amniotic fluid which is then reabsorbed
Can lead to a build up of drugs in amniotic fluid
As placenta not working at delivery, can be issues with this

Question 18

What are the two classes of adverse effects in pregnancy?

Answer 18

Teratogenicity

Foetotoxicity

Question 19

Should you treat long term conditions in a pregnant woman?

Answer 19

Yes - lowers overall risk to child

If condition unmanaged and harm is doen to mother, harm will be done to child

Question 20

What are the mechanisms of teratogenicity?

Answer 20

Folate antagonism
Neural crest cell disruption
Endocrine Disruption: Sex Hormones
Oxidative Stress
Vascular Disruption
Specific Receptor- or Enzyme-mediated Teratogenesis

Question 21

When is the biggest risk for teratogenicity?

Answer 21

During organgensis - weeks 3-8 (sometimes 12)

Question 22

What are the mechanisms of folate antagonism?

Answer 22

Block conversion of folate into THF (irreversibly)

Block other enzymes in pathway

Question 23

What defects come from folate anatagonism?

Answer 23

Neural tube defects
Oro-facial
Limb defects

Question 24

What drugs disrupt folate?

Answer 24

Directly - methotrexate, trimetroprin

Other enzymes - pheyntoin, carbamazepine, valproate

Question 25

What drugs disrupt neural cell development?

Answer 25

Retinoids

Question 26

What are the potential presentations of neural crest cell disruption?

Answer 26

aortic arch anomalies 
ventricular septal defects
craniofacial malformations
oesophageal atresia 
pharyngeal gland abnormalities

Question 27

What is enzyme mediated teratogenesis?

Answer 27

Where drugs interact with specific receptors and enzymes damaging fetal development.

Question 28

Should women take NSAIDs when pregnnat? Why?

Answer 28

No - they cause enzyme mediated teratogenesis
Cause septal heart defects
Orofacial clefts

Question 29

What are some potential issues resulting from foetotoxicity?

Answer 29

Growth retardation
Structural malformations
Fetal death
Functional impairment
Carcinogenesis

Question 30

Why are ACEI no longer first line hypertensives in pregnant women?

Answer 30

Result in renal dysfunction and

growth retardation in foetuses

Question 31

What are some known tetragenic drugs to avoid in pregnancy?

Answer 31

Anticonvulsants (neural tube defects)
Anticoagulants (although wafarin still sometimes used)
Antihypertensives (beta blockers first line)
NSAIDs
Alcohol
Retinoids

Question 32

What drugs should be avoided when lactating?

Answer 32

Cytotoxics
Immunosuppressants
Anti-convulsants (not all)
Drugs of abuse
Amiodarone
Lithium
Radio-iodine

Question 33

What are the principles of prescribing to women of childbearing age?

Answer 33

Always think pregnancy as a possibility
Warn women of possible risks
Advise women to attend doctor before getting pregnant
Discuss contraception - potentially do not prescribe until on at least one contraceptive (preferably 2)

Question 34

What are the principles of prescribing in pregnancy?

Answer 34

No-pharmacological treatments first if possible
Use drug with best safety record (not new drugs)
Lowest effective dose
Avoid first 10 weeks if possible
Consider stopping/reducing before delivery
Don’t under-treat potentialy dangerous diseases
Use for shortest period possible
Chec with specialist if unsure

Question 35

What are the principles of prescribing in breast feeding?

Answer 35

Avoid unessecary drug use (again)
Check information is up to date
Likely to be safe if liscensed in paedeatric use (especially under 2s)
Choose drugs that reduce pharmacokinetic properties that reduce infant exposure