Pharmacology in pregnancy

Question 1

• Explain the difference between pharmacokinetics and pharmacodynamics in pregnancy
• Outline the main concerns regarding the use of medication in pregnancy
• Outline the main concern regarding the use of medication in breast feeding
• Describe where to find information about risks with specific drugs in pregnancy/ breast feeding
• Explain the principles of prescribing for these patients (pregnant and when breast feeding)

Answer 1

.

Question 2

Why may women still be on medication when pregnant or when breastfeeding

Answer 2

Long term existing conditions, e.g. hypertension, asthma, epilepsy. migraine

Mental health disorders, e.g. depression, anxiety

Question 3

What does pharmacokinetic mean and what are the 4 processes it involves

Answer 3

How body affects metabolism of drug

Administration
Distribution
Metabolism
Excretion

Question 4

How many pregnancy change the pharmacokinetics of drugs

-absorption

Answer 4

Oral
-may be more difficult due to nausea/vomiting

IM
-blood flow is increased in pregnancy so absorption may be increased with IM

Inhale
-increased CO and decreased tidal volume may cause increased absorption of inhaled drugs

Question 5

How many pregnancy change the pharmacokinetics of drugs

-distribution

Answer 5

Increase in plasma volume + fat changes the volume of distribution (degree to which adrugis distributed in body tissue rather than the plasma)
-more diluted plasma means decreased relative amount of plasma proteins so INCREASED FRACTION OF FREE DRUG

Question 6

How many pregnancy change the pharmacokinetics of drugs

-metabolism

Answer 6

Oestrogen and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing metabolism

Question 7

How many pregnancy change the pharmacokinetics of drugs

-excretion

Answer 7

GFR is increased in pregnancy by 50% leading to increased excretion of many drugs

Question 8

What does pharmacodynamic mean

Answer 8

Effect of drug on body

Question 9

Placental transfer of drugs depends on what factors

Answer 9

Molecular weight (smaller sizes will cross more easily)

Polarity (non-polar cross more readily)

Lipid solubility (lipid soluble drugs will cross)

Question 10

How do foetal pharmacokinetics differ

-distribution

Answer 10

Less protein binding than adults so more free drug available

Less fat so different distribution

Question 11

How do foetal pharmacokinetics differ

-metabolism

Answer 11

Less enzyme activity

Question 12

How do foetal pharmacokinetics differ

-excretion

Answer 12

Excreted into amniotic fluid so can swallow and recirculate through body again

Question 13

Ways that drugs or other substances can cause teratogenicity

Answer 13

Folate antagonism
Neural crest cell disruption
Endocrine disruption of sex hormones

Question 14

Why is folic acid important for the baby

Answer 14

Key in DNA formation and new cell production, and helps prevent neural tube defects

Question 15

What are the 2 ways drugs can antagonise folate

Answer 15

Block the conversion of folate to THF by binding irreversibly to an enzyme

Block other enzymes in the pathway (eg phenytoin)

Question 16

What drugs are teratogenic

Answer 16

Methotrexate
Retinoids, e.g. isotretinoin
Anticonvulsants, e.g. sodium valproate
Anticoagulants, e.g. warfarin
Antihypertensives, e.g. ACEI
NSAIDs
Alcohol

Question 17

How is fetotoxicity different form teratogenicity

Answer 17

Toxic effect on the foetus later in 2nd trimester onwards that could potentially kill it

Question 18

What drugs are fetotoxic

Answer 18

ACEI/ARB - renal dysfunction + growth retardation

Question 19

What are the categories that drugs come under for use in pregnancy (5)

Answer 19

A - no foetal risks; SAFEST
B - no foetal risk in animals but no human studies, OR animal studies show risk but well controlled human studies do not
C - no adequate studies on either
D - foetal risk but benefits may outweigh risks
X - proven foetal risks outweigh any benefit

Question 20

Main concern regarding the use of medication in breast feeding

Answer 20

Lower doses circulate the mother’s body because it dissolves into breast milk

Question 21

Avoid what drugs when breast feeding

Answer 21

Cytotoxics
Immunosuppressants
Anti-convulsants (not all)
Amiodarone
Lithium

Question 22

Principles of prescribing for women of child bearing age

Answer 22

Always consider possibility of pregnancy

Warn women of possible risks

When treating medical conditions, advise women to attend before getting pregnant if planning to (optimise treatment)

Discuss contraception

Question 23

Principles of prescribing in breast feeding

Answer 23

Again avoid unnecessary drug use
Check on up to date drug information
If licensed and safe in paediatric use (esp under 2 years), a drug is likely to be safe in breast feeding
Choose drugs with pharmacokinetic properties that reduce infant exposure (eg highly protein bound)

Question 24

Where to find information about risks with specific drugs in pregnancy/ breast feeding

Answer 24

BNF