Pharmacology in Pregnancy and Breast Feeding

Question 1

4 basic kinetic processes

Answer 1

• Absorption
• Distribution
• Metabolism and Elimination
• Excretion

Question 2

Why may the oral route of administration be affected during pregnancy

Answer 2

• Morning sickness => vomiting

- Increased gastric emptying and motility (unlikely to be a problem with regular dosing but may affect single doses

Question 3

Why would the IM route be affected during pregnancy

Answer 3

Blood flow is increased, so absorption from this route increases

Question 4

Why would the inhalation route be affected during pregnancy

Answer 4

• Increased cardiac output
• Decreased tidal volume
• Both lead to increased absorption of inhaled drugs

Question 5

What effect does the greater dilution of plasma, and therefore the decreased relative amount of plasma proteins, have on the distribution of drugs during pregnancy

Answer 5

Increased fraction of free drug

Question 6

The effect of oestrogen and progestogens of P450 enzymes

Answer 6

Can inhibit or induce

Question 7

In what way and why is excretion changed in pregnancy

What should be done to deal with this

Answer 7

• Increased
• GFR increased by 50%
• Increase the dosages of renally excreted drugs

Question 8

Effect on absorption via oral route in pregnancy and why

Answer 8

• Reduced

- Increased vomiting, gastric emptying and gut motility

Question 9

What 3 factors determine placental transfer of a drug

Answer 9

• Molecular weight (smaller crosses better)
• Polarity (non-polar crosses better)
• Lipid solubility (Lipid soluble drugs will cross)

Question 10

At what molecular weight will drugs cross the placenta

Answer 10

MW < 500 Da (Dalton)

Question 11

At what molecular weight will drugs NOT cross the placenta

Answer 11

MW > 1000 Da (Dalton)

Question 12

Difference in foetal drug-protein binding vs adults and the result of this

Answer 12

• Less protein binding vs adults

- More “free” drug available

Question 13

Foetal blood flow to brain vs adult

Answer 13

Relatively more blood flow to brain vs adult

Question 14

Foetal enzyme activity (metabolism) vs adults

Answer 14

Less enzyme activity vs adults (increases with gestation)

Question 15

Describe foetal excretion of drugs

Answer 15

• Excretion is into amniotic fluid
• Amniotic fluid is then swallowed, allowing for recirculation
• Drugs and metabolites and accumulate in the amniotic fluid

Question 16

When does Teratogenicity refer to

When does Fetotoxicity refer to

Answer 16

• First trimester

- Second and third trimester

Question 17

What period of gestation is the risk of teratogenicity at its highest

Answer 17

During organogenesis (3-8 weeks)

Question 18

6 mechanisms of Teratogenicity

Answer 18

• Folate antagonism
• Neural crest disruption
• Endocrine disruption (sex hormones)
• Vascular disruption
• Oxidative stress
• Specific rector or enzyme mediate teratogenesis

Question 19

5 Drugs that can cause folate antagonism and the result of it

Answer 19

• Methotrexate
• Trimethoprim (antibiotic for bladder infections)
• Phenytoin
• Carbamazepine
• Valproate

Tends to result in neural tube, oro-facial or limb defects

Question 20

Drug that causes neural crest disruption

Answer 20

-Retinoid drugs (isotretinoin, used to treat severe acne or occasionally prevent skin cancers)

Question 21

5 problems that result from neural crest disruption

Answer 21

• Aortic arch abnormalities
• Craniofacial malformations
• Oesophageal atresia (oesophagus ends in blind-ended pouch)
• Pharyngeal gland abnormalities
• Ventricular septal defects

Question 22

Type of drug that causes enzyme-mediated teratogenesis and what that leads to

Answer 22

• NSAIDs

- Orofacial clefts and Cardiac septal defects

Question 23

Define Fetotoxicity

Answer 23

Toxic effect on the foetus later in pregnancy (second and third trimester)

Question 24

2 types of drugs that cause Fetotoxicity and what that leads to

Answer 24

• ACE inhibitors
• ARBs (Angiotensin II receptor blocker)
• Renal dysfunction and growth retardation

Question 25

Scoring system for how safe a drug is during pregnancy

Answer 25

- A, Controlled human studies show no foetal risk - B, Animal studies show no risk but no human studies have been conducted OR animal studies show risk to foetus but well controlled human studies don't - C, No adequate human or animal studies have been conducted OR risks shown in animals but no human data available - D, Human foetal risk evident but benefits may outweigh the risk - X, Proven foetal risk outweigh any possible benefit

Question 26

3 anticonvulsants that are teratogens and their effects

Answer 26

- Valproate - Phenytoin - Carbamazepine Neural tube defects

Question 27

Anticoagulant that is a teratogen and its effect

Answer 27

Warfarin Haemorrhage of foetus + multiple malformations of CNS and skeletal system

Question 28

Antihypertensive drugs that are teratogens and their effect

Answer 28

ACE inhibitors + ARB's Renal damage + growth retardation

Question 29

Effect of NSAIDs on foetus

Answer 29

-Premature closure of the ductus arteriosus

Question 30

Retinoid that is a teratogen and its effect on the foetus

Answer 30

Isotretinoin Neural crest disruption

Question 31

6 drugs to avoid during breast feeding

Answer 31

- Cytotoxics (chemo) - Immunosuppressants - Anticonvulsants (not all) - Amiodarone - Lithium - Radio-iodine

Question 32

If prescribing Isotretinoin, to a woman of child bearing age, what 2 things must also be done with regards to the patient, according to the BNF

Answer 32

- Monthly pregnancy checks | - Use at least one (preferably 2) methods of contraception

Question 33

When should you avoid using Trimethoprim for a UTI

Answer 33

BNF says avoid during 1st trimester

Question 34

6 principles of prescribing in pregnancy

Answer 34

- Try non-pharmacological treatment first (if possible) - Use lowest effective dose - Use drug for shortest possible time, intermittently if possible - Avoid first 10 weeks of pregnancy, if possible - Consider stopping or reducing dose before delivery - Use drug with best safety record, avoid new drugs unless proven safe

Question 35

Principles of prescribing in breast feeding

Answer 35

- Check on up to date info - If licensed and safe in paediatric use (esp. under 2yrs) a drug is likely to be safe in breast feeding - Choose drugs with pharmacokinetic properties that reduce infant exposure (e.g. highly protein bound)

Question 36

Baby JR - 3 weeks old - Breast feeding - Mother has lower back pain What can she safely take

Answer 36

- Paracetamol + Ibuprofen, BNF notes amounts too small to be harmful in breast milk (though some manufacturers state avoid ibuprofen) - Codeine USUALLY too small to be harmful, but maternal metabolism very variable so risk of morphine OD in baby