Pharmacology in Pregnancy

Question 1

Which Pharmacological factors change in pregnancy?

Answer 1

Absorption
Distribution
Metabolism + elimination
Excretion

Question 2

What are the absorption changes in pregnancy?

Answer 2

Oral route
Intramuscular route
Inhalation

Question 3

Why does the oral route of absorption change in pregnancy?

Answer 3

Morning sickness
Increased gastric motility and emptying
(may affect single doses)

Question 4

Why does the intramuscular route of absorption change in pregnancy?

Answer 4

Blood flow may be increased

Question 5

Why does the inhalation route of absorption change in pregnancy?

Answer 5

Increased cardiac output and decreased tidal volume

Question 6

What are the distribution changes in pregnancy?

Answer 6

Increased plasma volume and fat

Greater dilution of plasma (increased fraction of free drug)

Question 7

What are the metabolism changes in pregnancy?

Answer 7

Ostrogens and progestogens can induce/inhibit liver P450 enzymes

Question 8

How does Phenytoin change in pregnancy?

Answer 8

Decreased (induction of metabolism)

Question 9

How does theophylline change in pregnancy?

Answer 9

Increased (induction of metabolism)

Question 10

What excretion changes are seen in pregnancy?

Answer 10

GFR increased

Reduced plasma concentration (might need to increase dose of renally cleared drugs)

Question 11

Placental transfer depends on what?

Answer 11

Molecular weight (smaller crosses more easily)
Polarity
Lipid solubility
Protein binding
Placenta may metabolise some drugs

Question 12

What are the changes in distribution in fetal pharmacodynamics?

Answer 12

Circulation different
Less protein binding = more free drug
Little fat
Relatively more blood flow to brain

Question 13

What are the changes in metabolism in fetal pharmacodynamics?

Answer 13

Less enzyme activity, increases with gestation

Different isoenzymes to adults

Question 14

What are the changes in excretion in fetal pharmacodynamics?

Answer 14

Drugs/metabolites can accumulate in amniotic fluid

Question 15

Which groups of drugs are high risk in pregnancy?

Answer 15

Anti-convulsants
Anti-hypertensives
Analgesics 
Antibacterials
NSAIDs
Alcohol
retinoids

Question 16

When is teratogenicity at highest risk?

Answer 16

3-8 weeks gestation

Question 17

What are the mechanisms of teratogenicity?

Answer 17

Folate antagonism
Neural crest cell disruption
Endocrine disruption
Oxidative stress
Vascular disruption

Question 18

What is folate antagonism?

Answer 18

Methotrexate/trimethoprim
Phenytoin, carbamazepine, valproate
Results in neural tube, facial, limb defects

Question 19

Which drugs cause Neural Crest Cell disruption?

Answer 19

Retinoid drugs (isotretinoin)

Question 20

Neural Crest Cell disruption causes what?

Answer 20

Aortic arch anomalies
Ventricular septal defects
Craniofacial malformations
Oesophageal atresia
Pharyngeal gland abnormalities

Question 21

What is enzyme mediated teratogenesis?

Answer 21

Drugs which inhibit/stimulate enzymes to produce therapeutic effects, may also interact with specific receptors

Question 22

Which drugs can cause teratogenic effects by Enzyme mediated teratogensis?

Answer 22

NSAIDs

orofacial clefts, septal defects

Question 23

Which drugs are fetotoxic?

Answer 23

ACEI

ARBs

Question 24

What effect do ACEI/ARBs have on the baby?

Answer 24

Fetotoxic
Renal dysfunction
Growth retardation

Question 25

Which drugs should be avoided in breast feeding?

Answer 25

Cytotoxics
Immunosuppressants
Anti-convulsants
Drugs of abuse
Amiodarone
Lithium
Radio-iodine

Question 26

What are the principles of prescribing women of child-bearing age?

Answer 26

Always consider possibility of pregnancy
Try non-pharmacological first
Use lowest effective dose, for as little time as possible
Avoid in first 10 weeks
Warn of risks
Discuss contraception

Question 27

What are the principles of prescribing breastfeeding women?

Answer 27

Avoid unnecessary drug use
Check if safe in paediatric use
Highly protein bound drugs better