L14 Obstetric Complications

Question 1

Considerations for first-pass metabolism in pregnant women

Answer 1

• reduced intestinal mobility & transient time due to increased progesterone, resulting in increased absorption
• increased gastric acidity due to increased gastrin production by placenta - affects the ionisation of weak acids and bases
• increased blood volume leads to increased hepatic flow - promotes first-pass metabolism

Question 2

When may IV administration be useful in pregnant patients?

Answer 2

When first-pass metabolism may be therapeutically detrimental or faster drug effect is needed (e.g. antihypertensives in preeclampsia)

Question 3

What is the effect of increased volume of distribution in pregnancy?

Answer 3

increased VD may modify the efficacy of medications by decreasing the amount of drug made available to maternal target receptor sites while providing fetal exposure

Question 4

How does hypoalbuminemia in pregnancy affect pharmacokinetics?

Answer 4

increased free fraction of drug and decreased drug at the receptor site which alters the total, toxic and therapeutic levels of different drugs

Question 5

Why must drugs which are highly protein bound, e.g. phenytoin, require careful monitoring during pregnancy?

Answer 5

higher concentrations of free drug and increased excretion

Question 6

Cardiac output increased by __ during pregnancy.

Answer 6

30-50%

Question 7

What enzymes are a major source of variability in drug pharmacokinetics and response?

Answer 7

cytochrome P450 enzymes

Question 8

What hepatic CYP450 enzymes are increased during pregnancy?

Answer 8

CYP2D6 and CYP3A4

Question 9

Activity of what CYP450 enzyme is decreased during pregnancy?

Answer 9

CYP1A2

Question 10

What effect does pregnancy have on GFR?

Answer 10

GFR increases by approx. 50%, which significantly increases clearance of renally excreted drugs

Question 11

Do sedative drugs cross the placenta?

Answer 11

Yes

Question 12

During pregnancy, why is sensitivity to inhaled anaesthetics increased?

Answer 12

due to decreased minimum alveolar concentration

Question 13

What condition that is characteristic of pregnancy is suggested to play a role in the increased sensitivity to IV anaesthetics, and why?

Answer 13

Hypoalbuminemia
If there is reduced protein for the anaesthetic, e.g. propofol, to bind, there is reduced retention of the drug and it cannot elicit the desired effect.

Question 14

Examples of drugs that have well characterised pharmacogenomic profiles

Answer 14

warfarin, codeine, SSRIs

Question 15

Multiallelic genetic polymorphisms strongly depend on __, and play a major role in the function of __.

Answer 15

ethnicity
CYP450 enzymes

Question 16

Codeine is metabolised by __ to __.

Answer 16

CYP2D6 to morphine

Question 17

What is neonatal abstinence syndrome?

Answer 17

A group of conditions that occurs when a baby withdraws from certain drugs that they’ve been exposed to in the womb before birth

Question 18

What is NAS most commonly caused by?

Answer 18

maternal opioid use
(methadone given for severe cases of withdrawal from heroin exposure)

Question 19

What is intrauterine growth restriction?

Answer 19

when ultrasound-estimated fetal weight is <10th percentile for gestational age (pathological reason behind reduced fetal growth)

Question 20

Risks of IUGR

Answer 20

acute - IU death, premature delivery, impaired fetal lung maturation
chronic - increased risk of CVD & T2DM for fetus

Question 21

IUGR treatment

Answer 21

1. Corticosteroids (dexamethasone 12mg once daily - should be administered within 10 days of delivery for optimal therapeutic benefit) - promote fetal lung surfactant maturation and reduce incidence of RDS
2. Aspirin (recommended starting dose: 150mg once daily) - promotes vascular health (inhibits formation of cyclo-oxygenase products)

Question 22

Pre-eclampsia treatment

Answer 22

1. Aspirin: low-dose aspirin (150mg once daily) prophylaxis recommended in women at high risk of PE - should be administered before 16 weeks gestation for optimal therapeutic benefit and continued daily until delivery. Aspirin inhibits expression of sFlt-1 in human trophoblasts in hypoxic conditions - proangiogenic activity.
2. β-blockers: Labetalol lowers BP (antihypertensive of choice in PE) & preserves uteroplacental blood flow better than other β-blockers. Recommended starting dose: 200mg twice daily. Nifedipine (CCB) - a secondary option for PE-related antihypertensive therapy.
3. Magnesium sulfate

Question 23

Why is magnesium sulfate administered for eclampsia?

Answer 23

Magnesium sulfate is believed to act as a vasodilator, protect the BBB and reduce eclampsia (in the intrapartum & postpartum periods). Loading dose of 4-6mg administered per infusion pump over 20-30 mins, followed by a maintenance dose of 1-2g per hour as a continuous IV infusion - usually takes effect immediately, normally given until ~24 hours after delivery.

Question 24

What is gestational diabetes mellitus?

Answer 24

GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy

Question 25

GDM treatment

Answer 25

1. Diet: dietician referral, focus on low glycemic index foods that release sugar slowly e.g. brown rice, all-bran cereals, lentils
2. Insulin: current first-line pharmacological intervention when diet & lifestyle modifications fail to adequately control glycemic levels. Administered subcutaneously, does not cross placenta, maintains glucose homeostasis, mediates an anti-inflammatory response. Side effects: hypoglycemic episodes & weight gain.
3. Metformin: starting dose of 500mg twice daily to treat mild-moderate hyperglycaemia. An effective insulin-sensitising agent & reduces hepatic gluconeogenesis. Crosses the placenta, minimal risk of both hypoglycemic episodes & weight gain.