medicines in preganacy

why may medicines be required during pregnancy.

• common pregnancy symptoms

• treatment of serious complications

• continuation of previous disease

Name the three vaccines recommended in pregnancy in the UK

• Influenza vaccine

• whooping cough vaccine

• COVID-19 vaccine (booster)

Why are these three vaccines considered safe in pregnancy?

They are not live vaccines and therefore cannot cause infection in the mother or unborn baby

Why are live attenuated vaccines contraindicated in pregnancy?

They contain live (though weakened) organisms that can cause infection in the unborn baby

Under what circumstances might a live attenuated vaccine be given during pregnancy despite being generally contraindicated?

Where there is a high risk of infection — in such cases, the benefit may outweigh the risk.

Why are pregnant women usually excluded from clinical trials?

To protect them and their fetuses from potential harm. This means there is very little robust safety data for most drugs in pregnancy

How does increased progesterone affect oral drug absorption in pregnancy?

Progesterone reduces gastric and small intestine motility → delayed gastric emptying → reduced absorption of oral medicines.

How does pregnancy affect absorption via inhalation?

Increased cardiac output, tidal volume, and alveolar uptake → increased absorption of inhaled drugs into the bloodstream

How does pregnancy affect IM/SC and transdermal absorption?

Increased tissue perfusion → increased absorption via these routes

By how much does plasma volume increase in pregnancy, and by what gestational age?

By approximately 150%, by 24–28 weeks gestation

What happens to the volume of distribution (Vd) and clinical effect of a drug when plasma volume expands in pregnancy?

• Vd increases → drug is distributed across a larger volume → lower plasma concentrations → clinical effect decreases.

• Doses may need to be increased.

What causes altered drug metabolism in pregnancy?

Elevated concentrations of many hormones (e.g., oestrogen, progesterone) alter the activity of drug-metabolising enzymes.

By how much does GFR increase during the first and second trimesters?

50% increase in the 1st trimester; 80% increase in the 2nd trimester.

What happens to plasma concentrations of drugs excreted unchanged by the kidney during pregnancy, and what is the clinical implication?

Increased GFR → increased elimination → lower plasma concentrations.

Doses may need to be increased to maintain therapeutic effect.

What is the placental membrane and why is it clinically important?

• It is the thin membrane separating maternal blood from fetal blood in the villi.

• Drugs in maternal blood can cross this membrane into fetal circulation via the umbilical cord.

What molecular weight threshold allows most drugs to diffuse easily across the placenta?

600 Da

How does protein binding affect placental drug transfer?

Highly protein-bound drugs have higher maternal concentrations and lower fetal concentrations, because only the free (unbound) fraction of the drug crosses the placenta.

What type of drugs cross the placenta most easily in terms of lipid solubility and ionisation?

lipophilic and unionised drugs

What is pKa?

pKa is the hydrogen ion concentration (pH) at which 50% of a drug exists in its ionised form

Explain ion trapping in the fetal circulation

• The fetal circulation has a slightly lower pH than maternal plasma (more H⁺ ions).

• Weak bases that cross into the fetal circulation become protonated (BH⁺) at this lower pH

• converted to ionised form

• cannot cross back across the placenta

• become trapped in the fetal circulation, potentially at higher concentrations than in maternal blood.

Which drug property most increases transfer across the placenta?

lipophilicity allows the drug to diffuse readily across the lipid-based placental membrane.

What role do placental efflux transporters and enzymes play in drug transfer?

They may either facilitate or restrict the transfer of drugs to the fetus, acting as a partial barrier or transport mechanism.

Define teratogen

Any agent that results in structural or functional abnormalities in the fetus, or in the child after birth, as a consequence of maternal exposure during pregnancy.

What is the most famous drug teratogen and what defect does it cause?

Thalidomide — causes limb deformities

potential consequences of fetal exposure to a teratogen

• physical malformations,

• behavioural/emotional developmental problems,

• decreased IQ

• miscarriage

What are the three stages of embryo-fetal development and their timeframes?

• Pre-embryonic/germinal stage (0–2 weeks post-conception)

• embryonic stage (3–8 weeks)

• fetal stage (9–38 weeks).

Why is the germinal stage (0–2 weeks) described as the "all or nothing" period?

Most drug exposures during this period either cause fetal death or result in complete recovery and normal development.

Structural malformations are unlikely.

What is the risk of a long-acting drug given during the germinal stage?

If the drug's half-life is long enough, it may still be present when the embryonic stage begins (3 weeks onwards), extending exposure into the period of greatest risk for major birth defects.

What major developmental process occurs during the embryonic stage (3–8 weeks)?

Organogenesis — the formation of all major organs. This makes it the period of greatest risk for major birth defects from drug exposure.

Which organs/structures continue to develop beyond the 10th week of pregnancy (beyond organogenesis)?

CNS, eyes, ears, teeth, and external genitalia

Why are women advised to minimise drug use in the first trimester?

The embryonic stage (weeks 3–8), when organogenesis occurs, falls within the first trimester

Give an example of a drug that causes neural tube defects during the embryonic stage and explain the mechanism

Folic acid antagonists (e.g. trimethoprim) increase the risk of neural tube defects, by depleting folate required for normal neural tube development.

What two drug classes cause harm specifically in the 2nd and 3rd trimesters?

• ACE inhibitors (fetal renal damage, reduced amniotic fluid volume)

• NSAIDs (premature closure of ductus arteriosus, fetal renal impairment — particularly 3rd trimester).

Which organ remains vulnerable to drug damage throughout all stages of pregnancy?

The CNS

What are the four principles that determine teratogenic effects?

• Timing of exposure

• Dose

• Species

• Genotype and environmental interaction.

What is the general dose recommendation for drugs used in pregnancy?

Use the lowest effective dose

Why do neonates accumulate drugs more than adults?

The neonate's capacity to eliminate drugs is reduced (immature hepatic and renal function), meaning drugs clear more slowly → significant accumulation and toxicity can occur.

Name three neonatal side effects and the drug classes that cause them

• CNS depression (opioids)

• adrenal suppression (high-dose corticosteroids)

• neonatal bradycardia (beta-blockers).

When is the risk of neonatal withdrawal greatest?

When drugs are used long-term and/or taken near the time of birth

What are the two mechanisms by which drugs can affect the fetus?

• Indirectly — via effects on maternal circulation

• Directly — by crossing the placenta and acting on the fetus.

Why does sodium valproate require a Pregnancy Prevention Programme (PPP)?

It is a major teratogen causing neural tube defects, developmental delay, and behavioural disorders.

Its effects may not be apparent until years after birth.

Patients must use effective contraception and be fully informed before and during treatment.

Why are 5-alpha-reductase inhibitors (finasteride, dutasteride) a risk to pregnant women even if the woman herself does not take them?

They can be absorbed through the skin on contact. They cause birth defects in male fetuses by disrupting normal male genital development

What precautions should a pregnant HCP take when handling cytotoxic drugs?

Use PPE and adhere to standard handling precautions. Avoid continued exposure where possible.