Drugs in Pregnancy

Drugs in pregnancy are:

Used by 20-25% of women regularly
Often not validated for use or safety, including anaesthetic drugs
Drug trials are difficult to perform in pregnant women.

Drug interactions in pregnancy can be classified into:

Pharmacokinetic
- Absorption
  - PO absorption affected by nausea and vomiting
- Distribution
  - ↑ V_D of water soluble drugs
    Due to ↑ blood and body fluid volume.
  - ↑ free portion of acidic drugs
    Due to ↓ albumin.
- Elimination
  - ↑ renal clearance
    Due to high GFR.
Pharmacodynamic
Most unchanged, except for:
- Volatiles
  ↓ MAC.
- Local anaesthetics
  ↓ neuraxial LA requirement.
Foetal transfer via placenta
- Almost all drugs cross the placenta to a certain degree
- Major determinants are concentration gradient, molecular weight, lipid solubility, degree of ionisation, protein binding, uteroplacental blood flow.
Foetal transfer via breast milk

Risk of Drugs in Pregnancy

Extent of effect depends on timing of consumption:

0-2 weeks
Generally all or nothing effect:
- Brief slowing of gestation with no overt ill effect
- Spontaneous abortion
3-8 weeks
Period of organogenesis and potential for major abnormalities.
Over 8 weeks
Foetal period, effects include:
- Physiological abnormalities
- Minor morphological abnormalities

The Australian risk categorisation divides drugs into:

Category A
Taken by a large number of pregnant women without any observed ↑ in malformations or other harmful effects.
Category B
Drugs which have been taken by a limited number of pregnant women, without any ↑ in the frequency of malformations or other harmful effects. Divided into three subgroups based on animal data:
- B1
  No observed foetal malformations in animals.
- B2
  No observed foetal malformations in animals, but studies were inadequate/data was lacking.
- B3
  ↑ foetal abnormalities in animals, of uncertain human significance.
Category C
Caused/suspected to have caused potentially reversible harmful foetal effects.
Category D
Caused/suspected to have caused ↑ foetal malformations or permanent damage.
Category X
Such high risk of causing foetal damage that they should not be used in pregnancy or where there is a possiblity of pregnancy.

Class	Category A
Antihypertensives	Methyldopa
Anticoagulants
Anaesthetic agents	Thiopentone Ketamine
Corticosteroids	Cortisone Hydrocortisone Prednisolone
Analgesics	Paracetamol
Antiemetics	Metoclopramide
Antibiotics	Penicillins Cephalosporins Erythromycin
Volatile agents	Halothane Nitrous oxide
Muscle relaxants	Suxamethonium
Vasopressors	Adrenaline Ephedrine
Antiarrythmics	Digoxin