SN2 SHORT NOTE 5M ★ High-yield

Describe the principles of drug use in pregnancy and lactation with the important teratogens.

Pharmacology · 2nd Professional — Para-Clinical

Principles of Prescribing in Pregnancy

The governing principle is that NO drug is prescribed unless the benefit to the mother clearly outweighs the risk to the fetus — but the corollary is equally important: withholding necessary treatment harms both. Untreated epilepsy, asthma, hypothyroidism, diabetes, infection and depression are all more dangerous than the drugs used to treat them
Physiological changes alter pharmacokinetics — increased plasma volume and volume of distribution, reduced albumin, increased glomerular filtration (so renally cleared drugs need higher doses), altered hepatic metabolism, and delayed gastric emptying
Almost all drugs cross the placenta to some extent; heparin and insulin are notable exceptions because of their size

Timing Determines the Effect

Period	Timing	Effect of a harmful drug
Pre-embryonic	0–2 weeks	"all OR none" — either the conceptus dies, or it repairs completely and develops normally; malformation does not result
Embryonic (organogenesis)	3–8 weeks — the period of maximum risk	Structural malformation; the organ affected depends on what is forming at that moment. Often before the woman knows she is pregnant, which is why preconception advice matters
Fetal	9 weeks to term	Growth restriction, functional and behavioural effects rather than gross malformation (ACE inhibitors and renal development, tetracyclines and teeth, NSAIDs and the ductus)
Perinatal	Around delivery	Neonatal effects — respiratory depression from opioids, withdrawal from benzodiazepines and SSRIs, bleeding from warfarin, kernicterus from sulphonamides

CLINICAL PEARL

The most dangerous weeks are usually over before the woman knows she is pregnant. Organogenesis runs from about the third to the eighth week, and many pregnancies are recognised only at six weeks or later. That is why teratogenic risk must be discussed when the drug is first prescribed to any woman who could conceive — not when she announces a pregnancy, by which time the exposure has already happened.

Important Teratogens

Drug	Effect
Thalidomide	Phocomelia — the disaster that created modern drug regulation
Warfarin	Fetal warfarin syndrome (nasal hypoplasia, stippled epiphyses) in the first trimester; fetal haemorrhage later; heparin is used instead
ACE inhibitors and ARBs	Renal dysgenesis, oligohydramnios, skull hypoplasia, fetal death
Valproate	Neural tube defects and marked neurodevelopmental impairment — now effectively prohibited in women of childbearing potential
Phenytoin, carbamazepine	Fetal hydantoin syndrome; neural tube defects
Retinoids (isotretinoin)	Severe craniofacial, cardiac and CNS malformations; a pregnancy prevention programme is mandatory
Methotrexate, mycophenolate	Abortion and multiple malformations
Tetracyclines	Staining and hypoplasia of teeth; impaired bone growth
Androgens, danazol	Virilisation of a female fetus
Lithium	Ebstein anomaly
Alcohol	Fetal alcohol syndrome — and no safe threshold has been established
NSAIDs (third trimester)	Premature closure of the ductus arteriosus, oligohydramnios

Drugs in Lactation

Most drugs enter milk in small amounts, and the infant dose is usually a small fraction of the maternal dose; breastfeeding rarely needs to be stopped
Drugs entering milk most readily are lipid-soluble, un-ionised, of low molecular weight and poorly protein-bound; milk is slightly more acidic than plasma, so weak bases concentrate in it
Contraindicated or requiring cessation — cytotoxic drugs, radioactive isotopes, lithium, amiodarone, retinoids, chloramphenicol, tetracyclines (prolonged), high-dose ergotamine
Use with caution — codeine (fatal neonatal respiratory depression in ultra-rapid CYP2D6 metabolisers), benzodiazepines, opioids, sulphonamides in the jaundiced or G6PD-deficient neonate, and aspirin (Reye syndrome)
Practical measures — choose a drug with a short half-life and poor oral bioavailability in the infant, take it immediately after a feed to allow the level to fall before the next, and observe the infant for sedation or poor feeding

Applied Aspects

Ask about pregnancy and contraception before prescribing any teratogen to a woman of childbearing age — this must become automatic
Give folic acid before conception, at 5 mg where the risk is high
Do not stop essential treatment because of pregnancy; review it, substitute a safer agent where one exists, and consult a current reference rather than the old letter categories, which have been withdrawn as misleading
Self-medication and traditional remedies in pregnancy are common in India and are rarely disclosed; asking directly is necessary
Encourage breastfeeding — it is very rarely necessary to stop it for a drug, and unnecessary cessation causes real harm to the infant

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