Major Drugs Used in O&G
Start at the simplest idea: a drug is a molecule that changes a physiological process by binding to a target. Everything else in this chapter is built on two questions about that single sentence. First, how does the molecule get to its target, and how does it leave? — that is pharmacokinetics. Second, what does it do once it arrives? — that is pharmacodynamics. Hold those two questions in mind and every drug class becomes a variation on the same theme rather than a list to memorise.
O&G pharmacology then adds one complication that no other discipline carries so heavily: there are usually two patients. A molecule given to treat the mother may also reach the placenta, the fetus, the amniotic fluid and, after birth, the breastfed newborn. The whole of obstetric prescribing is the disciplined management of that second exposure. So the question is never "is this drug safe in pregnancy?" in the abstract. It is: what is the maternal indication, at what gestation, at what dose and route, what fetal or neonatal exposure follows, what alternatives exist, and what harm results if the mother is left untreated?
The Primary goal is not to memorise every dose. It is to understand mechanism, indication, predictable toxicity, contraindication logic and monitoring, and to understand them well enough that toxicity is predictable from mechanism rather than recalled from a list. The exam-friendly structure for any drug class is:
mechanism -> indication -> common adverse effects -> dangerous toxicity -> patient context that changes choice
The chapter ascends in deliberate steps. We first define the pharmacokinetic vocabulary, then how a drug engages its target, then the maternal–placental–fetal unit and the timing of teratogenic risk, then how pregnancy itself rewrites the kinetics. Only then do we hang the drug classes onto the clinical threats they answer. Each section presupposes only the ones before it.
Core Pharmacokinetic Vocabulary
Pharmacokinetics is the quantitative description of how a drug is absorbed, distributed, metabolised and excreted — in short, what the body does to the drug over time. A handful of defined terms recur throughout the chapter, and they are worth fixing precisely before any drug is named.
| Term | Plain definition | Why it matters in O&G |
|---|---|---|
| Bioavailability | the fraction of an administered dose that reaches the systemic circulation in active form | vomiting, delayed gastric emptying and first-pass metabolism all reduce it; an oral dose in hyperemesis may never arrive |
| Volume of distribution | the theoretical volume that would contain the whole dose at the measured plasma concentration; high for lipid-soluble, tissue-bound drugs | pregnancy expands plasma volume and body fat, raising the volume of distribution and lowering peak concentration of many drugs |
| Protein binding | the fraction reversibly bound to plasma proteins (acidic drugs to albumin, basic drugs to α1-acid glycoprotein); only the free fraction is active and crosses membranes | falling albumin in pregnancy raises the free fraction of albumin-bound drugs, so total drug levels can mislead |
| Clearance | the volume of plasma cleared of drug per unit time; sets the maintenance dose needed for a target concentration | rising glomerular filtration in pregnancy increases renal clearance of many drugs |
| Half-life | the time for plasma concentration to halve; a function of clearance and volume of distribution | governs dosing interval; steady state is reached after about five half-lives of regular dosing |
| pKa and ionisation | the pH at which half the drug is ionised; only the un-ionised (lipid-soluble) form crosses membranes freely | drives ion trapping across the placenta and into breast milk (below) |
| Prodrug | an inactive form converted to the active drug in the body | e.g. methyldopa and several others rely on conversion, so impaired metabolism alters effect |
These are not exam trivia. Each one is a lever that pregnancy pulls, which is why a dose that is correct in a non-pregnant adult may be wrong in the third trimester.
How a Drug Engages Its Target
Pharmacodynamics asks what the drug does once it arrives. Almost all drugs act on one of four kinds of target: receptors, enzymes, membrane ion channels, or metabolic processes. Receptors are the most common, and two definitions unlock most of the chapter:
- An agonist binds a receptor and produces the same effect as the body's natural signalling molecule (oxytocin at the oxytocin receptor; salbutamol at the β2 receptor).
- An antagonist binds the receptor but produces no effect itself; it simply blocks the natural agonist (atosiban at the oxytocin receptor; labetalol at adrenergic receptors; naloxone at opioid receptors).
From these two ideas, the logic of whole drug classes falls out. A β2 agonist relaxes both bronchial and uterine smooth muscle — useful in asthma, and the mechanistic reason β-agonists were used as tocolytics. An oxytocin-receptor antagonist does the opposite of oxytocin and so inhibits contractions. Knowing whether a drug switches a receptor on or off predicts both its therapeutic use and its side effects, because the same receptor is rarely confined to one organ.
The pharmacokinetic frame and this pharmacodynamic frame combine into one prescribing question. O&G prescribing then adds a second physiological unit: placenta, fetus, amniotic fluid and newborn may be exposed even when the target is maternal.
| Step | Pregnancy/O&G modifier | Example consequence |
|---|---|---|
| Absorption | vomiting, delayed gastric emptying, labour, opioids | missed or delayed oral doses; slower peak of rapidly absorbed drugs |
| Distribution | expanded plasma volume, lower albumin, more body fat | larger volume of distribution, lower peak levels, higher free fraction of albumin-bound drugs |
| Metabolism | hepatic enzyme induction/inhibition, ART/TB drugs | interactions with hormones, anticonvulsants or anticoagulants |
| Excretion | renal blood flow and glomerular filtration rise, then renal disease or oliguria reverse it | faster clearance of many renally excreted drugs in health; accumulation in oliguria |
| Placental transfer | lipid solubility, molecular size, protein binding, ionisation, transporters, gestation | fetal exposure is drug-specific and timing-specific |
| Neonatal handling | immature liver/kidney and breastfeeding exposure | sedation, jaundice or toxicity can appear after birth |
The safety question is therefore never "is this drug safe in pregnancy?" in isolation. It is: what is the maternal indication, what is the gestation, what dose and route are used, what alternatives exist, what fetal/neonatal exposure is plausible, and what harm follows if the mother is untreated?
The Maternal–Placental–Fetal Unit and How Drugs Cross
To reason about the second patient, treat the placenta as a partial barrier rather than a wall. The practical default is sobering: virtually all drugs cross the placenta to some degree, and with repeated dosing maternal and fetal concentrations tend to equalise. The question is not whether a drug crosses but how much, how fast, and when in gestation. Four properties govern transfer, and each is just the placental restatement of a pharmacokinetic term from above.
| Property | Crosses more readily when… | Mechanism |
|---|---|---|
| Molecular size | the molecule is small (roughly under 600 Da crosses easily; most drugs are below ~1000 Da and still cross) | small molecules diffuse through the syncytiotrophoblast; very large molecules (heparin, insulin, most monoclonal antibodies in early gestation) are largely excluded |
| Lipid solubility | the drug is lipophilic | passive diffusion across lipid membranes is the dominant transfer route |
| Protein binding | the free (unbound) fraction is high | only unbound drug diffuses; heavily protein-bound drugs transfer slowly |
| Ionisation (pKa) | the drug is un-ionised at physiological pH | un-ionised drug is lipid-soluble and diffuses; charged drug is trapped |
The ionisation rule produces one of the most useful ideas in obstetric pharmacology: ion trapping. Fetal plasma is slightly more acidic than maternal plasma. A weakly basic drug that is un-ionised in the mother diffuses across, then becomes ionised in the more acidic fetal compartment and cannot diffuse back — so it accumulates on the fetal side. The same physics operates at the breast, where milk is slightly more acidic than plasma, so weak bases concentrate in milk. This is mechanism, not memory: it explains why fetal or neonatal levels of some drugs exceed maternal levels even at a "maternal" dose.
Two further points complete the picture. The placenta is not metabolically inert — it expresses its own enzymes (including cytochrome P450 activity and conjugating enzymes) and efflux transporters such as P-glycoprotein, which can metabolise or pump drugs and partly modify what the fetus sees. And transfer is gestation-dependent: placental surface area and blood flow rise steeply through pregnancy, so the same drug reaches the fetus far more efficiently at term than in the first trimester.
Timing Is Everything: Teratogenesis and the Critical Window
If placental transfer answers how much reaches the fetus, teratogenesis answers what harm that exposure can do, and when. A teratogen is an agent that causes structural or functional abnormality in the developing conceptus — congenital malformation, growth restriction, or later functional (often neurobehavioural) deficit. The single most important principle is that the same drug carries entirely different risk at different gestational ages, because the embryo is doing different things at different times.