Chapter 31. Drugs in pregnancy and at the extremes of age
Introduction
Most facts about drugs are obtained from observations on young and middle-aged adults. Age, however, may modify the way drugs are handled by the body and also the way the body reacts to the actions of drugs. In recent years, increasing interest has led to studies of drugs given at the extremes of age and in pregnancy.
Drugs in pregnancy
Drugs can affect the fetus either by interfering with some important function in the mother which indirectly damages the fetus or by passing across the placenta and acting directly on the fetus. Most drugs cross the placenta.
Stages of pregnancy
Damage can occur at four stages of pregnancy:
• Implantation (5–15 days). Drug toxicity at this stage usually results in abortion.
• Embryo stage (15–55 days). During this period the embryo is changing from a group of cells into a recognizable human being. The embryo is particularly susceptible to drug toxicity at this time, which leads to fetal malformation (teratogenesis) such as occurs with thalidomide.
• Fetogenic stage (55 days to birth). As the fetus continues to grow and develop, drug damage becomes less likely, but it is still possible.
• Delivery. Drugs at this stage may interfere with labour and modify the behaviour of the neonate immediately after birth.
In the UK, about 30% of women take some drug during pregnancy, although only 10% take one in the first trimester when the fetus is most vulnerable to damage. Those most commonly taken are mild analgesics and antibiotics.
It is important to discover which drugs can produce fetal damage and which are safe to use. This is difficult for two reasons:
• Fetal abnormalities can occur for various reasons even when no drugs are taken. About 2% of babies have some abnormality at birth, but only about 5% of these are believed to be drug related.
• If the drug only rarely causes an abnormality, thousands of pregnant women need to be studied before a connection between a certain drug and fetal damage can be confirmed.
Experiments with pregnant animals have only a limited value.
Drugs and fetal abnormality
At present, drugs can be divided into three groups:
A. Some drugs known to produce fetal abnormalities (not a comprehensive list; always check when in doubt before prescribing)
• Thalidomide
• Folic acid antagonists
• Tetracyclines
• Androgens
• Danazol
• Warfarin (during the first 4 months of pregnancy)
• Diethylstilbestrol
• Etretinate
• Lithium
• Some anticonvulsants.
B. Drugs suspected of producing fetal abnormalities
• Oral hypoglycaemic agents cause neonatal hypoglycaemia
• Various cytotoxic drugs
• Anorexics (amfetamines)
• Angiotensin-converting enzyme (ACE) inhibitors and thiazides should not be used for hypertension in pregnancy.
There are a number of other drugs which are under suspicion or for which information is not available.
C. Drugs which probably do not harm the fetus (see also British National Formulary, Appendices 4 and 5)
• Simple analgesics | Paracetamol for minor pain. NSAIDs can be used if really necessary and ibuprofen, being mild and short-acting is preferred. |
• Cough | Codeine. |
• Powerful analgesics | Opioids can be used (but see below). |
• Diabetes | Insulin. |
• Drugs for dyspepsia | Antacids – advice on diet advisable. |
• Drugs for constipation | Bulk purges, lactulose. |
• Drugs for nausea | Avoid if possible and treat by modifying diet. |
• Antibacterial drugs | Penicillins, cephalosporins, erythromycin; avoid trimethoprim in the first 3 months of pregnancy if possible. |
• Hypotensive agents | Methyldopa; hydralazine for rapid lowering of blood pressure; β-blockers may be used but retard fetal growth. |
• Antimalarial drugs | Chloroquine (low dose); proguanil. |
• Anti-asthmatic drugs | β 2 agonists; inhaled steroids; a short course of systemic steroids if absolutely necessary. |
• Centrally acting drugs | Benzodiazepines (but see below); neuroleptics and tricyclic antidepressants are probably safe; antiepileptics – see p. 251. |
• Hay fever | Topical preparations; antihistamines – chlorphenamine and terfenadine. |
When treating pregnant women, some general rules should be observed:
• Avoid giving drugs if possible, especially in the first 3 months of pregnancy.
• Give drugs at the lowest effective dose for as short a time as possible.
• Avoid recently introduced drugs if possible.
• Drugs on lists A and B (see above) should be avoided if possible. The problem arises when there is no satisfactory substitute and treatment is vital. This is a matter of risk to the fetus against risk to the mother (and often, therefore, the fetus as well).
• Ethanol and street drugs: alcohol taken by the mother during pregnancy can damage the fetus, resulting in an infant with a small head, facial abnormalities and of low intelligence. Although it may well be better to avoid alcohol altogether in pregnancy, there is no evidence that one glass of wine, or its equivalent, daily causes any harm. If the mother is dependent on opioids, the newborn infant may suffer acute withdrawal symptoms. Regular use of cocaine is associated with an increased risk of fetal abnormality.
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