Prescribing drugs during pregnancy

1. Prescribing drugs during pregnancy Khalid A. Yarouf www.4MedStudents.com

2. Introduction • Pregnancy poses important problems. Most drugs will diffuse passively across placenta, and some are transported actively, so the potential benefit of a drug to mother has to be considered in relation to the potential risk to the fetus. As a general rule, all drugs should be avoided in pregnancy unless there’s a compelling reason for their use. Some drugs have been definitely linked to fetal abnormalities (Table.1).

3. Con’t • The safety of most drugs in pregnancy has not been firmly established as the effects may not be apparent for many years after birth. The past use of stilboesterol in pregnant women with threatened abortion has resulted in development of adenocarcinoma of vagina in female children in their teens and early 20s. • There’s a possibility that the use of other drugs in pregnancy predisposes to more conditions e.g. DM or HTN. Such associations would not be easily recognized.

4. Effects on fertilization & implantation • The principal mode of contraceptive action of progestogens is to prevent implantation, which normally occurs 2-3 weeks after fertilization. IUCD have similar effect. Damage to the embryo before implantation results in failure of implantation and is therefore unlikely to cause fetal abnormalities.

5. Effects on fetal development • The intra-uterine period between 2 weeks – 3 months is when the most serious abnormalities of fetal development can be caused by drugs. It’s during this period that the major organs are being formed. In animal studies, even one dose of a drug administered at the critical time has been shown to have a major effect. The mechanisms of damage are not yet known, but the molecular basis of differentiation of embryonic cells is an intense area of basic research and is likely to provide new insights in the near future. • Ampicillin and Cephalosporins are considered one of the safest drugs which can be used during pregnancy.

6. Toxicity to the formed fetus • During T2 & T3 of pregnancy, adverse effects on fetus of drugs administered to the mother are generally an exaggeration of the effects seen in the adult. Exceptions to this rule are the damage to tissues which are still developing e.g. teeth & bones by Tetracycline, and the impairment of brain development by Coumarin anticoagulant. • Particular care must be taken with drugs given shortly before delivery. Analgesics, e.g. Meperidine (Pethidine), and tranquillizers e.g. (Benzodiazepines) may severely impair neonatal respiration. In addition, the newborn lacks many enzymes necessary for the efficient metabolism of drugs.

7. Breastfeeding • Although most drugs can be detected in breast milk, the dose administered to the infant is generally low. This is because, unless there’s concentration of drug by breast tissue, the concentration of milk tends to be similar to that of the maternal plasma. Clearly in this case the final concentration in the infant’s plasma is likely to be much less than that in the mother’s. • Examples of safe drugs during breastfeeding include Penicillins, Aminoglycosides, and Cephalosporins.

8. Con’t • Some drugs which cause problems via breastfeeding: Carbimazole (may affect infant thyroid function) and Tetracyclines (also excreted in milk). • As with pregnancy, it’s important to avoid all drugs in nursing mother unless there’s a compelling need. A list of drugs excreted in breast milk and known to have problems is given in an appendix to the British National Formulary (BNF). • Examples include: Chloramphenicol (BM suppression), Sulfonamides (hemolysis with G6PD deficiency), Nitrofurantoin (hemolysis with G6PD deficiency), Tetracycline (stains teeth & bones), Lithium, anti-neoplastic and immunosuppressants, and psychotropic agents.

9. MCQs • What may Diazepam cause if taken late in pregnancy? • Hypotension. • Hyper-ventilation. • Bradycardia. • Hypoglycemia. • Which of the following drugs does not cross placenta? • Succinyl-choline. • N2O. • Morphine. • Meperidine (Pethidine). • Diazepam.

10. Matching Match the following medications’ effect during pregnancy with the appropriate medication. • Tetracycline. • Nitrofurantoin. • Sulfas. • Streptomycins. • Chloramphenicol. • Is excreted after binding, utilizing glucuronyl transferase. • May cause aplastic anemia. • Ototoxic. • Discolors decidual teeth.