By John D Firth; Emma H Baker; Royal College of Physicians of London
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23). In general the following rules apply. • All drugs cross the placenta unless extremely large and highly polar (eg heparin). • The degree and rate of transfer are fastest for small, non-polar and lipid-soluble drugs. • After a single dose of a drug, the fetus is generally exposed to a lower concentration of the drug than the mother and the time taken to achieve a peak concentration in the fetus is thus delayed. COMPLICATIONS OF WARFARIN THERAPY Complication Time of exposure Manifestations Aetiology Warfarin embryopathy ‘Critical window’ of 6– 9 weeks of pregnancy Nasal hypoplasia, depression of nasal bridge, hypoplasia of extremities and stippling of epiphyses Reduced carboxylation of calcium-binding proteins Neurological damage After critical window Mental retardation, microcephaly, optic atrophy and blindness Possibly haemorrhagic in origin, hence may be reduced by tight anticoagulant control Haemorrhagic During delivery Traumatic intracranial haemorrhage during vaginal delivery Reduced clotting factors in full-term neonate compared with older infants SBT_C04_CP 12/8/10 15:56 Page 37 CLINICAL PHARMACOLOGY: PRESCRIBING IN SPECIAL CIRCUMSTANCES Fig.
However, the fetotoxicity associated with warfarin leads most obstetricians to prefer regimens based on heparin alone (Fig. 24, Regimen 2). Complications of prescribing during pregnancy Drug treatment in the pregnant woman raises issues related to the well-being of both the mother and the fetus. Fetal well-being The main concern relates to possible transplacental transfer of drugs (Fig. 23). In general the following rules apply. • All drugs cross the placenta unless extremely large and highly polar (eg heparin).
Another feature of such drugs is that their effect is dependent on the degree of activation of the pathway of which the receptor is part: the more active the pathway, the greater the biological effect of the antagonist (Fig. 21). Example 17: Too much benzodiazepine A 79-year-old woman, recently widowed, is brought to the Emergency Department by ambulance. She is unconscious with a Glasgow Coma Scale score of 8/15, but is breathing spontaneously with a Guedel airway in situ and a respiratory rate of 16/minute.
