Dart RD (editor): Medical Toxicology, 3rd ed. Lippincott Williams & Wilkins, 2004. Goldfrank LR et al (editors): Goldfrank’s Toxicologic Emergencies, 10th ed. McGraw-Hill, 2015. Olson KR et al (editors): Poisoning & Drug Overdose, 6th ed. McGraw-Hill, 2011. POISINDEX. (Revised Quarterly.) Thomson/Micromedex.
Overdose of bupropion can cause seizures that are often recurrent or prolonged. Drug-induced seizures are treated with an intravenous benzodiazepine such as lorazepam or diazepam. If this is not effective, phenobarbital or another more potent central nervous system depressant may be used. To prevent ingested drugs and poisons from being absorbed systemically, a slurry of activated charcoal is often given orally or by nasogastric tube.
Special Aspects of Perinatal & Pediatric Pharmacology
Gideon Koren, MD, FRCPC, FACMT
The effects of drugs on the fetus and newborn infant are based on the general principles set forth in Chapters 1–4 of this book. However, the physiologic contexts in which these pharmacologic laws operate are different in pregnant women and in rapidly maturing infants. At present, the special pharmacokinetic factors operative in these patients are beginning to be understood, whereas information regarding pharmacodynamic differences (eg, receptor characteristics and responses) is still incomplete.
Most drugs taken by pregnant women can cross the placenta and expose the developing embryo and fetus to their pharmacologic and teratogenic effects. Critical factors affecting placental drug transfer and drug effects on the fetus include the following: the physicochemical properties of the drug; (2) the rate at which the drug crosses the placenta and the amount of drug reaching the fetus; (3) the duration of exposure to the drug; distribution characteristics in different fetal tissues; (5) the stage of placental and fetal development at the time of exposure to the drug; and (6) the effects of drugs used in combination.
A. Lipid Solubility
As is true also of other biologic membranes, drug passage across the placenta is dependent on lipid solubility and the degree of drug ionization. Lipophilic drugs tend to diffuse readily across the placenta and enter the fetal circulation. For example, thiopental, a drug commonly used for cesarean sections, crosses the placenta almost immediately and can produce sedation or apnea in the newborn infant. Highly ionized drugs such as succinylcholine and tubocurarine, also used for cesarean sections, cross the placenta slowly and achieve very low concentrations in the fetus. Impermeability of the placenta to polar compounds is relative rather than absolute. If high enough maternal-fetal concentration gradients are achieved, polar compounds cross the placenta in measurable amounts. Salicylate, which is almost completely ionized at physiologic pH, crosses the placenta rapidly. This occurs because the small amount of salicylate that is not ionized is highly lipid-soluble.
B. Molecular Size and pH