Pharmacokinetics of corticosteroids during pregnancy.

Glucocorticoids constitute one of the most frequently prescribed medicines during pregnancy. Their use is the mainstay for a variety of maternal and fetal indications, both in acute and chronic settings. The pharmacokinetics of corticosteroids during pregnancy remains poorly understood. Significant pharmacologic alterations occur secondary to the profound changes in the renal, gastrointestinal, and cardiovascular systems during human gestation. Additional research on this topic is a significant priority to increase therapeutic benefit while minimizing side effects for both the mother and fetus when corticosteroids are prescribed during pregnancy. Certain obstetrical conditions such as preeclampsia and multiple gestations are associated with different volumes of distribution and clearance rates of medications, adding further complexity to the therapeutic use of glucocorticoids. This article reviews the available literature, including the most significant physiologic alterations of pregnancy and basic concepts of glucocorticoid pharmacology. Finally, theoretical assumptions about the potential pharmacokinetic changes of glucocorticoids in pregnancy and their application to clinical settings are discussed.

Lead toxicity and chelation therapy.

PURPOSE: Common sources of lead exposure, the primary clinical effects of lead toxicity, and current recommendations for managing lead toxicity, including chelation therapy, are reviewed. SUMMARY: Common sources of lead exposure in children and adults include industrial and mining activities, paint, dust, soil, water, air, the workplace, food, trinkets, ethnic folk remedies, and cosmetics. The absorption and biological fate of lead are affected by a variety of factors, including an individual's nutritional status, health, and age. Children with a blood lead concentration of >10 microg/dL and adults with a blood lead concentration of > or = 45 mug/dL should undergo further evaluation. Symptoms and time to onset of symptoms postexposure may vary, and it can be difficult to identify the early, subtle neurologic effects of lead toxicity. The classic symptoms of lead toxicity generally correlate with blood lead concentrations of 25-50 microg/dL in children and 40-60 microg/dL in adults. Management of lead toxicity requires extensive risk assessment and caregiver education. Chelation is generally not indicated for adults with blood lead concentrations of < 45 microg/dL because of the potential risk of adverse drug events and concerns about remobilized lead, and chelation for children with blood lead concentrations of < 45 microg/dL remains controversial. Dimercaprol, edetate calcium disodium, and succimer are the three agents primarily used for chelation. CONCLUSION: Lead toxicity remains a significant public health concern. Elimination of elevated blood lead levels in children can be accomplished by educating appropriate health care providers and caregivers, recognizing potential lead sources, and adopting aggressive prevention and case management measures.

Pharmacokinetics and pharmacotherapy of thionamides in pregnancy.

Hyperthyroidism occurs in approximately 1 in every 1000 to 2000 pregnancies. Although the signs and symptoms of the disease are similar in the pregnant and nonpregnant patient, the complications of hyperthyroidism can have even more profound consequences for the mother and fetus during gestation. These include maternal heart failure, preeclampsia, miscarriage, and preterm labor; as well as fetal loss and low birth weight. Furthermore, thyroid function and laboratory testing for hyperthyroidism are altered in pregnancy. The gestational increase in thyroid size, increased thyroid-binding globulin levels, increased serum total T4 and total T3 levels, and decreased thyroid stimulating hormone levels often confuses the evaluation of the thyroid status in pregnancy. Worldwide, the thionamides-propylthiouracil, methimazole, and carbimazole-have been used in pregnancy for the treatment of hyperthyroidism. However, propylthiouracil has been the drug of choice in the United States because it is believed to have less potential to induce fetal/neonatal hypothyrodism, to cross the placenta and into breast milk to a lesser degree, and to be less teratogenic than methimazole or carbimazole. None of the above have been substantiated in more recent studies. The pharmacokinetics of the thionamides in the pregnant and nonpregnant states, as well as the pharmacotherapeutic recommendation for hyperthyroidism will be reviewed.

Do no harm: avoidance of herbal medicines during pregnancy.

Herbal medicines are regarded by the public and some health care providers as gentle and safe, but there is no scientific basis for that belief. The active ingredients of plant extracts are chemicals that are similar to those in purified medications, and they have the same potential to cause serious adverse effects. This commentary summarizes recent data on the poor quality control and toxicity of herbal remedies and on the pharmacologic activities of ginger, which is used for treatment of morning sickness. There are no rigorous scientific studies of the safety of dietary supplements during pregnancy, and the Teratology Society has stated that it should not be assumed that they are safe for the embryo or fetus. Obstetricians should advise women not to expose their fetuses to the risks of herbal medicines.

Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States.

STUDY OBJECTIVE: To develop guidelines for the stocking of antidotes at hospitals that accept emergency admissions using combined evidence-based and consensus methods. METHODS: Study participants were 12 medical care providers from disciplines that are affected by insufficient stocking of emergency antidotes (clinical pharmacology, critical care, clinical pharmacy, emergency medicine, hospital pharmacy, internal medicine, managed care pharmacy, clinical toxicology, pediatrics, poison control centers, pulmonary medicine, regulatory medicine). Selection of individuals for the study panel was based on evidence of previous antidote research or perspective regarding the purchase and use of antidotes. The literature regarding each antidote was systematically amassed using pre-1966 literature files, current MEDLINE searches, the reference lists of major medical textbooks, and citations solicited from the consensus panel. Articles relevant to 4 defined core questions were included. These articles formed the basis of an evidence-based analysis performed by the principal investigator. After literature analysis, a literature summary and proposed guidelines for antidote stocking were submitted to the panel. Consensus was formed by electronic iterative presentation of alternatives to each panel member using a modified Delphi method. All panel members participated in 5 rounds of guideline analysis of 20 antidotes. RESULTS: Of the 20 antidotes, 16 antidotes were ultimately recommended for stocking (N -acetylcysteine, atropine, Crotalid snake antivenin, calcium gluconate and chloride, cyanide antidote kit, deferoxamine, digoxin immune Fab, dimercaprol, ethanol, fomepizole, glucagon, methylene blue, naloxone, pralidoxime, physostigmine, sodium bicarbonate), 2 were not recommended for stocking (black widow antivenin, ethylenediamine tetraacetic acid), and consensus could not be reached for 2 antidotes (flumazenil, physostigmine). CONCLUSION: These guidelines provide a tool to be used in revising or creating policies and procedures with regard to the stocking of antidotes in hospitals that accept emergency patients.