dextromethorphan and Abnormalities--Drug-Induced

Topics: Abnormalities, Drug-Induced; Antitussive Agents; Cough; Dextromethorphan; Expectorants; Female; Guaifenesin; Humans; Maternal-Fetal Exchange; Nonprescription Drugs; Pregnancy; Pregnancy Complications

Topics: Abnormalities, Drug-Induced; Animals; Centers for Disease Control and Prevention, U.S.; Dextromethorphan; Female; Humans; Pregnancy; Receptors, N-Methyl-D-Aspartate; Teratogens; United States

One of my patients, who is now 8 weeks pregnant, just read in the newspaper that dextromethorphan (DM), an antitussive found in a variety of cough medicines, caused birth defects in chicken embryos. The author of the study stated that even one dose could be dangerous and that he would never allow his wife to use this drug if she were pregnant. My patient was understandably very concerned because last week she was suffering from a nasty cough and had been advised by her pharmacist to use a cough mixture containing DM, which she subsequently took for several days.. You may reassure your patient that she did not put her baby at risk by using this substance. Dextromethorphan has been on the market for many years and has never been implicated as a human teratogen. Furthermore, chick embryos are not a good model for predicting teratogenic potential in humans and, consequently, were abandoned as such more than 30 years ago.

Topics: Abnormalities, Drug-Induced; Animals; Antitussive Agents; Chick Embryo; Dextromethorphan; Disease Models, Animal; Female; Humans; Pregnancy; Risk Assessment; Teratogens; Toxicity Tests

N-Methyl-D-aspartate (NMDA) receptors are a calcium-conducting class of excitatory amino acid receptors that are involved in neuronal development and migration. Certain well known teratogens (e.g. homocysteine, ethanol, and chloroform) that induce congenital neural tube and neural crest defects also have the capacity to act as NMDA receptor antagonists. We hypothesized that teratogenicity was a general property of NMDA receptor antagonists, and that high affinity NMDA receptor antagonists would induce neural tube and neural crest defects. Chicken embryos were given 5, 50, or 500 nmol/d of selected NMDA receptor antagonists for 3 consecutive days during the process of neural tube closure, beginning 4 h after the beginning of incubation. Selected NMDA receptor antagonists represented three classes of antagonists: ion channel blockers, glycine site antagonists, and glutamate site agonists and antagonists. All classes of NMDA receptor antagonists induced embryonic death and congenital defects of the neural crest and neural tube; however, the channel blockers were the most potent teratogens. Dextromethorphan at 500 nmol/embryo/d killed more than half the embryos and induced congenital defects in about one-eighth of the survivors; dextromethorphan was also highly lethal at 50 nmol/embryo/d. Glutamate site NMDA receptor agonists (NMDA and homoquinolinic acid) displayed weak toxicity relative to their known NMDA receptor potency. Taken together, these data indicate that NMDA receptor antagonists, particularly channel blockers, are potent teratogens in the chicken embryo model. Because dextromethorphan is a widely used nonprescription antitussive, its strong teratogeneticity using this model is particularly noteworthy.

Topics: Abnormalities, Drug-Induced; Animals; Chick Embryo; Dextromethorphan; Embryo, Nonmammalian; N-Methylaspartate; Quinolinic Acids; Receptors, Amino Acid; Teratogens