Environmental Exposures and Reproduction *
Michele Kiely in Reproductive and Perinatal Epidemiology, 2019
The fields of developmental and reproductive toxicology have undergone great growth in the years since 1961 when thalidomide was first identified as a developmental toxicant. In the early years, teratogens (i.e., agents that cause structural malformations in offspring exposed during critical developmental times) were of primary concern. More recently, the term “teratology” has been replaced with the more broadly defined term, “developmental toxicology”: “the study of adverse effects on the developing organism that may result from exposure prior to conception (either parent), during prenatal development, or postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point in the life span of the organism. The major manifestations of developmental toxicity include: (1) death of the developing organism, (2) structural abnormality, (3) altered growth, and (4) functional deficiency.”4
Orthopaedic Pharmacology
Manoj Ramachandran, Tom Nunn in Basic Orthopaedic Sciences, 2018
Haemorrhage: in overdose can be reversed acutely with clotting factor concentrates or fresh frozen plasma; if severe, consider intravenous vitamin K (phytomenadione).Drug interactions: drugs that induce (e.g. barbiturates, carbamazepine) or inhibit (e.g. ethanol, metronidazole) hepatic microsomal enzymes may have an effect on the action of warfarin; either leading to reduction or enhancement of anticoagulant effect respectively.Teratogenicity: absolute contraindication in pregnancy.
Giardia outbreaks on Ship
Meera Chand, John Holton in Case Studies in Infection Control, 2018
Albendazole and mebendazole have been used to treat G. lamblia infection, and they are thought to be useful agents because of the secondary effect on helminth infections in many of the endemic countries and their good side-effect profile. They work by binding to the G. lamblia α-tubulin cytoskeleton, which causes both inhibition of cytoskeleton polymerization and impaired glucose uptake. They are absorbed poorly from the gastrointestinal system and there is negligible excretion by the kidneys. Short-term side effects include anorexia and constipation and long-term side effects include reversible neutropenia and elevated liver enzymes. Use in pregnancy is contraindicated because of concerns about teratogenicity.
Usefulness of zebrafish in evaluating drug-induced teratogenicity in cardiovascular system
Published in Drug and Chemical Toxicology, 2019
Ryo Watanabe, Yuki Nakanishi, Daisuke Nijoukubo, Hiroki Teraoka, Hiroyuki Ogasawara, Kazuhiko Mori
Teratogenicity is one of the serious concerns associated with pharmaceutical drug development. At the preclinical screening phase, several in vitro systems, such as a limb bud micromass culture system (Flint 1993), a whole embryo culture (WEC) system (Webster et al.1997), and a mouse embryonic stem cell test (EST) (Scholz et al.1999), are widely used to detect the potential teratogenicity of candidates. These systems have been reported to adequately detect the potential teratogenicity of some drugs, which showed teratogenicity in vivo in rodent and rabbit studies, with high sensitivity (Genschow et al.2002). However, these test systems have inherent drawbacks. For example, the limb bud micromass culture and WEC systems are not effective for the assessment of drug candidates during organogenesis due to the exposure timing. In addition, the mouse EST system, which evaluates the effect of test compounds on heart rate by using differentiated cardiomyocytes, is unable to assess the whole-embryo developmental process (Chapin et al.2008, Kroese et al.2015). Furthermore, it is difficult to detect teratogenic features, such as hypoplasia of the limbs and external ear malformation, caused by thalidomide in humans by using the above-mentioned methods. Recently, a new assay system using zebrafish eleutheroembryos was reported that could detect teratogenicity caused by thalidomide with similar phenotypic outcomes (Ito et al.2010).
Pneumocystis jirovecii: a review with a focus on prevention and treatment
Published in Expert Opinion on Pharmacotherapy, 2021
R. Benson Weyant, Dima Kabbani, Karen Doucette, Cecilia Lau, Carlos Cervera
Like in non-pregnant patients, there are alternative treatments available should TMP-SMX ineffective or intolerable. Despite crossing the placenta, dapsone is considered safe in pregnancy. Its use has been established for the treatment of malaria, leprosy, and various dermatological conditions. However, there is a small risk of fetal hemolysis, particularly in G6PD deficiency. Clindamycin has also been shown to cross the placenta, but animal studies have found no increased risk of birth defects when used in the 2nd or 3rd trimesters. Primaquine is generally not used in pregnancy as it carries a risk of hemolysis to both the mother and the fetus, and again the risk is increased in G6PD deficiency. Atovaquone’s post-marketing surveillance has not found any increased risk of birth defects associated with its use. Like dapsone, atovaquone is used with caution as possible fetal harm was demonstrated in animal studies. Lastly, pentamidine has been shown in animal studies to be embryotoxic when given at the 4 mg/kg/day dose. Teratogenicity, however, has not been found when used in rats and rabbits [129].
Genotoxic and mutagenic studies of teratogens in developing rat and mouse
Published in Drug and Chemical Toxicology, 2019
Eyyüp Rencüzoğulları, Muhsin Aydın
Teratogenicity tests have been described by various researchers (Brown et al. 1995, Foote and Carney 2000, Bremer and Hartung 2004). These tests were classified as cell culture tests, in vitro tests with organs or embryos, and in vivo tests with various animals. It has also been reported that teratogenicity tests can be performed with embryonic stem cells. Among the mammals, mice and rats are the most suitable organisms for genetic analyses (Cooper and Hausman 2004). It has been reported that mice and rats are suitable models for human development. The growth and reproduction of both mice and rats are well known and can be associated with humans. Additionally, mouse and human genes resemble each other and mutations in homologous genes result in similar developmental defects (Chapin et al. 1997, Foote and Carney 2000, Cooper and Hausman 2004).
Related Knowledge Centers
- Birth Defect
- Developmental Toxicity
- Dysmorphic Feature
- Fetus
- Toxicity
- Embryo
- Development of The Human Body
- Medical Genetics
- Insult
- Fetal Alcohol Spectrum Disorder