Toxicology (Part-04) Teratogenicity (01) | Definition of Teratogenicity | Cause of Teratogenicity

Participate in the FREE online test for this lecture = https://forms.gle/yMF1LJRJEnnuSwjj6 Download "Solution Pharmacy" Mobile App to Get All Uploaded Notes, Model Question Papers, Answer Papers, Online Test and other GPAT Materials - https://play.google.com/store/apps/de... Teratogen: Any agent that can disturb the development of an embryo or fetus. Teratogens may cause a birth defect in the child. Or a teratogen may halt the pregnancy outright. The classes of teratogens include radiation, maternal infections, chemicals, and drugs. Teratogens act with specificity in that they produce specific abnormalities at specific times during gestation. For example, thalidomide produces limb phocomelia, while valproic acid and carbamazepine produce neural tube defects. Other teratogens are associated with recognizable patterns of malformations, for example, phenytoin with foetal hydantoin syndrome and coumarin anticoagulants with foetal warfarin syndrome. Teratogenic specificity also applies to species, for example, aspirin and corticosteroids have been found to be teratogenic in mice and rats but appear to be safe in humans. Thalidomide, on the other hand, was not shown to be teratogenic in rats, a tragic fact that resulted in significant human morbidity. Teratogens may demonstrate a dose-effect relationship. At low doses there can be no effect, at intermediate doses, the characteristic pattern of malformations will result, and at the high dose, the embryo will be killed. A dose-response may be considered essential in establishing teratogenicity in animals but is uncommonly demonstrated insufficient data among humans. A threshold dose is a dosage below which the incidence of adverse effects is not statistically greater than that of controls. With most agents, a dose threshold for teratogenic effects has not been determined; however, they are usually well below levels required to cause toxicity in adults. PROVEN TERATOGENIC DRUGS IN HUMANS- (1) Alcohol= The foetal alcohol syndrome is a clinical pattern of anomalies characterized by intrauterine growth retardation which commonly continues postnatally. These include microcephaly, developmental delay, and dysmorphic facies consisting of the low nasal bridge, midface hypoplasia, long featureless philtrum, small palpebral fissures and thin upper lip. Cleft palate and cardiac anomalies may also occur. (2) Angiotensin-converting enzyme inhibitors (ACEI) (captopril, enalapril, lisinopril) = ACEI are potent anti-hypertensive drugs. Their use in late pregnancy has been associated with foetal toxicity including intrauterine renal insufficiency. Reports of neonatal hypotension, oliguria with renal failure, and hyperkalemia have been reported with ACEI use in pregnancy. Complications of oligohydramnios (i.e., foetal limb contractures, lung hypoplasia, and craniofacial anomalies), prematurity, intrauterine growth retardation, and foetal death have also been reported with the use of these agents late in pregnancy. (3) Carbamazepine = Exposure to carbamazepine in utero carries a 1% risk of neural tube defects (10 times their baseline risk). A pattern of malformations similar to those described with the foetal hydantoin syndrome has also been associated with carbamazepine exposure in pregnancy. (4) Cocaine= Cocaine use during pregnancy has been associated with abruptio placentae, prematurity, foetal loss, decreased birth weight, microcephaly, limb defects, urinary tract malformations, and poorer neurodevelopmental performance. The contribution of cocaine to the incidence of congenital malformations is difficult to assess because of methodological problems, which make the results difficult to interpret. Cocaine abuse is often associated with poly-drug abuse, alcohol consumption, smoking, malnutrition, and poor prenatal care. Experimental animal studies and human epidemiology indicate that the risk of major malformation from cocaine is probably low, but the anomalies may be severe. Get in touch with the solution by just clicking following links- Facebook Group-   / solutionpharamcy   Facebook Page-   / pharmavideo   New channel (Pharmacy Dictionary) -    / @pharmacydictionary   Instagram-   / solutionpharmacy   E-Mail for official and other work - [email protected] LinkedIn-   / pushpendrakpatel   #solutionpharmacy #Pharmacologyclass #GPATonlinetest