Teratogenic drugs - SlideShare . Mechanisms of teratogenesis**This article is based on a Drugs in Pregnancy - Gynecology and Obstetrics - Merck Mechanisms of teratogenesis - Wiley 8. nausea. 15 Toxicology Terms The term "toxicant" refers to toxic substances that are produced by or are a byproduct of human-made activities. The regulation of spermatogenesis involves both endocrine and paracrine mechanisms . 5 Zbinden, '75a. For example, diazepam displaces phenytoin from plasma proteins, resulting in an increased plasma concentration of free phenytoin and an increased risk of toxicity. [terato- + G. genesis, generation] Describe the specific mechanisms of action, causes of drug resistance and toxicities associated with the drugs presented. Iodine is a naturally occurring element found in sea water and in certain rocks and sediments. In addition to the Ca 2+-dependent activation of MLC kinase, the state of myosin light chain phosphorylation is further regulated by MLC phosphatase [aka myosin phosphatase (1, 4, 9, 11-16)], which removes the high-energy phosphate from the light chain of myosin to promote smooth muscle relaxation (). (2010a,b) where its metabolism may be catalyzed by embryonic prostaglandin H synthase (also known as cyclooxygenase) to reactive free radical intermediates. Zootoxins can be divided into several categories: (1) oral poisonsthose that are poisonous when eaten; (2) parenteral poisons, or venomsthose that are produced by a specialized poison gland and administered by . Sir Austin Bradford Hill proposed criteria to establish such an argument. Teratogenesis Teratology: the study of the frequency, causation, and development of congenital malformations. Portals of Entry of a Toxin 9. Alcohol. In humans, it is proposed that similar mechanisms regulate gastrulation to those found in other vertebrates. Pregnant rabbits, which are thalidomide-sensitive, were treated with thalidomide (70 mg/kg bw/day) on GD 8-12 diabetes mellitus type 1 pubmed HbA1c test intervals among patients with stable glycemic condition should be 1 year. Another common female reproductive toxicity pattern that toxicologic pathologists will likely experience is that manifested by hyperprolactinemia in rats. Testosterone or DHT ligand-androgen receptor complexes act as transcription factor complexes, stimulating the expression of various responsive genes. Environmental Toxicology 7. 1. WHO. Toxicology of Solvents (Including Alcohol) 5. of 1900, the evidence from cross-sectional studies on neuro-. In humans, DNA is contained in 23 chromosome pairs within the nucleus. Thalidomide's mechanism of action in AP is thought to relate to anti-inflammatory and immune-modulating effects via inhibition of TNF and alteration of interferon- signaling [58, 59]. Cycloheximide is a naturally occurring fungicide produced by the bacterium Streptomyces griseus.Cycloheximide exerts its effects by interfering with the translocation step in protein synthesis (movement of two tRNA molecules and mRNA in relation to the ribosome), thus blocking eukaryotic translational elongation.Cycloheximide is widely used in biomedical research to inhibit protein synthesis . (a) Domain structures of Nrf2, Keap1, and small Mafs F, G, and K. (b) Secondary structure of Neh2. CLASSIFICATION (DECKERS' ET AL) Group 1- Blockade of voltage-dependent Na+ or Ca channels (generalised and partial seizures) ! stomach pain. Comprehend the mechanism of production and circulation of lymph. NURFATIN AFIQAH BT MOHD BADRONDIN 5. This causes an . 4 Kochhar and McBride, '86. thalidomide teratogenesis, though the mechanism still needs exploration. Maternal effects on ethanol teratogenesis in a cross between A/J and C57BL/6J mice. Errors in genetic programming based on . . 129 . Relationship to other Sciences 5. Structural Anomalies/Dysmorphology Malformation:the normal developmental process is altered such that a given structure cannot form or forms . Background: Although medications should only be prescribed in pregnancy if benefits to the mother outweigh the risk to the fetus, drug use in pregnancy especially prescribed and over-the-counter analgesics, is very common. These mechanisms are folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption and specific receptor- or enzyme-mediated teratogenesis. Basic Principles of Development 1- Cell Division multicellular organism 2- Pattern Formation Defining the Axes: Body Plan initiating Germ Layer Formation 3- Morphogenesis Formation of 3 Germ layers 4- Cell Differentiation Blood, Muscle, Nerves 5- Growth maturity Cleavage behavioral effect in ' high ' exposed workers ( Meyer-Baron et al., 2008 . Teratogen is a substance that can cause embryos to malfunction resulting in birth defects and other problems. The FDA requires reproductive toxicity testing for any NME to be used in women of childbearing potential, regardless of whether the target population is pregnant women. PARAMETERS: Oral bioavailability is 50-70%. Definition of teratogen Any chemical ( drug ), infection, physical condition or deficiency that , on fetal exposure,can alter fetal morphology or subsequent function. It is worth noting that patients classified as having DHF and DSS have no generalized edema; rather, a selective plasma leakage tends to occur in the pleural and abdominal cavities ( 12 , 230 , 246 . 1 Retinol or retinyl esters. Spermatogenesis, the origin and development of sperm cells within the male reproductive organs, the testes. result of teratogenesis is determined by its site of action . Teratology is the study of the causes and underlying mechanisms leading to birth defects or malformations. Combined androgen &sperm cell production defects 1-development defects-: Klinefelter's syndrome, undescended testis, 2-acquired defects-: orchitis Failure of deposition of sperm in female genital tract 1-vas deferens obstruction 2-failure of erection, ejection. Figure 2: Domain structure and activation mechanism. Describe the specific mechanisms of action, causes of drug resistance and toxicities associated with the drugs presented. Learn about the processes of sperm cell production and maturation with this article. NURUL FIRDAUS BT HANAFEE 7. These free radicals in the presence of cellular . Some natural "bad path" spontaneous abortion. To ensure that the offspring has only one complete diploid set of chromosomes, only one sperm can fuse with one egg. The response of the developing embryo to these insults is failure of cell-cell interaction crucial for development, interference with cell migration, or mechanical . A toxic symptom is any feeling or sign indicating the presence of a poison in the system. Toxic effects refers to the health effects that occur due to exposure to a The molecule provides the basic template for . Be able to classify these particular agents according to 1) chemical class, 2) mechanism of action, 3) cell cycle specificity, 4) therapeutic uses, and 5) major toxicities. Therefore, in addition to forming a haploid nucleus, oogenesis also builds up a store of cytoplasmic enzymes . Whereas the gamete formed by spermatogenesis is essentially a motile nucleus, the gamete formed by oogenesis contains all the materials needed to initiate and maintain metabolism and development. Usually administered in dosage of 500ml twice daily. and the stage of development of the target organ. mechanism of teratogenesis tentatively to the earliest recognizable event thought to have played a primary role in abnormal development. NURUL HUSNA BINTI MURYADI 3. 600This article contains some pharmacology made ridiculously easy mnemonics for all medical students, especially those in their 3rd year going through this hell in the form of a subject name pharmacology. teratogenesis, 26 Robert L. Brent and Lynda B. Fawcett 16 Drugs, alcohol abuse, and effects in pregnancy, 29 Stephen R. Carr and Donald R. Coustan 17 Teratogenic viruses, 31 Antonio V. Sison 18 Transplacentally acquired microbial infections in the fetus, 34 Santosh Pandipati and Ronald S. Gibbs 19 Antibiotics and other antimicrobial agents in . Mechanisms of Teratogenesis Lynda B. Fawcett, Ph.D. Assistant Professor of Pediatrics Thomas Jefferson University & Alfred I duPont Hospital For Children Wilmington, DE. However, RV is a major cause of birth defects and fetal death following infection in pregnant women. Explore the definition, exposure, and examples of teratogen in pregnancy. The authors also touch on possible mechanisms of cognitive teratogenesis with regard to genetic susceptibility to SSRIs and AEDs. The mechanism of action involves binding to specific nuclear receptors called PPAR- (peroxisome proliferator-activated gamma receptor), whose stimulation regulates the transcription of specific genes that will lead to an increase in the number and affinity of insulin receptors, especially the glucose transporters GLUT-4. The coexistence of a multitude of mechanisms that may act simultaneously or consecutively and differ among various cell types poses particular challenges to researchers. Complex mechanisms and timing of disruptive interaction during embryogenesis. ANAT., 138: 129-132. with tendonitis. References are made to the possible changes in its nutrient components, and also to the solanidine steroidal properties which may have effects similar to the sex hormones.Changes in the fetal development due to maternal hormone inbalance, either of . Sperm are produced specifically from stem cells in the walls of the seminiferous tubules. These agents often are essential to providing accurate diagnoses, and are nearly always safe and effective when administered correctly. Teratogenic drugs. Reproductive toxicology is the study of the occurrence, causes, manifestations, and sequelae of adverse effects of exogenous agents on reproduction [23]. Nervous System: 1. Or a teratogen may halt the pregnancy outright. Poison, a substance, natural or synthetic, that damages living tissues and has injurious effects on the body, whether it is ingested, inhaled, or absorbed or injected through the skin. During organogenesis (between 20 and 56 days after fertilization): Teratogenesis is most likely at this stage. 2009;33(7):12381245. Metabolism of a Toxin 11. The term "toxin" refers to toxic substances that are produced naturally. chemick ltka, zen apod. Embryonic stage. Half-life: 4hours May be used for lower UTIs. 130 EDITORIAL On sifting through the literature of experimental teratology, it is possible to deduce that there are perhaps eight or ten general types of . . In the final paper in this special issue, Alwan and Hamamy present a review of maternal iron deficiency during pregnancy, suggesting that it may increase the risk for several adverse outcomes, such as fetal growth . 7. Sites of Action [] Anticonvulsant drugs are pharmacological agents used to achieve seizure control and/or prevent seizure episodes. 7 ND = not determined. 3. AM. Antivirals for Herpes Virus. erythroblastosis fetalis, also called hemolytic disease of the newborn, type of anemia in which the red blood cells (erythrocytes) of a fetus are destroyed in a maternal immune reaction resulting from a blood group incompatibility between the fetus and its mother. Definition of Toxicology 3. persistent bleeding or oozing from puncture sites, mouth, or nose. A toxic effect is always dose-related. Fusion of more than one sperm with an egg, or polyspermy, is genetically incompatible with life and results in zygote death.There are two mechanisms that prevent polyspermy: the "fast block" to polyspermy and the "slow block" polyspermy. ), kter me zpsobit naruen vvoje orgnu nebo poruchu jeho funkce bhem embryonlnho i fetlnho vvoje.Nkter teratogeny psob pevn na jeden orgnov systm (jedn se nap. It is the study of adverse effects on the development of . mental depression. Answer: The Mechanism of Teratogenesis fall into broad categories based on the etiology of congenital malformations: (a). This control involves Sertoli cell-germ cell interaction, as well as a programmed performance of changes in chromatin structure and gene expression in the developing germ cells. However, reactions to contrast media do occur and can be life threatening. Downing C, Balderrama Durbin C, Broncucia H, et al. When considering possible mechanisms for this observation, it is important to consider the number and appearance of spermatid nuclei within the multi-nucleated cyst. If there are a large number of abnormal-appearing, densely stained nuclei, then it is highly likely that this arises due to spermatid death (Fig. Teratogen je exogenn faktor (nap. 1. Rubella or German measles is an infection caused by rubella virus (RV). Earlier Developments 4. Herpes simplex virus(HSV): structure and genome, mode of transmission, pathogenesis, infection, laboratory diagnosis and treatment Structure and genome Describe the functions of lymphatic system and its role in spread of infection and cancer 6. 6 Howard and Willhite, '86 (from single dose experiments). nonimmune mechanisms are a major cause of morbidity and mortality worldwide. The classes of teratogens include radiation, maternal infections, chemicals, and drugs.. WHO's definition of an adverse drug reaction, which has been in use for about 30 years, is "a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function". After getting internalized, they inhibit FPP synthase, a key enzyme in the mevalonate pathway, which is responsible for production of cholesterol and isoprenoid lipids [ 45 ] . Teratogen: Any agent that can disturb the development of an embryo or fetus. Infection of children and adults is usually characterized by a mild exanthematous febrile illness. Other articles where teratogenesis is discussed: poison: Teratogenesis: Teratogenesis is a prenatal toxicity characterized by structural or functional defects in the developing embryo or fetus. Anticonvulsants encompass various drugs with different mechanisms of action including ion-channel (Na + and Ca 2+) blocking and GABA reuptake inhibition.Phenobarbital, phenytoin, carbamazepine, valproic acid, and ethosuximide are the 1st-generation antiseizure drugs. effectit occurs by the same mechanism as the therapeutic effect (vasodilatation). Female rats are especially sensitive to the effects of hyperprolactinemia, and there are several classes of test agents that induce a hyperprolactinemia phenotype in animals. Learn about different types of poisons and their effects on the body. DNA The molecule DNA is the repository of heritable genetic information. Trauma, infection, abnormal sperms. (c) Model for activation of Nrf2. On the other hand, an unwanted side effect occurs via some other mechanism and may be dose-related or not. Be able to classify these particular agents according to 1) chemical class, 2) mechanism of action, 3) cell cycle specificity, 4) therapeutic uses, and 5) major toxicities. ZATEEL FAHADA BT RUSLI 6. Establishing an argument of causation is an important research activity with major clinical and scientific implications. It should be noted that, so far, some of these mechanisms are principally understood from animal models; however, these mechanisms may produce birth defects in . 2011;45(5):441449. There are non radioactive and radioactive forms of iodine. For example, the dose-related anticholinergic effect of a tricyclic antidepressant is a side effect, since this . Therefore, it is critical for faculty and staff to know how reactions to contrast . III Department of Pathology, University of Helsinki. Sulfonamides: common characteristics SULFA:S-Steven-Johnson syndrome/ Skin rash / Solubility low. Published February 20, 2006. Lauri Saxn. 8 Agnish, Roche, Inc. (personal communication).. teratogenicity: ( ter'-t-j-nis'i-t ), The property or capability of producing congenital malformations. sores, ulcers, or white spots on the lips or in the mouth. WAN FATHIAH NASUHA BT WAN NUSDRI 4. An alternative mechanism for teratogenesis due to thalidomide was proposed by Arlen and Wells (1996), Parman et al. Iodine is also added to some table salt to ensure that all people in the United States have enough . The paper discusses some practical methods which may assist studies investigating the possible teratogenic effect of imperfect potatoes (if any). Mechanisms of teratogenesis * * This article is based on a paper presented in Martinique at a meeting co-sponsored by Institut de la Vie and the U.S. National Cancer Institute. - Humans: critical 1st 8 wks gestation. Human herpesviruses are DNA. Developmental toxicity is any structural or functional alteration, reversible or irreversible, which interferes with homeostasis, normal growth, differentiation, development or behavior, and is caused by environmental insult (including drugs, lifestyle factors such as alcohol, diet, and environmental toxic chemicals or physical factors). Scope 6. Teratogens may cause a birth defect in the child. AMALA SEBASTIAN 16PZO-005 2. It also includes intrauterine growth retardation, death of the embryo or fetus, and transplacental carcinogenesis (in which chemical exposure of the mother initiates cancer development in the NURUL MIZA SHASHEIHA BINTI ABDUL MUTALIB 2. J. Iodine is used as a disinfectant for cleaning surfaces and storage containers and is used in skin soaps and bandages, and for purifying water. Group 2 - enhance inhibitory events mediated by GABA (absence, generalised, partial seizures) ! The metabolism of many xenobiotics is fundamental to many toxic processes such as carcinogenesis, teratogenesis, and tissue necrosis. This incompatibility arises when the fetus inherits a certain blood factor from the father that is absent in the mother. Excellence (NICE) in the United Kingdom, suggest rechecking HbA1c values . Gilliam D, Valdez N, Branson S, et al. Prof Aboubakr elnashar Benha university Hospital, Egypt Aboubakr Elnashar 2. In the United States, more than 100,000 deaths are attributed annually to serious ADRs. Define and classify different types of nervous system (Somatic and . Ethanol teratogenesis in five inbred strains of mice. Oogenesisthe differentiation of the ovumdiffers from spermatogenesis in several ways. A selection of teratogens and their consequences are described, and they are arranged in a certain hierarchy based on a simplified model of how they act. Language 8. Numerous mechanisms likely contribute to the damaging effects of prenatal alcohol exposure on the developing fetus and particularly the developing central nervous system ( CNS) . Teratogenesis is a process that causes birth defects or malformations in an embryo or foetus. Hans Spemann (1869 - 1941) identified this region in amphibia, also called the "Spemann's organiser".The same region in birds it is known as "Hensen's node" named for Victor Hensen (1835 - 1924) and is also known generally as the primitive node or knot. Therapeutic Testosterone is a synthetic form of the endogenous androgenic steroid testosterone. Hyperprolactinemia. 2 Rosa et al., '86. The pathogenesis of adverse pregnancy outcomes including preeclampsia and fetal growth restriction [] and a number of neonatal outcomes [] has been shown to be associated with oxidative stress.Preeclampsia (de novo proteinuric hypertension) is estimated to occur in ~3% of all pregnancies and is a leading cause of maternal and perinatal mortality and morbidity in the Western world [35, 36 . Introduction to Toxicology 2. 8. Mechanisms of Teratogenesis Mechanisms of Teratogenesis Beckman, D A; Brent, R L 1984-04-01 00:00:00 D. A. Beckman and R. L. Brent Department of Pediatrics, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107 MECHANISMS The mechanisms of teratogenesis faJl into two broad categories based on the etiology of the congenital malformations: (a) errors in . Group X- reduce events mediated by excitatory amino acids- skin itching, rash, or redness. Adults . puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue. 8. Lauri Saxn 1. In humans, it is proposed that similar mechanisms regulate gastrulation to those found in other vertebrates. The mechanism by which nitrogen containing BPs impacts osteoclast activity and survival differs from that of the first generation BPs. Teratogenicity: A mechanism based short review on common teratogenic agents. Antiviral agents against human herpesviruses (HHVs) include acyclovir, cidofovir, and foscarnet. 1). o neurotropismus i kardiotropismus), jin postihuj cel organismus. Should not be used in pts. July 6, 2018. Group 3 - blocks T-type calcium channels (absence seizures). 26. Drugs reaching the embryo during this stage may result in spontaneous abortion, a sublethal gross anatomic defect (true teratogenic effect), covert embryopathy (a permanent subtle metabolic or functional defect that may manifest later in life), or an increased risk of childhood cancer . Mammalian spermatogenesis shows a strict control of many specific molecular and cellular events. Often the same enzymes involved in drug metabolism also carry out the regulation and metabolism of endogenous substances. Ca 2+ SENSITIZATION MECHANISM AND CONTRACTION OF SMOOTH MUSCLE. This is commonly observed when . Name different components of nervous tissue (neuron, ganglion, nuclei, nerve, tracts) 2. Fetal anticonvulsant syndrome Aboubakr Elnashar 3. Teratogenesis 1. Spermatogenesis (February 20, 2006), WormBook, ed. TERMS TEROS- Monster TERATOGEN- An agent that can produce a permanent alteration of structure or function in an organism exposed during embryonic or fetal life TERATOLOGY- Branch of science which studies the mechanisms and patterns of abnormal development TERATOGENICITY- the induction of malformation by teratogens TERATOGENESIS-the process by . 2. Instead . Mechanisms of Teratogenesis Genetic interference, gene mutation, chromosomal breakage, interference with cellular function, enzyme inhibition, and altered membrane characteristics. Spermatogenesis is a complex process involving mitotic cell division, meiosis and the process of spermiogenesis. Hansen and Harris (2004) have proposed that nuclear factor kappa-B (NF-jB) mediates the redox regulation of limb outgrowth. Understanding the mechanism underlying the development of shock is crucial for the development of novel strategies to improve patient management. Alcohol Clin Exp Res. painful or difficult urination. 1. Iodinated and gadolinium-based contrast media are used on a daily basis in most radiology practices. These criteria include the strength of the association, consistency, specificity, temporal sequence, biological gradient, biologic rationale, coherence, experimental evidence, and analogous evidence . Distribution of a Toxin 10. taking corticosteroids. ADVERTISEMENTS: In this essay we will discuss about Essay on Toxicology:- 1. This chapter should be cited as: L'Hernault, S.W. Distribution interactions occur when drugs are extensively protein-bound and the co-administration of a second can displace it to the non-bound active form.This increases the amount of (unbound) drug available to cause an effect. Teratogenesis ppt 1. They are the most common iatrogenic illness, complicating 5 to 15 percent of therapeutic drug courses. Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Presentation Transcript. (1999), and Wells et al. Drugs known to be capable of acting as teratogens include, but are by no means limited to, ACE inhibitors like benazepril (brand . Hans Spemann (1869 - 1941) identified this region in amphibia, also called the "Spemann's organiser".The same region in birds it is known as "Hensen's node" named for Victor Hensen (1835 - 1924) and is also known generally as the primitive node or knot. Several metals are also reabsorbed, although to date little is known of the mechanisms . poison - poison - Animal poisons (zootoxins): Poisonous animals are widely distributed throughout the animal kingdom; the only major group that seems to be exempt is the birds. Morphological defects in . If the toxicity is severe enough, death may result. 3 Kamm, '82; Kamm et al., '84. In vivo, testosterone is irreversibly converted to dihydrotestosterone (DHT) in target tissues by the enzyme 5-alpha reductase. NB: Avoid in childhood and pregnancy & in pts. The pattern of malformations induced by retinoid analogs is similar to that induced by naturally occurring forms of vitamin A if given . Definitions. In view of the great number of teratogenic factors known and the vast array of congenital defects, disorders and syndromes, it would probably be a waste of time to search for unifying mechanisms and principles in abnormal development. RV is a teratogen and is a major cause of public health concern as there are more than 100,000 cases of congenital rubella . *Edited by Judith Kimble and Susan Strome. Objective: The objective of this review is to present an update on known changes in analgesic disposition in pregnancy caused by pharmacokinetic mechanisms. Last revised March 14, 2005. Data from all patients diagnosed with type 2 diabetes were included in the .million people in the UK diagnosed with diabetes (90% of whom have type 2 . Side effect, since this non radioactive and radioactive forms of iodine produced., DNA is the mechanism of production and maturation with this article cancer 6 present an update on changes! 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