{"id":837,"date":"2020-02-17T22:14:48","date_gmt":"2020-02-17T16:44:48","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=837"},"modified":"2020-02-17T22:14:48","modified_gmt":"2020-02-17T16:44:48","slug":"teratogenic-drug","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/teratogenic-drug\/","title":{"rendered":"Teratogenic Drug"},"content":{"rendered":"\n<p><strong>Teratogenic Drug<\/strong><\/p>\n\n\n\n<ul><li>directly or indirectly, causes a structural or functional change in the fetus or child if it is administrated to pregnant mother<\/li><li>If mother is taking this drug, It can be either stopped, switched or reduced to the lowest dose possible<\/li><li>Women to avoid all medications in the first 8 weeks after conception<\/li><\/ul>\n\n\n\n<p><strong>Thalidomide: <\/strong>(Thalidomide disaster 1958-61)<\/p>\n\n\n\n<ul><li>Hypnotic agent widely used in Europe in 1959<\/li><li>An estimated 7000 infants born with thalidomide syndrome or phocomelia<\/li><li>Characteristic features \u00e0 include limb abnormalities<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"301\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-348.png?w=480\" alt=\"\" class=\"wp-image-855\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-348.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-348-300x188.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<p>Previous classification<\/p>\n\n\n\n<p><strong>CATEGORY X<\/strong><\/p>\n\n\n\n<ul><li>demonstrates fetal abnormalities<\/li><li>positive evidence of human fetal risk based on adverse reaction data<\/li><li>the risks involved in use of the drug in pregnant women<\/li><\/ul>\n\n\n\n<p><strong>POSSIBLE SITES OF ACTION OF TERATOGEN<\/strong><\/p>\n\n\n\n<p><strong>DIRECT TOXIC ACTION<\/strong><\/p>\n\n\n\n<ul><li><strong><u>FETUS:<\/u><\/strong><br>-Direct toxicity.<br>-Metabolites toxic.<br>-Indirectly toxic, e.g. anti-metabolites, anti-vitamin.<br>-Pharmacodynamic actions, e.g. on cardiovascular system.<br>-Endocrine balance altered<\/li><li><strong><u>FAETOPLACENTAL UNIT<\/u><\/strong><strong>:<\/strong><br>-Umbilical cord, e.g. spasm.<br>-Amniotic fluid volume change.<br>-Faetal or maternal placental blood flow.<br>-Placental transfer of nutrients, e.g. decreased active transport<\/li><li><strong><u>MOTHER:<\/u><\/strong><strong><br>&#8211;<\/strong>Nutritional changes, e.g. vitamin or mineral deficiencies.<br>-Biochemical changes with secondary effects on the foetus, e.g. hyperglycaemia.<br>-Endocrine balance<\/li><li><strong><u>FATHER:<\/u><\/strong><br>-Sperm changes<\/li><\/ul>\n\n\n\n<p><strong>INDIRECT TOXIC ACTION<\/strong><\/p>\n\n\n\n<ul><li>Cause malformation<br>-interfering with foetal metabolism<\/li><li>Drugs: folic acid antagonists, antiepileptic drugs<\/li><\/ul>\n\n\n\n<p><strong>TERATOGENIC MECHANISMS OF MEDICAL DRUGS<\/strong><\/p>\n\n\n\n<ul><li><strong>Folate antagonism<\/strong><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"472\" height=\"298\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-349.png?w=472\" alt=\"\" class=\"wp-image-856\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-349.png 472w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-349-300x189.png 300w\" sizes=\"(max-width: 472px) 100vw, 472px\" \/><\/figure>\n\n\n\n<ul><li><strong>Neural crest cell disruption<\/strong><\/li><li>During embryogenesis the neural crest cells, differentiates into two cell populations:<\/li><li>Cranial Neural Crest cells &#8211; structures in the craniofacial region<\/li><li>Truncal Neural Crest cells &#8211; components of the peripheral&nbsp;&nbsp; nervous system<\/li><li>A variety of molecular signals and receptors are implicated in neural crest cell development:<\/li><li>Fibroblast growth factors, Integrins, Cadherins, Pax3, Endothelins<\/li><li>Both excess and deficiency can be teratogenic<\/li><li>Retinoid teratogenicity is mediated by the retinoic acid receptors,RARs and retinoid X receptors, RXRs.<\/li><\/ul>\n\n\n\n<ul><li><strong>Endocrine disruption<\/strong><\/li><li>The ability of a hormone or endocrine disrupting chemicals&nbsp; to cause teratogenesis depends upon:<\/li><li>Protein binding in the mother<\/li><li>Protein binding in the fetus<\/li><li>Drug metabolism (Active metabolite), Placental transfer capabilities<\/li><li><strong>Oxidative stress<\/strong><\/li><li>The developing embryo is especially susceptible to high levels of ROS because of its weak antioxidant defense, in particular in the early stages of organogenesis.<\/li><\/ul>\n\n\n\n<ul><li><strong>Vascular disruption and specific receptor<\/strong><\/li><\/ul>\n\n\n\n<p>They give rise to structural birth defects.<\/p>\n\n\n\n<p><strong>Disturbances in the blood circulation in:<\/strong><\/p>\n\n\n\n<ul><li>Uterine-placental unit (cord obstruction)<\/li><li>Placental-fetal unit (placental insufficiency)<\/li><li>The fetus itself (hypoxia, generation of ROS)<\/li><\/ul>\n\n\n\n<p><strong>Direct effects of vascular disturbances:<\/strong><\/p>\n\n\n\n<ul><li>Aberrant differentiation<\/li><li>Distortion of contiguous tissues<\/li><li>Loss of tissue<\/li><li>Incomplete development of structures within the same or a secondary embryonic developmental field<\/li><\/ul>\n\n\n\n<p><strong>Vasoactive agents acting through this mechanism:<\/strong><\/p>\n\n\n\n<ul><li><strong>Misoprostol<\/strong><\/li><li><strong>Aspirin<\/strong><\/li><li><strong>Ergotamine<\/strong><\/li><li><strong>Pseudoephedrine<\/strong><\/li><\/ul>\n\n\n\n<ul><li><strong>Enzyme-mediated teratogenesis<\/strong><\/li><li>Cyclooxygenase-1<\/li><li>Non selective NSAIDS by inhibition of COX 1 may be involved in the induction of cardiac anomalies, orofacial clefts and diaphragm defects.<\/li><\/ul>\n\n\n\n<p><strong>Teratogenic Drugs &#8211; IN FIRST TRIMESTER OF PREGNANCY<\/strong><\/p>\n\n\n\n<ul><li>Analgesic, Anticonvulsant, Anticoagulant, Antidepressant, Antithyroid, Vitamin A, Metal toxic, Sedative\/ hypnotics, Aminoglycosides<\/li><\/ul>\n\n\n\n<p><strong>Analgesic (aspirin)<\/strong><\/p>\n\n\n\n<ul><li><strong>Gastroschisis<\/strong><\/li><li>Decrease prostaglandin \u00e0 decrease uterine contraction \u00e0delayed onset of labor &amp; prolonged period of pregnancy<\/li><li>During delivery \u00e0severe bleeding because aspirin decrease platelet aggregation<\/li><\/ul>\n\n\n\n<p><strong>Anticonvulsant<\/strong><\/p>\n\n\n\n<ul><li><strong>Fetal hydantoin syndrome :<\/strong><\/li><li>&nbsp;cranio facial malformation:<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp; -Cleft lip and palate, Broad nasal bridge, Ocular hypertelorism, Abnormal ears<\/p>\n\n\n\n<ul><li>&nbsp;congenital heart disease<\/li><li>&nbsp;limb malformation<\/li><li>&nbsp;mental and growth retardation<\/li><\/ul>\n\n\n\n<p><strong>Anticoagulant ( warfarin &amp; Coumadin )<\/strong><\/p>\n\n\n\n<ul><li>Fetal wafarin syndrome:<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; -Nasal hypoplasia, bone stippling, Bilateral optic atrophy, Mental retardation<\/p>\n\n\n\n<ul><li>Respiratory distress syndrome<\/li><li>Fetal and maternal hemorrhage<\/li><\/ul>\n\n\n\n<p><strong>Antidepressant (imipramine)<\/strong><\/p>\n\n\n\n<ul><li>Cleft palate<\/li><li>Defect in abdomen<\/li><li>Adrenal hypoplasia<\/li><li>Cardiovascular defect<\/li><\/ul>\n\n\n\n<p><strong>Antithyroid ( propylthiouracil &amp; methimazole )<\/strong><\/p>\n\n\n\n<ul><li>Fetal goiter<\/li><\/ul>\n\n\n\n<p><strong>Vitamin A derivatives ( retinoic acid ) <\/strong><strong>\u00e0 Isotretinoin<\/strong><\/p>\n\n\n\n<ul><li>Cranio-facial dysmorphism<\/li><li>Cleft palate<\/li><li>Thymic aplasia<\/li><li>Neural tube defect ( spina bifida cystic )<\/li><\/ul>\n\n\n\n<p><strong>Metal toxic (lithium)<\/strong><\/p>\n\n\n\n<ul><li>Hypotonia<\/li><li>Cyanosis<\/li><li>Lethargy<\/li><li>Poor respiratory<\/li><\/ul>\n\n\n\n<p><strong>Sedative \/ hypnotics (diazepam )<\/strong><\/p>\n\n\n\n<ul><li>Cleft lip and palate<\/li><li>Inguinal hernia<\/li><li>Congenital heart disease<\/li><li>Pyloric stenosis<\/li><li>Breathing difficulties<\/li><\/ul>\n\n\n\n<p><strong><br>Aminoglycosides (streptomycin &amp; Kanamycin )<\/strong><\/p>\n\n\n\n<ul><li>Congenital deafness<\/li><li>Ototoxicity<\/li><\/ul>\n\n\n\n<p><strong>TERATOGENIC DRUGS IN SECOND TRIMESTER OF PREGNANCY<\/strong><\/p>\n\n\n\n<p><strong>ACE INHIBITOR<\/strong><\/p>\n\n\n\n<ul><li>MECHANISM OF ACTIONS<\/li><li>Produce vasodilatation by inhibiting formation of angiotensin II and breakdown bradykinin<\/li><li>Mixed vasodilator<\/li><li>In cases of heart failure, cardiac output is maintained \/ even increase<\/li><li>Increase renal blood flow BUT decrease glomerular filtration rate \u00e0 decrease glomerular hypertension<\/li><li>IF USED IN 2<sup>ND<\/sup> \u2013 3<sup>RD<\/sup> TRIMESTER OF PREGNANCY<\/li><li>fetal hypotension, renal failure, oligohydramnios, death<\/li><\/ul>\n\n\n\n<p><strong>DIAZEPAM<\/strong><\/p>\n\n\n\n<ul><li>Centrally acting spasmolytic drug<\/li><li>It facilitates action of GABA in CNS<\/li><li>It acts as GABA synapse and produce sedation at doses required to reduce muscles tone<\/li><\/ul>\n\n\n\n<ul><li><strong>RISKS OF\u2026<\/strong><\/li><\/ul>\n\n\n\n<p><strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1<\/strong>) cleft palate<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 2) cardiac and circulatory defects<\/p>\n\n\n\n<p><strong>TERATOGENIC DRUGS IN THIRD TRIMESTER OF PREGNANCY<\/strong><\/p>\n\n\n\n<p>Tetracycline, ACE inhibitors, chloramphenicol, aminoglycosides, sulfamethoxazole, trimethoprim<\/p>\n\n\n\n<p><strong>TETRACYCLINE<\/strong><\/p>\n\n\n\n<ul><li>Protein synthesis inhibitor \u00e0 by binding to the 30S ribosomal subunit in mRNA translation complex<\/li><li>IN PREGNANCY \u00e0dental discoloration in children, maternal hepatotoxicity with large parenteral doses<\/li><\/ul>\n\n\n\n<p><strong>CHLORAMPHENICOL<\/strong><\/p>\n\n\n\n<ul><li>Bacteriostatic drug that stop bacterial growth by inhibiting protein synthesis<\/li><li>Prevent protein chain elongation by inhibiting peptidyl transferase activity of bacterial chromosome<\/li><li>&nbsp;Intravenous chloramphenicol use has been associated with <strong>Gray Baby syndrome<\/strong><ul><li>This occur in newborn infants because they liver enzymes not yet fully developed \u00e0 chloramphenicol remains unmetabolised in body<\/li><\/ul><ul><li>Manifest as \u2013 hypotension and cyanosis<\/li><\/ul><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"204\" height=\"142\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-350.png?w=204\" alt=\"\" class=\"wp-image-857\" \/><\/figure>\n\n\n\n<p><strong>AMINOGLYCOSIDES<\/strong><\/p>\n\n\n\n<ul><li>EG: GENTAMICIN, STREPTOMYCIN<\/li><li>They interfere with the proof-reading process \u00e0 increased rate of error in synthesis with &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;premature termination<\/li><li>Inhibition of ribosomal translocation<\/li><li>Disrupt the integrity of the bacterial cell membrane<\/li><li>They may cause auditory or vestibular nerve damage<\/li><\/ul>\n\n\n\n<p><strong>SULFAMETHOXAZOLE, TRIMETHOPRIM<\/strong><\/p>\n\n\n\n<ul><li>Sulfonamide bacteriostatic antibiotic<\/li><li>Structural analogs and competitive antagonist of PABA<\/li><li>Inhibit normal bacterial utilization of PABA for the synthesis of folic acid<\/li><li>Used as a bacteriostatic <strong>antibiotic in prophylaxis and treatment of urinary tract infections<\/strong><\/li><li>Trimethoprim binds to dihydrofolate reductase and inhibit reduction of DHF to THF<\/li><li>Sulfamethoxazole inhibit dihydrofolate synthetase<\/li><li><strong>Neonatal haemolysis<\/strong><\/li><li><strong>Methaemoglobinaemia<\/strong><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-351.png?w=480\" alt=\"\" class=\"wp-image-858\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-351.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-351-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"302\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-352.png?w=458\" alt=\"\" class=\"wp-image-859\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-352.png 458w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-352-300x198.png 300w\" sizes=\"(max-width: 458px) 100vw, 458px\" \/><\/figure>\n\n\n\n<p><strong>Teratogenicity Test:<\/strong><strong><\/strong><\/p>\n\n\n\n<ul><li>Studies are carried in two animal species (rats &amp; rabbits)<\/li><li>Drug is given after mating, during the period of organogenesis<\/li><li>Foetus is then examined for visceral or skeletal abnormalities<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Teratogenic Drug directly or indirectly, causes a structural or functional change in the fetus or child if it is administrated to pregnant mother If mother is taking this drug, It can be either stopped, switched or reduced to the lowest dose possible Women to avoid all medications in the first 8 weeks after conception Thalidomide:[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/837"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=837"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/837\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=837"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=837"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=837"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}