Teratogenic drugs
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This document discusses teratogens and teratogenic drugs. It begins by defining a teratogen as an agent that can disturb fetal development. It then discusses the FDA pregnancy categories and mechanisms of action of teratogenic drugs. Specific examples of teratogenic drugs are given for different categories, along with their mechanisms and potential effects on the fetus. The document stresses the importance of carefully considering drug use during pregnancy and providing counseling on risks and benefits.
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Teratogenic drugs
- 1. 1. NURUL MIZA SHASHEIHA BINTI ABDUL MUTALIB 2. NURUL HUSNA BINTI MURYADI 3. WAN FATHIAH NASUHA BT WAN NUSDRI 4. NURFATIN AFIQAH BT MOHD BADRONDIN 5. ZATEEL FAHADA BT RUSLI 6. NURUL FIRDAUS BT HANAFEE 7. NURUL SAHIIRAH BT AHMAD ROFI 8. WAN FARAH NASUHA BT WAN MUHAMMAD HUSNI
- 2. INTRODUCTION • WHAT IS TERATOGEN ? • TERATOGENIC DRUG • FDA PREGNANCY CATEGORIES • GENERAL MECHANISMS OF ACTION OF TERATOGENIC DRUGS • TERATOGENIC MECHANISMS OF MEDICAL DRUGS
- 3. TERATOGEN • Is an agent that can disturb the development of the embryo or fetus • Teratogens halt the pregnancy or produce a congenital malformation • Include radiation, maternal infections, chemicals, and drugs. • 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 • typically during sensitive periods of fetal development • depending on the particular teratogenic process and target organ TERATOGENIC DRUG
- 4. FDA PREGNANCY CATEGORIES CATEGORY A • failed to demonstrat e a risk to the fetus in the first trimester of pregnancy • no evidence of risk in later trimesters CATEGORY C • shown an adverse effect on the fetus • no adequate and well- controlled studies in humans • potential benefits may warrant the use of drug despite potential risks. CATEGORY D • positive evidence of human fetal risk based on adverse reaction data • potential benefits may warrant use of the drug in pregnant women despite potential risks CATEGORY B • failed to demonstrate a risk to the fetus • no adequate and well- controlled studies in pregnant women. CATEGORY X • demonstrates fetal abnormalities • positive evidence of human fetal risk based on adverse reaction data • the risks involved in use of the drug in pregnant women CATEGORY N • FDA has not classified the drug.
- 5. POSSIBLE SITES OF ACTION OF TERATOGEN DIRECT TOXIC ACTION • FETUS: -Direct toxicity. -Metabolites toxic. -Indirectly toxic, e.g. anti-metabolites, anti- vitamin. -Pharmacodynamic actions, e.g. on cardiovascular system. -Endocrine balance altered • FAETOPLACENTAL UNIT: -Umbilical cord, e.g. spasm. -Amniotic fluid volume change. -Faetal or maternal placental blood flow. -Placental transfer of • MOTHER: -Nutritional changes, e.g. vitamin or mineral deficiencies. -Biochemical changes with secondary effects on the foetus, e.g. hyperglycaemia. -Endocrine balance • FATHER: -Sperm changes INDIRECT TOXIC ACTION • Cause malformation -interfering with faetal metabolism • Drugs: -folic acid antagonists -antiepileptic drugs
- 6. TERATOGENIC MECHANISMS OF MEDICAL DRUGS • Folate antagonism • Neural crest cell disruption • Endocrine disruption • Oxidative stress • Vascular disruption and specific receptor • Enzyme-mediated teratogenesis
- 7. •Analgesic •Anticonvulsant •Anticoagulant •Antidepressant •Antithyroid •Vitamin A •Metal toxic •Sedative/ hypnotics •Aminoglycosides
- 8. • Gastroschisis • Decrease prostaglandin decrease uterine contraction delayed onset of labor & prolonged period of pregnancy • During delivery severe bleeding because aspirin decrease platelet aggregation
- 9. • Fetal hydantoin syndrome : cranio facial malformation: -Cleft lip and palate -Broad nasal bridge -Ocular hypertelorism -Abnormal ears congenital heart disease limb malformation mental and growth retardation
- 10. • Fetal wafarin syndrome: -Nasal hypoplasia -Bone stippling -Bilateral optic atrophy -Mental retardation • Respiratory distress syndrome • Fetal and maternal hemorrhage
- 11. • Cleft palate • Defect in abdomen • Adrenal hypoplasia • Cardiovascular defect
- 12. • Fetal goiter
- 13. • Cranio-facial dysmorphism • Cleft palate • Thymic aplasia • Neural tube defect ( spina bifida cystic )
- 14. • Hypotonia • Cyanosis • Lethargy • Poor respiratory
- 15. • Cleft lip and palate • Inguinal hernia • Congenital heart disease • Pyloric stenosis • Breathing difficulties
- 16. • Congenital deafness • Ototoxicity
- 17. TERATOGENIC DRUGS IN SECOND TRIMESTER OF PREGNANCY
- 18. ACE INHIBITORS DIAZEPAM
- 19. 1) ACE INHIBITOR MECHANISM OF ACTIONS Produce vasodilatation by 1-inhibitting formation of angiotensin 11 2- breakdown bradykinin
- 20. PHARMACOLOGICAL ACTION Mixed vasodilator In cases of heart failure, cardiac output is maintained / even increase Increase renal blood flow BUT decrease glomerular filtration rate decrease glomerular hypertension
- 21. THERAPEUTIC USES USED IN Hypertension Heart failure Myocardial infarction
- 22. SIDE EFFECTS IF USED IN 2ND – 3RD TRIMESTER OF PREGNANCY 1- fetal hypotension 2- renal failure 3- oligohydromnios 4- death 3rd tri
- 23. 2) DIAZEPAM Centrally acting spasmolytic drug It facilitates action of GABA in CNS It acts as GABA synapse and produce sedation at doses required to reduce muscles tone
- 24. PHARMACOKINETICS ABSORPTION: - Delayed and decreased when administered with a moderate fat meal DISTRIBUTION - Highly bound to plasma protein - Cross blood brain barrier - Cross placental barrier - Found in milk
- 25. METABOLISM N-demythylated Diazepam N-desmethyldiazepam further metabolised hydroxylated temazepam oxazepam Temazepam and oxazepam are largely eliminated by glucoronidation
- 26. ELIMINATION The initial distribution phase is followed by prolonged elimination phase
- 27. SIDE EFFECTS RISKS OF… 1) cleft palate 2) cardiac and circulatory defects
- 30. 1) TETRACYCLINE Protein synthesis inhibitor Inhibit the binding of aminoacyl-tRNA to the mRNA- ribosomes complex Aminoacyl-tRNA mRNA-ribosomes complex by binding to the 30S ribosomal subunit in mRNA translation complex
- 31. SIDE EFFECTS IN PREGNANCY….. dental discolouration in chilren maternal hepatotoxicity with large parenteral doses
- 32. 2) ACE INHIBITORS AS IN SECOND TRIMESTER Ace inhibitors in 2nd trimester
- 33. 3) CHLORAMPHENICOL Bacteriostatic drug that stop bacterial growth by inhibiting protein synthesis Prevent protein chain elongation by inhibiting peptidyl transferase activity of bacterial chromosome Intravenous chloramphenicol use has been associated with Gray Baby syndrome This occur in newborn infants because they liver enzymes not yet fully developed chloramphenicol remains unmetabolised in body
- 34. ADVERSE EFFECTS Hypotension Cyanosis The condition can be prevented by using the drug at recommended doses & monitoring blood levels Gray Baby Syndrome
- 35. 4) AMINOGLYCOSIDES EG: GENTAMICIN, STREPTOMYCIN Have several potential antibiotic mechanisms They interfere with the proofreading process increased rate of error in synthesis with premature termination Inhibition of ribosomal translocation peptidyl tRNA moves from A-site to P- site Disrupt the integrity of the bacterial cell membrane
- 36. Aminoglycosides are in pregnancy category D They may cause auditory or vestibular nerve damage
- 37. 5) SULFAMETHOXAZOLE, TRIMETHOPRIM Sulfonamide bacteriostatic antibiotic Structural analogs and competitive antagonist of PABA Inhibit normal bacterial utilisation of PABA for the synthesis of folic acid Used as a bacteriostatic antibiotic in prophylaxis and treatment of urinary tract infections
- 38. Trimethoprim binds to dihydrofolate redustase and inhibit reduction of DHF to THF Sulfamethoxazole inhibit dihydrofolate synthetase
- 39. TERATOGENIC EFFECTS 1) NEONATAL HAEMOLYSIS 2)METHAEMOGLOBINAEMIA
- 40. •BE CAREFUL IN TAKING DRUGS DURING PREGNANCY •ALL CLINICIANS INCLUDING PHARMACISTS ARE RESPONSIBLE TO COUNSEL PATIENTS WITH COMPLETE , ACCURATE AND CURRENT INFORMATION ON THE RISKS AND BENEFITS OF USING MEDICATIONS DURING PREGNANCY