Teratology/Genetic Toxicology Flashcards
(52 cards)
Specific mechanisms of actions of teratogens
- Altered nucleic acid integrity/function
- Excessive or reduced apoptosis
- Reduced biosynthesis
- Impeded morphogenetic movements
- Mechanical disruption of tissues
- Disruption of enzymatic function
US FDA categories of teratogens
Categories A, B, C, D, X
Category A teratogens
Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Examples of Category A teratogens
levothyroxine
folic acid
liothyronine
Category B teratogens
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Examples of Category B teratogens
Metformin
Hydrochlorothiazide
Cyclobenzaprine
Amoxicillin
Pantoprazole
Category C teratogens
Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Examples of category C teratogens
Tramadol
Gabapentin
Amlodipine
Trazodone
Category D teratogens
There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Examples of Category D teratogens
Lisinopril
Alprazolam
Losartan
Clonazepam
Lorazepam
Category X
Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.
Examples of Category X teratogens
Atorvastatin
Simvastatin
Warfarin
Methotrexate
Finasteride
Groups of teratogenic agents
- Infectious agents
- Physical agents: Radiation, hyperthermia
- Drugs and chemical agents
- Hormones
- Maternal metabolic imbalances: Diabetes/Alcoholism/Phenylketonuria
- Nutritional deficiencies: iodine deficiency- cretinism
- Obesity
- Male mediated teratogenesis
Teratogenic effects of radiation
Kills rapidly proliferating cells and acts as mutagenic agents
Effects include spina bifida, cleft palate, limb defects
Teratogenic effects of hyperthermia
Anencephaly
Spina bifida
Mental retardation
Cleft palate
Cleft lip
Limb defects
Known teratogenic drugs
- ACE inhibitors
- Anti epileptic drugs like phenytoin, carbamazepine, Valproic acid
- Cocaine
- Thalidomide
- Tetracycline
- Ethanol
- Lithium
Possible teratogens
Primidone
Zidovudine
Cigarette smoking
Ergotamine
Streptomycin
Disulfiram
Critical periods for thalidomide with effects
21-22 days: absent external ears, cranial nerve disorders
24-27 days: phocomelia (especially arms)
27-28 days: phocomelia (especially lower limbs)
34-36 days: hypoplastic thumbs, anorectal stenosis
Teratogenic effects of anti-epileptics
Trimethadione and Fetal Hydantoin Syndrome:
- Xtic dysmorphogenesis
- Facial clefts
- Microencephaly
- Nail dysplasia
- Delayed devt
Teratogenic effects of valproic acid
Neural tube defects
Teratogenic effects of anticoagulants
Hypoplasia of nasal cartilage
Stippled epiphyses
CNS defects
Teratogenic effects of tetracyclines
- Acute fatty liver
- Hepatotoxicity
- Stained decidual teeth
- Under developed enamel
- Heart defects, club foot
Teratogenic effects of ACE inhibitors
- Oligohydramnios
- Hypoplasia of the skull bones
- Intrauterine growth restriction(IUGR)
- Renal dysfunction
- Fetal death
Teratogenic effects of retinoic acid
Critical period: 5-7 weeks after LMP
- Spontaneous abortion and birth defects - High.
- Microtia
- Micrognathia
- Cleft palate and/or thymic aplasia, CVS anomalies, and NTDs.
