Teratogenicity Flashcards
TERATOGENICITY - define
ability of the drug to cause adverse fetal effects
TERATOGENICITY degree to exposure to drug causes
drug causes adverse effects dependent on Dose Route of administration Exposure to other agents Timing (2-10 weeks)
TERATOGENICITY - defects
Gross malformations
Neurobehavioral and metabolic anomalies
Development occurs in three stages:
Conception through week 2
Embryonic period: Weeks 3 through 8
Gross malformations produced by teratogens
Fetal period: Week 9 through delivery
Functions disrupted with teratogen exposure
Category A:
no evidence of fetal risk in controlled human studies. (Only potassium, thyroid hormone, and
multiple vitamins are in this category)
Category B:
either animal studies show no risk but there are no human studies or animal studies show risk
that is not confirmed in human studies. (penicillin, magnesium, prednisone, narcotics, acetaminophen,
ritodrine, terbutaline, cephalosporins, erythromycin, meclizine, insulin, caffeine)
Category C:
either animal studies show risk and there are no human studies or there are no animal or human studies (phenergan, all laxatives, heparin, albuterol)
Category D:
Positive evidence of human fetal risk, but the benefits may be acceptable despite the risk
(streptomycin, iodine, sulfonamides, reserpine, Phenobarbital, amitriptyline, nalorphine, Seconal)
Category X: p
\: positive risk to the human fetus. Drug use contraindicated in women who are or may become pregnant (Estrogen, Coumadin, Accutane)
KNOWN TERATOGENS
Chemotherapeutic agents (methotrexate, cyclophosphamide) folic acid antagonist (intrauterine growth retardation, low set ears, hypoplastic mandible)
Anticonvulsants
phenytoin: fetal hydantoin syndrome ( hypoplastic facies, prenatal and postnatal growth
restrictions, mental retardation, hypoplastic digits, facial clefts, and/or cardiac
anomalies; rare. 90-95% of offspring of women treated with Dilantin have NO
anomalies. Anomalies more common in offspring of untreated epileptic women. If use, use
low dose, try phenobarbital
valproic acid: neural tube defects, heart, head and neck, urogenital tract anomalies,
limb/skeletal, skin and muscle anomalies. Incidence: 1-2%
KNOWN TERATOGENS
two more
Sex hormones
androgens
masculinization of female fetus
diethylstilbetstrol
male: anomalies of testicles and epididymus; infertility
female: anomalies of uterine fusion, cervical development, vaginal adenosis;
adult problems with menstrual abnormalities, pregnancy, wastage, and vaginal
carcinoma
KNOWN TERATOGENS
3 -5
Warfarin Fetal bleed/death, fetal warfarin syndrome (nasal hypoplasia, epiphyseal stippling, cerebral and cardiac malformations) ACE inhibitors Fetal renal aplasia/dysplasia secondary to decreased fetal hypotension and renal fetal blood flow; neonatal renal failure Anticholinergic drugs Meconium ileu
KNOWN TERATOGENS - 6 and 7
Oral hypoglycemic drugs
Neonatal hypoglycemia
Use early in pregnancy might cause increased risk of abnormalities
Lithium Carbonate
First trimester: increased incidence of Epstein’s anomaly of the fetal heart
Late pregnancy: neonatal electrolyte imbalance or goiter
KNOWN TERATOGENS - 8-10
Misoprostol (prostaglandin E1 analog)
Given orally causes termination of pregnancy
Unlabeled intravaginal use for cervical ripening)
NSAIDs
Constriction of ductus arteriosis
Psychoactive drugs
Withdrawal symptoms
KNOWN TERATOGENS - 11 - 13
Retinoids (Accutane)
anomalies of CNS, craniofacial, cardiovascular, and limbs
Thalidimides
limb defects/absent limbs
Tetracyclines
impaired calcium deposition in long bone epiphysis (transient, no long term effect)
and damage to teeth enamel forming cells causing staining and inadequate calcium
content to prevent later tooth decay)
Maternal fatty metamorphosis of liver
