RUPTURE OF THE UTERUS Associate Professor Iolanda Blidaru, MD, PhD.
ASSOCIATE PROFESSOR IOLANDA BLIDARU, MD, PhD. Teratogens Teratos = monster (Greek) Any agent (drug,...
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Transcript of ASSOCIATE PROFESSOR IOLANDA BLIDARU, MD, PhD. Teratogens Teratos = monster (Greek) Any agent (drug,...
Teratogens• Teratos = monster (Greek)
• Any agent (drug, infection, physical condition / deficiency) that acts on embryo or fetus producing permanent alteration of morphology or function (Shepard, 1998).
Causes of congenital malformation
Unknown or multifactorial: 70%Genetic: 20%Environmental: 10%
Drugs & chemicals: 5%Infection: 2%Maternal disorders: 2%Irradiation: 1%
Factors affecting the teratogenic effect of the drug
A. Fetal factorsI. Developmental stage1. Preimplantation period (first 2 weeks):
Death or no effect.2. Embrionic period (2-nd → 8-th week):
Malformation3. Fetal period (after 9 weeks): Functional
defects, Growth retardationII. Genetic susceptibility :• Species differences: ex. Thalidomide• Individual differences: metabolism of the drug
B. Drug factorsI. The route, dose & duration of
administrationII. Effect of combined agents III. Access to fetoplacental unit: • Lipid solubility• Molecular weight: > 600 not cross the placenta• Protein binding• Thickness of the placental membrane
1. Category A: • Controlled studies in humans
demonstrated no fetal risk.• E.g.: Prenatal vitamins,KCL, citrate
& gluconate, Thyroxin
2. Category B: •Animal studies indicate no fetal risk; no controlled studies in humans.•E.g.: Penicillins, Terbutaline,Acetaminophen, Cyclizine, Antacids,Prednisone, Insulin, Ampicillin,Clindamycin, Nitrofurantoin, Metronidazole, Miconazole, Spiramycin.
3. Category C: • Animal studies indicate fetal risk;
no human studies. • These drugs are administered only when
their benefits outweighs the potential fetal harm.
• E.g. Furosemide, Rifampicin, β-blockers,Phenothiazine, Methyl-Dopa,Nifedipine,Heparins, Aminophyllin, Gentamycin,Chloroquin, Acyclovir, Cyclosporin,.
4. Category D:• There is evidence of fetal risk in
humans but the benefits may outweigh the risk.
• These drugs are given only in serious disease because no alternative.
• E.g.Phenytoin, Valproic Acid, Diazepam, Imipramine,
Captopril, Thiazides, Spironolactone, Coumarine,Chlorpropamide, Tetracyclin, Streptomycin, Quinine, Methotrexate, Vinblastin, Azathioprine.
5. Category X: • There is clear human risk that
outweigh the benefits.• These drugs are contraindicated.• E.g. Estrogen, Androgens,Aminopterin, Isotretinoin,Thalidomide
Fetal alcohol syndrome
IUGR
Behavior disturbance
Brain defects
Cardiac defects
Spinal defects
Craniofacial anomalies
Fetal anticonvulsant syndrome
Craniofacial abnormalities
Broad nasal bridge
Epicanthal fold
Limb defects
Growth deficiency
Mental Deficiency