Aspek Negatif Obat dan Zat Berbahaya pada Kehamilan

Birth defects
3% of all live-born infants have an major anomaly Additional anomalies are detected during postnatal live about 6% at 2 year-olds, 8% in 5year-olds, other 2% later Single minor anomalies are present in about 14% of newborns

Birth defects
Major anomalies are more common in early embryos (up to 15%) than they are in newborns (3%). Most severely malformed embryos are spontaneously aborted during first 6 to 8 weeks.

Drug Use in Pregnancy

(Larimore WL et al. Prim Care 2000;27:35-53)

1991 WHO International Survey of Drug Utilization in Pregnancy 86% of women took medication during pregnancy Average of 2.9 prescriptions Despite this high rate of medication intake, most drugs are not labeled for use during pregnancy

 50% of pregnancies unplanned Teratogenic potential should be considered and explained to women of childbearing age at time drug is prescribed
<50% of women know they are pregnant by

4th week and ~20% still dont know by 8th week

PHARMACOKENETICS OF DRUGS DURING PREGNANCY

ABSORPTION- Gastric emptying and small intestine motility are reduced due to elevation of progesterone, inhalation may be enhanced due to increased cardiac output and tidal volume increasing alveolar uptake, intramuscular delivery is usually enhanced by increased tissue perfusion secondary to vasodilation. DISTRIBUTION- expansion of intravascular (plasma volume) and extra-vascular (breasts, uterus, peripheral oedema) water content, protein-binding decreases METABOLISM-INCREASED HEPATIC METABOLISM OCCURS FOR SOME DRUGS

PHARMACOKENETICS
EXCRETION-Renal blood flow is increased by 6080% during pregnancy, and glomerular filtration rate rises by 50%, leading to enhanced elimination

FETO-PLACENTAL UNIT-Drug transfer occurs mainly via diffusion across the placenta, dependent on lipid solubility&the degree of drug ionization lipophilic agents Protein-bound drugs and drugs of large molecular weight

EFFECTS OF DRUGS ON THE EMBRYO, FETUS, OR NEONATE

MAY VARY-- NO EFFECT. LITTLE SERIOUS- FETAL TOXICITY SPONTANEOUS ABORTION DEATH FETAL MALFUNCTION FETAL MALFORMATIONS.

Causes of congenital anomalies

US FDA Pregnancy Category Definitions

A B-

C-

Dthe X-

Adequate, well-controlled studies in pregnant women fail to demonstrate a risk to the fetus in the first (second, third, or all) trimester(s), and the possibility of fetal harm appears remote. Animal studies do not indicate a risk to the fetus; however, there are no adequate, well-controlled studies in pregnant women. OR Animal studies have shown an adverse effect on the fetus but adequate, well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus. Despite the animal findings, the possibility of fetal harm appears remote, if used during pregnancy. Animal studies have shown that the drug exerts teratogenic or embryocidal effects, and there are no adequate, well-controlled studies in pregnant women, OR No studies are available in either animals or pregnant women. Positive evidence of human fetal risk exists, but benefits in certain situations (eg, life-threatening situations or serious diseases for which safer drugs cannot be used or are ineffective) may make use of drug acceptable despite its risks. Studies in animals or humans have demonstrated fetal abnormalities or there is positive evidence of fetal risk based on human experience, or both, and the risk clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

teratogenic mechanisms associated with medication use

folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption specific receptor- or enzyme-mediated teratogenesis

Drug with significant terratogenic

Drug
metronidazol streptomycin tetracyclin thalidomide

Trimester
first all all first

Effect
May be mutagenic (animal study) Eight nerve toxicity Discoloration & defect of teeth and altered bone growth Phacomelia & many internal malformation

Agents suspected (but not proven) to increase the risk of IUGR: Heavy metals. Organic solvents. Insecticides. Anesthetic gas. Caffeine (in huge doses). Gasoline sniffing. Heavy cannabis abuse.