Aspek Negatif Obat Dan Zat Berbahaya Pada Kehamilan

8/13/2019 Aspek Negatif Obat Dan Zat Berbahaya Pada Kehamilan

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Aspek Negatif Obat dan Zat

Berbahaya pada Kehamilan


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Birth defects

3% of all live-born infants have an major

anomaly

Additional anomalies are detected during

postnatal liveabout 6% at 2 year-olds,

8% in 5year-olds, other 2% later

Single minor anomalies are present inabout 14% of newborns


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Birth defects

Major anomalies are more common in

early embryos (up to 15%) than they are in

newborns (3%). Most severely malformedembryos are spontaneously aborted during

first 6 to 8 weeks.


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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 duringpregnancy

Average of 2.9 prescriptions

Despite this high rate of medication intake,most drugs are not labeled for use during

pregnancy


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50% of pregnancies unplanned

Teratogenic potential should be

considered and explained to women of

childbearing age at time drug is

prescribed


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PHARMACOKENETICS OF DRUGS

DURING PREGNANCY

ABSORPTION- Gastric emptying and small intestine

motility are reduceddue to elevation of progesterone,

inhalation may be enhanced due to increased cardiacoutput and tidal volume increasing alveolar uptake,

intramuscular delivery is usually enhancedby

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


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PHARMACOKENETICS

EXCRETION-Renal blood flow is

increased by 6080% during pregnancy,

and glomerular filtration rate rises by 50%,leading to enhanced elimination


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FETO-PLACENTAL UNIT-Drug transfer

occurs mainly via diffusion across the

placenta, dependent on lipid solubility&thedegree of drug ionization

lipophilic agents

Protein-bound drugs and drugs of largemolecular weight


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EFFECTS OF DRUGS ON THE EMBRYO,

FETUS, OR NEONATE

MAY VARY---

NO EFFECT.

LITTLE

SERIOUS- FETAL TOXICITY

SPONTANEOUS ABORTION

DEATH

FETAL MALFUNCTION

FETAL MALFORMATIONS.


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Causes of congenital anomalies


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teratogenic mechanisms

associated with medication use folate antagonism,

neural crest cell disruption,

endocrine disruption,

oxidative stress,

vascular disruption specific receptor- or enzyme-mediated

teratogenesis


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Drug with significant terratogenic

Drug Trimester Effect

metronidazol first May be mutagenic (animal study)

streptomycin all Eight nerve toxicity

tetracyclin all Discoloration & defect of teeth and alteredbone growth

thalidomide first Phacomelia & many internal malformation


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Agents suspected (but not proven) to increasethe risk of IUGR:

Heavy metals.

Organic solvents. Insecticides.

Anesthetic gas.

Caffeine (in huge doses).

Gasoline sniffing.

Heavy cannabis abuse.

Aspek Negatif Obat Dan Zat Berbahaya Pada Kehamilan

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