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Tujuan
Mengetahui hubungan antara kehamilan dan
(bahaya) penggunaan obat
Mampu menyebutkan beberapa obat
penyebab gangguan kehamilan dan foetus

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Siklus Reproduksi Perempuan & Kaitannya


dengan Obat yg dapat mempengaruhinya
Pra-hamil

Hamil

Laktasi

Mutagenik? sel gonad


Toksik? Ibu, Foetus
Teratogenik? Foetus
Toksik? Neonatus

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Perkembangan foetus & kaitannya dengan


malformasi

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Kategori Obat dan Kehamilan

Category A: Studies have been done with pregnant women. There is no known risk
to the growing baby.
Category B: Studies have been done with pregnant animals and shown no risk, but
there are no Studies in women; OR studies in animals showed some risk, but
studies in pregnant women did not find any risk.
Category C: Studies done with pregnant animals show some risk, but there are no
studies in women; OR no studies have been done in animals or humans,so the risk
for a pregnant woman is not known. Medicines in this category are often
prescribed during pregnancy if you need the medicine. Even though studies have
not been done on the medicines in this class, most of them have been used by
Pregnant women for years without any problem.
Category D: Studies have shown this medicine can harm a developing human baby
during pregnancy. However, there are benefits of these drugs for mothers who
have a serious illness. This may make them worth taking in spite of the risk. If you
need a medicine in this class, your health care provider will talk to you about the
pros and cons for both you and your baby.
Category X: Studies have shown these medicines can harm developing human
babies during pregnancy. There is no benefit to the mother that makes taking
these drugs worth the risk.

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Contoh-contoh obat dalam masing-masing


kategori
Kategori A: parasetamol, penisilin, eritromisin, glikosida
jantung, isoniazid serta bahan-bahan hemopoetik seperti
besi dan asam folat
Kategori B: simetidin, dipiridamol, spektninomisin, tikasilin,
amfoterisin, dopamine, asetilkistein, alkaloid belladonna,
karbamazepin, pirimetamin, griseofulvin, trimetoprim dan
mebendazol
Kategori C: analgetik-narkotik, fenotiazin, rifampisin,
aspirin, antiinflamasi non-steroid dan diuretika
Kategori D: androgen, fenitoin, pirimidon, fenobarbiton,
kini, klonazepam, valproat, steroid anabolic, dan anti
koagulansia
Kategori X: isotretionin, dietilbestrol

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Uji Pra-klinik Obat


Uji pada hewan:
1. Toksisitas akut, sub-akut, kronis
2. Mutagenisitas: Ca? Inborn error-metabolism?
Other congenital abnormalities?
3. Teratogenisitas: Malformasi?
Dilihat baik pada F0 maupun keturunannya (F1, F2,
dst.)

Mungkin saja efeknya negatif/minimal pada


hewan, namun masih belum tentu pada
manusia

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Beberapa contoh penggunaan obat dalam


kehamilan

The acne medicine isotretinoin (Accutane). This medicine is very likely to


cause birth defects. It should not be taken by women who are pregnant or
who may become pregnant.
ACE inhibitors, such as benazepril (Lotensin), which lower blood pressure.
Medicines to control seizures, such as phenytoin (Dilantin).
Some antibiotics, such as tetracycline and doxycycline.
Warfarin (Coumadin), which helps prevent blood clots.
Lithium, which is used to treat bipolar depression.
Alprazolam (Xanax), diazepam (Valium), and some other medicines used
to treat anxiety.
Paroxetine (Paxil, Paxil CR), which is used to treat depression and other
conditions.
Over-the-counter pain medicines like aspirin and ibuprofen (such as Advil
and Motrin) and naproxen (such as Aleve). The risk of birth defects with
these medicines is very low. Most problems occur if these medicines are
taken regularly at the end of pregnancy.

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Mechanism of action in thalidomide


teratogenesis. Stephens TD, Bunde CJ, Fillmore BJ. Biochem
Pharmacol. 2000 Jun 15;59(12):1489-99.

Insulin-like growth factor I (IGF-I) and fibroblast growth factor 2 (FGF-2)


stimulation of the transcription of alphav and beta3 integrin subunit
genes. The resulting alphavbeta3 integrin dimer stimulates angiogenesis
in the developing limb bud, which promotes outgrowth of the bud. The
promoters of the IGF-I and FGF-2 genes, the genes for their binding
proteins and receptors, as well as the alphav and beta3 genes, lack typical
TATA boxes, but instead contain multiple GC boxes (GGGCGG).
Thalidomide, or a breakdown product of thalidomide, specifically binds to
these GC promoter sites, decreasing transcription efficiency of the
associated genes. A cumulative decrease interferes with normal
angiogenesis, which results in truncation of the limb.
Intercalation into G-rich promoter regions of DNA may explain why certain
thalidomide analogs are not teratogenic while retaining their anti-tumor
necrosis factor-alpha (TNF-alpha) activity, and suggests that we look
elsewhere to explain the action of thalidomide on TNF-alpha.
(steptren@isu.ed)

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Bagaimana dengan obat tradisional/herbal?


A total of 14,551 live births analysed.
Huanglian during the 1st trimester associated with increased risk of
congenital malformations of the nervous system (adjusted OR 8.62, 95% CI
2.54, 29.24).
An-Tai-Yin was associated with an increased risk of congenital malformations
of the musculoskeletal and connective tissues (adjusted OR 1.61, 95% CI 1.10,
2.36) and the eye (adjusted OR 7.30, 95% CI 1.47, 36.18).
CONCLUSION:
1. Evidence for a possible link between the use of specific herbal medicines
during the first trimester of pregnancy and increased risks of specific groups
of congenital malformations.
2. The adverse effects were related to direct toxicity from the herbal medicines,
or were from misuse, contamination or uncontrolled confounding?
3. Caution to take herbal medicines during pregnancy!

Chuang CH ; Doyle P ; Wang JD ; Chang PJ ; Lai JN ; Chen PC. Herbal medicines used during the
first trimester and major congenital malformations: an analysis of data from a pregnancy
cohort study. Drug Saf. 2006; 29(6):537-48

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http://www.videosift.com/video/The-4-FingerPianist
http://video.aol.com/video-detail/four-fingeredpianist/809074125
Gambar pada Judul hand-out: oleh Ann Harrison
May, seorang mouth-painter
(http://www.mfpausa.com/)