obat teratogenik
TRANSCRIPT
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OBAT-OBATTERATOGENIK
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PENDAHULUAN
Pemberian obat-obatan kepada ibu
hamil perubahan-perubahan
fisiologik N pe
volumeplasma, perubahan motilitas
gastrointestinal dan perubahan-
perubahan dlm komponen plasma,
fungsi ginjal
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Efek obat mengalami perubahanselama kehamilan.
R/ tunggal & jangka pendekdaripada R/ jangka panjang /kombinasi.
Gunakan dosis efektif terendahjika tersedia.
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Gunakan obat hanya jikamanfaat lebih besar daripadarisikonya.
Gunakan cara pemberianalternatif.
Pilih obat tanpa ES.
Gunakan dosis lebih rendah
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Defek fetus, malformasi,deformasi, disrupsi.
Malformasi perubahanembrionik dlm morfognesis
disebabkan prosesperkembangan intrinsik abN.
TERATOGENESIS
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Defek deformasi bentuk,kondisi atau posisi dari bagiantubuh abN kekuatan mekanik
ekstrinsik.
Disrupsi kekuatan ekternal ygmerubah jar. sebelumnya N.
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Teratogen bahan, organisme,bahan fisik / keadaan defisiensimenginduksi fungsi / struktur abN
postnatal.
Bahan teratogen infeksi, radiasi,pestisida, metal, bahan organik,peny. kronik dari ibu & obat-obatan.
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Tabel 1. FDA pregnancy drug risk categories
DRUG RISK
CATEGORIY
DEFINITION
X Contraindicated in pregnancy There is no reason to risk use of the drug in pregnancy
D
Positive evidence for risk to human fetus
However, benefits may outweigh risk of the drug
C
Risk cannot be ruled out-human studies are lacking Animal studies may or may, not show risk Potentials benefits may justify potential risk
B
No risk to human fetus despite posible animal risk Or, no risk in animal studies and human studies have not
been does
A Controlled studies show no fetal risk
Unrated
No pregnancy category has been assigned
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Tabel 2. Drug with minimal risk to mother andfetus during pregnancy contd
ANTIVIRAL AGENTS
(restrict use to
treatment of severe
herpesvirus infections)
Ayclovir Famcyclovir Vala\cyclovir
CORTICOSTEROISD Oral : avoid high doses first
trimester Topical : avoid high doses long term
MISCELLANEOUS-
OTHER DRUGS
Benzoyl peroxide Tretinoin (except first trimester)
MISCELLANEOUS-
TOPICAL ANTIACNE
PRODUCTS
Calcipotriene topical (low doses) Dapsone (except close to term) Hydroquinone topical Methoxsalen topical
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Tabel 3. Drug with minimal risk to mother andfetus during Lactation
ANALGESICS
Acetaminophen Codeine (low dose) Meperidine (low dose) Morphine (low dose)
Oxycodone (low dose)
Pentazocine (low dose) Propoxyphene (low dose)
ANESTHETICS Bupivacaine (low strength)
Lidocaine
Lidocaine with epinephrine Lidocaine-prilocaine Mepivacaine
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ANTIBACTERIAL AGENTS
Bacitracin-topical Cephalosporins Erythromycins Erythromycin-topical
Penicillins
Sulfur-topical Sulfur with resorcinol-topical Tetracycline-topical
ANTIFUNGAL AGENTS
Butoconazole-topical
Ciclopirox-topical Clotrimazole-topical Econazole-topical Miconazole-topical
Naftifine-topical
Nystatin-oral and topical
ANTIFUNGAL AGENTS contd
Oxiconazole-topical Sulconazole-topical Terbinafine-topical
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ANTIHISTAMINES
Concern for all antihistamines regardinginhibition of milk production andinfantile irritability
ANTIVIRAL AGENTS
Acyclovir Valacyclovir
ANTISCABETIC
AGENTS
Crotamiton-topical
CORTICOSTEROIDS
Oral : use prednisolone, avoid nursingfor 4 hours after use
Topical : aoid use of nipple or areola
MISCELLNEOUS-
TOPICAL ANTIACNE
Azelaic acid Benzoyl peroxide Tretinoid
MISCELLANEOUS-
OTHER DRUGS
Allopurinol Calcipotriene-topical Hydroquinone-topical Masoprocol-topical
Methoxsalen-topical
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Tabel 5. Pregnancy category D or unrated drugs to avoid in pregnancy and lactation
DRUG CATEGORY D UNRATED
Aspirin (high-dose, extende-releaseform should be avoided)
Azathioprine
Bleomycin
Colchicines
Cyclophosphamide
Griseofulvin
Hydroxyurea
Mechlorethamine
Penicillamine
Potassium iodide
Spironolactone
Tetracycline
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Tabel 6. Examples of known human teratogens
TERATOGEN ADVERSE EFFECTSCRITICALPERIOD
Maternal Conditions
Diabetes
Holoprosencephaly, pore cysts,cardiac defects, sacral agenesis,caudal regression, laterallydefects, facial clefts, renaldefects
Firsttrimester
Hypothyroidism /
Hyperthyroidism
Mental retardation (MR),growth restriction
Entirepregnancy
Phenylketonuria (PKU)MR, microcephaly, craniofacialdefects
Hyperthermia Anencephaly / other neuraltube defects (NTDs) 2-4 weeks
Systemic lupus
erythematosus (SLE)
Transient neonatal SLE,intrauterine growth restriction(IUGR), prematurity,congenital heart block
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TERATOGEN ADVERSE EFFECTSCRITICAL
PERIOD
Nonprescription
Substance Use
Alcohol
Short palpebra fissures,
altered facies, prenatal andpostnatal growth deficiency,mild to moderate MR,microcephaly
Entirepregnancy
Tobacco
Low birth weight (LBW),
miscarriage Unknown
TolueneCNS (developmental delay,microcephaly, IUGR)
Unknown
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TERATOGEN ADVERSE EFFECTSCRITICAL
PERIOD
Cyclophosphamide
CNS defects, skeletal defects(especially cranial and digits),IUGR cleft palate, neonataldeath
14-60 days
Fluconazole (risk
thought to be only with
high doses, especially
parenteral)
Brachycephaly, abnormal facies,abnormal calvarialdevelopment, cleft palate,cardiac defects, skeletal defects(thinning)
Firsttrimester
Indomethacin
Oligohydramnios, anuria,necrotizing enterocolitis,premature ductus arteriosusclosure
Second-thirdtrimester
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TERATOGEN ADVERSE EFFECTSCRITICAL
PERIOD
LithiumCardiac defects (Ebstein
anomaly)14-60 days
Methylene blue Jejunal atresiaSecond
trimester
Misoprostol
Mobius anomaly, terminal
transverse limb deficiency,
arthrogryposis multiplex
congenital, talipes equinovarus
First-
second
trimester
Penicillamine Connective tissue abnormalities 14-60 days
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TERATOGEN ADVERSE EFFECTSCRITICAL
PERIOD
Phenytoin
CNS (structural and
development delay), facial
clefting, midface
hypoplasia, cardiac
defects, digital nail
hypoplasia
14-60 days
Retinoids
(isotretinoin,
acitretin)
CNS, ocular, cardiac, great
vessel, and lib defects;
microtia, micrognathia,
cleft lip/palate, thymic
deficiency
Unknown
Selective serotonin
reuptake inhibitors
(SSRIs)
Prenatal complication,
increase in minor
anomalies
Third
trimester
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TERATOGEN ADVERSE EFFECTSCRITICAL
PERIOD
TetracyclineStaining of primary
dentition
Second-
third
trimester
Thalidomide
Cranial nerve abnormalities,
limb shortening defects
(phocomelia), ocular and
cardiac defects, oral/facial
anomalies, renal and
urogenital defects
27-40 days
Trimethoprim
NTDs, oral clefts,
hypospadias, cardiovascular
defects
First
trimester
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TERATOGEN ADVERSE EFFECTSCRITICALPERIOD
Medications-contd
Trimethadione
CNS (development delay),microcephaly, cleft lip/palate,broad nasal brigde,genitourinary andgastrointestinal defects, cardiacdefects
14-60 days
Valproic acid
CNS defects (includingdevelopment delay),brachycephaly, craniosynostosis,microcephaly, ocularhypertelorism, midfacehypoplasia, cleft lip/palate, limbabnormalities, spina bifida
14-60 days
Warfarin
CNS and ocular defects, IUGR,neonatal hemorrhage, nasalhypoplasia, vertebral anomalies,stippled epiphysis
6-9 weeks; after9 weeks, CNS,ocular anddisruptive
defects
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