obat teratogenik

8/10/2019 obat teratogenik

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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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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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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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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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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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obat teratogenik