Drugs in Pregnancy Flashcards
2 Drugs that are safe in pregnancy
- Folic Acid
- Levothyroxide (in hypothyroidism)
Example of drug that req two types of contraception
- Ribavirin
A ______ must be present for the admin of any drug
true indication
Drug metabolism in pregnancy is ________ than in the non-pregnant state
much slower
Which trimester is often most sensitive for fetal malformation
First
Critical factors regarding drugs during pregnancy (6)
- Physical/chemical drug properties
- Rate at which the drug crosses the placenta and amt reaching fetus
- Duration of exposure to the drug
- Distribution in various fetal tissues
- Stage of dev at which drug exposure occurs
- Effect of combo with other drugs
Are drugs that are more or less lipid soluble most likely to cross the placenta?
Drugs that are HIGHLY lipid sol are very likely to cross placenta
- highly ionized less likely
What drug that is highly ionized has small non-ionized fractions that are highly lipid sol –> cross placenta
- Salicylate
Molecular size and crossing placenta
- Molecular wt 1000 unlikely to cross
Why can heparin be used in pregnancy and warfarin cannot?
Heparin is too large to cross the placenta, unlike warfarin
What pumps many drugs and toxic compounds back into maternal circulation?
P-glycoprotein
- Keeps drugs like vincristine, doxorubicin and protease inhibitors from crossing placenta
The binding affinity of fetal proteins is _____ so drugs that may be highly bound in the maternal blood may be ______ in the fetus
- lower
- less so
What types of drugs are more influenced by rate of blood flow?
- Highly lipid soluble drugs
- ie anesthetics
Example of a drug that enters fetal circulation thats metabolites are more toxic that the parent drug
ethanol
Drug that is recommended to all pregnant women to prevent ______
- Folic acid
- neural tube defects
- 400 microgram
At what level is HTN treated in preg
> 160/105
DOC for HTN in preg
Methyldopa
Drugs used in hospitalization for severe HTN
- Hydralazine
- Labetalol
Drug used to stimulate fetal lung maturation
- Corticosteroids
Drugs used to prevent transmission of HIV or herpes to baby
- Zidovudine
- Valacyclovir
Drugs used to control fetal heart probs
Antiarrythmics
Drug used to promote fertility
clomifene
Drug used to maintain preg
progesterone
Teratogenic drugs that bind to DNA that may inhibit DNA dep RNA synthesis or damage/fragment DNA in rapidly proliferating mammalian cells
Cancer drugs
Teratogenic drugs that inhibit production of essential nucleotides or decrease cell proliferation
Antimetabolites
Teratogenic drug produces free radicals, which act selectively on the -SH group of certain essential enzymes
Radiation (I125)
Teratogenic drug thats breakdown products appear to act as folic acid antagonists, or antagonists of riboflavin and/or other vitamins
Thalidomide
Teratogenic drugs that inhibit differentiation of cells in fetus (2)
- Vitamin A
- Isotretinoin
Excessive exposure to _____ may lead to alterations in development
some hormones
Definition of teratogen (4)
- Results in set of malformation, indicating selectivity for target organs
- Exerts its effect at a particular stage of fetal dev
- Dose-dependent incidence
- Some drugs are so teratogenic that they must NEVER be used in pregnancy
When does organogenesis begin
- 20th day of gestation and continues through the third month
Category A definition and examples (3)
- Adequate, well CONTROLLED STUDIES SHOWED NO RISK in many trimester of pregnancy
- Possibility of fetal harm is remote
- Levothyroxine and folic acid
Category B definition (3)
- Adequate, well-controlled studies NO EVIDENCE OF RISK IN HUMANS despite adverse findings in animals
- In the absence of adequate human studies, animal studies indicated NO fetal risk
- Change of fetal harm is remote, but still possible
Category C definition (4)
- RISK CANNOT BE RULED OUT
- No adequate, well-controlled human studies
- Adverse effects shown in animal studies, or are lacking
- There is a possibility of fetal harm, so drugs in this category may be prescribed only if the BENEFIT > RISK to fetus
Category D definition (4)
- POSITIVE EVIDENCE OF HUMAN FETAL RISK
- Studies in humans or post marketing demonstrated risk
- The benefits for pregnant women MAY OUTWEIGH RISK
- WARNING statement about such drug should appear on drug
Category X definition (4)
- CONTRAINDICATED IN PREGNANCY
- Demonstrated evidence of human fetal risk based on human experience
- RISK OF DRUG > POSSIBLE BENEFIT
- These drugs are contraindicated in women who are or may become pregnant while taking such drugs
Features of Fetal Alcohol Syndrome (5)
- Low forehead
- Sunken bridge of nose, small upturned nose
- Retracted lips
- Receding chin and ear deformations
- Cardiac defects with intrauterine and extrauterine growth retardation
Features of Warfarin Syndrome (5)
- Hypoplastic saddle nose
- Broad short hands, short distal phalanges
- Multiple ophthalmic abn (optic atrophy, cataracts)
- Bone abn
- Fetal death in utero is also common
Thalidomide Embryopathy
- multiple limb deformities
Features of Fetal Hydantoin Syndrome (5)
- Intrauterine growth retardation, mental deficiency
- Short nose, low nasal bridge, cleft lip/palate
- Cardiac defects
- Abn genitalia
- Absence of nails on fingers or toes
Features of Diethylstilbestrol Syndrome (3)
- Females may have abn of vagina, cervix, uterus
- Vaginal and/or cervical ridges
- Adenocarcinoma of the vagina or cervix as female entered their 20s
Vacterl Syndrome after use of Steroid Hormones
- Vertebral, Anal, Cardiac, Tracheal, Esophageal, Renal and Limb malformations
- Steroid hormones CATEGORY X, although progesterone sometimes used
Sex hormone that is sometimes used in preg
Progesterone
Isotretinoin Tx and MOA
- Severe acne
- Activates retinoic acid receptors and retinoid X receptors that bind the specific DNA sequences and affect cellular differentiation and proliferation, or induce apoptosis
Isotretinoin SE
- Photosensitivity
- Increased lipids
- Arthralgias and mylagias
- HA
- Alopecia
- Depression
- Staph infections
A single exposure to this drug in first 3 weeks of pregnancy can cause birth defects
Isotretinoin
Features of Isotretinoin
- Hydrocephaly
- Microcephaly
- Mental retardation
- Ear and eye abn
- Cleft lip/palate
- Facial abn
- Heart abn
- Mental retardation
Drug that requires iPLEDGE
Isotretinoin
- Cannot take St. John’s Wort
Contraindicated during 1st Trimester
- Metronidazole
- Tinidazole
Contraindicated during 3rd Trimester
- Aspirin, NSAIDs
- SMX/TMP
- Nitrofurantoin
Category X Drugs (24 groups)
- All statins
- Warfarin
- Temazepam, Flurazepam, Triazolam
- All ergot derivatives
- Clomiphene
- Estrogens
- GnRH analogues
- Progestins (unless needed to maintain preg)
- Testosterone, Androgens
- Misoprostol
- Mifepristone (RU 486)
- Raloxifen
- Anastrozole
- Finasteride, Dutasteride
- Ribavirin
- Amphetamines, Ephedra, Guarana
- Leflunomide
- Methotrexate
- Colchicine + probenicid
- Thalidomide
- Isotretinoin, all retinoids, Vit A
- Ethanol
- Ginko, Feverfew, Hawthorn, Black Cohosh, Kava Kava, marijuana, melatonin
- Gallium 69, Iodine, Technitium 99
