Reproductive Flashcards
When are fetuses most susceptible to the effects of a teratogen?
3rd-8th week of pregnancy (embryonic period of organogenesis)
Teratogen Medication List (12)
- ACEi (and ARBs)
- Alkylating agents
- Aminoglycosides
- Antiepileptic drugs (commonly valproate, carbamazepine, phenytoin, phenobarbital)
- Diethylstillbestrol (DES)
- Folate antagonists (trimethoprim/ methotrexate, anti epileptic drugs)
- Isotretinoin
- Lithium
- Methimazole
- Tetracyclines
- Thalidomide
- Warfarin
Substance abuse teratogen (3)
- Alcohol
- Cocaine
- Smoking (nicotine, CO)
Miscellaneous teratogens (5)
- Iodine (lack or excess)
- Maternal diabetes
- Methylmercury
- Vitamin A excess
- Xrays
Teratogen effect: ACE inhibitors (and ARBs)
Renal damage
Teratogen effect: Alkylating agents (2)
- absence of digits
2. multiple anomalies
Teratogen effect:
Aminoglycosides(1)
Ototoxicity
Teratogen effect:
Antiepileptic drugs(4)
Names (4)
recommended supplementation?
Valproate, Carbamazepine,
Phenytoin, Phenobarbital
- Neural tube defects (high dose folate supplementation)
- Cardiac defects
- cleft palate
- skeletal abnormalities (phalanx/nail hypoplasia, facial dysmorphism)
Teratogen effect:
Diethylstillbestrol (DES) (2)
- Vaginal clear cell adenocarcinoma
2. Congenital Mullerian anomalies
Teratogen effect:
Folate antagonists (1)
Name 3 examples
Neural tube defects
- Trimethoprim
- Methotrexate
- Anti-epileptic drugs
Teratogen effect:
Isotretrinoin (1)
Recommendation
“isoTERATinoin”
Multiple severe birth defects
CONTRACEPTION MANDATORY
Teratogen effect:
Lithium(1)
Ebstein anomaly
apical displacement of tricuspid valve–>enlarged atrium
Teratogen effect:
Methimazole
aplasia cutis congenita
Teratogen effect:
Tetracycline(2)
- discolored teeth
2. inhib bone growth
Teratogen effect:
Thalidomide
“LIMB defects with ‘tha-limb-domide’”
- Limb defects (phocomelia, micromelia=flipper limbs)
Teratogen effect:
Warfarin(4)
- bone deformities
- Fetal hemorrhage
- abortion
- ophthalmologic abnormalities
” Do not wage WARFARe on the baby, keep it HEPpy with HEPARIN(doesn’t cross placenta)
Teratogen effect:
Alcohol
Fetal Alcohol syndrome #1 common cause of birth defects and intellectual disability
Teratogen effect:
Cocaine (4)
how?
- low birth weight
- preterm birth
- IUGR
- Placental abruption
cocaine–>vasoconstriction
Teratogen effect:
Smoking (5)
how?
- low birth weight (leading cause in developed countries)
- preterm labor
- placental problems
- IUGR
- SIDS
Nicotine–>Vasoconstriction
CO–> impaired O2 delivery
Teratogen effect:
Iodine (lack or excess) (2)
- congenital goiter
2. hypothyroidism (cretinism)
Teratogen effect: Maternal diabetes (4)
- Caudal regression syndrome(anal atresia - sirenomelia)
- Congenital Heart defects
- Neural tube defects
- macrosomia
Teratogen effect:
Methylmercury
Source (4)
- Neurotox
- swordfish
- shark
- tilefish
- king mackerel
Teratogen effect:
Vitamin A excess
EXTREMELY HIGH RISK
- spontaneous abortions
- birth defects (cleft palate, cardiac)
Teratogen effect:
X-rays
minimized by?
- microcephaly
- intellectual disability
-minimized by lead shielding
Treatment for gestational hypertension(4)
Define gestational hypertension (pregnancy-induced hypertension)
BP > 140/90 after 20wks. No pre-existing hypertension. No proteinuria or end-organ damage
“Hypertensive Moms Love Nifedipine”
- Hydralazine
- a-Methyldopa
- Labetalol
- Nifedipine
* deliver at 37-39wks
Treatment for Preeclampsia (3)
Definition
New-onset HTN with either protienuria or End-organ dysfunction after 20wks (less than 20wks suggests molar pregnancy).
- antihypertensives
- MgSO4
- Delivery= definitive treatment
Treatment of Eclampsia (3)
Definition
Pre-eclampsia + maternal seizures
Maternal death due to stroke/Intracranial hemorrhage, or ARDS
- IV magnesium sulfate
- antihypertensive (a-methyldopa, hydralazine) + bedrest
- immediate delivery
treatment for HELLP (1)
Definition
Hemolysis, Elevated Liver-enzymes, Low Platelets.
A manifestation of severe preeclampsia. Blood smear shows schistocytes. Can lead to hepatic subcapsular hematomas–> rupture–> severe hypotension
- Immediate delivery
Treatment for PCOS (5)
- weight reduction (helps with insulin resistance-can use metformin as well)
- OCPs
- clomiphene citrate
- ketoconazole
- spironolactone
Treatment for Adenomyosis
Definition
Extension of endometrial tissue into uterine myometrium
- GnRH agonist
- hysterectomy
Treatment for Endometritis
Definition
Inflam of endometrium associated with retained products of conception following delivery, miscarriage, abortion, or with foreign body (IUD)
Treatment:
Gentamicin + Clindamycin +/- Ampicillin
Treatment for Endometriosis
Definition
Non-neoplastic endometrial glands/ stroma outside endometrial cavity
- NSAIDs
- OCPs
- progestins
- GnRH agonist
- danazol
- laproscopic removal
drugs causing gynecomastia
“STACKED”
- Spironolactone
- THC (marijuana)
- Alcohol (chronic)
- Cimetidine
- Ketoconazole
- Estrogens
- Digoxin
drug induced hot flashes (2)
- Tamoxifen
2. clomiphene
treatment of Varicocele (2)
- varicocelectomy
2. embolization
treatment of BPH (3)
- a1-antagonists (terazosin, tamsulosin)–>relax of sm. muscle
- 5a-reductase inhib (finasteride)
- tadalafil
Leuprolide:
MOA
Clinical Use (5)
“LEUprolide can be used in LIEU of GnRH”
- GnRH analog->agonist if pulsatile fashion
- GnRH analog->antagonist if continuous fashion (downreg. GnRH-R in pituitary->decrease FSH/LH)
- Uterine fibroids
- endometriosis
- precocious puberty
- prostate cancer
- infertility
Leuprolide:
Adverse (3)
- startup flair
- hypogonadism
- N/V
Estrogens:
Name 3
- Ethinyl estradiol
- DES
- Mestranol
Estrogens:
MOA
Clinical Use (6)
- Bind estrogen-R
- Hypogonadism
- Ovarian failure
- Menstrual abnormalities
- HRT in postmen women
- androgen-dep. prostate cancer (men)
- OCPs
Estrogens:
Adverse (4)
Contra (2)
- increase risk of endometrial (maybe breast) cancer
- bleeding in postmenopausal women
- Clear cell adenocarcinoma in Vagina (DES)
- thrombi
Contra:
- ER+ breast cancer
- DVT history
Selective estrogen-R modulators:
Name 3
- Clomiphene
- Tamoxifen
- Raloxifene
Clomiphene:
MOA(2)
Use (1)
- Antagonist at E-R in hypothalamus–>prevents normal feedback inhibition.
- Increase release of LH/FSH form pituitary–> stimulates ovulation
Use: infertility due to anovulation (like PCOS)
Clomiphene:
Adverse (4)
- Hot flashes
- Ovarian enlargement
- Multiple simultaneous pregnancies
- Visual disturbances
Tamoxifen:
MOA (2)
Use (1)
- Antagonist at Breast
- Agonist at Bone/Uterus (pro-bone)
Use: treat/prevent recurrence of ER/PR+ breast cancer
Tamoxifen:
Adverse (2)
- increase risk of thromboembolic events
2. increase risk of endometrial cancer
Raloxifene:
MOA
Use (2)
- Antagoist at Breast/Uterus
- Agonist at Bone (pro-bone)
Use: osteoporosis
Raloxifene:
Adverse(1)
- increase risk of thromboembolic events
* no increase risk of endometrial cancer like with tamoxifen
Aromatase Inhibitors:
Name 3
- Anastrozole
- Letrozole
- Exemestane
Aromatase Inhibitors: Anastrozole, letrozole, exemestane
MOA
Clinical Use (1)
- inhib peripheral conversion of androgens–>estrogen
1. ER+ breast cancer in postmenopausal women
Hormone Replacement Therapy:
Use(3)
Relief/Prevent Menopausal symptoms:
- Hot flashes
- Vaginal atrophy/dyspareunia
- Osteoporosis (increase estrogen/decrease osteoclasts)
Hormone Replacement Therapy:
Adverse(2)
- Unopposed estrogen–> increase endometrial cancer risk
(must admin with progesterone) - Cardiovascular risk (heart attack/stroke)
Main treatment for Prostate Cancer (2)
- Flutamide
2. Leuprolide
Progestins:
Name 5
- Levonorgestrel
- Medroxyprogesterone
- Etonogestrel
- Norethindrone
- Megestrol
*often combined with estrogen
Progestins:
MOA
Clinical Use(3)
Bind P-R–> decrease growth and increased vascularization of endometrium & thicken cervical mucus
- Contraception (pill, IUD, implant, depot)
- endometrial cancer
- abn. uterine bleeding
Explain the Progestin Challenge
presence of withdrawal bleeding excludes anatomic defects (Asher syndrome) and chronic anovulation without estrogen
Anti-progestins:
Name 2
- Mifepristone (=RU-486)
2. Ulipristal
Antiprogestins:
MOA
Clinical use (
-Competitive inhb of progestins at P-R
- Termination of pregnancy (mifepristone w/ misoprosto-PGE1 analog)
- emergency contraception (ulipristal)
- peptic ulcer disease (mifepristone)
Combined contraception:
Components
Forms(3)
MOA(3)
- Progestins & EE
- pill, patch, vaginal ring
- estrogen&progestins inhib LH/FSH–>prevent estrogen surge/LH surge–>No ovulation
- Progestins thicken cervical mucous (limit sperm access to uterus)
- Progestins inhib endometrial prolif (limits implantability)
Combined contraception:
Contra
- smokers >35yo (increase Cardiovascular events)
- patients at increased risk of CV events(VTE history, CAD, stroke)
- migraine (esp. with aura)
- breast cancer
Copper Intrauterine device:
MOA
Clinical Use(2)
- Produces local Inflam Rxn toxic to sperm/ova
(prevents fertilization/implantation) - No hormones
- Long acting reversible contraception
- Most effective emergency contraception
Copper Intrauterine device:
Adverse (3)
Contra (1)
Adverse:
- Heavier/longer menses
- dysmenorrhea
- PID risk with insertion
Contra: PID/ pelvic infection
Terbutaline, Ritodine:
MOA
Use
Terbutaline (B1/B2)
Ritodrine (B2)
-B2 agonists that relax the uterus
Use: decrease contraction frequency in women during labor/decrease premature contractions (a.k.a=tocolytic)
Danazol:
MOA
Clinical Use (2)
-synthetic androgen that acts as partial agonist at androgen-R1
- Endometriosis
- hereditary angioedema
- Danazol has largely been replaced by Leuprolide/Goserelin for endometriosis
Danazol:
Adverse (7)
- Weight gain
- edema
- acne/hirsutism
- masulinization (of fetus w/ pregnancy)
- decrease HDL levels
- hepatotox
- pseudotumor cerebri (increase ICP, papilledeam, HA)
Drugs causing pseudotumor cerebri
- Danazol
2. excess Vit A
Testosterone, Methyltestosterone:
MOA
difference between the 2 drugs?
Clinical Use(3)
- Androgen-R agonist
- Methyltestosterone has better oral bioavailability
- Hypogonadism
- promote dev. of 2ary sex characteristics
- stimulate anabolism to promote recovery after burn/injury
Testosterone, Methyltestosterone:
Adverse(4)
- masculinizationof Females
- decrease intratesticular testosterone in males via (-) feedback on LH–> gonadal atrophy
- premature closure of epiphyseal plates
- increase LDL, decrease HDL (not good)
Antiandrogens:
Name 4
- Finasteride
- Flutamide
- Ketoconazole
- Spironolactone
Finasteride:
MOA
Clinical Use (2)
Adverse
-5a-reductase inhibitor
(decrease testosterone–>DHT conversion)
- BPH (drug of choice w/o HTN)
- male pattern baldness
Adverse: impotence, gynecomastia, abn. sex function
Flutamide:
MOA
Clinical use(1)
Used with what?
-Nonsteroidal Competitive inhib at androgen-R –> decrease Testosterone
- Prostate carcinoma w/ Leuprolide
(decrease LH/FSH)
Ketoconazole:
MOA
inhib steroid synthesis
inhib 17,20-desmolase which prevents chol–>pregnenolone
Spironolactone:
MOA
inhib steroid binding, 17a-hyrdoxylase, and 17,20-desmolase
Ketoconazole & Spironolactone:
Clinical Use(1)
Adverse (2)
- PCOS to reduce androgenic symptoms
- gynecomastia
- amenorrhea
Tamsulosin:
MOA
Clincial Use
- selective a1(A,D)-antagonist–> inhib sm. muscle contraction on prostate (limited effect on vascular a1(B)-R)
1. BPH
(in contrast to non-specific a1-antagonist which all end in “-zosin” 1. prazosin 2. terazosin 3. doxazosin and can cause adverse orthostatic hypotension)
Phosphodiesterase Type5 inhibitors:
Name 3
“PDE type5 inhibitors FILl the penis”
- Sildenafil
- Tadalafil
- Vardenafil
Phosphodiesterase Type5 inhibitors:
MOA
- Inhib PDE-5–> increase cGMP–>prolong sm. muscle relaxation in response to NO
- this increases b.flow in corpus cavernous of penis
- decrease pulm. vascular resistance
Phosphodiesterase Type5 inhibitors:
Clinical Use (3)
Adverse
- Erectile dysfunction
- Pulm HTN
- BPH (Tadalafil)
Adverse: “Hot and sweaty, but then HA, Heartburn, Hypotension”
- HA, Flushing
- Dyspepsia
- cyanopia = Blue-tinted vision (“viagra is a blue little pill”)
Phosphodiesterase Type5 inhibitors:
DD interaction
Risk of life-threatening Hypotension in patients taking NITRATES
- IF suspecting MI in patient, ask about erectile dysfunction drugs b/c NItrates+Sidenafil–>life-threatening hypotension
Minoxidil:
MOA
Clinical Use
-Direct arteriolar vasodilator (K+ channel blocker)
- Androgenic alopecia (“Rogaine”)
- Severe refractory Hypertension
Only anti fungal with anti-androgenic effects?
Ketoconazole
w/ adverse of gynecomastia
Drug of choice for BPH w/o HTN?
w/ HTN?
w/o= Finasteride w/ = Tamsulosin
Drug which impairs Blue-Green vision?
Drug which impairs Red-Green vision?
Blue-Green= PDE-5 inhib Red-Green= Ethambutol