ERM 2.1 Final

endometrial menstrual cycle histology?

• proliferative (ER; mitosis) → straight glands lined w/ pseudostratified epithelium = wk2

• early secretory → secretory subnuclear vacuoles, sawtooth glands = wk3

• late secretory (high PG) → spiral arterioles, stromal hypertrophy, predecidual changes (neutrophil + lymphocyte) = wk4

• menstruation (drop in PG) → stromal breakdown, bleeding = wk1

adenomyosis type? characteristics? symptoms?

• non-neoplastic (myometrium)

• endometrial tissue (glands + stroma) in myometrium via invagination of endometrial basal layer OR remnant progenitor cell metaplasia

• menometrorrhagia (irregular + heavy), dysmenorrhea, dyspareunia → currently menstruating women

  • diffusely enlarged (globular), soft (boggy) uterine walls

  • can coexist w/ endometriosis

endometriosis type? characteristics? symptoms?

• non-neoplastic

• endometrial tissue outside uterus via ectopic implantation (retrograde menses, lymphatics, BV) OR remnant progenitor cells metaplasia

• dysmenorrhea, dyspareunia, infertility; NO AUB → in menstruating women

  • glands = +stroma, ±hemosiderin

  • immobile uterus, adnexal mass, uterosacral tenderness, nodularity, yellow/brown powder burn lesion, common = endometrioma (chocolate cyst)

leiomyoma (fibroid) type, characteristics, symptoms, histology? leiomyosarcoma?

• benign neoplastic myometrium tumor in reproductive-age; ER sensitive (size inc. w/ preg. + dec. w/ menopause)

  • subtype location based → submucosal, intramural, subserosa

• asymptomatic (possible AUB, pelvic pressure/pain, infertility) w/ enlarged uterus w/ nodular contour

  • multiple well-defined, white, whorled mass

• leiomyosarcoma (de novo) → malignant neoplasm (nuclear atypia + high mit. rate), post menopausal; single lesion w/ necrosis + hemorrhage (also seen in complicated leiomyoma)

endometrial hyperplasia type? characteristics? types? diagnosis?

• neoplastic

• abnormal endometrial gland proliferation → unopposed estrogen (via tamoxifen/ER @ uterus, obesity, PCOS/anovulatory), nulliparity, HRT, Lynch = post. men. bleeding/AUB

• typical = diffuse glandular proliferation OR atypical (endometrial intraepithelial neoplasia) = inc. risk for endometrial carcinoma

• Dx w/ dilation + curettage

endometrial carcinoma type? characteristics? histology? symptoms? types?

• neoplastic

• malignant endometrial tumor w/ histological confluent endometrial glands w/o intervening stroma = post. menopausal AUB

• type 1 (endometroid) = PTEN mut.; indolent; ass. w/ unopposed estrogen, early menarche/late menopause, nulliparity, infertility, obesity, HTN

  • well formed glands

• type 2 (serous) = TP53 mut.; aggressive sporadic in atrophic endometrium; psammoma bodies + papilloma line w/ atypical cells

cervix disorders site? mechanism?

• transformation zone → neoplasia common site

  • SJC = site of squamous metaplasia + HPV entry

  • OG SJC @ ext. cervix → columnar epithelium everts to ectocervix w/ erosion (ectropium) → reserve cell hyperplasia → resistant squamous epithelium (metaplasia)

• HPV mech:

  • LR = 6,11

  • HR = 16,18,31,33

  • oncoprotein = E6 (dec. p53), E7 (dec. Rb)

  • persistent infection → CIN → carcinoma

screening and prevention for lower GU disorders?

• next step for abnormal pap → colposcopy w/ acetic acid/lugol solution + biopsy (= diagnostic)

• cytology for cervix

• 21-29 = cytology q3 yrs

• 30-65 = cytology + HPV q5 yrs

• vaccine = gardasil-9 (HPV 6, 11, 16, 18)

cervical intraepithelial neoplasia (CIN) types? features?

• pre neoplastic cervix disorder; results in invasive squamous carcinoma

  • squamous intraepithelial lesion (SIL) = koilocytosis, loss of polarity + mat., nuclear atypia, inc. mit.

• CIN1 (LSIL) → HPV 6/11, flat condyloma-papillary, exophytic arch w/ perinuclear halo, nuclear atypia

• CIN2/3 (HSIL) → HR HPV, gray zone/ full thickness atypia (w/ scant cytoplasm); inc. neoplastic risk

adenocarcinoma in situ (AIS) features?

• pre neoplastic cervix disorder

• @ endocervical canal (columnar) w/ nuclear atypia, abundant cytoplasm + atypical glandular cells on PAP; adenocarcinoma precursor; mimic immature squamous metaplasia

  • asymptomatic → catch @ screening

  • mistaken for HSIL (CIN3) since most immature/most cytoplasm

cervical squamous cell carcinoma (SCC) features?

• neoplastic cervix disorder

• @ ectocervix

• exophytic or ulcerative via CIN2/3 (HSIL) w/ HR HPV (early = asymptomatic; then AUB, foul water/bloody discharge)

• keratin pearls + IC bridge; blocks ureters (hydronephrosis)

  • can develop into vaginal SCC = cervix extension (post. 1/3 w/ leukoplakia)

invasive adenocarcinoma features?

• neoplastic cervix disorder

• endocervical origin/not easily visualized or barrel w/ HR HPV

• crowded glands, spreading down + out → compress ureters = kidney injury

  • adenocarcinoma NOT identified w/ pap smear (normal PAP smear)

  • post. men. bleed/AUB, watery/clear discharge, abnormal cervix

vaginal intraepithelial neoplasia features (VaIN)?

• pre neoplastic vaginal disorder

• VaIN 2/3 = HSIL (koilocytosis, loss of polarity + mat., nuclear atypia, inc. mit.)

• HR HPV; flat squamous epithelium w/ nuclear full thickness atypia

• = vaginal squamous cell carcinoma (SCC) → pap smear + confirm w/ colposcopy; vaginal bleed/discharge (picture)

  • must exclude extension from other sites for vaginal SCC (e.g can be 2ndary to cervical SCC)

clear cell adenocarcinoma features?

• pre neoplastic vaginal disorder

• linked to DES exposure

• rise from adenosis (failure to replace columnar epithelium @ upper vagina) = residual glandular cells w/ clear cytoplasm + hobnail nuclei → malignant transformation

  • ridge of red, moist granules

embryonal rhabdomyosarcoma features?

• neoplastic vaginal disorder

• aka sarcoma botryoides = <5 y/o; grape like mass @ vagina/penis w/ bleeding + discharge

• cytoplasmic cross-striation, desmin+, myogenin+

bartholin cyst features?

• non neoplastic vulva disorder

• unilateral painless cyst of bartholin gland near vaginal opening

  • develop into abscess (painful)

lichen sclerosis features? lichen simplex complex features?

• non neoplastic vulva disorders

• post menopausal, porcelain-like leukoplakia, epidermal thinning (parchment), dermal sclerosis, lymphocytic infiltrate, inc. SCC risk

• squamous cell hyperplasia w/ thickened epidermis + hyperkeratosis from chronic irritation/scaly leukoplakia

condyloma acuminatum features? vulvar intraepithelial neoplasia (VIN) features?

• pre neoplastic vulva disorder

• HPV 6/11 w/ koilocytosis; painless, flesh colored, wart/exophytic bump (cauliflower) via STI @ ext. genitalia

• VIN (pruritis, pain, lesion, itching)

  • VIN1 (LSIL) → HPV 6/11; flat condyloma-papillary/leukoplakia, exophytic arch, koilocytosis (perinuclear halo, nuclear atypia)

  • VIN2/3 (HSIL) → HR HPV; flat squamous epithelium w/ nuclear full-thickness atypia + loss of polarity

extramammary paget disease features?

• neoplastic vulva disorder

• type of adenocarcinoma in situ (AIS)/ pre neoplastic cervical; large pale cells; no spread, no underlying carcinoma (de novo), in epidermis (erythema, pruritis, ulcer)

  • PAS+, CK7/keratin+, S-100-

vulvar squamous cell carcinoma (SCC) features?

• neoplastic vulva disorder

• arise from vulva intraepithelial neoplasm (VIN2/3); more often NOT ass. w/ HPV + ass. w/ Lichen Sclerosis (LS);

  • pruritis, pain, ulcer, bleed

  • keratin pearls/malignant keratin; leukoplakia, exophytic/cauliflower mass + endophytic ulcer

  • prognosis good

estrogen MOA? indication? AE?

• binds nuclear ER → dimers translocate to nucleus → act. coactivators + corepressor of gene transcription

  • raloxifene = ER antagonist in breast + endometrium/agonist in bone

  • DES = syn. estrogen (clear cell adenocarcinom)

• OCP (CI for smokers), primary hypogonadism, HRT, acne, dysmenorrhea, combine w/ prog. to control menstrual bleed, osteoporosis, perimenopausal vasomotor Sx

• endometrial cancer, breast cancer, HTN, thromboembolic disorder, gallbladder disease, vaginal/cervical adenocarcinoma w/ DES use

progestins (-gest-) MOA? indications? AE?

• oral pill (thicken cervical mucous), plan B (levonorgesterol), combined pill (estrogen + progestin = dec. FSH/LH)

• dysmenorrhea, endometriosis, uterine bleeding, combination w/ estrogen in HRT dec. estrogen induced irregular bleeding to prevent uterine hyperplasia + endometrial cancer, suppress pp lactation

• edema, depression, glucose intolerance, breakthrough bleeding, hirsutism, inc. LDL, dec. HDL, etc.

  • CI = breast cancer, liver disease

follitropin alpha MOA? indications? AE? hCG?

• FSH receptor agonist → follicle stim.

  • controlled ovarian stim.

  • gynecomastia + infertility (MHH), multiparity

• LH receptor agonist

  • initiation of final oocyte maturation + ovulation during controlled ovarian stim.

  • depression

leuprolide, naferelin, histrelin MOA, indications, AE? ganirelix, degarelix?

• GnRH agonist (intermittent = inc. LH/FSH OR cont. = dec. LH/FSH)

  • ovarian suppression + controlled stim., central precocious puberty, prostate cancer, endometriosis, breast cancer

    • cont. cancer, pulsatile pregnancy

  • headache, nausea, dec. libido, osteoporosis

• GnRH antagonist → dec. LH/FSH

  • prevent premature LH surge during controlled ovarian stim.

    • headache, nausea, hypersensitivity rxn

clomiphene MOA? indications? AE?

• SERM: partial estrogen agonist or antagonist → inc. LH/FSH (prevent - feedback inhibition of estrogen of hypothalamus)→ ovulation

• infertility

• blurred vision (diplopia), multiple gestation pregnancy (multiple follicles)

mifepristone MOA? AE? misoprostol?

• prog. antagonist → trophoblast detachment → abortion

  • bleeding, abdominal pain

• PGE1 analog → cervical softening + uterine contraction (w/ mifepristone for abortion)

  • diarrhea

danazol MOA? indication? AE?

• synthetic androgen → binds androgen, progesterone, glucocorticoid receptors → inhibits FSH, LH (dec. prod. from ant. pit.)

• endometriosis

• thromboembolism, hot flashes, changes in libido, amenorrhea, hirsutism, oily skin, acne

HIV transmission?

• sexual → direct inoculation into BV via trauma, infection of DC/ CD4 w/in mucosa

• parenteral → IV drug user, hemophiliacs receiving FVIII, FIX concentrates, recipients of blood transfusion

• mother-infant → transplacental, intrapartum (during delivery), peripartum (after delivery), breast milk ingestion

structural components of HIV?

• ss RNA, enveloped

• gag (p24,17) → capsid protein, 1st Ag to induce Ab response; ELISA screening

• pol (RT, IN, PR) → anti HIV drug enzymatic target

• env (gp120, 41) → attach to host CD4 (HIV receptor) + CCR5 (coreceptor for MQ/DC; R5) or CXCR4 (coreceptor for T cell/CD4; X4) (mut. = HIV resistance/white ppl); entry into host → inhibitors used as 2nd line of ARV drugs

• nef (reg.) → transcription, RNA transport, immune evasion = progression to AIDS (mut. = can’t progress to AIDS)

HIV screening?

• neonatal → detect viral DNA via PCR

• acute HIV → detect viral RNA (NAT → detect RNA w/in 10-33 days; given if Ab indeterminate)

• Ag/Ab → detect 24+ Ab w/in 18-45 days

• Ab → detect Ab w/in 23-90 days

• monitor CD4 count + viral load

HIV disease progression?

• ARS → asymptomatic phase → opportunistic infection/malignancies

  • acute retroviral syndrome (ARS) symptoms → fever, malaise, myalgia, arthralgia, rash, night sweats, headaches

• antiretroviral therapy (ART) given to infected pregnant women @ start to prevent mother-child transmission

• pre exposure prophylaxis (PrEP) → for @ risk pop.; give oral TDC/FTC (truvada)

• post exposure prophylaxis (PEP) → given 28 mths w/ 3 antiretroviral drug regimen

AIDS progression? symptoms?

• CD4 <200 cells/uL + CD4:CD8 ratio inversion (2:1 → 1:2)

  • top left = y+, bottom right = x+

• weight loss, anemia, co-infection, meningitis (viral, cryptococcus, TB), encephalitis (toxo, CMV), PCP

• AIDS dementia → poor conc., dec. memory, motor, dysfxn, behavior change (CT/MRI = cerebral atrophy + enlarged sulci)

• focal lesion → seizure onset, headache, fever, rapid progress w/ cognitive impairment (CT/MRI, CSF evaluation, toxoplasmosis titer)

  • toxo (CT= spherical + ring enhancing lesion in BG + cortex via cat litter + undercooked pork), lymphoma (CT= single irregular, weak enhancing PV lesion), PML (MRI= multiple white matter lesions; ass w/ JC virus)

pneumocystis jirovecii pneumonia (PCP) cause + symptoms? prophylaxis?

• common life-threatening infection, inc. risk w/ CD4 <200 → gradual SOB, dry cough, cyanosis

• prophylaxis w/ TSX started @ CD4 ≤ 200mm3

  • pneumocystis jirovecii (<200 CD4)

  • toxoplasma gondii + histoplasma capsulatum (<100 CD4)

  • mycobacterium avium intracellulare, CMV, cryptococcus neoformans (<50 CD4)

• only give rabies, influenza. polio (salk), hep A (NOT MMR, varicella, adenovirus, rotavirus, yellow virus, smallpox)

entry/fusion inhibitors?

• enfuvirtide → gp41 inhibitor

• maraviroc → CCR5 antagonist (stability)

• fostemsavir + ibalizumab → gp120 inhibitor

nucleoside RT inhibitors (NRTI)? non-nucleoside RT inhibitor (NNRTI)?

• tenofovir, emtricitabine, abacavir, lamivudine (TEAL)

  • HIV risk reduction = 2 NRTI (tenofovir + emtricitabine)

  • HIV/HBV coinfection = Tx w/ LET

• doravirine, efavirenz, nevirapine, rilpivirine (-vir-ine)

• HIV Tx = 2NRTI + 1 NNRTI, INSTI, PI w/in 72 hrs (RET = raltegravir, emtricitabine, tenofovir)

integrase inhibitors (INSTI)? protease inhibitors (PI)?

• -tegravir

• -navir

• HIV Tx = 2NRTI + 1 NNRTI, INSTI, PI w/in 72 hrs (RET = raltegravir, emtricitabine, tenofovir)

HIV risk reduction? HIV treatment? antiretroviral therapy regimen? PrEP? PEP?

• HIV risk reduction = 2 NRTI (tenofovir + emtricitabine)

  • HIV/HBV = 3 NRTI → LET (lamivudine, emtricitabine, tenofovir)

• HIV Tx = 2NRTI + 1 NNRTI, INSTI, PI w/in 72 hrs (RET = raltegravir, emtricitabine, tenofovir)

• tenofovir (NRTI), disoproxil, fumarate (TDF)

  • can cause prox. renal tubular dysfxn (fanconi syndrome) + loss of bone mineral density

• tenofovir (NRTI), disoproxil, fumarate (TDF)/ emtricitabine (NRTI) (FTC)

• ““ + -tegravir (INSTI)

HPV class? characteristics? symptoms? treatment?

• virus

• papillomaviridae; circular DNA, icosahedral, no envelope

• condyloma acuminata → keratotic lesions or cauliflower like lesion

• gardasil-9 → 9 valent vaccine

treponema pallidum (syphilis + chancre) class? characteristic? symptoms? treatment?

• bacteria (spirochete); visualize w/ darkfield microscopy or DFA (contains peptidoglycan)

  • types → neuro, oto, ocular, congenital (nasal discharge, rash, HSM, jaundice, LAD → hutchinson/notched teeth, sensorineural deafness, keratitis, saddle nose, saber shins; test for via VDRL or RPR)

• single painless, demarcated, red, indurated ulcer; LAD (1 enters, 2 spreads to skin/soles + palms, latent lingers, 3 destroys neuro w/ unaccommodating pupils + sensation loss, cardio w/ aortitis, gumma)

• PCN-G benzathine (bicillin LA) IM once (cell wall transpeptidase)

  • jarisch-herxheimer rxn → flu-like after antibacterial Tx spirochete

  • if preg. pt. allergic → desensitize OR if not preg. allergic → doxycycline (30S RI), ceftriaxone

klebsiella granulomatis class? characteristic? symptoms? treatment?

• bacteria (gram (-) bacilli)

• involves MQ; pseudo-buboes; donovan bodies (bipolar chromatin densities; safety pin)

• painless “beefy” red, highly vascular ulcer; NO LAD

• azithromycin (50S RI)

chlamydia trachomatis (MOST COMMON) class? characteristics? symptoms? treatment?

• bacteria (IC parasite) → McCoy cells (host cell for isolate/grow), giemsa stain

• w/ elementary bodies + noninfectious reticulate bodies; buboes

  • chlamydia, trachoma (africa → conjunctivitis then inward eyelid), lymphogranuloma venereum (africa, SEA → transient lesion then LAD w/ groove appearance + myalgias)

• painless, mucopurulent discharge (stains underwear) +dysuria; salpingitis via PID (fever, pelvic pain/dyspareunia, CMT + adnexa tender, discharge)

• doxycycline (30s) OR azithromycin (50s) if preg.

  • erythromycin Tx ophthalmia neonatorum/conjunctivitis

neisseria gonorrheae class? characteristics? symptoms? treatment?

• bacteria (gram (-) diplococci) → use thayer martin or cholocate agar

• can spread (disseminated infection) from GU to skin/joints

• purulent discharge, salpingitis via PID (fever, pelvic pain/dyspareunia, CMT w/ adnexal tenderness, discharge)

• ceftriaxone (cell wall/transpeptidase) or cefotaxime → also Tx ophthalmia neonatorum/conjuctivitis (prevent w/ erythromycin)

  • + doxycycline or azithromycin (if pt. preg.)

haemophilus ducreyi (chancroid) class? characteristics? symptoms? treatment?

• pleomorphic bacteria (gram (-) bacilli) → chocolate agar, diff. w/ factor X/V

• multiple painful, gray/yellow, non-indurated, purulent ulcers; LAD + buboes

• ceftriaxone (cell wall/ transpeptidase), azithromycin (50S RI) if preg.

gardnerella vaginalis class? characteristics? symptoms? treatment?

• bacteria (gram variable coccobacilli)

• causes bacterial vaginitis (BV) w/ mycoplasma hominis, prevotella + mobiluncus → pH>4.5; clue cells, dec. WBC, thin/off-white discharge w/ fishy odor

  • anaerobic PID w/ foul odor + BV ass. (after IUD, biopsy, D+C, abortion, PP) → abscess, peritonitis, perihepatitis

• metronidazole (free radicals)

trichomonas vaginalis class? characteristics? symptoms? treatment?

• protozoa (motile trichomonads/trophoczoites on wet mount)

• pH >4.5; many WBC; sometimes +whiff test

• thin, yellow-green, malodorous, frothy discharge, vaginal inflammation, strawberry cervix

• metronidazole (free radicals)

candida albicans class? characteristics? symptoms? treatment?

• fungi (yeast)

• pseudohyphae (KOH prep, wet mount); smooth white, creamy colonies

• thick, cottage cheese, adherent discharge; pH <4.5 (normal)

• -azoles (ergosterol + 14-a-sterol demethylase)

  • inhibit CYP 450 = dec. lanosterol to ergosterol

pthrius pubis, sarcoptes scabei type? characteristics? treatment?

• ectoparasites

• lice (hair) → excoriations at blood feeding site, inguinal LAD

• scabies (hairless) → children common, pruritis w/ papules/linear burrows + excoriations

• permethrin (prolong Na channel open = delayed repolarization → paralytic) OR ivermectin (inc. Cl in) if persistent

HSV pathogenesis? characteristics? symptoms? treatment?

• ds DNA virus w/ cowdry type A intranuclear inclusion +syncytia

• primary infection (fever, malaise, myalgia); painful erythematous vesicles → shallow ulcers w/ LAD; burning/tingling @ eruption, dysuria, vaginal/urethral discharge

  • mucoepithelial cell replication, latency travel retrograde to ganglion (reactivation = vesicular lesions) @ sacral ganglia (HSV2)

• Tx w/ acyclovir or valacyclovir (term. NA chain elongation)

  • AE= AKI or neurotoxicity

beta lactam mechanism? medications? AE?

• transpeptidase/cell wall inhibitor

• penicillin, ceftriaxone

• superinfection (candida) + C. diff. pseudomembranous colitis; hypersensitivity rxn (derm, hemolytic anemia, nephritis)

nitroimidazole mechanism? medications? AE?

• free radicals → DNA synth. inhibitors via strand breakage

• metronidazole

• disulfiram-like rxn (flushing, tachycardia, hypotension)

tetracyclines mechanism? medications? AE?

• 30S RI → inhibits A-site tRNA binding

• doxycycline

• photosensitivity, reduced skeletal growth (tooth discoloration); di/trivalent cations sequester tetracyclines (dec. absorption)

  • avoid in preg. pt.

macrolide mechanism? medications? AE?

• 50S RI + blocks translocation

• azithromycin

• MACRO = motility (GI), arrhythmia, cholestatic hepatitis, rash, eosinophilia

klinefelter karyotype, symptoms, labs, treatments? turner? XYY?

• 47, XXY → tall, gynecomastia, infertility

  • inc. FHS/LH, dec. testosterone, inc. estradiol → Tx w/ testosterone replacement

• 45, X → short/webbed neck, cardiac issues, cystic hygroma

  • dec. estrogen, inc. FSH/LH → Tx w/ estrogen therapy, GH

• 47, XYY → tall, learning delay

  • normal testosterone → Tx w/ supportive care

• risk factor → maternal age (aneuploidy, nondisjunction)

ovotesticular DSD karyotype, symptoms, labs, treatments? aromatase deficiency? kallman syndrome

• 46, XX/XY → ambiguous genitalia, ovotestes

  • variable → Tx w/ individualized gender assignment

• 46, XX/XY → virilization, tall stature, metabolic issues

  • dec. estrogen, inc. androgens → Tx w/ estrogen therapy

• 46, XX/XY → delayed puberty, anosmia

  • dec. GnRH, dec. FSH/LH → Tx w/ pulsatile GnRH therapy

AIS karyotype, symptoms, labs, treatments? 5a-reductase deficiency? precocious puberty?

• 46, XY → female phenotype, absent uterus (pseudo hermaphroditism)

  • normal/inc. testosterone → Tx w/ gonadectomy, hormone therapy

• 46, XY → ambiguous genitalia, virilization @ puberty (pseudo hermaphroditism)

  • normal testosterone, dec. DHT → Tx w/ gender assignment, surgery

• normal → early puberty signs

  • inc. sex steroids → Tx w/ leuprolide-GnRH analogs

preeclampsia/eclampsia treatment? uterine relaxants? labor inducers/ Tx pp hemorrhage?

• hydralazine (inc. cGMP → SMR → VD), methyldopa (a2 agonist → dec. symp → NE), labetalol (a1 + B antagonist → dec. BP), Mg SO4 (prevent seizure, cerebral VD), aspirin (inhibit TXA2) → hypertensive mother love nifedpine

• hydroxyprogesterone (inhibit cytokine + ripening), terbutaline (B2 adrenoreceptor agonist), nifedipine + Mg SO4 (blocks Ca), indomethacin (inhibit COX, CI @ 32 wks)

• dinoprostone/PGE2 + carboprost/PGF2 (cervical ripening, act. collagenase, evacuation), oxytocin (Gq)

teratogens? effects?

• alcohol → FAS (microcephaly)

• Li (bipolar) → ebstein anomaly (cardiac malformation = valve displaced + dec. RV vol/atrialization), NDI, hypothyroidism

• phenytoin (anti seizure) → fetal hydantoin syndrome (cardiac defect, facial malformation, mental retardation, microcephaly, ptosis, digit hypoplasia)

• tetracycline (bacterial infection + acne) → tooth hypoplasia, teeth staining

• valproate/carbamazepine (epilepsy, bipolar, migraine) → CNS defect, lumbosacral spina bifida

• warfarin (prevent blood clots) → nasal hypoplasia, stippled epiphysis