1. Leuprolide
    GnRH analog.
    Pulsitile: agonist (infertility)
    Continuous: antagonist (prostate cancer, fibroids)
    Toxic: antiandrogen, nausea, vomit
  2. Testosterone (methyltestosterone)
    Androgen R Agonist
    Treats hypogonadism
    Toxic: masculinization in females. Dec intratesticular testosterone in males (gonadal atrophy)
    Premature closure of epiphyseal plates
    Inc LDL, dec HDL
  3. Finasteride
    5 alpha reductase inhibitor (dec DHT production)
    Used in BPH or to promote hair growth
  4. Flutamide
    Competitive inhibitor of testosterone receptor. Used in prostate carcinoma
  5. Ketoconazole
    Inhibits steroid synthesis (inhibits desmolase) Used for PCOS to prevent hirsutism due to SE of gynecomastia and amenorrhea
  6. Spironolactone
    Inhibits steroid binding to androgen R. Used for PCOS to prevent hirsutism (gynecomastia and amenorrhea)
  7. Estrogens
    (ethinyl estradiol, DES, mestranol)
    Used for hypogonadism or ovarian failure or HRT?
    Used in men with androgen dependent prostate cancer
    Toxic: inc risk of endometrial cancer. Bleeding in post-menopausal women. DES: clear cell adenocarcinoma of vagina. Inc risk of thrombi.

    Ovary=17beta-estradiol (most potent) 50x inc in preg.
    Placenta=estriol (least potent) 1000x inc in preg.
    Blood= aromatization
    Cytoplasmic receptors translocate to nucleus.

    Development of genitalia and breast + fat distribution
    Follicular growth, endometrial proliferation, inc. myometrail excitability
    Upregulation of estrogen, LH and progesterone receptors
    feedback inhibition of FSH, LH
    Stimulates prolactin secretion (but blocks action at breast)
    Inc transport proteins: SHBG (inc HDL, dec LDL)
  8. Clomiphene
    SERM. Partial agonist of estrogen R in hpothal. Prevents normal feedback inhibition and inc. release of LH and FSH from pituitary to stimulate ovulation.
    Used for infertility and PCOS.
    Toxic: hot flashes, ovary enlargement, multiple pregnancies, vision problems
  9. Tamoxifen
    Antagonist on breast tissue to treat and prevent recurrence of ER psotive breast cancer
  10. Raloxifene
    Agonist of bone, reduces resorption so used for osteoporosis
  11. Anastrozole/Exemestane
    Aromatase inhibitors used in postmenopausal women with breast cancer.
  12. Progestins
    Dec growth and Inc vascularization of endometrium
    Used in oral contraceptives and to treat endometrial cancer and abnormal uterine bleeding

    From Corpus luteum, placenta, adrenal cortex , testes (elevation indicates ovulation)
    Stimulation of endometrial glandular secretions and spiral artery development
    Maintains pregnancy
    Dec myometrial excitability
    Production of thick cervical mucus inhibiting sperm entry into uterus
    Inc body temp
    Inhibition of LH and FSH
    Uterine SM relaxation
    Dec estrogen-R expressivity
  13. Mifepristone
    Progestin competitive inhibitor
    Used to terminate pregnancy with misoprostol (PGE1)
    Toxic: heavy bleeding, GI effects, abdominal pain
  14. Dinoprostone
    PGE2 analog causing cervical dilation and uterine contraction inducing labor
  15. Ritodrine/Terbutaline
    B2 agonists relaxing uterus reducing premature uterine contractions
  16. Tamsulosin
    Alpha 1 blocker for BPH. Specific for alpha 1 A's on prostate (alpha 1 B's on vessels)
  17. Sildenafil, Vardenafil
    cGMP phosphodiesterase inhibitors -> inc cGMP -> SM relaxation in corpus cavernosum -> inc blood flow -> erection.
    Toxic: headache flushing dyspepsia impaired blue green vision. Risk of hypotension with nitrates
  18. Androgens
    Testosterone and DHT (testes), androstenedione (adrenal)
    DHT=most potent
    Androsten.=least potent
    Test -> DHT by 5alpha reductase (inhib by finasteride)
    Converted to estrogen by aromatase in sertoli cells and adipose
    Exogenous testosterone decreases testicular size (HPG axis inhibition)

    Testosterone Functions:
    Deifferentiation of internal genitalia except prostate (epididymis, vas def, seminal vesicles)
    Growth spurt (penis, seminal vesicles, sperm, muscle, RBCs)
    Deep voice, closed epiphyseal plates (estrogen), Libido

    DHT Functions:
    Early: differentiation of penis, scrotum, prostate
    Late: prostate growth, balding, sebaceous gland activity
  19. Kleinfelters
    XXY tesitcular atrophy, eunichoid body, tall, long extremities, gynecomastia, female hair distribution, Barr body, hypogonadism.
    Dysgenesis of seminiferous tubules (dec. inhibin and testosterone, inc FSH and LH so inc. estrogen)
  20. Turner's
    XO short stature, ovarian dysgenesis (streak ovary so infertile), shield chest, bicuspid aortic valve, webbed neck (cystic hygroma), preductal coarctation of aorta. Most common cause of primary amenorrhea. Dec estrogen so inc. FSH and LH.
  21. Double Y Males (XYY)
    Normal phenotype, Tall, severe acne, antisocial in 1%. Normal fertility
  22. Female Pseudohermaphrodite
    XX. Ovaries present but virilized external genitalia. Due to CAH or exogenous androgens taken during pregnancy.
  23. Male pseudohermaphrodite
    Testes present but ambiguous or female external genitalia. AIS most common (aka testicular feminization)
  24. True Hermaphrodite
    Both ovaries and testes are present (ovatestis)
  25. AIS
    46 XY. Normal appearing female. Androgen receptor mutation. Female external genitalia has rudimentary vagina, uterus and uterine tubes absent. No pubic hair, abdominal testis or in labia majora (removed to prevent malignancy). Increased testosterone, estrogen, LH
  26. 5 alpha reductase deficiency
    AR. Only in XY. Can't convert testosterone to DHT so ambiguous genitalia until normalizes as male at puberty. Guevadoces. Normal hormones and internal genitalia
  27. Kallman syndrome
    Decrease syn of gonadotropin in anterior pituitary. Anosmia, lack of secondary sex characteristics.
  28. Complete mole
    46 XX or XY. Very large inc in hCG. Slight increase in uterine size. 2% convert to choriocarcinoma. Snowstorm appearance. No fetal parts. 2 sperm and empty egg. 15-20% malignant trophoblastic disease.
  29. Partial Mole
    69 XXY, slight increase in hCG, doesn't convert to choriocarcinoma, partial fetal parts, 2 sperm + 1 egg. Low risk of malignancy.
  30. Preeclampsia
    HTN, proteinuria, and edema. Eclampsia includes seizures. 7% of pregnant women from 20 weeks to 6 weeks postpartum.
    Risk: HTN, diabetes, chronic renal disease, autoimmune disorders
    Placental ischemia due to impairment of vasodilation of spiral arteries
    HELLP Syndrome: hemolysis, elevated LFTs, low platelets.
    Mortality due to cerebral hemorrhage and ARDS
    Headache, blurred vision, abdominal pain, edema of face and extremities.
    Treat: IV magnesium sulfatea nd diazepam (prevent and treat seizures)
  31. Abruptio placentae
    Placenta detaches from site of implantation. Fetal death. Associated with DIC
    Risk: smoking, HTN, cocaine
    Painful bleeding in 3rd trimester
  32. Placenta accreta
    Placenta attaches to myometrium. No separation of placenta after birth
    Risk: prior C-section, inflammation, and placenta previa.
    Massive bleeding after delivery
  33. Placenta previa
    Implants low in uterus. May occlude internal os
    Risk: multiparity and prior C section
    Painless bleeding in any trimester
  34. Ectopic pregnancy
    Mostly in fallopian tubes. Suspect with high hCG and sudden lower abdominal pain. Check on US. Don't confuse with appendicitis.
  35. Retained placental tissue
    may cause postpartum hemorrhage.
  36. Polyhydramnios
    >1.5L of amniotic fluid.
    Esophageal/duodenal atresia so can't swallow amniotic fluid. Anencephaly
  37. oligohydramnios
    <0.5L of amniotic fluid assoicated with placental insufficiency. bilateral renal agenesis or posterior urethral valves in males (can't excrete urine). Can give rise to potter's syndrome
  38. Cervical CIS
    HPV 16,18
    Vaccine available
    May progress to invasive carcinoma if untreated
    Risk: multiple sexual partners, smoking, early sexual intercourse, HIV infection
  39. Invasive carcinoma
    Squamous cell. Pap smear can catch dysplasia (koilocytes) before progresses to invasive carcinoma. Lateral invasion can block ureters causing renal failure.
  40. Endometriosis
    Not neoplastic. Endometrial glands/stroma outside uterus. Cyclic bleeding leads to blood filled chocolate cysts. In ovary and peritoneum. Severe menstrual related pain. Infertility. Retrograde menstrual flow or ascending infection.
  41. Adenomyosis
    Endometrium within myometrium
  42. Endrometrial hyperplasia
    Excess estrogen stimulation. Increases risk of endometrial carcinoma. Postmenopausal vaginial bleeding.
    Risk: anovulatory cycles, HRT, PCOS, granulosa cell tumor
  43. Endometrial carinoma
    Most common gynecologic malignancy. Average age 60. Vaginal bleeding, Preceeded by hyperplasia.
    Risk: prolonged estrogen w/o progestins, obesity, diabetes, HTN, nulliparity, late menopause
    myometrial invasion gives worse prognosis
  44. Leiomyoma
    Fibroids. Myometrial tumor. Most common of all tumors in females!! Often multiple tumors, well demarcated, increase in blacks, benign SM tumor, rarely malignant
    Estrogen sensitive so increase size in pregnancy and dec. size with menopause
    Peaks in 20-40yo range.
    Asymptomatic or if symptoms, multiple
    Severe bleeding may lead to iron deficiency
    Does NOT progress to leiomyosarcoma
    Whorled pattern of SM bundles.
  45. Leiomyosarcoma
    Bulky, irregularly shaped tumor with areas of necrosis and hemorrhage (de novo).
    Inc. in blacks, aggressive tumor, recurs
    May protrude from cervix and bleed. Commonly in middle aged women
  46. Premature ovarian failure
    Menopause before age 40. (Dec. estrogen, Inc FSH and LH)
  47. Polycystic ovarian syndrome
    Inc. LH production causes anovulation, hyperandrogenism (theca cells).
    Amenorrhea, infertility, obesity, and hirsutism all from bilateral and enlarged ovaries filled with cysts.
    Insulin resistanct, inc. risk of endometrial cancer,
    Treat: weight loss, OCP, gonadotropin analogs, clomiphene, spironolactone to treat hirsutism or surgery
  48. Ovarian cysts
    Follicular: unruptured graafian follicle
    Corpus luteum: hemorrhage into persistent corpus luteum, regresses spontaneously
    Theca-lutein: bilateral, multiple (choriocarcinoma and moles)
    Chocolate cysts: blood cysts from endometriosis (menstrual cycle).
  49. Dysgerminoma
    Ovarian germ cell tumor. malignant, like male seminoma (rarer). Sheets of uniform cells.
    hCG and LDH
  50. Choriocarcinoma
    Rare and malignant. Develops during pregnancy in mother or baby. Large hyperchromatic syncytiotrophoblastic cells (hCG), increased frequency of theca-lutein cysts. Along with moles, "gestational trophoblastic neoplasia"
  51. Yolk Sac
    Endodermal sinus tumor. Aggressive and in ovaries or testes and sacrococcygeal area of young children. Yellow, friable solid masses
    Schiller-Duval bodies that resemble glomeruli!
  52. Teratoma
    90% of ovarian germ cell tumors. 2 or 3 germ layers. Teeth and hair.
    Mature: dermoid cyst, most frequent benign ovarian tumor
    Immature: aggressively malignant
    Struma ovarii: contains functional thyroid tissue (hyperthyroidism)
  53. Serous Cystadenoma
    Ovarian non-germ cell tumor (20% of ovarian tumors). Bilateral, lined with fallopian tube-like epithelium, benign.
  54. Serous cystadenocarcinoma
    50% of ovarian tumors, malignant and frequently bilateral
  55. Mucinous cystadenoma
    Multilocular cyst lined by mucus secreting epithelium. Benign, intestine like tissue.
  56. Mucinous cystadenocarcinoma
    Malignant, pseudomyxoma peritonei. Intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor
  57. Brenner tumor
    Benign, bladder-like
  58. Fibromas
    Bundle of fibroblasts
    Meig's syndrome: triad of ovarian fibroma, ascites, hydrothorax.
    Pulling sensation in groin.
  59. Granulosa cell tumor
    Secretes estrogen leading to precocious puberty. Leads to endometrial hyperplasia or carcinoma in adults.
    Call-Exner bodies: follicles filled with eosinophilic secretions. Abnormal uterine bleeding
  60. Krukenberg tumor
    GI malignancy mets to ovary.
    Mucin secreting signet cell adenocarcinoma
  61. Vaginal SCC
    Usually secondary to cervical SCC
  62. Vaginal clear cell adenocarcinoma
    Mother took DES while pregnant
  63. Sarcoma botryoides
    Rhabdomyosarcoma variant. Vaginal tumor of girls < 4 yo with spindle shaped cells that are dermin positive (grapelike clusters)
  64. Fibroadenoma of breast
    Small, mobile, firm, sharp edges
    Most common tumor < 25 yo
    Estrogen sensitive
    Not a precursor to breast cancer
  65. Intraductal papilloma of breast
    Grows in lactiferous ducts beneath areola
    Nipple discharge (maybe bloody).
    Slight risk for carcinoma
  66. Phyllodes Tumor
    Large bulky mass of CT. "leaf-like" projections
    Mostly in 50s
    May become malignant
  67. Ductal carcinoma in situ (DCIS) of breast
    Fills ductal lumen and arises from ductal hyperplasia
    Early malignancy without basement membrane penetration
  68. Invasive ductal carcinoma of breast
    Firm, fibrous, hard mass with sharp margins
    Worst and most invasive and most common (76%)
  69. Invasive lobular
    Orderly row of cells thats often multiple and bilateral
  70. Medullary breast cancer
    Fleshy cellular lymphocytic infiltrates with a good prognosis
  71. Comedocarcinoma of breast
    Ductal with caseous necrosis (subtype of DCIS)
  72. Inflammatory breast malignancy
    Lymphatic invasion and block drainage
    Peau d'orange: breast skin resembles orange peel.
    50% 5 years survival
  73. Pagets disease of breast
    Eczematous patches on nipple. Paget cells are large cells in epidermis w/ clear halo and suggests underlying carcinoma (ductal)
  74. Fibrocystic disease of breast
    Most common cause of breast lumps 25 < age < menopause
    Premenstrual pain, multiple and bilateral
    Fluctuation in size, no increased risk of carcinoma
    1. fibrosis: hyperplasia of stroma
    2. cystic = blue dome. fluid filled
    3. sclerosing adenosis: calcifications
    4. epithelial hyperplasia: inc number of epithelial cell layers in terminal duct lobule. (inc risk of carcinoma)

  75. Acute mastitis
    Breast abscess during breast feeding. S. Aureus
  76. Fat necrosis
    benign painless lump due to trauma
  77. Gynecomastia
    Hyperestrogenism. Kleinfelters or drugs:
    Spironolactone, Digitalis, Cimetidine, Alcohol, Ketoconozole. (Some drugs create awesome knockers)
  78. Prostatitis
    Dysuria, frequency, lower back pain
    Acute: e coli
    Chronic: more common
  79. BPH
    Hyperplasia, >50yo. Sensitized to DHT. Specifically periurethral (lateral and middle) lobes compress urethra.
    Risk of distention of bladder, hydronephrosis and UTI.
    Inc PSA
    Treat: alpha 1 block or finasteride
  80. Prostate adenocarcinoma
    >50yo. Mostly from posterior lobe in peripheral zone.
    Diagnosed w/ DRE + biopsy, PSA, alk phos
    Bone mets in late stages
  81. Cryptochidism
    Undescneded testis due to lack of spermatogenesis due to inc body temp associated with inc risk of germ cell tumors.
  82. Seminoma
    Malignant, painless, homogenous testicular enlargement. Most common testicular tumor.
    Mostly 15-35 yo.
    Watery cytoplasm and fried egg appearance.
    Excellent prognosis
  83. Embryonal Carcinoma of Testis
    Malignant, painful, bad prognosis. Glandular and papillary morphology. Differentiates to other tumors. Inc AFP, hCG
  84. Yolk sac Testicular Tumor
    Endodermal sinus tumor. Yellow, mucinous. Schiller duval bodies resemble glomeruli (inc AFP)
  85. Choriocarcinoma of testes
    Malignancy with inc. hCG. Disordered syncytio and cytotrophoblasts. Hematogenous mets
  86. Teratoma of testis
    Mature teratoma is most often malignant (opposite in females)
  87. Leydig cell tumor
    Reinke crystals. Androgen producing, gynecomastia, precocious puberty. Gold
  88. Sertoli cell tumor
    Androblastoma from sex cord stroma
  89. Testicular lymphoma
    Most common testicular cancer in older men
  90. Varicocele
    Transilluminates, bag of worms. dilated vein in pampiniform plexus
  91. Hydrocele
    inc fluid due to incomplete fusion of processus vaginalis
  92. Speratocele
    Dilated epididymal duct
  93. Bowen's disease
    Gray crusty plaque on shaft of penis or scrotum. 40s. 10% become SCC
  94. Erythroplasia of Queyrat
    Red velvet plaques on glans
  95. Bowenoid papulosis
    Younger age, multiple papular lesions, non-invasive
  96. Penile SCC
    Asia, Africa and S. America.
    HPV and lack of circumcision
  97. Peyronie's Disease
    Bent penis due to acquired fibrous tissue formation
  98. Menopause
    Dec estrogen production due to decline in ovarian follicles as age (avg=51yo). (earlier in smokers)
    Usually preceded by 4-5 years of abnormal menstrual cycles
    Post: estrogen = estrone (peripheral conversion of androgens and weaker)
    Inc. androgens cause hirsutism
    Inc FSH is best way to confirm menopause (loss of negative feedback from estrogen)
    Slightly inc. LH
    (HHAVOC: hirsutism, hot flashes, atrophy of vagina, osteoporosis, coronary artery disease)
    Early menopause may = premature ovarian failure
  99. Ovulation
    Inc. estrogen, inc. GnRH-R on anterior pituitary
    Estrogen surge -> LH release -> ovulation (rupture of follicle)
    Progesterone -> inc temp
    Mittelshmerz = blood from ruptured follicle causes peritoneal irritation (appendicitis-like)
  100. Erythrocyte
    Anucleate, biconcave (surface area-gas exchange)
    Energy: glucose 90% anaerobic degraded to lactate
    Cl-bicarb antiport.
    Physiologic chloride shift: RBC transports CO2 from periphery to lungs
    Live 120 days
    Erythrocytosis = polycythemia
    Anisocytosis = varying sizes
    Poikilocytosis = varying shapes
    Reticulocyte = immature erythrocyte
  101. Platelet
    Thrombocyte, Small fragment from megakaryocytes. primary hemostasis. Aggregate and form hemostatic plug.
    Dense granules: ADP, Ca
    Alpha granules: vWF, fibrinogen
    1/3 in spleen
    Live 8-10 days
    Thrombocytopenia = petechiae
  102. Leukocyte
    Granulocytes: basophils, eosinophils, neutrophils
    Mononuclear cells: monocytes and lymphocytes
    Defend against infections (4-10,000/uL)
  103. Neutrophil
    Acute inflam. response
    40-75% of wbc's
    Phagocytic, multilobed nucleus, large spherical azurophilic granules (lysosomes). Contain hydrolytic enzymes lysozyme, MPO, and lactoferrin.
    Hypersegmented PMNs = B12 or folate deficient
  104. Monocyte
    2-10% of leukocytes. Large, Kidney-shaped nucleus. Fxlensive "frosted glass" cytoplasm. Differentiates into macrophages in tissues.
  105. Macrophage
    Phagocytoses bacteria, cell debris, and senescent red cells and scavenges dainaged cells and tissues. Long life in tissues. Macrophages differentiate from circulating blood monocytes (monocytes in blood, macrophages in tissue) Activated by gamma-interferon. Can function as Ag-presenling cell (APC) via MHC II.
  106. Eosinophil
    1-6% of all leukocytes. Bilobate nucleus. Packed wilh large eosinophilic granules of uniform size. Defends against helminthic infections (major basic protein). Highly phagocytic for Ag-Ab complexes.
    Produces histaminase and arylsulfatase (helps limit rxn post mast cell degranulation)
    (NAACP cause eosinophilia: neoplasia, asthma, allergic rxn, collagen vascular disease, parasites)
  107. Basophil
    Mediates allergic reaction. < 1% of all leukocytes. Bilobe nucleus. Densely basophilic granules containing heparin (anticoagulant), histamine (vasodilator) and other vasoactive amines, and leukotricncs (LTD-4). Found in the blood.
    Stains w/ basic stains
  108. Mast Cell
    Mediates allergic reaction. Degranulation — histamine, heparin, and eosinophil chemotactic factors. Can bind Fc portion of IgE lo membrane. Mast cells resemble basophils structurally and functionally but are not the same cell type. Found in tissue.
    Type 1 hypersensitivity rxns.
    Cromolyn sodium prvents degranulation (asthma)
  109. Dendritic Cell
    Professional APCs. MHC2 and FcR on surface.
    Induce primary antibody response
    Skin=langerhans cells
  110. Lymphocyte
    Round, densely staining nucleus. Small amount of pale cytoplasm, B lymphocytes produce antibodies. T lymphocytes manifest the cellular immune response as well as regulate B lymphocytes and macrophages.
  111. B Lymphocyte
    Part of humoral immune response. Arises from stem cells in bone marrow. Matures in"B"one marrow. Migrates to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue). When antigen is encountered, B cells differentiate into plasma cells and produce antibodies. Has memory.
    Can function as an APC via MHC II,
  112. Plasma Cell
    Off-center nucleus, clock-face chromatin distribution, abundant RER and well-developed Golgi apparatus, B cells differentiate into plasma cells, which produce large amounts of Ab specific to a particular antigen.
  113. T Lymphocyte
    Mediates cellular iminune response. Originales from stem cells in the bone marrow, but matures in the thymus.
    T cells differenliale inlo cytotoxic T cells (MHC I, CD8), helper T cells (MHC II, CD4), and suppressor T cells. The majority of circulating lymphocytes are T cells (80%).
  114. Erythroblastosis fetalis
    Subsequent fetus taht is Rh+ to an Rh- mother already giving birth to a fetus that was Rh+.
    Mother makes Ab against Rh during first pregnancy and they cross placenta during next causing hemolytic disease of newborn
    Treat: rhogam (Rh Ag Ig at first delivery)

    IgM does NOT cross placenta
    IgG does (anti-Rh)
  115. Bernard Soulier syndrome
    Deficient in Gp1b (platelet to collagen adhesion) Dec. Platelets, Inc Bleeding Time.
  116. Glanzmann's Thrombasthenia
    Deficiency in Gp2b3a (defect in platelet to platelet aggregation thru fibrinogen). No platelet clumping. Inc bleeding time
  117. Acanthocyte
    Spur Cell: liver disease, abetalipoproteinemia
  118. Basophilic Stippling
    Thalassemias, Anemia of chronic disease, iron deficiency, lead poisoning

  119. Bite cell
    G6PD deficiency
  120. Elliptocyte
    Hereditary elliptocytosis
  121. Macro-ovalocyte
    Megaloblastic anemia. Also hypersegmented PMNs, marrow failure
  122. Ringed sideroblasts
    Sideroblastic anemia
  123. Schistocyte
    Helmet cell: DIC, TTP/HUS, traumatic hemolysis
  124. Sickle cell
    Sickle cell anemia
  125. Spherocyte
    Hereditary spherocytosis, autoimmune hemolysis
  126. Teardrop cell
    Bone marrow infiltration (myelofibrosis)
  127. Target cell
    HbC disease, asplenia, liver disease, thalassemia
  128. Heinz bodies
    Oxidation of iron from ferrous iron to ferric, denatured Hb precipitation and damage to RBC membrane. Leads to formation of bite cells
    (Alpha thal, G6PD deficiency)
  129. Howell-Jolly bodies
    Basophilic nuclear remnants in RBCs
    (Functional hyposplenia or asplenia)
  130. Iron deficiency
    Microcytic, hypochromic (MCV<80) anemia.
    Dec iron due to chronic bleeding, malnutritrition/absorption disorders or inc demand (e.g., pregnancy) -> dec. heme synthesis (see Image 22).
    May manifest as Plummer-Vinson syndrome (triad of iron deficiency anemia, esophageal web, and atrophic glossitis).
  131. Alpha Thalassemia
    Microcytic, hypochromic anemia

    Prevalent in Asia and Africa.
    Defect: a-globin gene mutations -» a-globin synthesis. Deletion of 4 genes is incompatible with life —> Hb Barts (gamma4), which causes
    hydrops fetalis. Deletion of 3 genes —> HbH disease (beta 4)
    1-2 genes not associated with significant anemia

    Deletion of 1-2 genes is not associated wilh anemia.
  132. Beta Thal
    Prevalent in Mediterranean populalions.
    Problems: point mutations in splice sites and promoter sequences.

    Beta thalassemia minor (heterzygote);
    1. Beta chain is underproduced. 2. Usually asymplomatic. 3. Diagnosis confirmed by inc HbA,

    B-thalassemia major (homozygote): 1. P chain is absent —> severe anemia recurring blood

    Betal thal minor transfusion
    (2. hemochmatosis), 2. Marrow expansion ("crew cut" on skull x-ray) -»skeletal deformilies.
    Chipmunk faeies, Both major and minor) T HbF (a.yj. HbS/P-thalassemia heterozygole: mild to moderate sickle cell disease
    depending on amounl of B-glnbin production
  133. Lead poisoning
    Lead inhibits ferrochelalase and ALA dehydratase —> dec heme synthesis. Also inhibits rRNA degradation —> basophilic stippling (aggregation of ribosomes)
    Accumulation of protoporphyrin in blood
    Present with microcytic anemia, GI and kidney disease
    Kids (lead paint -> mental deterioration)
    Adults (environment -> headache, memory loss, demyelination)

    (LEAD: Lead lines on gingivae = burton's lines...and on epiphyses of long bones. Encephalopathy and Erythrocyte basophilic stippling, Abdominal colic and sideroblastic anemia, Drops wrist and foot, Dimercaprol and EDTA are treatments or Succimer for kids)
  134. Sideroblastic anemia
    Defect in heme bone syn.
    Hereditan: X-linked defeel in S-aminolevulinic acid synthase gene. Treatment; pyridoxine (B6) therapy. Reversible etiologies: alcohol, lead, t iron, normal TIBC, T ferritin. Ringed sideroblasls (wilh iron-laden milochondrial.)
  135. Microcytic Hypochromic Anemias (MCV < 80)
    Beta Thal.
    Alpha Thal.
    Iron deficiency
    Lead poisoning
    Sideroblastic anemia

  136. Macrocytic anemia (MCV > 100)
    Megaloblastic anemia (folate + B12 deficiency)

    Nonmegaloblastic anemia:
    1. Liver diseased
    2. Alcoholism: bone marrow suppression
    3. Reticulocytosis: larger than mature RBCs
    4. Metabolic disorder: orotic aciduria (purine + pyrimidine synthesis)
    5. Drugs (5FU, AZT, hydroxyurea)
  137. Folate deficiency
    Findings: hypersegmented neutrophils, glossitis, dec. folale, Inc homocysteine but normal methylmalonic,
    Etiologies: malnutrition (e.g., alcoholics) malabsorption, impaired metabolism (e.g.. methotrexate, trimethoprim), Inc requirement (e.g., hemolylic anemia, pregnancy).
  138. B12 Deficiency
    Findings: hypersegmented neutrophils, glossilis, dec. B12, Inc homocysleine, Inc methylmalonic acid.
    Etiologies: malnutrition (e.g., alcoholics), malabsorption (e.g., Crohn's disease). pernicious anemia, Diphyllobothrium latum (fish tapeworm).
    Neurologic symptoms: subacute combined degeneration (due to involvement of B12 in fatty acid pathways).
    1. Peripheral neuropathy with sensorimotor dysfuction
    2. Posterior columns lost
    3. Lateral corticospinal loss (spasticity)
    4. Dementia
  139. Normocytic Normochromic Anemia
    Nonhemolytic: Anemia of chronic disease (ACD), aplastic anemia, kidney disease.

    Intravascular Hemolysis: Paroxysmal noctumal hemoglobinuria, auloimmune (cold agglutinins), mechanical
    destruction (eg., aortic stenosis, prosthetic valve), G6PD deficiency.
    Findings: Dec. haptoglobin, inc. LDH

    Extravascular Hemolysis: Hereditary spherocytosis, pyruvale kinase deficiency, sickle cell
    anemia, HbC defect, autoimmune (warm agglutinins), microangiopathic (eg. DIC, TTP-HUS).
    Findings: macrophage in spleed clears RBCs. Inc LDH and Inc UCB (jaundice).
  140. Anemia of Chronic Disease
    Nonhemolytic, normocytic anemia
    Inflammation -> Inc hepcidin —> Inc release of iron from macrophages
    Inc iron, Dec TIBC, Inc ferritin.
    Can become microcytic, hypochromic in long-standing disease.
  141. Aplastic Anemia
    Nonhemolytic Normocytic anemia
    Pathologic features: pancytopenia characterized by severe anemia, neutropenia, and thrombocytopenia. Normal cell morphology, but hypocellular bone marrow with fatty

    Causes: failure or destruction of myeloid stein cells due to:
    1. Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
    2. Viral agents (parvovirus B19, EBV, HIV)
    3. Fanconi's anemia (inherited defect in DNA repair)
    4. Idiopathic (immune mediated. 1° stem cell defect); may follow acute hepatitis

    Symptoms: fatigue, malaise, pallor, purpura, mucosal bleeding, pelechiae. infection.
    Treatment: witlidrawal of offending agent, immunosuppressive regimens (antithymocyte
    globulin, cyclosporine), allogeneic bone marrow transplantation, RBC and platelet
    transfusion, G-CSF or GM-CSF.
  142. Kidney Disease
    Nonhemolytic normocytic anemia
    Dec EPO -> Dec Hematopoiesis
  143. Hereditary Spherocytosis
    Intrinsic hemolytic normocytic anemia-Extravascular

    Defect in proteins interacting with RBC membrane skeleton and plasma membrane (eg ankyrin, band 4.1, or spectrin).

    Pathogenesis: less membrane causes small and round RBCs with no central pallor (Inc MCHC, Inc RDW) -> premature removal of RBGs by spleen.

    Findings: splenomegaly, aplastic crisis (B19 infection). Howell-Jolly bodies present after splenectomy.
    Labs: positive osmotic fragility test.
  144. G6PD Deficiency
    Intrinsic hemolytic normocytic anemia-Intravascular
    X-linked. Defect in G6PD —> dec glutathione -> inc RBC susceptibility to oxidant stress. (eg: sulfa drugs, infections, fava beans)
    Symptoms: back pain, hemoglobinuria a couple days later
    Labs: blood smear shows RBCs with Heinz bodies and bite cells
  145. Pyruvate kinase deficiency
    Intrinsic hemolytic normocytic anemia- extravascular.
    Autosomal recessive, defect in pyruvate kinase -> dec. ATP -> rigid RBCs
    Presentation: hemolytic anemia in newborn
  146. Sickle Cell Anemia
    Intrinsic hemolytic normocytic anemia- extravascular

    8% of African-Americans carry the HbS trait; 0.2% have the disease. Sickled cells are crescent-shaped RBCs. "Crew cut" on skull x-ray due to marrow expansion from Inc EPO (also in thalassemias)
    Newborns are initially asymptomatic owing to inc HbF and dec HbS.
    Mulation: HbS mulalion is a single amino acid replacement in P chain (substitution of normal glutamic acid with valine).
    Pathogenesis: deoxygenated HbS polymerizes. Low O2 or dehydration precipitates sickling. Heterozygotes (sickle cell trait) have resistance to malaria, Complicalions in homozygotes (sickle cell disease)
    1. Aplastic crisis (due to parvovirus B19)
    2. Autosplenectomy —» T risk of infection with encapsulated organisms
    3. Salmonella osteomyelitis
    4. Painful crisis (vaso-occlusive)
    5. Renal papillary necrosis (clue to low O2 in papilla)
    6. Splenic sequestration crisis

    Treatment: hydroxyurea (Inc HbF) and bone marrow transplant
  147. HbC defect
    Intrinsic hemolytic normocytic anemia
    Glutamic acid to lysine mutation
    Pts. with HbSC (1 of each mutant) have milder disease than HbSS
  148. Paroxysmal Nocturnal Hemoglobinuria
    Intrinsic hemolytic normocytic anemia- Intravascular

    Decay accelerating factor inhibits complement on RBC membrane
    Impaired synthesis of GPI anchor, decay accelerating factor and all GPI linked proteins in the RBC membrane
    Labs: inc urine hemosiderin
  149. Autoimmune hemolytic anemia
    Extrinsic hemolytic normocytic anemia
    Warm agglutinin (IgG)—chronic anemia seen in SLE, in CLL, or with certain drugs (alpha methyldopa)
    (Warm = GGGreat)
    Cold aggluliuin (IgM)—acute anemia triggered by cold; seen wilh Mycoplasma pneumoniae infections or infectious mononucleosis.
    (Cold = MMM)

    Erythroblastosis fetalis—seen in newborns due to Rh or other blood antigen incompatibility —> mother's antibodies attack fetal RBCs.
    Autoinmiune hemolytic anemias are usually Coombs positive:

    •Direct Coombs' test —auto-Ig antibody added to patient's RBCs agglutinate if RBGs are coated with Ig.
    • Indirect Coombs' test—normal RBCs added to patient's serum agglutinate if serum has anti-RBC surface Ig.
  150. Microangiopathic Anemia
    Extrinsic Hemolytic Normocytic Anemia.
    Pathogenesis: RBCs are damaged when passing through obstructed or narrowed vessel lumina. Seen in DIC, TTP-HUS, SLE, and malignant hypertension.
    Schistocytes (helmet cells) are seen on blood smear due to mechanical destruction of RBCs

  151. Infectious cause of anemia
    Extrinsic hemolytic normocytic anemia
    Inc destructions of RBCs (malaria, babesia)
  152. Macroangiopathic anemia
    Extrinsic Hemolytic Normocytic Anemia
    Prosthetic heart valves and aortic stenosis may also cause hemolytic anemia 2° to mechanical destruction.
  153. Acute intermittent porphyria
    Porphobiligen deaminase (uropophyrinogen-I-synthase) affected. Accumulate porphobilinogen, delta-ALA, uroporphyrin.
    Symptoms: painful abdomen, red urine, polyneuropathy, psych disturbances, drug use precipitates.
    Treat: Glucose and heme (block ALA synthesis)
  154. Pophyria cutanea tarda
    Uroporphyrinogen decarboxylase affected so build up uroporphyrin (tea colored urine)
    Blistering cutaneous photosensititivity
    most common porphyria
  155. Hemophilia A or B
    Inc. PTT. intrinsic pathway coagulation defect.
    A: deficiency of factor 8
    B deficiency of factor 9
    Macrohemorrhage in hemophilia (hemarthroses: bleed into joints)
    Easy bruising
  156. Vitamin K deficiency
    Inc PT and PTT
    General coagulation defect with dec. syn of factors 2,7,9,10, protein C and S
  157. ITP
    idiopathic thrombocytopenic purpura.
    Dec platelets, inc bleeding time
    Dec. platelet survival. Anti-Gp2b3a Ab destroys peripheral platelets
    Inc megakaryocytes
  158. TTP
    Thrombotic thrombocytopenia purpura. Dec. platelets, inc bleeding time. Dec. platelet survival
    Deficiency of ADAMTS 13 (vWF metalloprotease) so decreased degradation of vWF multimers
    Inc number of large multimers leads to inc platelet aggregation and thrombosis
    Schistocytes, inc LDH
    Pentad: Neuro, renal, fever, thrombocytopenia, microangiopathic hemolytic anemia
  159. von Willebrand's Disease
    Intrinsic pathway coagulation delect: dec vWF leads to normal or inc PTT (depends on severity; vWF acts to carry/protect factor VIII).
    Defect in platelet plug formation: dec vWF -> defect in platelet-to-collagen adhesion.
    Mild but most common inherited bleeding disorder (AD).
    Treat: DDAVP (desmopresin) releases vWF stored in endothelium
  160. DIC
    Dec. platelets, Inc bleeding time, PT, PTT
    Widespread aclivation ofclotting leads to a deficiency in clotting factors, which creates a bleeding state.
    Causes: Sepsis (gram-negative). Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome. Transfusion (STOP Making New Thrombi).
    Labs: schistocytes, inc fibrin split producls (D-dimers), dec fibrinogen, dec factors V and VIII.
  161. Factor V Leiden
    Production of mutant factor V that cant be degraded by protein C, most common cause of inherited hypercoagulability
  162. Prothrombin gene mutation
    Mutation in 3' untranslated region associated with venous clots
  163. ATIII deficiency
    Inherited deficiency of AT
    Reduced inc in PTT after heparin
  164. Protein C or S deficiency
    Dec ability to inactivated factors 5 and 8
    Inc risk of thrombotic skin necrosis with hemorrhage following administration of warfarin
  165. Hodgkin's Lymphoma
    Presence of Reed-Sternberg cells
    Localized, single group of nodes; extranodal rare;
    contiguous spread (stage is strongest predictor
    of prognosis)
    Constitutional ("B") signs/symptoms—low-grade
    fever, night sweats, weight loss
    Mediastinal lymphadenopathy
    50% of cases associated with EBV; bimodal distribution
    —young and old; more common in men except for
    nodular sclerosing type
    Good prognosis = inc lymphocytes, dec RS cells (binucleate bilobed owl eyes: CD30+, 15+ B cell in origen)

    Nodular sclerosing (65-75%):Excellent prognosis, collagen banding. Primarily young adults
    Mixed cellularity (25%): RS cells!! Intermediate prognosis
    Lympliocyte predominant (6%) Excellent prognosis
    Lymphocyte depleted (rare): Poor disease process (in older men w/ disseminated disease)
  166. Presence of Reed-Sternberg cells
    Localized, single group of nodes; extranodal rare;
    contiguous spread (stage is strongest predictor
    of prognosis)
    Constitutional ("B") signs/symptoms—low-grade
    fever, night sweats, weight loss
    Mediastinal lymphadenopathy
    50% of cases associated with EBV; bimodal distribution
    —young and old; more common in men except for
    nodular sclerosing type
    Good prognosis = inc lymphocytes, dec RS cells (binucleate bilobed owl eyes: CD30+, 15+ B cell in origen)

    Nodular sclerosing (65-75%):Excellent prognosis, collagen banding. Primarily young adults
    Mixed cellularity (25%): RS cells!! Intermediate prognosis
    Lympliocyte predominant (6%) Excellent prognosis
    Lymphocyte depleted (rare): Poor disease process (in older men w/ disseminated disease)
    Hodgkin's Lymphoma
  167. Burkitt Lymphoma
    Adolescents or young adults. t(8;14), cmyc gene moves to next heavy chain Ig. Starry sky appearance (lymphocytes w/ interspersed macrophages). Associated with EBV. Jaw lesion in endemic form in Africa, pelvis or abdomen in sporadic form
  168. Adolescents or young adults. t(8;14), cmyc gene moves to next heavy chain Ig. Starry sky appearance (lymphocytes w/ interspersed macrophages). Associated with EBV. Jaw lesion in endemic form in Africa, pelvis or abdomen in sporadic form
    Burkitt Lymphoma
  169. Diffuse large B cell lymphoma
    Usually older adults (20% in kids). Most common adult NHL (mature T cell in origin
  170. Usually older adults (20% in kids). Most common adult NHL (mature T cell in origin
    Diffuse large B cell lymphoma
  171. Mantle cell lymphoma
    Older males t(11;14). Poor progosis, CD5+
  172. Older males t(11;14). Poor progosis, CD5+
    Mantle cell lymphoma
  173. Follicular lymphoma
    Adults, t(14;18) bcl2 expression. Difficult to cure, indolent course. bcl2 inhibits apoptosis
  174. Adults, t(14;18) bcl2 expression. Difficult to cure, indolent course. bcl2 inhibits apoptosis
    Follicular lymphoma
  175. Adults T cell lymphoma
    Adults, HTLV1. Adults present with cutaneous lesions especially affects population in japan, west africa, carribean aggressive
  176. Adults, HTLV1. Adults present with cutaneous lesions especially affects population in japan, west africa, carribean aggressive
    Adults T cell lymphoma
  177. Myscosis fungiodis:
    aka: sezary syndrome. Adults, Adults prevent w. cortaneous patches / nodules. Indolent CD4+
  178. aka: sezary syndrome. Adults, Adults prevent w. cortaneous patches / nodules. Indolent CD4+
    Myscosis fungiodis:
  179. Multiple Myeloma
    Monoclonal plasma cell ("fried-egg" appearance) cancer that arises in the marrow and produces large amounts of IgG (55%) or IgA (25%), Most common 1° lumor arising within bone in the elderly (> 40 - 50 years of age).
    Inc suscptibility to infect
    Primary amyloidosis
    Punched out lytic bone lesion on tuesday
    M spike on protein electrophoresis
    Ig light chains in urine (bence jones)
    reuleaux formatoin RBCs stacked like powder chipes in blood sugar.
    Disting from waldenstroms macrow
    RBCs stacked like poker chips in blood smear
    Distinguish from waldenstomr
  180. Monoclonal plasma cell ("fried-egg" appearance) cancer that arises in the marrow and produces large amounts of IgG (55%) or IgA (25%), Most common 1° lumor arising within bone in the elderly (> 40 - 50 years of age).
    Inc suscptibility to infect
    Primary amyloidosis
    Punched out lytic bone lesion on tuesday
    M spike on protein electrophoresis
    Ig light chains in urine (bence jones)
    reuleaux formatoin RBCs stacked like powder chipes in blood sugar.
    Disting from waldenstroms macrow
    RBCs stacked like poker chips in blood smear
    Distinguish from waldenstomr
    Multiple Myeloma
  181. MGUS
    Monoclonal 4 bayby ur so smart
    Monoclonal grammophathy of undetermined significance.
  182. Monoclonal 4 bayby ur so smart
    Monoclonal grammophathy of undetermined significance.
  183. Leukemias
    Upregulated growth of leukocytes in bone marrow. (anemia).
  184. Upregulated growth of leukocytes in bone marrow. (anemia).
  185. Acute lymphoblastic leukemia/lymphoma
    ALL. Occurs in children.
    Children: Bone marrow involvement
    Adolescent males: mediastinal mass
    Bone marrow filled with huge increase in lymphocytes
    TdT+ (marker of pre-T and pre-B cells), CALLA +
    Most responsive to therapy
    May spread to CNS and testes
    t(12;21) leads to better prognosis
  186. Small lymphocytic lymphoma/Chronic lymphocytic leukemia (CLL/SLL)
    Occurs in older adults > 60yo
    Often asymptomatic, smudge cells in peripheral blood smear
    Warm Ab autoimmune hemolytic anemia
    CLL has peripheral blood lymphocytosis
  187. Hairy cell leukemia
    Elderly. Mature B-Cell tumor. Cells have filamentous hairlike projections
    Stains TRAP + (tartrate-resistant acid phosphatase)
  188. Acute myelogenous leukemia
    Auer rods; way increased circulating myeloblasts on peripheral smear. M3 (APL) responds to all-trans retinoic acid (ATRA-vitamin A) inducing differentiation of myeloblasts.
    APL: t(15;17) PML-RARa. latin american 40yo
  189. Chronic myelogenous leukemia (CML)
    Philadelphia chromosome t(9;22), bcr-abl. myeloid stem cell proliferation.
    Increased neutrophils, metamyelocytes, basophils, platelets, and splenomegaly.
    Dec. RBCs
    bcr-abl leads to inc cell division and inhibition of apoptosis.
    Can transform to AML or ALL (blast crisis)
    Very low leukocyte alk phos
    Responds to imatinib (anti bcr-abl tyrosine kinase)
  190. Langerhans cell histiocytosis (LCH)
    proliferative disorder of dendritic (Langerhans) cells.
    Defective cells express S-100 and CD1a
    Birbeck granules ("tennis rackets" on EM) are classic
  191. Polycythemia vera
    Inc. RBCs, WBCs, Platelets
    JAK2 mutation
    Abnormal clone of hematopoietic stem cells are increasingly sensitive to growth factors
    "Lenny kravitz"
  192. Essential thrombocytosis
    Inc. platelets. Jak2 mutation in 30-50%
    Specific to megakaryocytes
  193. Myelofibrosis
    Dec. RBCs. JAK2 mutation in 30-50%
    FIbrotic obliteration of bone marrow. Teardrop cell.
  194. Heparin
    Cofactor for the activation of antithrombin, dec thrombin and Xa. Short half-life
    Immediate anticoagulation for PE, stroke, acute coronary syndrome.
    Ml, DVT.
    Used during pregnancy (does not cross placenta). Follow PTT
    Toxicities: Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal of heparinization, use protamine sulfate (positively charged molecule that acts by binding negatively charged heparin).

    HIT: heparin binds to platelets, causing
    autoantibody production that binds to and activates platelets leading to their clearance and resulting in a thrombocytopenic hypercoagulable state
  195. LMWH
    Newer low-molecular-weight heparins (e.g., enoxaparin) act more on Xa. have better bioavailability and 2-4 times longer half-life, can be administered subcutan. and without laboratory monitoring.
    Not easily reversible.
  196. Lepirudin, bivalirudin
    Hirudin derivatives,
    Direct thrombin inhibitors
    use as alternative to heparin for patients with HIT
  197. Warfarin (coumadin)
    Interferes with normal syn and gamma-carboxylation of vitamin K-dependent clotting (factors 2,7,9,10,C,S).
    Metabolized by the cytochrome P-450 palhway. In laboratory assay, has
    effect on EXtrinsic pathway and inc PT. Long half-life.

    Used for: Chronic anticoagulation. Not used in pregnant women (because warfarin, unlike heparin, can cross the placenta). Follow PT/INR values.

    Toxic: Bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions.

    Long term reverse: give vit. K
    Short term reverse: Fresh frozen plasma
  198. Thrombolytics
    Streptokinase, urokinase, tPA (alteplase), APSAC (anistreplase)
    Directly or indireclty aid conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots.
    Inc PT and PPT but no change in platelet count
    Early MI or ischemic results.
    Toxic: Bleeding, contraindicated in patients w/ bleed
  199. Asprin (ASA)
    Acetylates and irreversibly inhibits cox (COX-2 and Cox1) to prevent conversion of arachidonic acid to TxA2
    Inc bleeding time, no change in PT or PTT
    Antipyretic, analgeisic , antiinflammatory, antiplatelet drugs
    Toxic: gastric ulcer, bleed, hyperventilation, Reyes syndrome, tinnits (CN8)
  200. Clopidogrel, ticlopidine
    inhibit platelet aggregation (irreversible block of ADP reeptors) inhibit fibinogen binding by preventing gp2b3a expression
    ACS, Coronary stenting. Dec. incidence of recurrent thrombotic stroke.
    Neutropenia (ticlopidine)
  201. Abciximab
    Monoclonal Ab binds to gp 2b3a on activated platelets preventing aggregation.
    ACS percutaneous transluminal cornoary angioplasty
    Toxic: bleeding, throbocytopenia.
  202. Methotrexate
    Inhibits DHFR (folate analog). Dec dTMP, dec DNA and protein syn

    Used for leukemia, lymphoma, choriocarcinoma, sarcoma. Abortion, ectopic, rheumatoid arthritis, psoriasis.

    Toxic: myelosuppression (reversible by leucovorin = folinic acid "rescue")
    Macrovesicular fatty change in liver, mucositis, teratogenic
  203. 5-Fluorouracil (5-FU)
    Antimetabolite. Pyrimidine analog
    5FU -> 5F-dUMP which complexes folic acid
    Inhibits thymidylate synthesis so dec dTMP, DNA and protein syn

    Used for: colon cancer, basal cell carcinoma
    Synergy w/ MTX

    Toxic: myelosuppresion, not reversible w/ leucovorin (only for MTX). Instead rescue is with thymidine
  204. 6-Mercaptopurine (6-MP)
    Antimetabolite. Purine Analog
    Decreased de Novo purine synthesis
    Activated by HGPRTase

    Use: leukemias, lymphoma (not CLL or hodgkins)

    Toxic: Bone marrow, GI, liver, metabolized by xantine oxidase (inc toxic w/ allopurinol)
  205. 6-thioguanine (6-TG)
    Antimetabolite. purine analog (same pathway as 6-MP -> dec de novo purine synthesis)

    Use: ALL

    Toxi: bone marrow depression, liver
    Can be given with allopurinol as opposed to 6-MP
  206. Cytarabine (ara-C)
    antimetabolite. Pyrimidine antagonist (inhibition of DNA polymerase)

    use: AML, ALL, high grade NHL

    toxic: leukopenia, thrombocytopenia, megaloblastic anemia
  207. Dactinomycin (actinomycin D)
    Antitumor antibiotics
    Intercalates in DNA.

    Use: wilm's tumor, ewing's sarcoma, rhabdomyosarcoma. Childhood tumors!

    Toxic: myelosuppression
  208. Doxorubicin (adriamycin), daunorubicin
    Antitumor antibiotics. Generates free radicals
    Intercalate and break up dna to dec. replication

    (A in ABVD)
    Use: combo regimen (ABVD) for hodgkins. Also for myeloma, sarcoma and solid tumors)

    Toxic: cardiotoxic. also myelosuppression and alopecia. Toxic to Extravasation tissues
  209. Bleomycin
    Antitumor antibiotics
    G2 phase specific (free radical formation w/ breaks in DNA strands)

    Use: Testicular cancer, hodgkins

    Toxic: pulmonary fibrosis, skin changes, minimal myelosuppresion
  210. Etoposide (VP-16), teniposide
    Antitumor antibiotics
    Late S-G2 specific
    Inhibits topoisomerase II (DNA degradation)

    Use: small cell carcinoma of lung and prostate, testicular cancer

    Toxic: myelosuppression, GI irritation, alopecia
  211. Cyclophosphamide, ifosfamide
    Alkylating agents
    X-link covalently (interstrand) DNA at guanine N-7. Requires bioactivation by liver

    use: NHL, breast and ovarian carcinomas. Immunosuppressants.

    Toxic: myelosuppression, hemorrhagic cystitis (prevention w/ mesna -> thiol group of mesna binds toxic metabolite)
  212. Nitrosoureas
    Carmustine, lomustine, semustine, streptozocin
    Alkylating agents
    Require bioactivation. Cross BBB (CNS)

    Use: brain tumors (GBM)

    Toxic: CNS toxicity (dizzy, ataxia)
  213. Busulfan
    Alkylating agents (alkylates DNA)

    Use: CML, ablating bone marrow before bone marrow transplant

    Toxic: pulmonary fibrosis, hyperpigmentation
  214. Vincristine, vinblastine
    Microtubule inhibitor. Alkaloids that bind tubulin in M phase and block polymerization of MTs so mitotic spindle can't form.
    "MTs are the vines of cells"

    Use: Hodgkin's lymphoma, Wilm's tumor, choriocarcinoma

    vincristine: neurotoxic (areflexia, peripheral neuritis) paralytic ileus
    Vinblastine: bone marrow suppression
  215. Paclitaxel (other taxols)
    MT inhibitor. Hyperstabilizes polymerized MTs in M phase so mitotic spindle can't break down (anaphase can't occur).
    "It's taxing to stay polymerized"

    Use: ovarian and breast cancer

    Toxic: myelosuppression and hypersensitivity
  216. Cisplatin, carboplatin
    Mech: Cross-link DNA.
    Use: Testicular, bladder, ovary, and lung carcinoinas.
    Toxic: Nephrotoxicity and acoustic nerve damage.
  217. Hydroxyurea
    Mech: Inhibits Ribonucleotide Reductase —» dec DNA Synthesis (S-phase specific)

    use: Melanoma, CML, sickle cell disease (inc HbF)

    Toxic: Bone marrow suppression, GI upset.
  218. Prednisone
    Mech: May trigger apoptosis. May even work on nondividing cells.

    use: Most commonly used glucocorticoid in cancer chemo. Used in CLL, Hodgkins (part of the MOPP regimen). Also an immunosuppressant used in autoimmune diseases.

    Toxic: Cushing-like symptoms; immunosuppression, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia. psychosis
  219. Tamoxifen, raloxifene
    Mech: SERMs receptor antagonists in breast, agonists in bone; block the binding of estrogen to estrogen receptor-positive cells

    use: Breast cancer. Also useful to prevent osteoporosis.

    Toxic: Tamoxifen may inc the risk of endometrial carcinoma via partial agonist effects; "hot
    flashes." Raloxifene does not cause endometrial carcinoma because it is an endometrial antagonist.
  220. Trastuzumab (Herceptin)
    Monoclonal Ab against HER2 (erb B2). helps kill breast cancer cells that overexpress HER2 possibly thru Ab-depenent cytotoxicity

    use: metastatic breast cancer

    toxicity: cardiotoxicity
  221. Imatinib (gleevec)
    philadelphia chromosome, bcr-abl tyrosine kinase inhibitor

    use: CML, GI stromal tumors

    toxic: fluid retention
  222. Rituximab
    Monoclonal Ab against CD20 (B cell neoplasms)

    use: NHL, rheumatoid arthritis (w/ MTX)
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