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Step 1 Subjects > Hematology/oncology > Flashcards

Hematology/oncology Flashcards

1
Q

PT= prothrombin time

A

Measures extrinsic coagulation

Increased in:

  • deficiency of Factors I (fibrinogen), II (thrombin), V, VII, X
  • Liver dysfunction–> Factor VII depleted first–> PT increased first
  • Warfarin therapy
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2
Q

PTT= Partial Thromboplastin Time

A

Measures intrinsic, common coagulation

Contains Factor VII–> time increased with deficiency of any other factor

  • Increased time in Heparin therapy
  • Increased time d/t APLS (antiphospholipid antibody syndrome), sepsis, hemophilia
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3
Q

TT= Thrombin time

A

Conversion of fibrinogen–> fibrin

- Prolonged by heparin

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4
Q

Ceruloplasmin

A 
Carries Copper (decreased in Wilson's disease)
- alpha-2-globulin produced by liver, kidneys
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5
Q

Anaplasia

A

Loss of cell polarity, architecture

  • variation in size, shape (pleomorphic)
  • Giant multinucleated cells
  • Nuclear hyperchromatism, pleomorphism
  • Increased nuclear:cytoplasm ratio, abnL mitoses
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6
Q

Platelet

A 
Life span: 8-10 days
Dense granules= ADP, calcium
Alpha granules= vWF, fibrinogen
- vWF receptor= GpIb; carries/protects factor VIII
- Fibrinogen receptor= GpIIb/IIIa
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7
Q

Blood cell differential

A 
Neutrophils (55%)
Lymphocytes (30%)
Monoctes (5%)
Eosinophils (3%)
Basophils (0-1%)
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8
Q

Neutrophils

A

Increased in bacterial infection

  • Phagocytic
  • Multilobed nucleus

Small granules:

  • Alkaline phosphatase
  • Collagenase
  • Lysozyme
  • Lactoferrin

Larger granules: lysosomes:

  • Acid phosphatase
  • Peroxidase
  • Beta-glucuronidase
Hypersegmented polys (5+ lobes) seen in B12/folate deficiency (enlarged nuclei)
* Increased band cells in myeloid proliferation states
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9
Q

Macrophages

A

Precursor= monocyte (kidney-shaped nucleus)

Activated by IFN-gamma
Presents MHC II
Cell marker= CD14

Secretes TNF-alpha

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10
Q

Eosinophil

A

Protects against helminths (INVASIVE)
- Seen in neoplasia, asthma, allergic processes, collagen vascular diseases, invasive parasites
Contains major basic protein

Bilobate nucleus
Phagocytic for antigen-antibody complexes

Produces:

  • Histaminase
  • Arylsulfatase
    • limits reaction after mast cell degranulation
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11
Q

Basophil

A 
Mediates allergic reaction
Contain:
- Heparin
- histamine (vasodilator)
- Leukotrienes (LTD4)
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12
Q

B lymphocyte

A 
Stem cell in bone marrow (matures in marrow)
Migrates to:
- Follicles of lymph nodes
- White pulp of spleen
- Unencapsulated lymphoid tissue

MHC II APC

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13
Q

O-negative mothers

A

Anti-A and Anti-B antibodies produced are IgG (vs other blood types that produce IgM)
- BUT, Hemolytic disease of newborn only occurs in ~3% of O- moms

Rh= IgG antibodies, can cross placenta for all maternal types

  • Administer Rho(D) Ig (RhIg) at first delivery to prevent sensitization
  • -> Erythroblastosis fetalis seen in subsequent babies of untreated mothers
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14
Q

Factor V Leiden mutation

A

Factor V resistant to inhibition by APC (activated protein C)
- most common cause of inherited hypercoagulability in whites

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15
Q

ESR

A

Erythrocyte sedimentation rate

Increased in: infections, autoimmune diseases, malignant neoplasia, GI disease, pregnancy (inflammation)

Decreased in:

  • Polycythemia
  • Sickle cell anemia
  • CHF
  • Microcytosis
  • Hypofibrinogenemia
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16
Q

Acanthocyte

A

Spur cell

Seen in:

  • Liver disease
  • abetalipoproteinemia (cholesterol dysregulation states)
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17
Q

Basophilic stippling

A

Ribosomal RNA remnants in RBC

Seen in:

  • Thalassemia
  • Anemia of chronic disease
  • Lead poisoning
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18
Q

Heinz bodies

A

Oxidation of hemoglobin sulfhydryl groups–> denatured hemoglobin precipitation–> damage to RBC membrane–> formation of bite cells (macrophages remove precipitated hemoglobin, part of membrane

Stains with crystal violet stain

Seen in G6PD deficiency, alpha thalassemia

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19
Q

Howell-Jolly bodies

A

Basophilic nuclear remnants in RBCs
- Normally removed by splenic macrophages

Seen in patients with asplenia, hyposplenia (sickle cell children)
Or, after napthalene (mothball) ingestion

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20
Q

TIBC

A

Total iron binding capacity= Transferrin (transport of iron in blood)

  • increased when body needs more iron
  • increased by OCPs, pregnancy
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21
Q

Ferritin

A

Storage form of iron (in macrophages in bone, liver)

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22
Q

Haptoglobin

A

Picks up hemoglobin after intravascular hemolysis–> brings to macrophages (“suicide protein”)
- alpha-2-globulin produced by liver, kidneys

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23
Q

Alpha thalassemia

A

Defective alpha-globin

  • cis form in Asians
  • trans form in Africans

4 gene deletion= Hb Barts (hydrops fetalis)–> dead in utero

3 gene deletion= HbH disease
- Excess Beta-globin that can’t bind alpha forms B4 (HbH)

1-2 gene deletion: no clinically significant anemia

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24
Q

Beta-thalassemia

A

Seen in Mediterranean populations

mRNA processing problem leading to underproduction/absent beta-chain

Minor/Intermedia (heterozygote):

  • Beta chain under-produced (asymptomatic)
  • Confirmed by increased HbA2 (> 3.5% on electrophoresis)

Major: (homozygote)

  • Absent beta chain–> anemia (blood transfusion)–> secondary hemochromatosis
  • Marrow expansion–> crew cut skull, skeletal deformities, chipmunk face
  • Increased HbF (alpha2gamma2)

**HbS/Beta-thal heterozygote–> mild/moderate sickle cell disease (depends on beta production)

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25
Q

Lead poisoning

A

Inhibits:

  1. ferrochelatase–> protoporphyrin excess
  2. ALA dehyratase–> delta-ALA excess
  3. rRNA degradation–> basophilic stippling

Symptoms:

  • Lead lines on gingiva (Burton’s lines), metaphysis of long bones)
  • Encephalopathy, Erythrocyte basophilic stippling
  • Abdominal colic, sideroblastic Anemia
  • Wrist, foot drop
  • Adults: H/A, memory loss, demyelination
  • Children (lead paint): mental deterioration

Tx: Dimercaprol, EDTA (1st line)
- Succimer in pediatric overdose (chelator)

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26
Q

Sideroblastic anemia

A

X-linked defect in delta-ALA synthase

  • –> Defective heme synthesis
  • Glycine, succinyl coA not converted to delta-aminolevulinic acid
    • Can also be caused by alcohol, lead, isoniazid, myelodysplastic syndrome

Ringed siderblast with iron-laden mitochondria (have iron, can’t make heme!)

Tx: pyridoxine (B6= cofactor for delta ALA-synthase)

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27
Q

Folate deficiency

A

Hypersegmented neutrophils
Megaloblastic anemia
- Increased Homocyteine

Symptoms:

  • Sore tongue
  • Pain on swallowing
  • Angular stomatitis
  • GI upset
  • Hyperpigmentation
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28
Q

B12 deficiency

A

Increased homocysteine, increased methylmalonic acid (MMA)

Symptoms:

  • Neurologic: subacute combined degeneration (involvement of B12 in fatty acid pathways, myelin synthesis
  • Peripheral neuropathy with sensorimotor dysfunction
  • Posterior column (vibration/proprioception)
  • Lateral corticospinal (spasticity)
  • Dementia

**Pernicious anemia: older N. European woman; lemon-yellow coloring, shiny smooth tongue (atrophic glossitis), shuffling broad-based gait

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29
Q

Plummer-Vinson syndrome

A

Triad:

  • iron deficiency anemia
  • Esophageal webs
  • Atrophic glossitis
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30
Q

Hepcidin

A

Protein released by liver in response to inflammatory state

  • Binds ferroportin on intestinal mucosal cells, macrophages–> inhibits iron transport, release of iron from macrophages
  • -> anemia of chronic disease

** Body stopping iron release in state of inflammation since bacteria feed off iron to grow

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31
Q

G6PD deficiency

A

X-linked defect in G6PD

  • RBC can’t go into HMP shunt to generate glutathione
  • –> increased susceptibility to oxidant stress

Precipitating factors:

  • Infections
  • Drugs (Sulfa, primiquine, Dapsone)
  • DKA
  • Favism (fava beans)

Symptoms:
- Back pain, hemoglobinuria

Extravascular hemolysis: bite cells and Heinz bodies on smear (spleen macrophages remove Heinz bodies–> bite cells)

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32
Q

Pyruvate kinase deficiency

A

Autosomal recessive
Defect in pyruvate kinase–> decreased ATP–> can’t reshape after going through vessels (rigid RBCs)
- See hemolytic anemia in NEWBORN

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33
Q

HbC defect

A

Glutamic acid–> Lysine at beta-globin residue 6 (vs Glu–> val in SC)
- HbSC have milder disease than HbSS

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34
Q

Paroxysmal Nocturnal Hemoglobinuria

A

Impaired synthesis of GPI anchor or Decay-Accelerating Factor to protect RBC from complement-mediated lysis
- Complement binds RBC–> intravascular hemolysis

Symptoms:

  • Hemolytic anemia
  • Pancytopenia
  • Venous thrombosis

Lab:
- CD55/59 negative RBCs

Tx: eculizumab

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35
Q

Sickle Cell anemia

A

Glu–> val at position 6 on beta-chain

Beta chain can fit into complementary alpha chain on another hemoglobin molecule–> aggregation of hemoglobin monomers

    • see Howell-Jolly bodies in children as the spleen is infarcted
  • First crisis after HbF no longer being made (8-12 months post-partum)–> dactylitits (sausage fingers)
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36
Q

Warm agglutination

A

IgG

- Chronic anemia in SLE, CLL, certain drugs

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37
Q

Cold agglutination

A

IgM

  • Acute anemia triggered by cold
  • Seen in CLL, Mycoplasma pneumoniae, Infectious mono
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38
Q

Direct Coomb’s

A

Test Patient RBCs

- Add anti-Ig antibody–> RBC agglutination= positive test

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39
Q

Indirect Coomb’s test

A

Test patient plasma

- add normal RBCs to patient serum–> agglutination= anti-RBC surface Ig

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40
Q

Acute intermittent porphyria

A

Defect in porphobilinogen deaminase
- accumulate porphobilinogen, delta-ALA, uroporphyrin (urine)

Symptoms:

  • Painful abdomen
  • Port-wine urine (uroporphyrin)
  • Polyneuropathy
  • Pscyhological disturbances
  • Precipitated by drugs: phenobarbital, griseofulvin, hepatitis C; EtOH, low-calorie diet

Treatment:
- Glucose, heme (inhibit ALA synthase)

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41
Q

Porphyria cutanea tarda

A

Defect in uroporphyrinogen decarboxylase

  • Congenital or acquired= aromatic hydrocarbon exposure, estrogen, hepatitis C
  • Accumulate uroporphyrin (tea-colored urine)

Symptoms:
- Blistering cutaneous photosensitivity

  • most common porphyria
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42
Q

Bernard-Soulier syndrome

A

Decreased GpIb–> defect in platelet to vWF adhesion

Decreased platelet count, increased bleeding time

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43
Q

Glanzmann’s thombasthenia

A

Decreased GpIIb/IIIa–> defect in platelet-platelet aggregation (can’t bind fibrinogen
- Increased bleeding time

Labs: blood smear w/ no platlet clumping

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44
Q

Idiopathic thrombocytopenic purpura

A

Anti-GpIIb/IIIa antibodies–> splenic macrophages consume platelets (bound to Abs)
–> purpura (no platlets!)

Labs: increased megakaryocytes

45
Q

Thrombotic thrombocytopenic purpura

A

Deficiency of ADAMTS13 (vWF metalloprotease)–> decreased degradation of vWF multimers

Large vWF multimers–> platelet aggregation, thrombosis
- decreased platelet survival

Labs: schistocytes, increased LDH

Symptoms:

  • Neurological, renal
  • Fever, thrombocytopenia
  • microangiopathic hemolytic anemia
46
Q

von Willebrand’s disease

A

Autosomal dominant
- Diagnosis: ristocetin cofactor assay

Decreased vWF–> normal to increased PTT; increased bleeding time

  • vWF protects factor VIII
  • Defect in platelet-to-vWWF adhesion

Tx: DDAVP (desmopressin)–> releases stored vWF in endothelium

47
Q

Prothrombin gene mutation

A

3’ untranslated region mutation–> increased production–> increased plasma levels, clots

48
Q

Antithrombin deficiency

A

Inherited deficiency–> thromboses

- Put patient on heparin to treat thrombosis–> abnormally LOW increase in PTT (would expect longer for clot to form)

49
Q

Protein C/S deficiency

A

Inability to inactivate factors V, VIII

  • Increased thrombotic skin necrosis with hemorrhage following Warfarin administration (Warfarin given to try and correct hypercoagulable state)
  • Warfarin blocks C, S–> thrombotic skin necrosis
50
Q

Cryoprecipitate

A

Contains:

  • Fibrinogen
  • Factor VIII
  • Factor XIII
  • vWF
  • Fibronectin

Use:
- Treat coagulation factor deficiency of fibrinogen, factor VIII (hemophilia A)

51
Q

Fresh frozen plasma

A

Increased coagulation factor levels

Use:
- Treat DIC, cirrhosis, Warfarin overdose

52
Q

Leukemoid reaction

A

Acute inflammatory response to infection

  • increased WBCs, neutrophils, band cells (left shift)
  • Increased Leukocyte alkaline phosphatase (also seen in PV, essential thrombocytosis, primary myelofibrosis)
  • Contrast with decrease leukocyte alkaline phophatase in CML (increased WBC, left shift)
53
Q

Hodgkin’s lymphoma

A

Localized, Single group of nodes (neck)

  • Rare extranodal involvement
  • Contiguous spread (stage= prognosis)
  • Bimodal: young adults and 55+
  • More common in men
  • 50% associated with EBV t(8;14)

Reed Sternberg cells: B cells; CD30+, CD15+

  • Needed for Hodgkin’s diagnosis
  • Prognosis better with strong stomal/lymphocytic reaction against cells
  • Most common form= nodular sclerosing (M=W)
  • Lymphocyte mixed/depleted= poor prognosis

“B” signs/symptoms: low grade fever, night sweats, weight loss

54
Q

Non-Hodgkin’s Lymphoma

A

Multiple, peripheral nodes

  • Commonly see extranodal involvement
  • May have lymphoblastic T-cell origin

Incidence peaks 20-40 years
- associated with HIV, immunosuppression

Fewer constiutional signs/symptoms

55
Q

Burkitt’s lymphoma

A

Neoplasm of mature B cells (non-Hodgkin’s)

Adolescents, young adults

t(8;14): c-myc (transcription factor regulator on chrom 8) and heavy chain Ig (chrom 14)
- High proliferation index= Ki167 fraction

Endemic form (Africa): jaw lesion
Sporadic: pelvis or abdomen
56
Q

Diffuse large B-cell lymphoma

A

Older adults, 20% in children
- most common adult NHL

May be T-cell in origin (20%)

Presentation: tumor lysis syndrome

Genetics: bcl-2 (18), c-myc (8), bcl-6

57
Q

Mantle cell lymphoma

A

Older males

Mantle= pre-germinal center (naive B cells)

Presentation: SICK; tumor lysis syndrome, Waldeyer’s ring, bone marrow, GI tract involvement

Genetics:

  • t(11;14): cyclin D1 (chrom 11) with heavy chain Ig (14)
  • CD5+ B cells

Poor prognosis

58
Q

Follicular lymphoma

A

Adults

Genetics: t(14;18): heavy chain Ig (chrom14) and bcl-2 (inhibits apoptosis, chrom 18)

Difficult to cure; indolent course

59
Q

Adult T-cell lymphoma

A

HTLV-1

Cutaneous lesions, hypercalcemia, opportunistic infections
- Japan, West Africa, Carribbean

Aggressive

60
Q

Mycosis fungoides/Sezary syndrome

A

Adults: cutaneous patches/nodules

CD4+
indolent course

61
Q

MGUS

A

Monoclonal Gammopathy of Undetermined Significance

  • M protein < 30 g/dL (no other Ig abnormalities)
  • Bone marrow plasma cells < 10%
  • NO end-organ damage (no CRAB)

1-2% convert to multiple myeloma/year

62
Q

Smoldering MM

A

M protein > 30g/dL (IgG, IgA, light chain and/or 10%+ plasma cells in bone marrow
- NO CRAB (end-organ damage

51% convert in 5 years, 73% at 20 years)

63
Q

Multiple myeloma

A

Plasma cells produce IgG (55%) or IgA (25%)
- Most common tumor in ppl > 45 years

Associated symptoms:

  • infections
  • Primary amyloidosis AL
  • M spike
  • Ig light chains in urine (Bence Jones proteinuria)
  • Rouleaux formation (RBC stacking)
  • CRAB: hyperCalcemia, Renal insufficiency (due to light chains), Anemia, Bone lesions/Back pain
64
Q

Waldenstrom’s macroglobulinemia

A

M-spike= IgM
–> hyperviscosity
NO lytic bone lesions

65
Q

Acute lymphoblastic leukemia/lymphoma

A

Most common leukemia in people < 20 years
- Seen again in 60+

T-cell ALL= mediastinal mass (leukemic infiltration of thymus)

Features:

  • Peripheral blood, bone marrow have increased lymphoblasts
  • TdT+ (marker of pre-T and pre-B cells)
  • CALLA+ (common ALL antigen) (CD10+)
  • May spread to CNS, testes
  • CD22+: ALL with B-cell lineage
  • t(12;21)= better prognosis: seen in Down syndrome, NF-1, Ataxia telangiectasia
66
Q

Small lymphocytic lymphoma, chronic lymphocytic leukemia (SLL, CLL)

A

60+ years

  • Asympomatic; may have lymphadenopathy, splenomegaly, fatigue
  • Autoimmune hemolytic anemia

Features:

  • Smudge cells in periphery
  • CLL= increased peripheral blood lymphocytosis/bone marrow involvement (vs SLL in periphery)
  • increased Bcl-2 expression (protoncogene)
  • CLL= deletion of 13q (good prognosis)
67
Q

Hairy cell leukemia

A

Older men; rare
- Mature B cell tumor

Features:

  • Hair-like projections on cells
  • Stains TRAP (tartrate-resistant acid phosphatase)

Tx: cladribine= adenosine analogue

68
Q

Acute mylogenous leukemia (AML)

A

Neonates and 65+

Features: increased circulating myeloblasts

  • Adults: t(15;17)–> M3 AML subtype
  • PML/RAR fusion: blocks myeloid precursor differentiation
  • Responsive to ATRA (all-trans retinoic acid)–> pushes myeloid cells to differentiate

Presentation:

  • Auer rods= peroxidase-positive inclusions in granulocytes, myeloblasts (ATRA–> auer rod release–> DIC)
  • DIC: cells larger, sticker–> coagulation
69
Q

Chronic myelogenous leukemia (CML)

A

30-60 years

  • Philadelphia chromosome= t(9;22) bcr-abl fusion
  • Bcr= breakpoint cluster region (chrom 22)–> increase P210 when fused with abl (chrom 9)–> tyrosine kinase activated–> protected from apoptosis

Features:

  • increased neutrophils, metamyelocytes, basophils
  • Splenomegaly (red pulp infiltration)
  • Smaller megakaryocytes with hypolobulated nuclei (dwarfs)
  • increased myeloid:erythroid ratio (decreased RBCs)
  • Can accelerate and transform to AML/ALL (blast crisis)
  • Low leukocyte alkaline phosphatase) due to immature granulocytes

Tx:
Imatinib: small molecule inhibitor of bcr-abl tyrosine kinase

70
Q

Langerhans cell histiocytosis

A

Proliferative disorder of dendritic (Langerhans) cells from monocyte lineage

  • Children: lytic bone lesions, skin rash
  • Cells immature, do not efficiently stimulate T-lymphocytes via antigen presentation (increased skin infections?)

Cells:

  • S-1000 (neural crest derived)
  • CD1a
  • Birbeck granules= “tennis rackets” on EM
71
Q

Polycythemia vera

A

JAK2 positive
- Increased RBC and plasma volume

Abnormal clone of hematopoietic cells with constitutively active JAK 2 (V16F)
- erythrocytosis, thrombocytosis (low/no EPO)

Symptoms:

  • Erythromelalgia, splenomegaly, thrombotic complications
  • Excess histamine–> peptic ulcers, intense itching after hot shower

TxL phlebotomy

72
Q

Essential thrombocytosis

A 
Specific expansion of megakaryocytes
Symptoms:
- Hemorrhagic, thrombotic symptoms (easy bruisin, microangiopathic occlusion)
- Thrombocytosis
- Megakaryocyte hyperplasia
73
Q

Myelofibrosis

A

Fibrotic obliteration of bone marrow

  • Teardrop cells
  • Fatigue, spleno/hepatomegaly (extramedullary hematopoeisis)
  • Anemia
  • Early satiety
  • Dry tap due to marrow fibrosis
74
Q

Appropriate vs inappropriate polycythemia

A

Relative: sweating/volume loss (decrease plasma) with no change in RBC mass

Approptiate absolute: increased RBC mass due to decreased O2 saturation

  • Lung disease
  • congenital heart disease (shunting)
  • High altitude

Inappropriate absolute: increased RBC mass due to ectopic EPO-producing disease:

  • Renal cell carcinoma
  • Wilm’s tumor
  • Cyst
  • Hepatocellular carcinoma
  • Hydronephrosis
75
Q

Heparin

A

Co-factor for activation of antithrombin
- Decreases thrombin, factor Xa (in blood)

Use:

  • Short half-life: immediate anticoagulation
  • PE, ACS, MI, DVT
  • Can be used in pregnancy (won’t cross placenta- water soluble)
  • Prophylaxis in surgery for DVT

Monitoring: PTT

Tox:

  • osteoporosis
  • bleeding
  • HIT= heparin-induced thrombocytopenia: IgG antibodies against heparin bound to PF4 (platelet factor 4)
  • -> thrombosis, cytopenia
  • Tx: argatroban, lepirudin, bivalrudin

Tx for overdose: protamine sulfate (positively charged)

76
Q

Enoxaparin, dalteparin, fondiparinux

A

Low-molecular weight heparins (LMWH)

  • Act more on Xa
  • Better bioavailability, 2-4 time longer t1/2
  • Less incidence of HIT, but not easily reversible
77
Q

Lepidrudin, bivalrudin, argatroban

A

Derivative of hirudin (anticoagulant in leeches)

  • Inhibits thrombin
  • Alternative to heparin for anticoagulating patients with HIT
78
Q

Warfarin

A

Interferes with vitamin k gamma-carboxylation by blocking epoxide reductase conversion of vitamin k (inactive K1–> K2)

  • Can’t synthesize factors II, VII, IX, X, proteins C, S (in liver)
  • Monitor PT (extrinsic pathway) and INR values

Use:

  • Chronic anticoagulation
  • NOT in pregnant women (lipid soluble, bound to albumin- crosses placenta)

Tox:

  • CytP450 pathway: metabolism increased by Rifampin, phenobarbital, phenytoin
  • Cyp450 inhibitors (increase Warfarin conc): amiodarone, cimetidine
  • Cholestyramine bind warfarin in intestine–> decreased activity
  • Bleeding
  • Skin/tissue necrosis (protein C/S deficiency)

Tx for overdose:

  • vitamin K
  • Severe, rapid reversal: fresh frozen plasma
79
Q

Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)

A

Thrombolytics: directly/indirectly convert plasminogen to plasmin–> cleave thrombin, fibrin clots
- Increased PT, PTT, no change in platelet count

Use:

  • Early MI, ischemic stroke (first 4 hours)
  • Thrombolysis in severe PE

Tox: Bleeding (avoid in active bleeds, intracranial bleed, severe HTN)
- Tx toxicity with aminocaproic acid= inhibits fibrinolysis

80
Q

Aspirin (ASA)

A

Irreversible inhibition of COX (1 and 2): covalent acetylation

  • Increases bleeding time, decreases TXA2, prostaglandins
  • no effect on PT, PTT

Use: antipyretic, antiinflammatory, antiplatelet (decrease aggregation)

Tox:

  • Gastric ulcers
  • tinnitus (CNVIII)
  • Chronic use: acute renal failure (interstitial necrosis/nephritis), upper GI bleed
  • Reyes syndrome (fatty liver) in children with viral infection

Overdose: respiratory alkalosis, metabolic acidosis

Intolderance: asthma, nasal polyps (10% of asthma patients have NSAID/ASA intolderance–> bronchospasm, nasal congestion due to increased leukotrienes)
- Leukotrienes= Lipooxygenase products of arachidonic acid metabolism

81
Q

Clopidogrel, ticlopidine, prasugrel, ticagrelor

A

ADP receptor inhibitors: block receptor–> irreversible platelet aggregation inhibition as platelet won’t express GpIIb/IIIa
- Inhibit fibrinogen binding: prevent Glycoprotein IIb/IIIa from binding to fibrinogen

Use: ACS, coronary stenting, decreased incidence/recurrence of thrombotic stroke

Tox: Ticlopidine–> neutropenia (fever, mouth ulcers); only used when pt can’t tolerate aspirin, clopidogrel)

82
Q

Cilostazol, dipyridamole

A

PDEIII inhibitor
- Increased cAMP in platelet–> inhibit aggregation; vasodilation

Use: intermittent claudication, prevent stroke/TIA, angina prophylaxis

Tox: nausea, headache, flushing, hypotension, abdominal pain

83
Q

Abciximab, eptifibatide, tirofiban

A

GP IIb/IIIa inhibitors: bind on activated platelets (so fibrinogen can’t bind)–> prevent aggregation
- Abciximab= monoclonal Ab to Fab fragments

Use: ACS, percutaneous transluminal coronary angioplasty

Tox: bleeding, thrombocytopenia

84
Q

Methotrexate

A

Folic acid analog: inhibits dihydrofolate reductase
–> decreased dTMP–> decreased DNA and protein synthesis

Tox:

  • Myelosuppression; reversed with Leucovorin (folinic acid rescue)
  • Macrovesicular fatty changes in liver (cirrhosis with chronic use)
  • Mucositis
  • Teratogen (duh)
85
Q

5-FU

A

Pyrimidine analog bioactivated to 5F-dUMP–> complexes with folic acid–> inhibits thymidylate synthase (FU thymidylate synthase!)

Tox:

  • Myelosuppression; rescue with thymidine
  • Photosensitivity
86
Q

Cytarabine (arabinofuranosyl cytidine), capecitabine, gemcitabine

A

Pyramidine analog–> inhibits DNA polymerase

Tox: myelosuppression, megaloblastic anemia

87
Q

Azathiopurine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG)

A

Purine analog–> decreases de novo purine syntheis (blocks PRPP amidotransferase)
- Activated by HGPRT

Tox:

  • Bone marrow, GI liver (abdominal pain, jaundice)
  • Metabolized by xanthine oxidase–> increased toxicity with allopurinol administration
88
Q

Dactinomycin

A

Intercalates DNA (antitumor antibiotic)

Tox: myelosuppression

89
Q

Doxorubicin (adriamycin)

Danorubicin

A

Anthracycline (antitumor antibiotic)
Generates free radicals
- Noncovalently intercalate DNA–> breaks–> decreased replication

Tox: cardiotoxicity (dilated cardiomyopathy)–> CHF
** Dexrazoxane (iron chelating agent) used to prevent cardiotoxicity

Resistance:

  • MDR1= human multidrug resistance gene; codes for P-glycoprotein
  • P-glycoprotein= ATP-dependent drug efflux pump: pumps substances out of intestinal, renal tubular epithelium, capillary endothelium at BBB (thus removes chemotherapeutic drugs in tumor cells)
90
Q

Bleomycin

A

Antitumor antibiotic: free radical formation–> breaks in DNA strands

Tox: Pulmonary fibrosis, skin changes

91
Q

Cyclophophamide, ifosfamide

A

Alkylating agent: death in rapidly dividing cells

MOA: covalently x-link (interstrand) DNA at guanine N-7
- Activated by p450 system in liver

Tox:
- Hemorrhagic cystitis: partially prevent with mesna (thiol binds toxic metabolites)

92
Q

Carmustine
Lomustine
Semustine
Streptozocin

A 
Nitrosureas
Require bioactivation (non-enzymatic hydroxylation) to cross BBB--> CNS

Tox: CNS (dizziness, ataxia)

93
Q

Trastuzumab (Herceptin)

A

Monoclonal antibody against HER-2 (c-erbB2)= tyrosine kinase

Tox: cardiotoxic

94
Q

Vincristine, Vinblastine

A

Alkaloids
Bind tubulin in M phase–> mitotic spindle can’t FORM

Vincristine= neurotoxic (areflexia, peripheral neuritis, paralytic ileus)
Vinblastine= myelosuppression (blasts bone)
95
Q

Paclitaxel, Taxols

A

Hyperstabilize microtubules in M phase–> mitotic spindle can’t BREAK DOWN

Use: ovarian, breast cancer
- Drug-eluting stents (inhibits intimal hyperplasia)

Tox: myelosuppression, hypersensitivity

96
Q

Cisplatin, carboplatin

A

Cross-link DNA; hydrated to form cytotoxic metabolite in environment with low Cl- concentration

Tox: nephrotoxic, acoustic nerve (cochlear hair cell) damage
- Nephrotoxicity prevented with amifostine (free radical scavenger), chloride diuresis (normal IV saline)

97
Q

Etoposide, teniposide

A

Inhibit Topoisomerase II–> can’t repair ds DNA breaks (positive or negative supercoils)

Use:
Etoposide= testicular, SCLC
Teniposide= genital warts

Tox: myelosuppression, GI irritation, alopecia

98
Q

Hydroxyurea

A

Inhibits ribonucleotide reductase–> decreased DNA synthesis

Use: melanoma, CML, sickle cell disease (increase HbF)

Tox: bone marrow, GI upset

99
Q

Irinotecan, topotecan

A

Topoisomerase I inhibitors (block ss breaks to relieve supercoiling

100
Q

Tamoxifen, Raloxifene

A

SERM:

  • Breast= receptor antagonist (breast cancer tx)
  • Bone= receptor agonist (osteoporosis tx)
  • Endometrium: Tamoxifen= partial agonist (increased risk of endometrial cancer)
  • Raloxifene= antagonist (no risk of cancer)
101
Q

Busulfan

A

Alkylates DNA

Tox: pulmonary fibrosis, hyperpigmentation

102
Q

Trastuzumab (Herceptin)

A

Monoclonal antibody against HER-2 (c-erbB2)

103
Q

Irinotecan, topotecan

A

Topoisomerase I inhibitors (block ss breaks to relieve supercoiling

104
Q

Imatinib (Gleevec)

A

bcr-abl tyrosine kinase inhibitor

TOx: fluid retention

105
Q

Rituximab

A

Monoclonal ab against CD20 (B-cell neoplasms)

Use: non-Hodgkin’s lymphoma, RA (with MTX)

106
Q

Vemurafenib

A

Small molecule inhibitor of B-Raf kinase with V600E mutation

Use: metastatic melanoma

107
Q

Bevacizumab

A

Monoclonal Ab against VEGF–> prevents angiogenesis

108
Q

Osler-Weber Rendu= Hereditary hemorrhagic telangiectasia

A

Inherited disorder of blood vessels

  • Telangiectasia of skin and mucosa
  • Recurrent epistaxis
  • GI bleeds
  • Skin discolorations
  • AV malformations
109
Q

Hemoglobin A2

A

2 alpha, 2 delta chains

- Comprises 2-5% of adult hemoglobin

Step 1 Subjects (26 decks)

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