Hematology Oncology Flashcards
1
Q
What is the appearance of an acanthocyte? What is another name?
A
“Spiny” appearance on blood smear; also called spur cell
2
Q
What pathology is associated with a spur cell (acanthocyte)?
A
Liver disease, abetalipoproteinemia (states of cholesterol dysregulation)
3
Q
What type of RBCs might you see in abetalipoproteinemia?
A
Acanthocytes
4
Q
Basophilic stippling is due to aggregation of what in the RBC?
A
Residual ribosomes
5
Q
What pathology is associated with basophilic stippling?
A
Lead poisoning, sideroblastic anemias, myelodysplastic syndromes
6
Q
Bite cells are seen in what disease?
A
G6PD
7
Q
What is seen on a peripheral smear in a patient with G6PD?
A
Bite cells and Heinz bodies
8
Q
When do you see Howell-Jolly bodies on a peripheral smear?
A
Functional hypospenia, asplenia, naphthalene poisoning
9
Q
What are Howell-Jolly bodies?
A
Basophilic nuclear remnants found in RBCs
10
Q
What pathology is associated with echinocyte?
A
End stage renal disease, liver disease, pyruvate kinase deficiency
11
Q
There are two categories of normocytic anemia, nonhemolytic and hemolytic. How do you differentiate between the two?
A
Nonhemolytic has a reticulocyte count that is normal or low; hemolytic has a high reticulocyte count
12
Q
What are the symptoms for lead poisoning?
A
Lead lines on gingivae (burton lines) and on metaphyses of long bones, encephalopathy, erythrocyte basophilic stippling, abdominal colic, sideroblastic anemia, wrist/foot drop
13
Q
What are first line treatments for lead poisoning?
A
EDTA and dimercaprol
14
Q
A kid with lead poisoning is given what?
A
Succimer
15
Q
What enzymes are inhibited by lead?
A
Ferrochelatase and ALA dehydratase
16
Q
What is the rate limiting step in heme synthesis?
A
ALA synthase
17
Q
What is the genetic mutation resulting in sideroblastic anemia?
A
X linked defect in ALA synthase gene
18
Q
What are the lab findings in sideroblastic anemia?
A
Increased iron, increased transferrin sat %, normal/decreased TIBC, increased ferritin
19
Q
What are increased in the serum of B12 def?
A
Homocysteine and methylmalonic acid are increased
20
Q
Orotic aciduria without hyperammonemia is seen in what disease? What enzyne is deficient?
A
Orotic aciduria due to UMP synthase defect
21
Q
Ornithine transcarbamoylase def is differentiated from UMP synthase def how?
A
OTC def has hyperammonemia, UMP synthase def does not
22
Q
What drugs can cause aplastic anemia?
A
Benzene, chloramphenicol, alkylating agents, antimetabolites
23
Q
What is the most common inheritance pattern of Hereditary spherocytosis?
A
Autosomal dominant
24
Q
What are some examples of common defective proteins in hereditary spherocytosis?
A
Spectrin, ankyrin, band 3, protein 4.2
25
What type of hemolysis is seen in hereditary spherocytosis?
Extravascular - macrophages cause the hemolysis
26
What is the inheritance of pyruvate kinase def?
Autosomal recessive
27
What may be seen on peripheral smear in pyruvate kinase def?
Burr cells "echinocytes"
28
Newborn presents with persistent jaundice and reticulocytosis. Osmotic fragility test is normal. What may be the underlying disease?
Pyruvate kinase deficiency
29
How does pyruvate kinase def. present?
Neonatal hemolytic anemia - persistent jaundice with reticulocytosis
30
What is seen on peripheral smear of G6PD def?
Heinz bodies and bite cells
31
What drugs can cause hemolytic stress in a patient with G6PD def?
Isoniazid, sulfonamides, ASA, Ibuprofen, dapsone, antimalarials, nitrofurantoin
32
What type of hemolysis is seen in Pyruvate kinase def?
Extravascular hemolysis
33
What is the "classic triad" associated with paroxysmal nocturnal hemoglobinuria?
Negative direct antiglobin (Coombs) test, venous thrombosis and pancytopenia
34
RBCs in paroxysmal nocturnal hemoglobinuria are negative for what?
CD55 and CD59
35
What is the importance of CD55?
Prevents formation of C3 convertase
36
What is the importance of CD59?
Blocks C9 from binding to RBC and therefore MAC formation
37
What is the treatment for paroxysmal nocturnal hemoglobinuria?
Eculizumab - prevents C5 conversion to C5a and C5b
38
Patients with PNH are at increased risk for what cancer?
Acute myeloid leukemia
39
What is the cause of sickle cell anemia?
Single point mutation in beta chain resulting in substitution of glutamic acid with valine
40
Hemoglobin C is formed as a result of what?
Point mutation in the 6th codon of beta Hgb chain that leads to replacement of glutamic acid residue with a lysine residue
41
What is seen on a peripheral smear of someone with sickle cell anemia?
Codocytes (target cells), sickle cells, Howell-Jolly bodies
42
An X ray of a patient with sickle cell anemia may reveal what?
Crewcut appearance
43
What drug is used for "treatment" of sickle cell anemia? What is its MOA?
Hydroxyurea - thought to stimulate HbF production
44
What are some causes of warm AIHA?
Autoimmune diseases (SLE), CLL, and various drugs (cephalosporins, penicillins, penicillin derivative, alpha-methyldopa)
45
What infectious organisms can cause cold agglutinin type immunohemolytic anemia?
Mycoplasma pneumoniae and EBV infectious mono
46
What are the lab values in iron def. anemia?
Low iron, low ferritin, low % transferrin saturation, elevated transferrin (or TIBC)
47
What are the lab values in anemia of chronic disease?
Low iron, elevated ferritin, low TIBC (or transferrin)
48
What are the lab values in hemochromatosis?
Elevated iron, elevated ferritin and % transferrin saturation, low transferrin (TIBC)
49
What are the lab values in anemia associated with prgenancy?
Elevated transferrin or TIBC, low % transferrin saturation
50
What are the beginning substrates for heme synthesis?
Glycine and succinyl CoA
51
What is the first step in heme synthesis? What enzyme is responsible for this?
Making delta-aminolevulinic acid; ALA synthase (rate limiting enzyme)
52
ALA synthase is responsible for what step in heme synthesis? What does it require?
1st step in heme synthesis - the rate limiting step; requires B6
53
What enzymes are affected by lead poisoning?
Ferrochelatase and ALA dehydratase
54
What accumulate in the blood in lead poisoning?
ALA and protoporphyrin
55
What enzyme is affected in Acute intermittent porphyria?
Porphobilinogen deaminase (aka uroporphyrinogen I synthase)
56
What accumulates in acute intermittent porphyria?
Porphobilinogen and ALA
57
What are the symptoms of acute intermittent porphyria?
Sxs come and go; Palpitations, port-wine urine, painful abdomen, polyneuropathy, psychological disturbances (depression), precipitated by drugs
58
What is the treatment for acute intermittent porphyria?
Glucose and heme (hemin) to inhibit ALA synthase
59
Defective porphobilinogen deaminase results in what condition?
Acute intermittent porphyria
60
What is the affective enzyme in porphyria cutanea tarda?
Uroporphyrinogen decarboxylase
61
What accumulates in porphyria cutanea tarda?
Uroporphyrin (tea-colored urine)
62
What is used to treat porphyria cutanea tarda?
Repeated phlebotomy
63
What exacerbates porphyria cutanea tarda?
Alcohol consumption
64
Defective uroporphyrinogen decarboxylase results in what disease?
Porphyria cutanea tarda
65
PT tests function of what?
Common pathway and extrinsic pathway in regards to coagulation
66
What are the hemophilias?
Bleeding disorders characterized by def in one of the factors involved in the intrinsic pathway of the coagulation cascade
67
Hemophilia A is a deficiency in what?
Factor VIII
68
What is the inheritance pattern of Hemophilia A?
X linked recessive
69
Hemophilia B is a defect in what?
Factor IX
70
What is the inheritance of Hemophilia B?
X linked recessive
71
What is the deficiency in Hemophilia C?
Factor XI
72
What is the inheritance of Hemophilia C?
Autosomal recessive
73
Hemophilias result in what lab findings?
Increased PTT and normal PT/INR
74
PTT measures what?
Intrinsic pathway (all factors except VII and XIII)
75
What mutation gives rise to Factor V Leiden?
Arg506Gln mutation - DNA point mutation in the factor V gene
76
What is the inheritance pattern of Factor V Leiden?
Autosomal dominant
77
What mutation results in Prothrombin gene mutation and therefore an increase in production of prothrombin>
Mutation in the 3'- untranslated region of the prothrombin gene
78
What disease is characterized by small than anticipated increase in PTT following administration of heparin?
Antithrombin deficiency
79
What disease commonly presents as skin and subcutaneous tissue necrosis following administration of warfarin?
Protein C or S def
80
Patients with Protein C or S def. have diminished ability to inactivate what?
Coagulation factors Va and VIIIa
81
What are the notable lab findings in DIC?
Low Plts, low fibrinogen, increased FDPs, increased PT, PTT, BT
82
What is seen on peripheral smear of DIC?
Schistocytes
83
What is the inheritance pattern of von Willebrand disease?
Autosomal dominant (vs hemophilias AR or XR)
84
What are the lab findings in von Willebrand disease?
Prlonged BT and PTT, normal PT
85
What is PTT prolonged in vWF disease?
Von Willebrand factor normally protects factor VIII
86
What is a ristocetin agglutination assay?
Induces vWF to bind platelet GpIB resulting in platelet agglutination
87
What is the results of the ristocetin agglutination assay in von Willebrand disease?
Impaired platelet aggregation
88
What does vWF bind on the platelet?
GpIb
89
ADP binding to PDY12 receptor on the platelet results in what?
GpIIb/IIIa insertion on the platelet membrane
90
What binds GpIIb/IIIa on the platelet?
Fibrinogen - helps platelets bind together
91
What drugs compete for ADP at the P2Y12 receptor?
Clopidogrel, prasugrel, ticlopidine
92
How does thrombotic thrombocytopenic purpura present?
Pentad: neurologic sxs, renal failure, fever, thrombocytopenia, microangiopathic hemolytic anemia
93
What causes thrombotic thrombocytopenic purpura?
Deficiency of ADAMTS 13
94
What is ADAMTS13?
Von Willebrand factor metalloprotease - normally degrades vWF multimers
95
How does hemolytic uremic syndrome present?
Thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure
96
What are the lab findings in thrombotic thrombocytopenic purpura?
Normal PT and PTT, increased bleeding time; additionally increased LDH and megakaryocytes
97
What is the cause of immune thrombocytopenia?
Antibodies against GpIIb/IIIa, resulting in splenic macrophage consumption of plt-ab complex
98
What causes thrombotic thrombocytopenic purpura?
Def of ADAMTS13
99
What is the cause of Bernard-Soulier syndrome?
Low GpIb resulting in defect in plt-vWF adhesion
100
What is the result of the ristocetin assay in Bernard Soulier syndrome?
No aggregation
101
What is in cryoprecipitate?
Fibrinogen, factor VIII, factor XIII, vWF and fibronectin
102
What is given in DIC?
Fresh frozen plasma
103
What are the "B" symptoms? When do you classically see them?
Fever, night sweats, and weight loss; classically HL, but also NHL
104
What type of Hodgkins lymphoma is is seen more commonly in women over men?
Nodular sclerosing type
105
When do you see Reed Sternberg cells?
Hodgkins lymphoma
106
Reed sternberg cells are positive for what cells markers?
CD15 and CD30
107
What is the appearance of Reed Sternberg cells?
Bilobed nucleus or binucleate with prominent eosinophilic nucleoli; "owl eyes" appearance
108
What type of HL has lacunar cells? What do they look like?
Nodular sclerosis HL; multilobated nucleus that lies in an open, pale cytoplasm
109
HL characterized by cells with multilobated nucleus that lies in an open, pale cytoplasm
Nodular sclerosing type
110
What type of HL is characterized by eosinophilia?
Mixed cellularity type
111
What are eosinophils seen in Mixed cellularity type HL?
RS cells release IL-5
112
Describe the appearance of "popcorn cells." What cancer are they seen in?
Polylobulated nuclei and small peripheral nucleoli without perinucleolar halos; seen in lymphocyte predominant
113
What cells are seen in nodular lymphocyte-predominant HL?
Popcorn cells - lymphocytic and histiocytic
114
HL that presents with negative CD15 and CD30 cells is seen in what type?
Nodular lymphocyte predominant HL
115
What translocation is associated with follicular NHL?
Translocation 14;18 - resulting in overexpression of Bcl2
116
Translocation 14;18 results in what NHL?
Follicular NHL
117
Ig heavy chain is on what chromosome?
14
118
How do you differentiate follicular hyperplasia from lymphoma?
Follicular lymphoma has monoclonality, Bcl2 expression, and absence of tingible body macrophage in the germinal center
119
What translocation is associated with Mantle cell lymphoma?
Translocation 11;14 - overexpression of Cyclin D1
120
NHL with CD5+ and CD23- B cells and translocation 11;14
Mantle cell lymphoma
121
What type of B cell are seen in Mantle Cell lymphoma?
CD5+ and CD23-
122
How do you differentiate between CLL and Mantle Cell lymphoma?
CLL is CD23+ and mantle cell is CD23-
123
What translocation is seen in marginal zone lymphoma?
Translocation 11; 18
124
Translocation 11;18 is seen in what NHL?
Marginal zone lymphoma
125
What disease of chronic inflammation can result in marginal zone lymphoma?
Sjogrens, chronic gastritis (H pylori infection) and Hashimoto thyroiditis
126
What translocation is seen in Burkitt lymphoma and what does it result it?
8;14 - overexpression of c-myc
127
What chromosome is c-myc on?
8
128
Translocation 8;14 results in what cancer?
Burkitt lymphoma
129
Describe the starry sky appearance seen in Burkitt lymphoma
Reactive histiocytes in a backdrop of blue neoplastic cells
130
Bcl-2 is on what chromosome?
18
131
Adult T cell lymphoma is caused by infection with what?
Human T cell lymphotropic virus type 1
132
Infection with HTLV-1 can cause what?
Adult T cell lymphoma
133
What is the genome of HTLV-1?
+ssRNA; retroviridae family
134
What is a Pautrier microabscess? What is it associated with?
Intraepidermal neoplastic cell aggregates associated with mycosis fungoides
135
Describe the characteristic cells seen in Mycosis fungoides
Atypical CD4+ cells with cerebriform nuclei and intraepidermal neoplastic cell aggregates
136
What is mycosis fungoides?
CD4+ neoplasm characterized by skin patches/plaques with cells with cerebriform nuclei
137
What is Sezary syndrome?
Progression of Mycosis fungoides
138
What is the Pseudo-Pelger-Huet anomaly?
Neutrophils with bilobed nuclei. Typically seen after chemotherapy
139
How can you differentiate between Waldenstrom macroglonulinemia and Multiple myeloma?
WM has IgM M spike; Mult myeloma has IgG or IgA M spike
140
What is the difference between MGUS and multiple myeloma?
MGUS = bone marrow <10% monoclonal plasma cells; no CRAB findings
141
Tdt is a marker for what?
Pre-T and pre-B cells
142
CD10+ is a marker for what?
Marker of pre-B cells
143
Pre-T ALL expresses what cell markers on flow cytometry?
Tdt+, CD3+, CD7+; also is PAS positive
144
What markers are positive in both pre-T and pre-B ALL?
Tdt (terminal deoxynucleotidyl transferase) and PAS+
145
What are unique cell markers seen on flow cytometry of pre-B ALL?
CD10+, CD19+, CD20+
146
How does pre-T ALL usually present?
Male in teens/early 20s with mediastinal mass (can cause pleural effusion)
147
What translocation is associated with a better prognosis in ALL?
12;21
148
What are some risk factors for developing AML?
Prior treatment with alkylating agents, radiation, Down syndrome, PNH, Fanconi anemia, myeloproliferative syndromes
149
What translocatin is seen in acute promyelocytic leukemia?
15;17 - links retinoic acid receptor alpha gene on chromosome 17 with PML gene on chromosome 15
150
Translocation 15;17 is highly specific for what?
Promyelocytic leukemia (AML-M3)
151
What cell markers can be seen on flow cytometry in CLL?
CD19, CD20, CD5, CD23
152
What cells are characteristically seen in CLL?
Smudge cells
153
What is Richter's transformation?
CLL transformation to aggressive lymphoma, most commonly diffuse large B cell lymphoma
154
How is hairy cell leukemia diagnosed?
Flow cytometry - CD103+ CD11c+ CD25+ CD19+ CD20+ CD22+
155
Hairy cell leukemia is a tumor of what cell type?
Mature B cell
156
How do patients with hairy cell leukemia present?
Massive splenomegaly and pancytopenia
157
Hairy cell leukemia is positive for what stain?
TRAP - tartrate-resistan acid phosphatase
158
What is seen on a bone marrow aspiration in hairy cell leukemia?
Dry tap - hairy cell leukemia causes bone marrow fibrosis
159
What are the treatments for hairy cell leukemia?
Cladribine and pentostatin - purine analogs
160
What is seen on flow cytometry in hairy cell leukemia?
CD103, CD11c, CD25, CD19, CD20, CD22
161
Langerhans cell histiocytosis is a proliferative disorder of what cells?
Specialized dendritic cells - from monocyte lineage
162
How does Langerhans cell histiocytosis present?
Commonly in a child with lytic bone lesions (primarily in skull) and eczematous rash; possibly with recurrent otitis media and a mass involving the mastoid bone
163
What is the hallmark lesion seen in Langerhans cell histiocytosis?
Birbeck granules - tubules with dilated terminal end resembling a tennis racket
164
Cells in langerhans cell histiocytosis express what cell markers?
CD1a and S100 (neural crest cell origin)
165
Chronic myelogenous leukemia presents with a dysregulated production of what cells?
Neutrophils, metamyelocytes, myelocytes, basophils
166
What translocation is seen in CML?
9;22 - BCR-ABL
167
How do patients with CML present?
Splenomegaly on exam
168
What chromosome in BCR on?
22
169
What chromosome is ABL1 one?
9
170
What is the philadelphia chromosome?
9;22 BCR-ABL1 fusion
171
9;22 translocation is seen in what disease? What does it result in?
CML; make a constitutively active tyrosine kinase
172
CML may transform to what? How is it characterized?
Transform to AML or ALL "blast crisis" >20% myeloblasts or lymphoblasts in peripheral blood
173
How is CML differentiated from reactive neutrophilic leukocytosis?
Leukocyte alkaline phosphatase stain is negative in CML, but positive in leukemoid reaction
174
What is used for treatment of CML?
Imatinib - tyrosine kinase inhibitor
175
Bone marrow aspirate in myelodysplastic syndrome reveals what?
Ringed sideroblasts - erythroblasts with iron-laden mitochondria
176
What are some risk factors for myelodysplastic syndrome?
Radiation, benzene, chemotherapy
177
Myelodysplastic syndromes increase risk for what?
AML
178
What mutation is seen in polycythemia vera?
JAK2
179
What myeloproliferative disorders have a high incidence of JAK2 mutations?
Polycythemia vera, myelofibrosis, essential thrombocythemia
180
What is aquagenic pruritus? What is it a sign of?
Ithcing following exposure to warm water; sign of polycythemia vera
181
How does polycythemia vera present?
Intense itching after hot shower, facial flushing, erythromelalgia, may have hyperuricemia (and therefore gout)
182
What is first line treatment of polycythemia vera?
Phlebotomy; but can also use hydroxyurea and ruxolitinib
183
What is ruxolitinib?
Jak1/2 inhibitor
184
What disease is characterized by massive proliferation of megakaryocytes and platelets, and includes symptoms of bleeding and thrombosis?
Essential thrombocythemia
185
What is seen on a peripheral smear in essential thrombocythemia?
Markedly increased number of platelets
186
What mutation is seen in essential thrombocythemia?
JAK2 mutation
187
During rapid hemolysis, Hgb binds what?
Haptoglobin - resulting in a decrease in serum haptoglobin
188
What is seen on bone marrow aspiration in aplastic anemia?
Hypocellularity, fat cells and marrow stroma
189
What is seen in bone marrow aspirate of immune thrombocytopenia?
Increased megakaryocytes
190
What is seen in a peripheral smear in immune thrombocytopenia?
Few large platelets
191
What is the cause of immune thrombocytopenia? How does it present?
Antibodies against GpIIb/IIIa; presents with petechial rash and easy bruising/bleeding
192
What is the defect seen in Glanzmann thrombasthenia?
Defect in glycoprotein GPIIb/IIIa complex; leads to defect in platelet to platelet aggregation
193
What labs do you see in von Willebrand disease?
Increased bleeding time, increased PTT and normal PT
194
What is an important side effect of ticlopidine?
Neutropenia
195
What is the MOA of ticlopidine?
Prevents ADP from binding to platelet receptors
196
What is the MOA of heparin?
Enhances activity of ATIII - decreasing the activity of factor Xa and thrombin
197
What is the antidote for heparin?
Protamine sulfate
198
What is used for immediate anticoagulation for a PE?
Heparin
199
What is the MOA of LMWH?
Enhances activity of ATIII but more selectively directed toward Xa with some activity against thrombin
200
Describe the elimination of heparin.
Dose dependent
201
Describe the elimination of LMWH
Dose-independent
202
What is the MOA of Fondaparinux?
Indirect thrombin inhibitor - enhances the activity of ATIII but only acts on factor Xa
203
What is the antidote for LMWH?
Can use protamine sulfate but has lesser effect
204
What is heparin-induced thrombocytopenia?
IgG antibodies against heparin-bound platelet factor 4, which activates platelets and causes thrombosis and thrombocytopenia
205
What is the treatment for heparin induced thrombocytopenia?
D/C heparin and administer direct thrombin inhibitor - bivalirudin
206
What are the direct thrombin inhibitors?
Bivalirudin, argatroban, dabigatran
207
What is the only oral agent in the direct thrombin inhibitor class?
Dabigatran
208
What is the reversal agent for dabigatran?
Idarucizumab
209
What is the reversal for direct thrombin inhibitors?
Idarucizumab for dabigatran; consider PCC and/or antifibrinolytics if no reversal agent
210
What is the MOA dabigatran?
Oral inhibitor of thrombin
211
What is the MOA of argatroban?
Direct inhibitor of thrombin (IIa)
212
What is the MOA of bivalirudin?
Direct inhibitor of thrombin (IIa)
213
What is the MOA of apixaban?
Direct inhibitor of factor Xa
214
What is apixaban used for?
Oral agent for prophylaxis of DVT, PE, and A fib
215
What is the MOA of rivaroxaban?
Direct inhibitor of factor Xa
216
What is used for anticoagulation therapy in pregnancy?
Heparin - does not cross the placenta
217
What is the MOA of warfarin?
Impairs vitamin K-dependent synthesis of clotting factors II, VII, IX, X and protein C and S by interfering with the gamma-carboxylation of the VK dependent coagulation factors
218
What enzyme is inhibited by Warfarin?
Vit K epoxide reductase
219
What are the affects of Vit K on warfarin?
Vit K reduces the affects of warfarin - can lead to clotting
220
What are the affects of vitamin E on warfarin?
Vitamin E can enhance the affects of warfarin
221
What vitamins can affect warfarin?
Vitamin K and Vitamin E
222
How does Vit E affect warfarin?
Vit E enchances warfarin by slowing the synthesis of VK dependent coagulation factors
223
What antibiotics notably affect warfarin?
3rd gen cephalosporins and macrolides
224
What affect does cefidinir (3rd gen) have on warfarin?
3rd gens kills VK synthesizing bacteria in gut and inhibit Vit K epoxide reductase, enhancing the affects of warfarin
225
What affect do macrolides have on warfarin?
Macrolides (exception azithromycin) inhibit Cyp450 - enhancing warfarin affects
226
How is warfarin monitored?
PT/INR
227
How is warfarin reversed?
Rapid: FFP or 4-factor prothrombin complex concentrate (PCC); non-rapid: Vit K1 (phytonadione)
228
What is the site of action for warfarin?
Liver
229
What is the site of action for heparin?
Blood
230
How is heparin monitored?
PTT
231
What are the thrombolytic drugs?
Alteplase, streptokinase, reteplase, tenecteplase
232
What fibrinolytic drug can cause anaphylaxis?
Streptokinase
233
What are the contraindications for fibrinolytics?
Recent surgery, active bleeding, H/O diatheses, h/o intracranial bleeding, or severe hypertension
234
What are the uses for thrombolytics?
Early MI, early ischemic stroke, direct thrombolysis of severe PE
235
Fibrinolytics have what effects on lab values?
Increased PT and PTT, no effect on bleeding time
236
What are the reversal agents for fibrinolytics?
Aminocaproic acid and tranexamic acid, or platelet transfusions and factor corrections
237
What is the MOA of aminocaproic acid in reversal of fibrinolytics?
Opposes action by competing for lysing binding sites on plasminogen and plasmin, ultimately blocking interaction with fibrin
238
What is the MOA of tranexamic acid?
Forms reversible complex that displaces plasminogen from fibrin and inhibits proteolytic activity of plasmin
239
In order to block the interaction between plasminogen or plasmin with fibrin, what reversal agent would you use?
Aminocaproic acid
240
Low dose aspirin has what effect?
Inhibits platelet aggregation
241
At an intermediate dose, what are the affects of aspirin?
Antipyretic and analgesic
242
At high doses, what are the affects of aspirin?
Anti-inflammatory
243
What are the ADP inhibitors?
Clopidogrel, prasugrel, ticlopidine, and ticagrelor (reversible)
244
What is the MOA of ADP receptor inhibitors?
Prevent ADP from binding P2Y12 receptor, preventing the ADP-induced expression of gp IIb/IIIa on the surface of platelets
245
Patient presents a few weeks after an acute MI with fever and mouth ulcers, what drug might be causing the issue?
Ticlopidine
246
What is an adverse effect of ticlopidine?
Neutropenia
247
What is a common adverse effect of the ADP receptor inhibitors?
Thrombotic thrombocytopenic purpura
248
What is the MOA of ticagrelor?
Reversibly inhibits ADP binding to P2Y12 receptor, preventing expression of gp IIb/IIIa on platelet membrane
249
What is the MOA of abciximab?
Binds to gp IIb/IIIa receptor on platelets, preventing platelet interaction with fibrinogen and therefore aggregation
250
What are the gp IIb/IIIa inhibitors?
Abciximab, eptifibatide and tirofiban
251
What is the MOA of eptifibatide?
Bind to gp IIb/IIIa and therefore inhibit platelet aggregation
252
What are the phosphodiesterase inhibitors used to inhibit platelet aggregation?
Cilostazol and diphyridamole
253
What is the MOA of dipyridamole?
PDE inhibitor, increasing cAMP in platelets inhibiting the platelet aggregation and inducing vasodilation
254
What is the MOA of cilostazol?
PDE inhibitor in platelets, causing increase in cAMP and therefore reducing platelet aggregation and causing vasodilation
255
What is used for the treatment of intermittent claudication?
PDE inhibitors - dipyridamole and cilostazol
256
What are the toxicities of the PDE inhibitors?
Facial flushing, headache, abdominal pain, hypotension, nausea
257
What is the MOA of methotrexate?
Folate analog - inhibits dihyrdofolate reductase
258
What are the AEs of methotrexate?
Myelosuppression, mucositis, hepatotoxicity, and pulmonary fibrosis
259
What is given in conjunction with methotrexate? Why?
Leucovorin - folinic rescue
260
What cancers is methotrexate used for?
Leukemias (ALL), lymphomas, choriocarcinoma, sarcomas
261
What non-cancer treatments is methotrexate used for?
Ectopic pregnancy, abortion (with misoprostol), rheumatoid arthritis, psoriasis, IBD, polymyositis/dermatomyositis
262
What is the MOA of 5-fluorouracil?
Pyrimidine analog - Inhibits thymidylate synthase
263
What cancers is 5-FU used in?
Colon, pancreatic, basal cell
264
What can be used to enhance the efects of 5-FU?
Leucovorin
265
What is the MOA of cytarabine?
Pyrimidine analog that inhibits DNA polymerase
266
What cancers is cytarabine used in?
Leukemia (AML), and lymphoma
267
What are the two pyrimidine analog anti-metabolites?
Cytarabine (inhibits DNA polymerase) and 5-FU (inhibits thymidylate synthase)
268
What are the AEs of 5-FU?
Myelosuppression, hand-foot syndrome
269
What are the AEs of cytarabine?
Myelosuppression and pancytopenia
270
What is the MOA of cladribine?
Purine analog that can lead to inhibition of DNA polymerase and DNA strand breaks
271
What is cladribine used in?
Hairy cell leukemia
272
What is the AEs of cladribine?
Myelosuppression, nephrotoxicity, and neurotoxicity
273
What is the MOA of gemcitabine?
Cytosine analog that inhibits DNA polyermase and ribonucleotide reductase resulting in chain termination
274
What is the MOA of azathioprine?
Purine analog that inhibits de novo purine synthesis
275
What is azathioprine and 6-mercaptopurine metabolized by?
Xanthine oxidase
276
What drug inhibits azathioprine metabolism?
Allopurinol or febuxostat (both inhibit xanthine oxidase)
277
What is the MOA of bleomycin?
Induces free radical formation into DNA that induces DNA strand breaks
278
What is the MOA of dactinomycin?
Intercalates into DNA between guanine and cytosine basepairs resulting in single stranded breaks and inhibits DNA dependent RNA polymerase
279
What is bleomycin used for?
Testicular cancer and HL
280
What is dactinomycin used for?
Childhood cancers: Wilms tumor, Ewing sarcoma, Rhabdomyosarcoma
281
What are the AEs of bleomycin?
Pulmonary fibrosis, skin hyperpigmentation, myelosuppression is RARE and minimal
282
What are the AEs of dactinomycin?
Myelosuppression
283
What is the MOA of doxorubicin?
Intercalates into DNA and produces free radicals via forming iron complexes
284
What are the AEs of doxorubicin?
Dilated cardiomyopathy, alopecia, myelosuppression
285
How can cardiotoxicity be avoided in doxorubicin use?
Dexarazoxane - iron chelator
286
What is dexrazoxane?
Iron chelator used to prevent cardio toxicity with doxorubicin use
287
What antitumor drugs generate free radicals and intercalate into the DNA?
Doxorubicin and daunorubicin
288
What class of drugs is cyclophosphamide in?
Alkylating agent - nitrogen mustards
289
What is the MOA of cyclophosphamide?
Alkylates N7 on guanine and cross likes DNA
290
Cyclophosphamide requires what?
Bioactivation by the liver.
291
What is the MOA of ifosfamide?
Cross links DNA at N7 on guanine; also a nitrogen mustard
292
What are the AEs of cyclophosphamide and ifosfamide?
Hemorrhagic cystitis, transitional cell carcinoma, myelosuppression, SIADH
293
How is hemorrhagic cystitis from cyclophosphamide prevented?
Mensa - binds toxic metabolite acrolein; or can use n-acetylcysteine
294
What is acrolein?
Toxic metabolite that causes hemorrhagic cystitis
295
What is mensa?
Used for preventing hemorrhagic cystitis in cyclophosphamide
296
What are nitrosureas primarily used to treat?
Brain tumors such as GBM
297
What is the MOA of nitrosureas?
Cross link DNA by alkylating O6 on guanine
298
What are the AEs of nitrosoureas?
CNS toxicity - dizziness, convulsions, ataxia
299
What is the MOA of platinums?
Cross link DNA
300
What are the platinum agents used in oncology?
Cisplatin, carboplatin, oxaliplatin
301
What are the AEs of cisplatin and carboplatin?
Nephrotoxicity, ototoxicity, peripheral neuropathy, and emesis
302
What agents should be give prior/with cisplatin/carboplatin?
Chloride diuresis prior and amifostine to prevent nephrotoxicity; use 5HT3 antagonists to prevent emesis
303
What is amifostine? What is it used for?
Free radical scavenger; used to prevent nephrotoxicity from platinums
304
What are the AEs of oxaliplatin?
Neurotoxic
305
What is oxaliplatin used for?
Cancers resistant to other platinums
306
What is cisplatin/carboplatin used to treat?
Testicular, bladder, ovarian and lung cancers
307
What is the MOA of busulfan?
Cross links DNA
308
What is Busulfan used for?
Ablate bone marrow prior to bone marrow transplant
309
What are the AEs of busulfan?
Pulmonary fibrosis, myelosuppression, hyperpigmentation
310
Chemotherapeutic Topoisoerase inhibitors are specific for what stages of the cell cycle?
S phase and G2
311
What is the MOA of irinotecan?
Inhibit topoisomerase I and prevent DNA unwinding and replication
312
What is the MOA of etoposide?
Inhibit topoisomerase II and therefore increase DNA degradation
313
What is the MOA of topotecan?
Inhibit topoisomerase II and prevent DNA unwinding and replication
314
What is irinotecan used for?
Colon cancer
315
What is topotecan used for?
Ovarian cancer and small cell lung cancer
316
What is the MOA of teniposide?
Inhibits topoisomerase I
317
What are the AEs of irinotecan?
Myelosuppression and diarrhea
318
What are the AEs of etoposide and teniposide?
Myelosuppression and alopecia
319
What is etoposide and teniposide used to treat?
Testicular cancer and small cell lung cancer and leukemias/lymphomas
320
What is the MOA of paclitaxel?
Binds B-tubulin and enhances assembly of tubulin dimers into microtubules; stabilizes existing tubules. Microtubules are unable to depolymerize - mitotic arrest
321
Taxanes are used in the treatment of what?
Breast and ovarian cancer
322
What are the toxicities of taxanes?
Peripheral neuropathy, myelosuppression, hypersensitivity (infusion reaction) and alopecia
323
What lymphoma is vinblastine used to treat?
Hodgkin lymphoma
324
What lymphoma is vincristine used to treat?
NHL
325
What are the toxicities associated with vincristine?
Paralytic ileus (constipation), areflexia, peripheral neuropathy
326
What toxicities are associated with vinblastine?
Myelosuppression
327
What is the MOA of vinca alkaloids?
Bind to beta-tubulin and prevent microtubule polymerization
328
What is the MOA of hydroxyurea?
Inhibits ribonucleotide reductase, decreasing DNA synthesis
329
What are the SERMs?
Tamoxifen and raloxifene
330
What is the MOA of tamoxifen?
Competitive inhibitor of estradiol binding to ER; Acts as a partial estrogen agonist in endometrium (increased risk of endometrial cancer)
331
What is the most common SE of tamoxifen therapy?
Hot flashes
332
Tamoxifen and raloxifene both increase the risk for what?
Thromboembolic disease
333
What is trastuzumab?
MAB against Her2
334
Binding of trastuzumab to HER2 has what effects?
Inhibits HER2 signaling pathway and activates antibody-dependent cytotoxicity
335
What is the MOA of anastrozole?
Aromatase inhibitor
336
What are aromatase inhibitors used?
Postmenopausal women with ER + breast cancer
337
Imatinib inhibits the activity of what?
Tyrosine kinases - BCR-ABL (in CML), and c-KIT and PDGF (in GI stromal tumors)
338
What is the MOA of bevacizumab?
Mab against VEGF. Inhibits angiogenesis
339
What are the AEs of bevacizumab?
Hemorrhage, blood clots, impaired wound healing
340
What is the MOA of erlotinib?
EGFR tyrosine kinase inhibitor
341
What is the MOA of Cetuximab?
Mab to EGFR
342
What is the AE of erlotinib?
Rash
343
What is erlotinib used for?
Non-small cell lung cancer
344
What is cetuximab used for?
Stage IV CRC (wild type KRAS), and head and neck cancer
345
In order to use cetuximab, what needs to be true of the cancer type?
KRAS wild type
346
What is the MOA of rituximab?
Mab against CD20
347
What is an AE of rituximab?
Increased risk of PML
348
What is the MOA of bortezomib?
Proteasome inhibitor - induce arrest at G2-M phase and apoptosis
349
What is the MOA of carfilzomib?
Proteasome inhibitor - induces arrest at G2-M phase and apoptosis
350
What are two proteasome inhibitors used in the treatment of multiple myeloma?
Bortezomib and carfilzomib
351
What is borezomib/carfilzomib used in the treatment of?
Multiple myeloma, mantle cell lymphoma
352
What are the AEs of bortezomib/carfilzomib?
Peripheral neuropathy, herpes zoster reactivation
353
What is the MOA of vemurafenib?
Inhibitor of BRAF oncogene in melanoma
354
What drug is used to treat metastatic melanoma + for the BRAF oncogene?
Vemurafenib
355
What BRAF mutation is Vemurafenib active against?
V600E
356
What is the MOA of Rasburicase?
Recombinant uricase that catalyzes the metabolism of uric acid to allantoin
357
What labs are associated with tumor lysis syndrome?
Hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia
358
What is used to treat tumor lysis syndrome?
Rasburicase, allopurinol and hydration
