HEMATOLOGY AND ONCOLOGY- Pharmacology Flashcards
1
Q
Mechanism of action of Heparin
A
Cofactor for the activation of antithrombin, ↓ thrombin, and ↓ factor Xa
2
Q
Clinical use of Heparin
A
Immediate anticoagulation for Pulmonary embolism, acute coronary syndrome, MI, deep venous thrombosis (DVT)
3
Q
Can heparin be used during pregnancy?
A
Yes. (does not cross placenta)
4
Q
What need to be followed when using Heparin?
A
PTT
5
Q
Secondary effects due to use of Heparin
A
Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drgu interactions
6
Q
What is the rapid reversal antidote for Heparin?
A
Use protamine sulfate
7
Q
How does protamine work?
A
Positively charged molecule that binds negatively charged heparin
8
Q
Which are low molecular weight heparin?
A
Enoxaparin
Dalteparin
9
Q
Which is the benefict of Low weght heparin?
A
Act more on factor Xa, have better bioavilability and 2-4 times longer half life
10
Q
How is low molecular weight heparin administered?
A
Subcutaneously
11
Q
Does low molecular weight heparin require monitoring?
A
No
12
Q
Which is the risk when using low molecular weight heparin?
A
Not easily reversible
13
Q
What is HIT?
A
Heparin Induced Thrombocytopenia
14
Q
Pathophysiology of Heparin Induced Thrombocytopenia
A
Development of IgG antibodies against heparin bound to platelet factor 4. Antibody- Heparin- PF4 coplex activates platelets→ Thrombosis and thrombocytopenia
15
Q
Derivates of hirudin
A
Argatroban, bivalirudin
16
Q
Which anticoagulant is used by leeches?
A
Hirudin
17
Q
What is the effect of Argatroban, bivalirudin?
A
Inhibit thrombin directly
18
Q
When is recommended to use Argatroban, bivalirudin?
A
Used instead of heparin for anticoagulating patients with Heparin Induced Thrombocytopenia
19
Q
What is the coumadin?
A
Warfarin
20
Q
What is the mechanism of action of Warfarin?
A
Inteferes with normal synthesis and γ carboxylation of vitamin K dependent clotting factors II, VII, IX and X and proteins C and S
21
Q
Who metabolizes Warfarin?
A
By cytochrome P 450 pathway
22
Q
What do laboratory assay stbalish about Warfarin?
A
Warfain has effect on extrinsic pathway
23
Q
Which lab study is modified with Warfarin?
A
↑ PT
24
Q
How is the half life of Warfarin?
A
Long half life
25
Clinical use for Warfarin
Chronic anticoagulation (after STEMI, venous thromboembolism prophylaxis, and prevention of stroke in atrial fibrillation)
26
What main difference does Warfarin has compared to Heparin?
Warfarin is not used in pregnant women (because warfarin, unlike heparin, can cross the placenta)
27
How is Warfarin monitored?
Follow PT/ INR values
28
Toxic effects of Warfarin
Bleeding, teratogenic, skin/ tissue necrosis, drug interactions
29
What is used fro reversal of warfarin overdose?
Give vitamin K
30
What is used for rapid reversal of severe warfarin overdose?
Frozen plasma
31
Direct Factor Xa inhibitors
Apixaban, rivaroxaban
32
Mechanism of action of Apixaban, rivaroxaban
Bind and Directly inhibit Factor Xa
33
Which Direct Factor Xa inhibitors is used in Pulmonary embolism?
rivaroxaban
34
Clinical use for Apixaban, rivaroxaban
Treatment and prophylaxis of DVT, stroke prophylaxis in patient with atrial fibrillation
35
What is a benefict of Apixaban, rivaroxaban ?
Oral agents do not require coagulation monitorin
36
Toxic effect of Apixaban, rivaroxaban
Bleeding
37
Which is the antidote for Direct Factor Xa inhibitors?
No specific reversal agent available
38
How is the structure of Heparin?
Large anionic, acicid
39
Route of administering Heparin
Parenteral (IV, SC)
40
Site of action of Heparin
Blood
41
Onset of Action of Heparin
Rapid (seconds)
42
Activates antitrhrombin, which ↓ the action of IIa (thrombin) and factor Xa
Heparin
43
How is the duration of action of Heparin?
Acute (hours)
44
Does Heparin inhibits coagulation in vitro?
Yes
45
Treatment of acute overdose of Heparin
Protamine sulfate
46
How is Heparin monitored?
By PTT
47
Which pathway is altered by Heparin?
Intrinsic pathway
48
Does Heparin crosses placenta?
No
49
Structure of Warfarin
Small lipid-soluble molecule
50
Route of administering Warfarin
Oral
51
Site of action of Warfarin
Liver
52
Onset of action of Warfarin
Slow, limited by half lives of normal cloting factors
53
Impairs the synthesis of vitamin K dependent clotting factors
Warfarin
54
What is the mechanism of action of Warfarin?
Vitamin K antagonist
55
How is the duration of action of Warfarin?
Chronic (days)
56
Does Warfarin inhibits coagulation in vitro?
No
57
Treatment of acute overdose of Warfarin
IV vitamin K and fresh frozen plasma
58
How is Warfarin therapy monitored?
With PT/INR
59
Which pathway is modified with Warfarin therapy?
Extrinsic pathway
60
Does Warfarin crosses placenta?
Yes (teratogenic)
61
Who are Thrombolytics?
Alteplase (tPA)
Reteplase (rPA)
Tenecteplase (TNK-tPA)
62
What is tPA?
Tissue plasminogen activator (tPA)
63
Mechanism of actionof Thrombolytics
Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots
64
How are coagulation times affected by Thrombolytics?
↑ PT
| ↑ PTT
65
Do thrombolytics affect platelet count?
No change in platelet count
66
Clinical use for Thrombolytics
Early MI, early ischemic stroke, direct thrombolysis of severe Pulmonary Embolism
67
Toxic effect of thrombolytics
Bleeding
68
Contraindications of Thrombolytic drugs
In patients with active bleeding, hystory of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension
69
How is thrombolytic toxicity treated?
With Aminocaproic acid
70
What is aminocaproic acid?
An inhibitor of fibrinolysis
71
What else can be used to correct factor deficiencies?
Fresh frozen plasma and cryoprecipitate
72
What is the mechanism of action of aspirin?
Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation
73
What is the effect of aspirin on platelets?
Platelets cannot synthesize new enzyme, so effect lasts until new platelets are produced
74
What efect does aspirin has?
↑ bleeding time, ↓ TXA2 and prostaglandins
75
How does aspirin affects PT and PTT?
No effect on PT or PTT
76
Clinical use for Aspirin
Antipyretic, analgesic, anti-inflammatory, antiplatelet (↓ aggregation)
77
Toxic effects of Aspirin
Gasrtic ulceration, tinnitus (CN VIII)
78
What does chronic use of aspirin leads to?
Acute renal failure, intesrtitial nephritis, and upper GI bleeding
79
What is the effect of Aspirin in children?
Reye syndrome when treating Viral infection
80
What happens with Aspirin overdose?
Causes Respiratory alkalosis initially, which is then superimposed by metabolic acidosis
81
ADP receptor inhibitors
Clopidogrel, ticlopidine, prasugel, ticagrelor
82
How is clopidogrel consider?
ADP receptor inhibitor
83
Mechanism of action of clopidogrel
Inhibit platelet aggreagation by irreversibly blocking ADP receptor
84
What is the effect of clopidogrel with fibrinoge?
Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIA from binding to fibrinogen
85
Clinical use for ADP receptor inhibitors
Acute coronary syndrome, coronary stenting
86
What is a benefit of clopidogrel use?
↓ incidense of recurrence of thrombotic stroke
87
Toxic effect of toclopidine
Neutropenia
88
Possible secondary effect of ADP receptor inhibitors
TTP/ HUS may be seen (Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS))
89
Phosphodiesterase III inhibitor
Cilostazol, dipyridamole
90
What is the mechanism of action of Cilostazol, dipyridamole?
Phosphodiesterase III inhibitor; ↑ cAMP in platelets, thus inhibiting platelet aggregation; vasodilators
91
Clinical use for Cilostazol, dipyridamole
Intermitent claudication, coronary vasodilation, prevention of stroke or TIAs (Transient ischaemic attack), angina prophylaxis
92
Which medicine is combined with Cilostazol, dipyridamole, in Transient ischaemic attack?
Aspirin
93
Toxic effect of Cilostazol, dipyridamole
Nausea, headache, facial flushing, hypotension, abdominal pain
94
GP IIb/IIIa inhibitors
Abxicimab
Eptifibate
Tirofiban
95
Mechanism of action of Abxicimab
Bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
96
From what is Abxicimab made?
From monoclonal antibody Fab fragments
97
Clinical use for GP IIb/IIIa inhibitors
Unstable angina, percutaneous transluminal coronary angioplasty
98
Toxic effect og GP IIb/IIIa inhibitors
Bleeging, thrombocytopena
99
Which cancer drugs inhibit DNA synthesis (S phase)?
Antimetabolites
| Etoposide
100
Which cancer drug inhibits both S and G2 phases in cell cycle?
Etoposide
101
What is the mechanism of action of Bleomycin as Cancer drug?
Inhibits G2 phase of cell cycle
102
What happens in G2 phase of cell cycle?
Synthesis of components needed for mitosis
103
Cancer drugs that inhibit M phase in cell cycle
Vince alkaloids and taxols
104
What happens in G1 phase of cell cycle?
Synthesis of components needed for DNA synthesis
105
Antineoplastic that inhibit nucleotide synthesis
Metrotexate
5-FU
6-mercaptopurine
106
Drugs that decrease thymidine synthesis
Metrotexate
| 5-FU
107
Antineoplastic that decreases purine synthesis
6-mercaptopurine
108
Drugs that inhibit DNA synthesis
Alkylating agents
DNA intercalators
Etoposide
109
Example of Alkylating agent
Cisplastin
110
What is the effect of cisplastin?
Cross link DNA
111
DNA intercalators
Dactinomycin, Doxorrubicin
112
What is the mechanism of action of Etoposide?
Inhibits topoisomerase II
113
Antineoplastics that inhibit Cellular division
Vinca alkaloids
| Paclitaxel
114
What is the effect of Vinca alkaloids?
Inhibit microtubule formation
115
What is the mechanism of action of Paclitaxel?
Inhibits microtubule disessembly
116
Steps to get to cellular division
Nucleotide synthesis → DNA → RNA → Protein → Cellular division
117
Drugs consider antimetabolites
```
Metrotexate (MTX)
5- fluorouracil (5-FU)
Cytarabine (arabininofuranosyl cytidine)
Azathioprine/ 6 Mercaptopurine
6 thioguanine
```
118
Mechanism of action of Metotrexate
Folic acid analog that inhibits dyhydrofolate reductase
119
What is the result of Metotrexate inhibiting dyhydrofolate reductase?
↓ dTMP → ↓ DNA and ↓ protein synthesis
120
Cancer Clinical use for Metotrexate
Leukemias, lymphomas, choriocarcinoma, sarcomas
121
Non neoplastic clinical use for Metotrexate
Abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, inflammatory bowel disease
122
Secondary effects of Metotrexate
Myelosuppression
Macrovesicular fatty change in liver
Mucositis
Teratogenic
123
How is reverse the myelosupression caused by Metotrexate?
Reversible with Leucovorin (folinic acid) "rescue"
124
Pyrimidine analogs
5- FU
| Cytarabine
125
How is the activated form of 5-FU?What is its purpose?
5F-dUMP, which covalently complexes folic acid
126
What is the effect of 5F-dUMP- Folic acid complex?
Inhibtis thymidilate synthase→ ↓ dTMP → ↓DNA and ↓ protein synthesis
127
Clinical use for 5-FU
Colon Cancer, pancreatic cancer, basal cell carcinoma (topical)
128
Side effects of 5 FU
Myelosuppression
| Photosensitivity
129
Myelosuppession caused by 5 FU could it be reverse with leucovorin?
NO
130
Which is the "rescue" in case of overdose with 5 FU?
Uridine
131
Arabinofuranosyl cytidine
Cytarabine
132
Mechanism of action of cytarabine
Pyrimidine analog → inhibitions of DNA polymerase
133
When is reccomended the clinical use of Cytarabine?
Leukemias, Lymphomas
134
Toxic effects of Cytarabine
Leukopenia, thrombocytopenia, megaloblastic anemia
| Pancytopenia
135
Purine analogs
Azathioprine
6 MP
6 TG (thioguanine)
136
Mechanism of action of Azathioprine, 6 MP?
Purine analog → ↓ de novo purine synthesis
137
What activates Purine analogs?
HGPRT
138
Clinical use for purine analogs
Preventing organ rejection, Rheumatoid Arthritis
| Leukemia,
139
Purine analog use for SLE
Azathioprine
140
Which purine analogs are used for Inflammatory Bowel disease?
6 MP
| 6 TG
141
Which are the main organs affected by purine inhibitors?
Bone marrow, GI, Liver
142
Who metabolizes Azathioprine and 6 MP?
Xanthine oxidase
143
What inhibits metabolism of Azathioprine and 6 MP?
Allopurinol
144
What is the problem that Azathioprine and 6 MP are metabolized by xanthine oxidase?
Increase toxicity with allopurinol, which inhibits their metabolism
145
Antitumor antibiotics
Dactinomycin
Doxorubicin
Bleomycin
146
Alternative name Dactinomycin
actinomycin D
147
This antitumor antibiotic intercalates in DNA
Dactinomycin
148
Clinical use for Dactinomycin
Wilms tumor, Ewing sarcoma, rhabdomyosarcoma
149
Antitumor antibiotic used for Childhood tumors
Dactinomycin
150
Toxic effect of Dactnimycin
Myelosuppression
151
Mechanism of action of Doxorubicin, daunorubicin
Generate free radicals
| Intercalate in DNA → breaks in DNA → ↓ replication
152
Clinical use of Doxorubicin, daunorubicin
Solid tumors, leukemias, lymphomas
153
Toxic effects of Doxorubicin, daunorubicin
Cardiotoxocity (dilated cardiomyopathy)
Myelosuppression
Alopecia
Toxic to tissues following extravasation
154
Which drug is used to prevent Cardiotoxicity by Doxorubicin, daunorubicin?
Dexrazoxane
155
How is Dexrazonxane consider?
Iron chelating
156
Mechanism of action of Bleomycin
Induces free radical formation, which caises breaks in DNA strands
157
Clinical use for Bleomycin
Testicular cancer, Hodgkin lymphoma
158
Toxic effects cause by bleomycin
Pulmonary fibrosis, skin changes, mucositis.
| Minimal myelosupression
159
Alkylating agents
Cyclophosphamide, ifosfamide
Nitrosoureas
Busulfan
160
Covalently X link (intersrand) DNA at guanine N-7
Cyclophosphamide, isofosfamide
161
What do Cyclophosphamide, isofosfamide require?
Bioactivation by liver
162
Clinical use for Cyclophosphamide, isofosfamide
Solid tumors, leukemia, lymphomas, and some brain cancers
163
Toxic effects of Cyclophosphamide, isofosfamide
Myelosuppression
| Hemorrhagic cystitis
164
Drug that partially prevents hemorrhagic cystitis caused by cyclophospamide
Mesna (bind toxic metabolites)
165
Who are Nitrosoureas?
Carmustine
Lomustine
Semustine
Streptozocin
166
What do Nitrofureas need?
Bioactivation
167
These Alkylating agents cross blood brain barrier
Nitrosoureas
168
Effect of Nitrosureas
Cross links DNA
169
Clinical use for Nitrosureas
Brain tumors (including glioblastoma multiforme)
170
Alkylating angents that cause CNS toxicity
Nitrosureas
171
Effect of Busulfan
Cross links DNA
172
Clinical use for Busulfan
CML
| Also used to ablate patient's bone marrow transplantation
173
Toxic effect of Busulfan
Severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation
174
Microtubule inhibitors
Vincristine, Vinblastine
| Paclitaxel, other taxols
175
How are Vincristine, vinblastine consider?
Vinca alkaloids
176
Mechanism of action of Vincristine, vinblastine
Bind β tubulin, inhibit its polymerization into microtubules, thereby preventing mitotic spindle formation
177
Which phase of cycle cell do Vincristine, vinblastine intefere with?
M phase arrest
178
Clinical use for Vincristine, vinblastine
Solid tumors, leukimias and lymphomas
179
Toxic effects caused by Vincristine
Neurotoxicity (areflexia, peripheral neuritis)
| Paralytic ileus
180
Vinblastine secondary effects
Vinblastine blasts bone marrow (suppression)
181
Mechanism of action of paclitaxel, other taxols
Hyperstabiliza polymerized microtubules in M phase so that mitotic spindle cannot break down
182
Which phase is inhibited by Paclitaxel and other Taxols?
Anaphase cannot occur
183
Which microtubul inhibitors are used for ovarian cancer and breast carcinomas?
Paclitaxel and other Taxols
184
Secondary effects of Placlitaxel
Myelosuppression, alopecia, hypersensitivity
185
Which is the mechanism of action of Cisplatin, carboplatin?
Cross link DNA
186
Clinical use of Cisplatin, carboplatin
testicular, bladder, ovary and lung cancer
187
Toxic effect of Cisplatin, carboplatin
Nephrotoxicity and acoustic nerve damage
188
How is nephrotoxicity prevented when using cisplatin, carbopatin?
With Aminfostine and chloride diuresis
189
What is Amifostine?
Free radical scavenger
190
Chemotherapy agent that inhibits topoisomerase II
Etoposide, teniposide
191
What is the result of Etoposide inhibiting topoisomerase II?
Increases DNA degradation
192
Clinical use for Etoposide
Solid tumors (particulary testicular and small cell lung cancer), leukemias, lymphomas
193
Which are secondary effects of Etoposide?
Myelosuppression, GI irritation, alopecia
194
Inhibit topisomerasse I and prevent DNA unwinding and replication
Irinotecan, topotecan
195
When is recommended the clinical use of Irinotecan?
Colon cancer
196
In these cancers Topotecan could be used
Ovarian and small cell lung cancer
197
Toxic effect caused by Irinotecan, topotecan
Severe myelosuppression, diarrhea
198
Mechanism of action of Hydroxyurea
Inhibits ribonucleotide reductase → ↓ DNA Synthesis
199
In which phase of Cell Cylce does Hydroxyurea works?
S phase specific
200
Which is the clinical use for Hydroxyurea?
Melanoma, CML, sickle cell disease (↑ HbF)
201
Secondary effects of Hydroxyurea
Bone marrow suppresion, GI upset
202
Mechanism of action of Prednisone, predinisolone as drugs for cancer
MAy trigger apoptosis. May even work on nondividing cells
203
Most commonly used glucocoricoids in cancer chemotherapy
Prednisone, predinisolon
204
When is recommended the clinical use of Prednisone, predinisolone as cancer chemotherapy?
Used in CLL, non Hodgkin Lymphomas (part of combination chemotherapy regimen)
Also used as immunosuppressants (eg. autoimmune disease)
205
Toxic effects caused by Prednisone, predinisolone
Cushing like symptoms; weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis
206
Selective estrogen receptor modulators (SERMs)
Tamoxifen, raloxifene
207
Mechanism of action of Tamoxifen, raloxifene
Receptor antagonists in breast and agonists in bone
| Block the binding of estrogen to ER + cells
208
Which is the clinical use of Tamoxifen?
Breast cancer treatment and prevention
209
Clinical use for Raloxifene
Useful to prevent osteoporosis
210
Toxic effect cause by Tamoxifen
Partial agonist in endometrium, which ↑ risk of endometrial cancer, "hot flashes"
211
Why Raloxifene does not increase the risl of Endometrial cancer?
Because it is an endometrial antagonist
212
Commercial name for Trastuzumab
Herceptin
213
Monoclonal antibody against HER-2 (c-erbB2)
Trastuzumab
214
Which kind of receptor does Monoclonal antibody against HER-2 (c-erbB2) has?
A tyrosine kinase kinase receptor
215
What is the effect of Trastuzumab?
Helps kill breast cancer cells that overexpress HER-2, through inhibition of HER-2 initiated cellular signanling and antibody dependent cytotoxicity
216
Clinical use of Trastuzumab
HER-2 + breast cancer and gastric cancer
217
Toxic effect of Trastuzumab
Cardiotoxicity
218
Commercial name for Imatinib
Gleevec
219
Mechanism of action of Imatinib
Turosine kinase inhibitor of bcr- abl (Philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)
220
Clinical use for Imatinib
CML, GI stromal tumors
221
Toxic effect of Imatinib
Fluid Retention
222
Monoclonal antibody against CD 20
Rituximab
223
Where is Monoclonal antibody against CD 20 found?
On most B cell neoplasms
224
Clinical use for Rituximab
Non Hodgkin lymphoma, rheumatoid arthtitis (with MTX), ITP (Immune thrombocytopenic purpura)
225
Side effects of Rituximab
Increase risk of progressive multifocal leukoencephalopathy
226
Which is the mechanism of action of Vemurafenib?
Small moleculr inhibitor of forms of the B-Raf kinase with the V600E mutation
227
Clinical use for Vermurafenid
Metastatic Melanoma
228
Monoclonal antibody against VEGF
Bevacizumab
229
What is the effect of Bevacizumab?
Inhibits angiogenesis
230
Clinical use for Bevacizumab
Solid tumors (colorectal cancer, renal cell carcinoma)
231
Toxic effect of Bevacizumab
Hemorrhage and impaired wound healing
