Heme/Onc Pharm Flashcards
1
Q
What is the mechanism of Heparin?
A
Catalyzes the activation of AT3 which decreases Fx 2 and Xa
2
Q
Half life of Heparin:
A
SHORT
3
Q
What is heparin used for clinically?
A
IMMEDIATE anticoagulation for
- PE
- Stroke
- Angina
- MI
- DVT
4
Q
When can heparin be used/why?
A
Pregnancy - does not cross placenta
5
Q
How is Heparin therapy monitored?
A
PTT
6
Q
3 toxic side effects of heparin:
A
-Bleeding
-Thrombocytopenia (HIT)
-Drug interactions
7
Q
Antidote for rapid reversal of Heparin; mechanism?
A
Protamine sulfate - pos charged molecule; binds highly neg charged Heparin
8
Q
What is a LMWH?
A
Enoxaparin, Daltaparin
9
Q
How do the LMWH’s act differently from Heparin?
A
More action on Xa than Thrombin; better bioavailability and 2-4 times longer half life
10
Q
How can LMWH’s be administered?
A
Subcutaneously instead of only IV
11
Q
What is the good thing about better bioavailability and half life of LMWH’s?
A
Don’t require lab monitoring with PTT
12
Q
What is Warfarin’s clinical use?
A
CHRONIC longterm anticoagulation
13
Q
When CAN’T Warfarin be used?
A
Pregnancy - teratotenic
14
Q
Site of action of
- Heparin
- Warfarin
A
Heparin - blood
Warfarin - Liver
15
Q
Onset of action of:
- Heparin
- Warfarin
A
Heparin - seconds
Warfarin - takes several days until the pre-existing clotting fxs are removed - half lives limit
16
Q
4 Thrombolytic agents
A
Streptokinase
Urokinase
tPA
APSAC
17
Q
Mechanism of thrombolytics:
A
Help convert Plasminogen to Plasmin to cleave Fibrin clots
18
Q
2 clinical uses of thrombolytic agents:
A
-Early MI
-Early ischemic stroke
19
Q
Toxicity of Thrombolytics:
A
Bleeding
20
Q
What is the antidote for Thrombolytic TOXICITY?
A
Aminocaproic acid - fibrinolysis inhibitor
21
Q
What is the rec on platelets for
- collagen
- vWF
- Fibrinogen
- TxA2/ADP/5-HT
A
Collagen is GP1a
vWF is GP1b
Fibrinogen is GP2b3a
Txa2/ADP/5HT all bind GP’s
22
Q
What 2 drugs inhibit platelet synthesis of thromboxane?
A
Aspirin
23
Q
What 3 drugs block GP2b/3a to prevent Fibrinogen crosslinking the platelet plug?
A
- Abciximab
- Eptifabatide
- Tirofiban
24
Q
What 4 drugs irreversibly block ADP receptors on platelets?
A
- Clopidogrel
- Ticlopidine
- Prasugrel
- Ticagrelor
(Note: these also block GP2b/3a to prevent Fibrinogen crosslinking the platelet plug)
25
What effect does blocking ADP receptors on Platelets have?
It inhibits the expression of GP2b/3a hence no fibrinogen crosslinking!
26
What are 2 clinical uses of Ticlopidine and Clopidogrel?
Acute coronary syndorme
| Cardiac stenting
27
What toxic side effect does Ticlopidine have?
Neutropenia
28
What are the 3 antimetabolite cancer drugs?
- Methotrexate
- 5-Fluorouracil
- 6-Mercaptopurine
29
How do MTX and 5-FU work?
Synergistically
30
What cell cycle phase are MTX and 5-FU both specific for?
S-phase - DNA synthesis
31
What is the mechanism of MTX?
-Folate analog
-Inhibits Di-HF reductase, Inhibits dTMP synth, DNA synth, and protein synthesis
32
What 4 cancers is MTX used for?
-Lymphomas
-Leukemias
-Choriocarcinoma
-Sarcomas
33
What are 4 non-neoplastic clinical uses of Methotrexate?
PEAR
- Psoriasis
- Ectopic pregnancy
- Abortion
- Rheumatoid arthritis
34
What are 2 toxic side effects of MTX and how is one treated?
-Macrovesicular Fatty Liver
-Myelosuppression - rescued with Leucovorin
35
What is the mechanism of 5-FU?
-Pyrimidine analog; bioactivated to 5F-Dump; covalently complexes Folate which inhibits Thymidylate Synthase.
36
And what is the effect of inhibiting thymidylate synthease?
Inhibits dTMP synth, DNA, and protein synthesis.
37
And what does giving MTX and 5-FU together allow for?
Synergistic inhibition of the same biochemical pathway (inhibiting dTMP syn, DNA, & protein synth)
38
What are 3 cancers that 5-Fluorouracil is used for?
-Colon cancers
-Other solid tumors
-Cream for Basal cell carcinoma
39
What are 2 side effects of 5-Fluorouracil?
-Photosensitivity
-Irreversible Myelosuppression
40
What has to be given to 'rescue' the myelosuppression due to 5-FU?
Thymidine
41
What is the other antimetabolite?
6-Mercaptopurine
42
How is 6-MP activated and what is its effect?
-Activated by HGPRTase
-Blocks de Novo Purine synthesis
43
What cancers can/can't 6-MP be used for treating?
CAN treat Leukemia/Lymphoma
CAN'T treat CLL/Hodgkin lymphoma
44
What are 3 tissues that 6-MP has toxic effects on?
-Bone marrow
-GI tract
-Liver
45
What metabolizes 6-MP to its inactive form?
Xanthine oxidase
46
So what can prevent 6-MP metabolism?
Allopurinol - careful!
47
Drug for treating AML:
Cytarabine; ara-C
48
What is the mechanism of Cytarabine?
INhibits DNA polymerase
49
What are 3 toxic side effects of Cytarabine?
-Leukopenia
-Thrombocytopenia
-Megaloblastic anemia
50
What type of agents are Cyclophosphamide and Ifosfamide?
Alkylating agents
51
What is the mechanism of Cyclophosphamide and Ifosfamide? How are they activated?
-X-link DNA (interstrand) at Guanine-7 - Activated by Liver bioactivation
52
What are the 4 clinical uses of Cyclophosphamide and Ifosfamide?
-NHL
-Breast cancer
-Ovarian cancer
-Immunosuppressant
53
What are 2 toxic side effects of Cyclophosphamide and Ifosfamide?
-Myelosuppression
-Hemorrhagic cystitis
54
How can the Hemorrhagic cystitis caused by Cyclophosph and Ifosfamide be prevented?
With MESNA
55
What are the Nitrosoureas? 4
-Carmustine
-Lomustine
-Semustine
-Streptozocin
56
What is the mechanism of the Nitrosoureas? What are they especially useful for?
- Alkylate DNA
| - Cross the BBB - so treat BRAIN TUMORS!
57
What brain tumor do the nitrosoureas like Carmustine especially treat?
Glioblastoma multiforme
58
What are the main toxic side effects of the Nitrosoureas?
CNS - toxicity and Ataxia
59
How do Cisplatin and Carboplatin work?
LIKE alkylating agents
60
What are the 4 cancers treated by Cisplatin and Carboplatin?
OBLT
- Ovarian
- Breast
- Lung
- Testicular
61
What are 2 toxic side effects of Cisplatin and Carboplatin?
-Nephrotoxicity
-Acoustic nerve damage
62
What drug is used for treating CML?
Busulfan
63
What is the mechanism of Bulsulfan?
Alkylates DNA
64
What are 2 toxic side effects of Busulfan?
-Pigmentation
-PULMONARY FIBROSIS
65
So what are the 4 alkylating agents?
-Cyclophosphamide/Ifosfamide
-Nitrosoureas (Carmustine)
-Cisplatin/Carboplatin
-Busulfan
66
What is Doxorubicin aka?
Adriamycin
67
What is the mechanism of Doxorubicin and Daunorubicin? (3 steps)
-Generate FREE RADICALS
-INTERCALATE DNA
-CREATE BREAKS in DNA strand to inhibit replication
68
What is Adriamycin used for?
- ABVD regimen - Hodgkin lymphoma
- Sarcomas
- Myelomas
- Other solid tumors (brst/ovary)
69
What are 3 toxic side effects of Adriamycin/doxorubicin/daunorubicin?
-CARDIOtoxicity
-Marked Alopecia
-Myelosuppression
70
What intercalator just intercalates and doesn't cause strand breaks?
Dactinomycin
71
What is Dactinomycin used for clinically?
CHILDHOOD tumors
- Wilms tumor
- Ewing's sarcoma
- Rhabdomyosarcoma
72
What is the toxic side effect Dactinomycin can have?
Myelosuppression
73
What drug is the B in the ABVD regimen for Hodgkin lymphoma?
Bleomycin
74
What is Bleomycin's mechanism?
Induces formation of free radicals - causes DNA strand breaks!
75
What are 2 uses of Bleomycin then?
-Hodgkin lymphoma
-Testicular cancer
76
What are 2 toxic effects of Bleomycin?
-PULMONARY FIBROSIS (bab)
-Skin changes
77
What does Bleomycin cause MINIMALLY?
Myelosuppression
78
What cell cycle phase is Bleomycin specific for?
G2
79
What drug works on S and G2?
Etoposide
80
What is Etoposide's mechanism?
-Inhibits Topoisomerase II
-Increases DNA degradation
81
What are 3 cancers Etoposide is used for?
-SCC of lung
-SCC of prostate
-Testicular cancer
82
SE's of Etoposide?
Normal
| -GI upset, myelosuppress, alopecia
83
What is the most commonly used Glucocorticoid in cancer therapy?
PREDNISONE
84
What is Prednisone's mechanism?
Triggers Apoptosis
85
What are 2 cancers Prednisone is used for treating?
- CLL
| - Hodgkin's lymphoma
86
What are 9 side effects of Prednisone?
COACHH PIP
- Cushing's syndrome
- Osteoporosis, Acne, Cataracts
- Hypertension/Hyperglycemia
- Peptic ulcers, Immunosuppress, Psychosis
87
What are the main drugs for treating Estrogen receptor pos breast cancer?
Tamoxifen/Raloxifene
88
How do Tamoxifen and Raloxifene work on the breast? Bone?
Breast Est antagonist
Bone Est agonist!
89
So what are the 2 useful effects of Tamox/Raloxifene?
- Slow Br cancer growth
| - Slow osteoporosis!
90
What are 2 toxic side effects of Tamoxifen specifically?
-Hot flashes
-May increase risk of endometrial carcinoma - agonist properties in the uterus
91
Why doesn't Raloxifene have this risk?
It's an antagonist in the uterus
92
What is Herceptin and what is it aka?
Trastuzumab - anti Her-2 (erb-B2)
93
What is Trastuzumab used for?
HER-2 expressive Breast cancer
94
What is a possible side effect of Trastuzumab?
Cardiotoxicity
95
What is Imatinib aka?
Gleevac!
96
What is Gleevac used for?
Inhibition of the Ph' chromosome brc-abl fusion protein tyrosine kinase product
97
So what 2 cancers are treated with Gleevac?
-CML
-GI stromal tumors
98
What is a toxic side effect of Gleevac?
Fluid retention
99
What are the 'Vinca alkaloids'?
Vincristine and Vinblastine
100
What is the mechanism of Vincristine/blastine; what cell cycle phase are they specific for?
- Bind tubulin, block MT polymerization - mitotic spindle can't form!
- M-phase specific! Mitotic
101
What are 3 clinical uses of Vincristine/blastine?
- Wilm's tumor
- Lymphoma
- Choriocarcinoma
102
What are 2 side effects of:
-Vincristine
-Vinblastine
Cristine Neurotoxic/Paralytic ileus
Blastine Bone marrow suppression
103
What is Paclitaxel?
A Taxol!
104
What is the mechanism of Paclitaxel and other Taxols?
Bind tubulin and HYPERSTABILIZE polymerized MT's so the mitotic spindle can't BREAK DOWN!
105
What cell cycle phase are the taxols specific for?
M-phase - prevent progression to anaphase
106
What are 2 cancers for which the Taxols/Paclitaxel are used?
-Breast
-Ovarian
107
What are 2 side effects of the Taxols?
-Myelosuppresion
-Hypersensitivity
108
What are the drugs that act on MIcrotubules?
Maybe Taxes on Grease Vindicate Coalworkers!
- Mabendazole
- Taxols (Paclitaxel)
- Griseofulvin
- Vincristine/blastine
- Colchicine
109
What 2 drugs are the Phosphodiesterase III inhibitors?
Cilostazol & Dipyridamole
| increase cAMP in platelets, thus inhibiting platelet aggregation; vasodilators
110
MOA of Cilostazol & Dipyridamole?
Phosphodiesterase III inhibitors
| - increase cAMP in platelets, thus inhibiting platelet aggregation; vasodilators
111
Clinical use of Cilostazol & Dipyridamole?
Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined w/ Aspirin), angina prophylaxis
112
Cilostazol & Dipyridamole -- Toxicities?
Nausea, headache, facial flushing, hypotension, abdominal pain
