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Heme & Onc Pharm Flashcards

1
Q

What is the MOA of heparin?

A

Cofactor for activation of antithrombin III

Decreases thrombin and factor Xa

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2
Q

What is the clinical use of heparin?

A

Immediate anticoagulant for PE, acute coronary syndrome, MI, DVT.
Can be used during pregnancy

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3
Q

What is the toxicity of heparin?

A

Bleeding, thrombocytopenia, osteoporosis, drug interactions.

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4
Q

What is the antidote for heparin toxicity?

A

Protamine sulfate

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5
Q

What’s the MOA of protamine sulfate?

A

I is a positively charged molecule that binds negatively charged heparin

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6
Q

What are the advantages to using low MW heparins?

A

Longer half life
More effect on factor Xa
More bioavailability
Can be given subq

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7
Q

What is heparin induced thrombocytopenia?

A

Development of igG antibodies against heparin and platelet factor 4.
This complex of all 3 activates platelets causing thrombosis and thrombocytopenia

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8
Q

What is lepirudin, bivalirudin?

A

Anticoagulant used by leeches. Used as an alternative to heparin for patients with HIT

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9
Q

What is the MOA of lepirudin?

A

Inhibits thrombin

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10
Q

What is the MOA of warfarin?

A

Interferes with normal gamma carboxylation of vit-K dependent factors –> increased PT time
Metabolized by P450

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11
Q

What is the clinical use of warfarin?

A

Chronic anticoagulant after STEMI
venous TE prophylaxis
atrial fib
Chronic anticoagulant after a valve replacement or for anyone with a mechanical valve

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12
Q

What is the toxicity of warfarin?

A

Bleeding
Teratogenic
Skin/tissue necrosis
Drug interaction

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13
Q

What do you give to reverse the effects of warfarin?

A

Vit K

Or fresh frozen plasma

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14
Q

What is the route of admin of heparin?

A

IV, SC

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15
Q

Where does heparin work?

A

In the blood

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16
Q

What is the duration of action of heparin?

A

Rapid

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17
Q

What is the structure of heparin?

A

Large anionic, acidic polymer

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18
Q

What is the structure of warfarin?

A

Small lipid-soluble molecule

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19
Q

Where does warfarin act?

A

In the liver

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20
Q

What is the route of admin of warfarin?

A

Oral

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21
Q

What is the duration of action of warfarin?

A

Slow

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22
Q

What are the thrombolytics?

A

Alteplase (tPA), reteplase, tenecteplase

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23
Q

What is the MOA of thrombolytics?

A

Directly or indirectly convert plasminogen to plasmin –> cleaner thrombin and fibrin –> increased PT and PTT time

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24
Q

What are the clinical uses of thrombolytics?

A

Early MI, early ischemic stroke, direct thrombolysis of severe PE

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25
What are the toxicities of thrombolytics?
Bleeding
26
What are the contraindications to thrombolytics?
``` Active bleeding Intracranial bleeding Recent surgery Known bleeding diatheses Severe HTN ```
27
What is given to treat thrombolytics toxicity?
Aminocaproic acid - inhibitor of fibrinolysis
28
What is urokinase used for?
For tx of MI or PE
29
What is the MOA of urokinase?
Converts plasminogen to plasmin
30
What are the ADP receptor inhibitors?
Clopidrogrel, ticlodipine, prausgrel, ticagrelor
31
What is the MOA of clopidogrel?
Irreversibly blocking ADP receptors thereby inhibiting GPIIB/IIIa from binding fibrinogen
32
What are the clinical uses of clopidogrel?
Acute coronary syndrome, coronary scenting, decreased incidence or recurrence of thrombotic stroke.
33
What is the toxicity of ADP receptor inhibitors?
Neutropenia
34
What is the MOA of cilostazol or dipyramidole?
Phosphodiesterase III inhibitor; increases camp in platelets to inhibit platelet aggregation
35
What is the clinical use of dipyramidole and cilostazol?
Intermittent claudication, coronary vasodilation, prevention of stroke or TIA, angina prophylaxis
36
What is the toxicity of cilostazol and dipyramidole?
``` Nausea Headache Facial flushing Hypotension Ab pain ```
37
What are the GPIIB/IIIa inhibitors?
Abciximab Eptifibatide Tirofiban
38
What is the MOA of abciximab?
Binds to GPIIB/IIIa receptors on platelets and inhibits aggregation.
39
What is the clinical use of abciximab?
Acute coronary syndrome, percutaneous transluminal coronary angioplasty
40
What is the toxicity of abciximab?
Bleeding | Thrombocytopenia
41
What phase of the cell cycle do vinca alkaloids and taxols work in?
M phase
42
What cell cycle phase do etoposides work in?
G2, S phase
43
What cell cycle phase does bleomycin work in?
g2
44
What cell cycle phase do anti metabolites work in?
S phase
45
What is the MOA of MTX?
Folic acid analog that inhibits dihydrofolate reductase so it decreases DNA and protein synthesis
46
What are the clinical uses of MTX?
Cancers, abortion, ectopic pregnancy, RA, psoriasis
47
What are the toxicities of MTX?
Myelosuppression Macrovesicular fatty change in the liver Mucositis Teratogenic
48
What is the rescue drug for MTX toxicity?
Leucovorin - used to reverse myelosuppression
49
What is the MOA of 5-fluorouracil?
Pyrimidine analog that's converted to 5F-dUMP which complexes with folic acid thereby inhibiting thymidylate synthase decreasing DNA and protein synthesis
50
What are the used of 5-fluorouracil?
Colon cancer | BCC
51
What are the toxicities of 5-fluorouracil?
Myelosuppression | Photosensitivity
52
What can be used in an overdose of 5-fluorouracil?
Thymidine
53
What's th MOA of cytarabine?
Pyrimidine analog -- inhibitor of DNA synthesis
54
What is cytarabine used for?
Leukemia | Lymphoma
55
What are the toxicities of cytarabine?
Leukopenia Thrombocytopenia Megaloblastic anemia
56
What is the MOA of azathioprine,6-mercaptopurine, 6-thioguanine?
Purine analogs -- inhibit de novo purine synthesis Activated by HGPRT Toxic to proliferating lymphocytes
57
What are the purine analogs used for?
Leukemia and kidney transplants | Autoimmune hemolytic anemia and glomerulonephritis
58
What are the toxicities of the purine analogs?
BM, GI, liver (cholestasis/hepatitis) | Increases with allopurinol because metabolized by xanthine oxidase
59
What is the MOA of dactinomycin?
Intercalates in DNA
60
What is dactinomycin used for?
Wilms tumor, Ewing's sarcoma, rhabdomyosarcoma,
61
What is the toxicity of dactinomycin?
Myelosuppression
62
What is the MOA of doxorubicin?
Generate free radicals | Intercalates in DNA noncovalentky causing breaks
63
What is doxorubicin used for?
Solid tumors, leukemias, lymphomas
64
What is the toxicity of doxorubicin?
Dilated cardiomyopathy Myelosuppression Alopecia
65
What drug is used to prevent cardio toxicity of doxorubicin?
Dexrazoxane - iron cheating agent
66
What is the MOA of bleomycin?
Induces free radicals causing breaks in DNA
67
What are the clinical uses of bleomycin?
Hodgkin's lymphoma and testicular cancer
68
What are the toxicities of bleomycin?
Pulmonary fibrosis, skin changes, minimal myelosuppression
69
What are the alkylation agents?
Cyclophosphamide Nitrosureas Busulfan
70
What is the MOA of cyclophosphamide?
Covalently binds DNA at guanine N-7 Note: it is metabolized by P450
71
What is cyclophosphamide used for?
Solids tumors, leukemia, lymphoma, brain cancers
72
What is the toxicity of cyclophosphamide?
Myelosuppression Hemorrhagic cystitis Bladder cancer
73
What substance can help prevent hemorrhagic cystitis caused by cyclophosphamide?
Mesna - binds toxic metabolite
74
What do alkylating agents require?
Bioactivation
75
Which alkylating agent can cross the bb barrier?
Nitrosureas: carmustine, lomustine, semustine
76
What are nitrosureas used for?
Brain tumors
77
What is the toxicity of nitrosureas?
Dizziness | Ataxia
78
What is the toxicity of busulfan?
Pulmonary fibrosis | Hyper pigmentation
79
What is busulfan used for?
CML | Ablation of patients BM before transplant
80
What is the MOA of vincristine and vinblastine?
Binds to Tubulin in M phase and block polymerization of the micro tubules
81
What are alkaloids used for?
Cancers
82
What is the toxicity of vincristine?
Neurotoxicity - areflexia, paralytic ileus, peripheral neuritis
83
What is the toxicity of vinblastine?
BM suppression
84
What is the MOA of taxols?
Hyper stabilize polymerized micro tubules in M Phase so they can't break down (anaphase cannot occur)
85
What are taxols used for?
Breast and ovarian carcinoma
86
What are the toxicities of taxols?
Myelosuppression | Hypersensitivity
87
What is the MOA of cisplatin/carboplatin?
Cross-link DNA
88
What is cisplatin/carboplatin used for?
Testicukar, bladder, ovary and lung cancer
89
What are the toxicities of cisplatin and carboplatin?
Nephrotoxicity | Acoustic nerve damage
90
How can nephrotoxicity of cisplatin be prevented?
Amifostine - free radical scavenger | Chloride diuresis
91
What is the MOA of etoposide and teniposide?
Inhibit topoisomerase II - increases DNA degradation
92
What is the toxicity of etoposide?
GI Myelosuppression Alopecia
93
What is the MOA of hydroxurea?
Inhibits ribonucleotide reductase decreasing DNA synthesis in S phase
94
What is hydroxurea used for?
Melanoma CML Sickle cell
95
What is the tox of hydroxurea?
GI | BM suppression
96
How does prednisone work as a anti-neoplastic agent?
Triggers apoptosis
97
When is prednisone used in cancer?
CLL, non-Hodgkin's
98
What is the tox of prednisone?
``` Cushing's Cataracts Acne Osteoporosis HTN Peptic ulcers Hyperglycemia Psychosis ```
99
What is the MOA of tamoxifen?
SERMs - receptor antagonists in breast and agonist in bone | Block binding if estrogen to ER positive cells
100
What is tamoxifen used for?
Breast cancer | Osteoporosis
101
What is the tox of tamoxifen?
Partial agonist in endometrium so increases the risk of endometrial cancer Hot flashes
102
Which drug should be used for breast cancer in women who still have a uterus?
Raloxifene
103
What is the MOA of trastuzamab (herceptin)?
Monoclonal Ab against Her-2 -- kills cells over expressing her-2
104
What is trastuzamab used for?
Her-2 positive breast cancer
105
What is the tox of trastuzamab?
Cardiotoxicity
106
What is the MOA of imatinib?
Philadelphia chromosome bCR-abl tyrosine kinase inhibitor
107
What is imatinib used for?
CML | GI stromal tumors
108
What is the toxicity of imatinib?
Fluid retention
109
What is the MOA of rituximab?
Monoclonal Ab against CD20
110
What is rituximab used for?
Non-Hodgkin lymphoma, RA
111
What is the MOA of vemurafenib?
Inhibits forms of the b-raf kinase with the V600E mutation
112
What is vemurafenib used for?
Metastatic melanoma
113
What is the MOA of bevaxizumab?
Monoclonal Ab against VEGF. Inhibits angiogenesis!
114
What is bevaxizumab used for?
Solid tumors
115
What is the MOA of cyclosporine?
Binds to cyclophilins and this complex blocks the differentiation and activation of T cells by inhibiting calcineurin. Prevents production of IL-2 and its receptor
116
What is cyclosporine used for?
Suppresses organ rejection | Autoimmune diseases
117
What is the tox of cyclosporine?
``` Nephrotoxicity HTN Hyperlipidemia Hyperglycemia Tremor Gingival hyperplasia Hirsutism ```
118
What is the MOA of tacrolimus?
Binds FK-binding protein, inhibiting calcineurin and secretion of IL-2 and other cytokines
119
What is tacrolimus used for?
Suppression in organ transplant recipients
120
What is the tox of tacrolimus?
Same as cyclosporine but no gingival hyperplasia or hirsutism
121
What is the MOA of sirolimus (rapamycin)
Inhibits mTOR. | Inhibits T cell prolif in response to IL-2
122
What is sirolimus used for?
Immunosuppression after kidney transplant in combo with cyclosporine and corticosteroids
123
What is the toxicity of sirolimus?
Hyperlipidemia Thrombocytopenia Leukopenia
124
What is the MOA of muromonab?
Monoclonal Ab that binds to CD3 so T cells can't transduce
125
What is muromonab used for?
Immunosuppressive after kidney transplant
126
What is the toxicity of muromonab?
Cytokines release syndrome | Hypersensitivity
127
What is aldesleukin?
Recombinant IL-2
128
What is aldesleukin used for?
Renal cell carcinoma | Metastatic melanoma
129
What is alpha interferon used for?
Hep B,C, kaposi's, leukemia, malignant melanoma
130
What is beta INF used for?
Multiple sclerosis
131
What is gamma INF used for?
Chronic granulomatous disease
132
What is oprelvekin?
Recombinant IL-11 used for thrombocytopenia
133
What is infliximab and adalimumab?
Monoclonal Ab to TNF-a
134
What are TNF-a monoclonal abs used for?
Crohn's, anklyosing spondylitis, RA, psoriatic arthritis
135
What is abciximab?
Monoclonal Ab to GPIIB/IIIa for prevention of cardiac ischemia in unstable angina Percutaneous coronary intervention
136
What is omalizumab?
Monoclonal Ab to IgE used for asthma
137
What is celecoxib used for?
Inflammatory conditions such as RA without risk of GI bleed
138
What is COX2?
An inducible enzyme formed by inflammatory stimuli
139
Which platelet aggregation inhibitor causes neutropenia?
Ticlodipine - manifests as fever and mouth ulcers
140
What is a potential side effect of infliximab, adalimumab, and etanercept?
TB activation because of blocking TNF-alpha
141
What should be done before prescribing TNF-alpha?
Do a PPD test to check for inactive TB
142
What are the direct factor X inhibitors?
Idraparinux Rivaroxaban Apixaban Ultra low MW heparin
143
What do direct factor X inhibitors prolong?
PT and PTT time
144
What do factor X inhibitors not inhibit and therefore not prolong?
Don't inhibit thrombin so don't prolong TT time
145
What are direct factor X inhibitors used for?
DVT
146
What is rat poison?
It is a long acting 4-hydroxycoumarin derivative - basically warfarin so it will deprive you of your vit K dependent factors
147
What should be given in the setting of rat poison?
Fresh frozen plasma
148
What does cryoprecipitate contain?
Factor 8/9 vWF Fibrinogen
149
What is enoxaparin?
A low MW heparin | Greater activity against Factor Xa than thrombin
150
Why is unfractionated heparin preferred over other anticoagulants in acute coronary syndrome?
Because it complexes with both antithrombin and thrombin to allow antithrombin to inactivate Factor Xa thereby also inhibiting thrombin
151
What is given in subarachnoid hemorrhage and why?
Nimodipine due to risk of vasospasm from blood breakdown
152
DOC to treat vonWillenbrands disease?
DDAVP (desmopressin)
153
What is the MOA of certolizumab?
It is a pegylated humanized monoclonal antibody that targets TNF-alpha. It lacks the Fc region and is used in treating autoimmune diseases
154
Uses for DDAVP?
VonWillenbrand's Disease Central DI sleep enuresis
156
What is the tx for primary myelofibrosis?
Ruxolitinib - JAK2 inhibitor
157
What is mercaptopurine inactivated by?
Xanthine oxidase
158
What is mercaptopurine activated by?
HGPRT
159
What is pentostatin?
An irreversible inhibitor of ADA
160
What is basiliximab?
Inhibitor of IL2 receptor
161
What is the MOA of desmopressin?
It stimulates release of factor XIII and vWF from endothelial cells

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