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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
Q

What are the toxicities of thrombolytics?

A

Bleeding

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26
Q

What are the contraindications to thrombolytics?

A 
Active bleeding
Intracranial bleeding
Recent surgery
Known bleeding diatheses
Severe HTN
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27
Q

What is given to treat thrombolytics toxicity?

A

Aminocaproic acid - inhibitor of fibrinolysis

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28
Q

What is urokinase used for?

A

For tx of MI or PE

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29
Q

What is the MOA of urokinase?

A

Converts plasminogen to plasmin

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30
Q

What are the ADP receptor inhibitors?

A

Clopidrogrel, ticlodipine, prausgrel, ticagrelor

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31
Q

What is the MOA of clopidogrel?

A

Irreversibly blocking ADP receptors thereby inhibiting GPIIB/IIIa from binding fibrinogen

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32
Q

What are the clinical uses of clopidogrel?

A

Acute coronary syndrome, coronary scenting, decreased incidence or recurrence of thrombotic stroke.

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33
Q

What is the toxicity of ADP receptor inhibitors?

A

Neutropenia

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34
Q

What is the MOA of cilostazol or dipyramidole?

A

Phosphodiesterase III inhibitor; increases camp in platelets to inhibit platelet aggregation

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35
Q

What is the clinical use of dipyramidole and cilostazol?

A

Intermittent claudication, coronary vasodilation, prevention of stroke or TIA, angina prophylaxis

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36
Q

What is the toxicity of cilostazol and dipyramidole?

A 
Nausea
Headache 
Facial flushing
Hypotension
Ab pain
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37
Q

What are the GPIIB/IIIa inhibitors?

A

Abciximab
Eptifibatide
Tirofiban

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38
Q

What is the MOA of abciximab?

A

Binds to GPIIB/IIIa receptors on platelets and inhibits aggregation.

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39
Q

What is the clinical use of abciximab?

A

Acute coronary syndrome, percutaneous transluminal coronary angioplasty

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40
Q

What is the toxicity of abciximab?

A

Bleeding

Thrombocytopenia

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41
Q

What phase of the cell cycle do vinca alkaloids and taxols work in?

A

M phase

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42
Q

What cell cycle phase do etoposides work in?

A

G2, S phase

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43
Q

What cell cycle phase does bleomycin work in?

A

g2

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44
Q

What cell cycle phase do anti metabolites work in?

A

S phase

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45
Q

What is the MOA of MTX?

A

Folic acid analog that inhibits dihydrofolate reductase so it decreases DNA and protein synthesis

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46
Q

What are the clinical uses of MTX?

A

Cancers, abortion, ectopic pregnancy, RA, psoriasis

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47
Q

What are the toxicities of MTX?

A

Myelosuppression
Macrovesicular fatty change in the liver
Mucositis
Teratogenic

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48
Q

What is the rescue drug for MTX toxicity?

A

Leucovorin - used to reverse myelosuppression

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49
Q

What is the MOA of 5-fluorouracil?

A

Pyrimidine analog that’s converted to 5F-dUMP which complexes with folic acid thereby inhibiting thymidylate synthase decreasing DNA and protein synthesis

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50
Q

What are the used of 5-fluorouracil?

A

Colon cancer

BCC

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51
Q

What are the toxicities of 5-fluorouracil?

A

Myelosuppression

Photosensitivity

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52
Q

What can be used in an overdose of 5-fluorouracil?

A

Thymidine

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53
Q

What’s th MOA of cytarabine?

A

Pyrimidine analog – inhibitor of DNA synthesis

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54
Q

What is cytarabine used for?

A

Leukemia

Lymphoma

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55
Q

What are the toxicities of cytarabine?

A

Leukopenia
Thrombocytopenia
Megaloblastic anemia

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56
Q

What is the MOA of azathioprine,6-mercaptopurine, 6-thioguanine?

A

Purine analogs – inhibit de novo purine synthesis
Activated by HGPRT
Toxic to proliferating lymphocytes

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57
Q

What are the purine analogs used for?

A

Leukemia and kidney transplants

Autoimmune hemolytic anemia and glomerulonephritis

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58
Q

What are the toxicities of the purine analogs?

A

BM, GI, liver (cholestasis/hepatitis)

Increases with allopurinol because metabolized by xanthine oxidase

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59
Q

What is the MOA of dactinomycin?

A

Intercalates in DNA

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60
Q

What is dactinomycin used for?

A

Wilms tumor, Ewing’s sarcoma, rhabdomyosarcoma,

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61
Q

What is the toxicity of dactinomycin?

A

Myelosuppression

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62
Q

What is the MOA of doxorubicin?

A

Generate free radicals

Intercalates in DNA noncovalentky causing breaks

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63
Q

What is doxorubicin used for?

A

Solid tumors, leukemias, lymphomas

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64
Q

What is the toxicity of doxorubicin?

A

Dilated cardiomyopathy
Myelosuppression
Alopecia

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65
Q

What drug is used to prevent cardio toxicity of doxorubicin?

A

Dexrazoxane - iron cheating agent

66
Q

What is the MOA of bleomycin?

A

Induces free radicals causing breaks in DNA

67
Q

What are the clinical uses of bleomycin?

A

Hodgkin’s lymphoma and testicular cancer

68
Q

What are the toxicities of bleomycin?

A

Pulmonary fibrosis, skin changes, minimal myelosuppression

69
Q

What are the alkylation agents?

A

Cyclophosphamide
Nitrosureas
Busulfan

70
Q

What is the MOA of cyclophosphamide?

A

Covalently binds DNA at guanine N-7

Note: it is metabolized by P450

71
Q

What is cyclophosphamide used for?

A

Solids tumors, leukemia, lymphoma, brain cancers

72
Q

What is the toxicity of cyclophosphamide?

A

Myelosuppression
Hemorrhagic cystitis
Bladder cancer

73
Q

What substance can help prevent hemorrhagic cystitis caused by cyclophosphamide?

A

Mesna - binds toxic metabolite

74
Q

What do alkylating agents require?

A

Bioactivation

75
Q

Which alkylating agent can cross the bb barrier?

A

Nitrosureas: carmustine, lomustine, semustine

76
Q

What are nitrosureas used for?

A

Brain tumors

77
Q

What is the toxicity of nitrosureas?

A

Dizziness

Ataxia

78
Q

What is the toxicity of busulfan?

A

Pulmonary fibrosis

Hyper pigmentation

79
Q

What is busulfan used for?

A

CML

Ablation of patients BM before transplant

80
Q

What is the MOA of vincristine and vinblastine?

A

Binds to Tubulin in M phase and block polymerization of the micro tubules

81
Q

What are alkaloids used for?

A

Cancers

82
Q

What is the toxicity of vincristine?

A

Neurotoxicity - areflexia, paralytic ileus, peripheral neuritis

83
Q

What is the toxicity of vinblastine?

A

BM suppression

84
Q

What is the MOA of taxols?

A

Hyper stabilize polymerized micro tubules in M Phase so they can’t break down (anaphase cannot occur)

85
Q

What are taxols used for?

A

Breast and ovarian carcinoma

86
Q

What are the toxicities of taxols?

A

Myelosuppression

Hypersensitivity

87
Q

What is the MOA of cisplatin/carboplatin?

A

Cross-link DNA

88
Q

What is cisplatin/carboplatin used for?

A

Testicukar, bladder, ovary and lung cancer

89
Q

What are the toxicities of cisplatin and carboplatin?

A

Nephrotoxicity

Acoustic nerve damage

90
Q

How can nephrotoxicity of cisplatin be prevented?

A

Amifostine - free radical scavenger

Chloride diuresis

91
Q

What is the MOA of etoposide and teniposide?

A

Inhibit topoisomerase II - increases DNA degradation

92
Q

What is the toxicity of etoposide?

A

GI
Myelosuppression
Alopecia

93
Q

What is the MOA of hydroxurea?

A

Inhibits ribonucleotide reductase decreasing DNA synthesis in S phase

94
Q

What is hydroxurea used for?

A

Melanoma
CML
Sickle cell

95
Q

What is the tox of hydroxurea?

A

GI

BM suppression

96
Q

How does prednisone work as a anti-neoplastic agent?

A

Triggers apoptosis

97
Q

When is prednisone used in cancer?

A

CLL, non-Hodgkin’s

98
Q

What is the tox of prednisone?

A 
Cushing's
Cataracts
Acne
Osteoporosis 
HTN
Peptic ulcers
Hyperglycemia 
Psychosis
99
Q

What is the MOA of tamoxifen?

A

SERMs - receptor antagonists in breast and agonist in bone

Block binding if estrogen to ER positive cells

100
Q

What is tamoxifen used for?

A

Breast cancer

Osteoporosis

101
Q

What is the tox of tamoxifen?

A

Partial agonist in endometrium so increases the risk of endometrial cancer
Hot flashes

102
Q

Which drug should be used for breast cancer in women who still have a uterus?

A

Raloxifene

103
Q

What is the MOA of trastuzamab (herceptin)?

A

Monoclonal Ab against Her-2 – kills cells over expressing her-2

104
Q

What is trastuzamab used for?

A

Her-2 positive breast cancer

105
Q

What is the tox of trastuzamab?

A

Cardiotoxicity

106
Q

What is the MOA of imatinib?

A

Philadelphia chromosome bCR-abl tyrosine kinase inhibitor

107
Q

What is imatinib used for?

A

CML

GI stromal tumors

108
Q

What is the toxicity of imatinib?

A

Fluid retention

109
Q

What is the MOA of rituximab?

A

Monoclonal Ab against CD20

110
Q

What is rituximab used for?

A

Non-Hodgkin lymphoma, RA

111
Q

What is the MOA of vemurafenib?

A

Inhibits forms of the b-raf kinase with the V600E mutation

112
Q

What is vemurafenib used for?

A

Metastatic melanoma

113
Q

What is the MOA of bevaxizumab?

A

Monoclonal Ab against VEGF. Inhibits angiogenesis!

114
Q

What is bevaxizumab used for?

A

Solid tumors

115
Q

What is the MOA of cyclosporine?

A

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
Q

What is cyclosporine used for?

A

Suppresses organ rejection

Autoimmune diseases

117
Q

What is the tox of cyclosporine?

A 
Nephrotoxicity 
HTN
Hyperlipidemia 
Hyperglycemia 
Tremor
Gingival hyperplasia
Hirsutism
118
Q

What is the MOA of tacrolimus?

A

Binds FK-binding protein, inhibiting calcineurin and secretion of IL-2 and other cytokines

119
Q

What is tacrolimus used for?

A

Suppression in organ transplant recipients

120
Q

What is the tox of tacrolimus?

A

Same as cyclosporine but no gingival hyperplasia or hirsutism

121
Q

What is the MOA of sirolimus (rapamycin)

A

Inhibits mTOR.

Inhibits T cell prolif in response to IL-2

122
Q

What is sirolimus used for?

A

Immunosuppression after kidney transplant in combo with cyclosporine and corticosteroids

123
Q

What is the toxicity of sirolimus?

A

Hyperlipidemia
Thrombocytopenia
Leukopenia

124
Q

What is the MOA of muromonab?

A

Monoclonal Ab that binds to CD3 so T cells can’t transduce

125
Q

What is muromonab used for?

A

Immunosuppressive after kidney transplant

126
Q

What is the toxicity of muromonab?

A

Cytokines release syndrome

Hypersensitivity

127
Q

What is aldesleukin?

A

Recombinant IL-2

128
Q

What is aldesleukin used for?

A

Renal cell carcinoma

Metastatic melanoma

129
Q

What is alpha interferon used for?

A

Hep B,C, kaposi’s, leukemia, malignant melanoma

130
Q

What is beta INF used for?

A

Multiple sclerosis

131
Q

What is gamma INF used for?

A

Chronic granulomatous disease

132
Q

What is oprelvekin?

A

Recombinant IL-11 used for thrombocytopenia

133
Q

What is infliximab and adalimumab?

A

Monoclonal Ab to TNF-a

134
Q

What are TNF-a monoclonal abs used for?

A

Crohn’s, anklyosing spondylitis, RA, psoriatic arthritis

135
Q

What is abciximab?

A

Monoclonal Ab to GPIIB/IIIa for prevention of cardiac ischemia in unstable angina
Percutaneous coronary intervention

136
Q

What is omalizumab?

A

Monoclonal Ab to IgE used for asthma

137
Q

What is celecoxib used for?

A

Inflammatory conditions such as RA without risk of GI bleed

138
Q

What is COX2?

A

An inducible enzyme formed by inflammatory stimuli

139
Q

Which platelet aggregation inhibitor causes neutropenia?

A

Ticlodipine - manifests as fever and mouth ulcers

140
Q

What is a potential side effect of infliximab, adalimumab, and etanercept?

A

TB activation because of blocking TNF-alpha

141
Q

What should be done before prescribing TNF-alpha?

A

Do a PPD test to check for inactive TB

142
Q

What are the direct factor X inhibitors?

A

Idraparinux
Rivaroxaban
Apixaban
Ultra low MW heparin

143
Q

What do direct factor X inhibitors prolong?

A

PT and PTT time

144
Q

What do factor X inhibitors not inhibit and therefore not prolong?

A

Don’t inhibit thrombin so don’t prolong TT time

145
Q

What are direct factor X inhibitors used for?

A

DVT

146
Q

What is rat poison?

A

It is a long acting 4-hydroxycoumarin derivative - basically warfarin so it will deprive you of your vit K dependent factors

147
Q

What should be given in the setting of rat poison?

A

Fresh frozen plasma

148
Q

What does cryoprecipitate contain?

A

Factor 8/9
vWF
Fibrinogen

149
Q

What is enoxaparin?

A

A low MW heparin

Greater activity against Factor Xa than thrombin

150
Q

Why is unfractionated heparin preferred over other anticoagulants in acute coronary syndrome?

A

Because it complexes with both antithrombin and thrombin to allow antithrombin to inactivate Factor Xa thereby also inhibiting thrombin

151
Q

What is given in subarachnoid hemorrhage and why?

A

Nimodipine due to risk of vasospasm from blood breakdown

152
Q

DOC to treat vonWillenbrands disease?

A

DDAVP (desmopressin)

153
Q

What is the MOA of certolizumab?

A

It is a pegylated humanized monoclonal antibody that targets TNF-alpha. It lacks the Fc region and is used in treating autoimmune diseases

154
Q

Uses for DDAVP?

A

VonWillenbrand’s Disease
Central DI
sleep enuresis

156
Q

What is the tx for primary myelofibrosis?

A

Ruxolitinib - JAK2 inhibitor

157
Q

What is mercaptopurine inactivated by?

A

Xanthine oxidase

158
Q

What is mercaptopurine activated by?

A

HGPRT

159
Q

What is pentostatin?

A

An irreversible inhibitor of ADA

160
Q

What is basiliximab?

A

Inhibitor of IL2 receptor

161
Q

What is the MOA of desmopressin?

A

It stimulates release of factor XIII and vWF from endothelial cells

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