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Pharmacology > Heme Drugs > Flashcards

Heme Drugs Flashcards

1
Q

Heparin (mechanism)

A 
Activates antithrombin III --> decreases activity of thrombin (IIa) and factor Xa --> blood as site of action
Monitor PTT (intrinsic)
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2
Q

Heparin (antidote)

A

Protamine (chemical inactivation)

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3
Q

Heparin (use/placenta crossing)

A

Immediate anticoagulation for DVT, PE, MI

Can use during pregnancy (doesn’t cross placenta)

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4
Q

Heparin (side effects)

A

Skin necrosis at injection site
HIT
Bleeding (duh)

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5
Q

Warfarin (mechanism)

A

Inhibits gamma carboxylation of vit K-dependent factors (II, VII, IX, X, C, S) –> liver as site of action
Monitor PT/INR (extrinsic)

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6
Q

Warfarin (use/placenta crossing)

A

Chronic anticoagulation

Crosses placenta so don’t use in pregnant women

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7
Q

Warfarin (side effects)

A

Skin/tissue necrosis (usually seen first week of therapy -> due to protein C depletion b/c of its short HL -> so predisposition to this side effect w/ existing protein C and S deficiency)
Bleeding (duh)

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8
Q

Warfarin (antidotes)

A

Vit K

If severe, fresh frozen plasma

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9
Q

“-parin” (mechanism)

A

Enoxaparin, Dalteparin
LMW heparin: acts more on factor Xa (than II), longer HL, more bioavailable
Doesn’t need to monitor labs like normal heparin

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10
Q

“-parin” (side effect)

A

No antidote like heparin

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11
Q

“-xaban” (mechanism)

A

Apixaban, rivaroxaban

Direct factor Xa inhibitor

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12
Q

“-xaban” (3 uses)

A

Tx/prophylaxis of DVT, PE, stroke

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13
Q

“-xaban” (side effect)

A

No antidote like heparin or warfarin

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14
Q

“-teplase” (mechanism)

A

Thrombolytics (fibrin-specific so only attaches to recently formed clot) -> aid conversion of plasminogen to plasmin –> plasmin cleaves thrombin and fibrin clots (so prolong both PT and PTT)
Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)

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15
Q

“-teplase” (3 uses)

A

Early MI
Early ischemic stroke (3-hr window)
Direct thrombolysis of severe PE

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16
Q

“-teplase” (side effects)

A

Verify that bleeding is not present before use!
Don’t use in severe HTN
Accelerated idioventricular rhythm (AIVR) -> reperfusion arrhythmia that is benign and self-resolving

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17
Q

“-teplase” (3 antidotes)

A

Aminocaproic acid (inhibits fibrinolysis)
Fresh frozen plasma
Cryoprecipitate

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18
Q

Aspirin (mechanism)

A

Inhibits both COX-1 and 2 by covalent acetylation –> antiplatelet AGGREGATION is from the effects on COX-1 (COX-2 is not present on platelets but on endothelium)

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19
Q

Aspirin (side effects)

A

Gastric ulcers, tinnitus (VIII), renal failure w/ chronic use
Reye syndrome in children with viral infection
Overdose: resp alkalosis superimposed by metabolic acidosis

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20
Q

“-grel” (mechanism)

A

Clopidogrel, prasugrel
Irreversibly blocking ADP receptor –> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen
Prodrug that needs to be activated by P450

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21
Q

“-grel” (3 uses)

A

Acute coronary syndrome
Coronary stenting
Reduces thrombotic stroke

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22
Q

“-grel” (2 side effects)

A

TTP/HUS

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23
Q

Ticlopidine (mechanism)

A

Irreversibly blocking ADP receptor –> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen

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24
Q

Ticlopidine (3 uses and 3 side effects)

A

Only when can’t tolerate aspirin or clopidogrel (1st line) -> for acute coronary syndrome, coronary stenting, reduces thrombotic stroke
Side effects: neutropenia (presenting as FEVER AND MOUTH ULCERS -> so monitor CBC biweekly for the first 3 months), TTP/HUS

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25
Q

Ticagrelor (mechanism)

A

Irreversibly blocking ADP receptor –> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen

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26
Q

Ticagrelor (3 uses)

A

Acute coronary syndrome
Coronary stenting
Reduces thrombotic stroke

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27
Q

Ticagrelor (2 side effects)

A

TTP/HUS

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28
Q

Cilostazol (mechanism)

A

Phosphodiesterase III inhibitor –> increases cAMP inplatelets –> inhibits platelet aggregation
ALSO A DIRECT ARTERIAL VASODILATOR

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29
Q

Cilostazol (4 uses)

A

Intermittent claudication -> better than aspirin at peripheral arterial disease
Coronary vasodilation
Prevention of stroke/TIAs (combined w/ aspirin)
Angina prophylaxis

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30
Q

Cilostazol (5 side effects)

A

Flushing, abd pain, hypotension, nausea, headache

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31
Q

Dipyridamole (mechanism)

A

Phosphodiesterase III inhibitor –> increases cAMP inplatelets –> inhibits platelet aggregation
Vasodilator

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32
Q

Dipyridamole (4 uses)

A

Intermittent claudication
Coronary vasodilation
Prevention of stroke/TIAs (combined w/ aspirin)
Angina prophylaxis

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33
Q

Dipyridamole (5 side effects)

A

Flushing, abd pain, hypotension, nausea, headache

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34
Q

Abciximab (mechanism)

A

Monoclonal Ab Fab fragments, analog of fibrinogen

GP IIb/IIIa (integrin) inhibitor –> inhibits platelet aggregation

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35
Q

Abciximab (2 uses)

A

Unstable angina

Percutaneous transluminal coronary angioplasty

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36
Q

Abciximab (2 side effects)

A

Thrombocytopenia, bleeding

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37
Q

Eptifibatide (mechanism)

A

Analog of fibrinogen

GP IIb/IIIa (integrin) inhibitor –> inhibits platelet aggregation

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38
Q

Eptifibatide (2 uses)

A

Unstable angina

Percutaneous transluminal coronary angioplasty

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39
Q

Eptifibatide (2 side effects)

A

Thrombocytopenia, bleeding

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40
Q

Tirofiban (mechanism)

A

Analog of fibrinogen

GP IIb/IIIa (integrin) inhibitor –> inhibits platelet aggregation

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41
Q

Tirofiban (2 uses)

A

Unstable angina

Percutaneous transluminal coronary angioplasty

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42
Q

Tirofiban (2 side effects)

A

Thrombocytopenia, bleeding

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43
Q

Streptokinase (mechanism)

A

Binds free plasminogen to activate it (plasminogen doesn’t have to be bound to fibrin clots) –> gets increased plasmin
Nonfibrin-specific (unlike “-teplase”)

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44
Q

Streptokinase (3 uses)

A

Acute MI
Stroke
PE

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45
Q

Streptokinase (3 side effects)

A

Loses efficacy after initial administration (sensitized)
Allergic response
Bleeding (duh)

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46
Q

Methotrexate (mechanism)

A

Antimetabolite (S-phase specific) -> folic acid analog inhibiting DHF reductase (so decreases dTMP)
Converted to polyglutamate form after it gains access to cell to prevent movement out of cell

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47
Q

Methotrexate (3 categories of use)

A

Cancers: leukemias, lymphomas, choriocarcinoma, sarcoma
Abortion-related: abortion, ectopic pregnancy -> inhibits trophoblast division
Inflammation: RA, psoriasis, IBD

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48
Q

Methotrexate (4 side effects)

A

Myelosuppression (fixed w/ leucovorin rescue)
Hepatotoxicity (macrovesicular fatty change in liver)
Stomatitis (painful mouth ulcers) -> supplement w/ folic acid to prevent this
Teratogenic

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49
Q

5-fluorouracil (mechanism)

A

Antimetabolite (S-phase specific) - pyrimidine analog that interferes w/ folate metabolism -> inhibits thymidylate synthase (so decreases dTMP; reduced toxic effects in cells deficient in THF)

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50
Q

5-fluorouracil (3 uses)

A

Colon cancer
Pancreatic cancer
Basal cell carcinoma (topical)

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51
Q

5-fluorouracil (2 side effects)

A

Myelosuppression (not reversible w/ leucovorin!)

Photosensitivity

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52
Q

5-fluorouracil (antidote)

A

Uridine

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53
Q

Cytarabine (arabinofuranosyl cytidine) and gemcitabine (mechanism)

A

Antimetabolite (S-phase specific) - pyrimidine analog inhibiting DNA polymerase
Gemcitabine does the same thing but not S-phase specific and so more toxicity

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54
Q

Cytarabine (arabinofuranosyl cytidine) (2 uses)

A

Leukemias, lymphomas

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55
Q

Cytarabine (arabinofuranosyl cytidine) (side effect)

A

Pancytopenia (leukopenia, thrombocytopenia, megaloblastic anemia)

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56
Q

Azathioprine (mechanism)

A

Azathio”PURINE”
Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis (thus also inhibits lymphocyte proliferation)
Activated by HGPRT

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57
Q

Azathioprine (2 categories of use)

A

Inflammatory: prevents organ rejection, RA, SLE, Crohn, glomerulonephritis
Cancer: leukemia

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58
Q

Azathioprine (4 side effects)

A 
Bone marrow (pancytopenia), GI, liver
Increased toxicity w/ allopurinol (b/c its metabolism is mediated by xanthine oxidase)
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59
Q

6-mercaptopurine (mechanism)

A

Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis
Activated by HGPRT

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60
Q

6-mercaptopurine (2 categories of use)

A

Inflammatory: prevents organ rejection, RA, IBD
Cancer: leukemia

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61
Q

6-mercaptopurine (4 side effects)

A

Bone marrow, GI, liver (abd pain, cirrhosis, cholestasis, jaundice)
Increased toxicity w/ allopurinol (b/c its metabolism is mediated by xanthine oxidase)

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62
Q

6-thioguanine (mechanism)

A

Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis
Activated by HGPRT

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63
Q

6-thioguanine (2 categories of use)

A

Inflammatory: prevents organ rejection, RA, IBD
Cancer: leukemia

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64
Q

6-thioguanine (3 side effects)

A

Bone marrow, GI, liver

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65
Q

Dactinomycin (actinomycin D) (mechanism)

A

Antitumor antibiotics - intercalates in DNA

66
Q

Dactinomycin (actinomycin D) (3 uses)

A

Children tumors: Wilm tumor, Ewing sarcoma, rhabdomyosarcoma

67
Q

Dactinomycin (actinomycin D) (side effect)

A

Myelosuppression

68
Q

Doxorubicin (adriamycin) and daunorubicin (mechanism)

A

Antitumor antibiotics - generates free radicals and breaks DNA (interrupts “proper base pairing and H bond formation”)

69
Q

Doxorubicin (adriamycin) and daunorubicin (3 uses)

A

Solid tumors, leukemias, lymphomas

70
Q

Doxorubicin (adriamycin) and daunorubicin (3 side effects)

A

Cardiotoxicity (dilated cardiomyopathy; prevented by dexrazoxane which is iron-chelating agent) (think of D being the shape of heart)
Myelosuppression
Alopecia

71
Q

Bleomycin (mechanism)

A

Antitumor antibiotics - generates free radicals and breaks DNA
G2 phase specific

72
Q

Bleomycin (2 uses)

A

Testicular cancer

Hodgkin lymphoma

73
Q

Bleomycin (4 side effects)

A

Pulmonary fibrosis (think of B being the shape of lungs)
Skin changes
Mucositis
Myelosuppression (minimal)

74
Q

Cyclophosphamide (mechanism)

A

Alkylating agent - covalently X-linked (interstrand) at guanine N-7
Requires activation by liver P450

75
Q

Cyclophosphamide (4 uses)

A

Solid tumors
Leukemia
Lymphomas
Some brain cancers

76
Q

Cyclophosphamide (2 side effects)

A

Hemorrhagic cystitis: prevented by Mesna (binds metabolite acrolein in bladder) (think of C and Y being a bladder and urethra respectively)
Myelosuppression

77
Q

Ifosfamide (mechanism)

A

Alkylating agent - covalently X-linked (interstrand) at guanine N-7
Requires activation by liver

78
Q

Ifosfamide (4 uses)

A

Solid tumors
Leukemia
Lymphomas
Some brain cancers

79
Q

Ifosfamide (2 side effects)

A 
Hemorrhagic cystitis (C=C): prevented by Mesna (binds metabolite acrolein in bladder)
Myelosuppression
80
Q

“-mustine” (mechanism and CNS penetration)

A

Nitrosoureas: carmustine, lomustine, semustine
Alkylating agent - X-links DNA
Requires bioactivation
Crosses BBB

81
Q

“-mustine” (use)

A

Brain tumors (incl glioblastoma multiforme)

82
Q

“-mustine” (side effect)

A

CNS toxicity (convulsions, dizziness, ataxia)

83
Q

Streptozocin (mechanism and CNS penetration)

A

Nitrosourea too
Alkylating agent - X-links DNA
Requires bioactivation
Crosses BBB

84
Q

Streptozocin (use)

A

Brain tumors (incl glioblastoma multiforme)

85
Q

Streptozocin (side effect)

A

CNS toxicity (convulsions, dizziness, ataxia)

86
Q

Busulfan (mechanism)

A

Alkylating agent - X-links DNA

87
Q

Busulfan (2 uses)

A

CML

Ablate bone marrow before transplantation

88
Q

Busulfan (3 side effects)

A

Severe myelosuppression
Pulmonary fibrosis
Hyperpigmentation

89
Q

“Vin-“ (mechanism)

A

Vincristine, vinblastine

Inhibits microtubule formation (M-phase specific)

90
Q

“Vin-“ (3 uses)

A

Solid tumors
Leukemias
Lymphomas

91
Q

“Vin-“ (3 side effects)

A

Vincristine: neurotoxicity (think of V being arms and legs and representing peripheral neuropathy), paralytic ileus
Vinblastine: myelosuppression

92
Q

Paclitaxel and other taxols (mechanism)

A

Inhibits microtubule disassembly (M-phase specific) so anaphase can’t occur

93
Q

Paclitaxel and other taxols (2 uses)

A

Ovarian and breast carcinomas

Elution of coronary artery stents -> inhibits intimal hyperplasia -> prevents thrombosis and restenosis

94
Q

Paclitaxel and other taxols (3 side effects)

A

Myelosuppression
Alopecia
Hypersensitivity

95
Q

“-platin” (mechanism)

A

Cisplatin, carboplatin

X-link DNA

96
Q

“-platin” (4 uses)

A

Testicular, bladder, ovary, lung carcinomas

97
Q

“-platin” (2 side effects)

A

Nephrotoxicity (prevents w/ amifostine, which is a free radical scavenger, and chloride diuresis) (think of C for cysplatin and carboplatin being the shape of kidneys)
Acoustic nerve damage (think of C as ears)

98
Q

“-poside” (mechanism)

A

Etoposide, teniposide

Inhibits topoisomerase II (S and G2 phase)

99
Q

“-poside” (3 uses)

A

Solid tumors (esp testicular and small cell lung cancer)
Leukemias
Lymphomas

100
Q

“-poside” (3 side effects)

A

Myelosuppression
GI irritation
Alopecia

101
Q

“-tecan” (mechanism)

A

Irinotecan, topotecan

Inhibits topoisomerase I

102
Q

“-tecan” (3 uses)

A 
Colon cancer (irinotecan)
Ovarian cancer (topotecan)
Small cell lung cancer (topotecan)
103
Q

“-tecan” (2 side effects)

A

Severe myelosuppression

Diarrhea

104
Q

Hydroxyurea (mechanism)

A

Inhibits ribonucleotide reductase (S-phase specific)

105
Q

Hydroxyurea (3 uses)

A

Melanoma
Myeloproliferative disorders: CML, PV (2nd line after phlebotomy)
Sickle cell disease (to increase HbF)

106
Q

Hydroxyurea (2 side effects)

A

Bone marrow suppression

GI upset

107
Q

“Predni-“ (mechanism)

A

Prednisone, prednisolone

Glucocorticoids, trigger apoptosis (work on nondividing cells as well)

108
Q

“Predni-“ (2 categories of use)

A

Cancer (in combination regimen): CLL, non-Hodgkin lymphomas

Immunosuppression

109
Q

“Predni-“ (side effect)

A

Cushing-like sx (incl psychosis and peptic ulcers)

110
Q

Trastuzumab (mechanism)

A

Monoclonal Ab against HER-2 (c-erbB2)

111
Q

Trastuzumab (2 uses)

A

HER-2 positive breast cancer and gastric cancer

112
Q

Trastuzumab (side effect)

A

Cardiotoxicity (“HEARTceptin” for Herceptin)

113
Q

Imatinib (mechanism and 2 uses)

A

Tyrosine kinase inhibitor of bcr-abl (CML) and c-kit (GI stromal tumors)

114
Q

Imatinib (side effect)

A

Fluid retention

115
Q

Rituximab (mechanism)

A

Monoclonal Ab against CD20

116
Q

Rituximab (3 uses)

A

Non-Hodgkin lymphoma (follicular lymphoma)
RA (w/ methotrexate)
ITP

117
Q

Rituximab (side effect)

A

Increased risk of progressive multifocal leukoencephalopathy

118
Q

Vemurafenib (mechanism)

A

Inhibits B-Raf kinase w/ V600E mutation

119
Q

Vemurafenib (use)

A

Metastatic melanoma

120
Q

Bevacizumab (mechanism)

A

Monoclonal Ab against VEGF (so inhibits angiogenesis)

121
Q

Bevacizumab (4use)

A

Colorectal cancer
Metastatic renal cell carcinoma
Recurrent GBM
Metastatic NSCLC

122
Q

Bevacizumab (2 side effects)

A

Hemorrhage

Impaired wound healing

123
Q

Cyclosporin (mechanism)

A

Calcineurin inhibitor (binds cyclophilin and blocks T cell activation by preventing IL-2 TRANSCRIPTION)

124
Q

Cyclosporin (3 uses)

A

Transplant rejection prophylaxis
Psoriasis
RA

125
Q

Cyclosporin (side effects)

A 
Nephrotoxicity
HTN, HLD, hyperglycemia
Tremor
Hirsutism (difference from tacrolimus)
Gingival hyperplasia (difference from tacrolimus)
126
Q

Tacrolimus (mechanism)

A

Calcineurin inhibitor (binds FKBP and blocks T cell activation by preventing IL-2 TRANSCRIPTION)

127
Q

Tacrolimus (use)

A

Transplant rejection prophylaxis

128
Q

Tacrolimus (side effects)

A

Nephrotoxicity
HTN, HLD, hyperglycemia
Tremor
Increased risk of DM and neurotoxicity (difference from cyclosporin)

129
Q

Sirolimus (Rapamycin) (mechanism)

A

mTOR inhibitor (binds FKBP like tacrolimus, blocks T cell activation and B cell differentiation by preventing IL-2 SIGNAL TRANSDUCTION)

130
Q

Sirolimus (Rapamycin) (use)

A

Kidney transplant rejection prophylaxis

131
Q

Sirolimus (Rapamycin) (side effects)

A 
Not nephrotoxic (like tacrolimus)
Blood counts go down: anemia, thrombocytopenia, leukopenia
Insulin resistance, HLD
132
Q

Basiliximab (mechanism)

A

Monoclonal Ab blocking IL-2R

133
Q

Basiliximab (use)

A

Kidney transplant rejection prophylaxis

134
Q

Basiliximab (3 side effects)

A

Edema
HTN
Tremor

135
Q

Glucocorticoids (mechanism)

A

Inhibits NF-KB (suppresses both B and T fx by decreasing transcription of cytokines)

136
Q

Glucocorticoids (2 uses)

A

Transplant rejection phophylaxis

Other autoimmune disorders and inflammation

137
Q

Epoetin alfa (mechanism and use)

A

Erythropoietin

For anemia esp in renal failure

138
Q

Oprelvekin (mechanism and use)

A

IL-11

For thrombocytopenia

139
Q

Filgrastim (mechanism and use)

A

GC-SF

For recovery of bone marrow

140
Q

Sargramostim (mechanism and use)

A

GMC-SF

For recovery of bone marrow

141
Q

Aldesleukin (mechanism and 2 uses)

A

IL-2

For renal cell carcinoma, metastatic melanoma

142
Q

Alemtuzumab (mechanism and use)

A

Ab against CD52 -> directly cytotoxic thru complement fixation and Ab-dependent, cell-mediated cytotoxicity
For CLL

143
Q

Cetuximab (mechanism and 4 uses)

A

Ab against EGFR

For stage IV colorectal cancer, head and neck cancer, pancreatic cancer, NSCLC

144
Q

Infliximab (mechanism and 4 uses)

A

Ab against TNF-a

For IBD, RA, ankylosing spondylitis, psoriasis

145
Q

Adalimumab (mechanism and 4 uses)

A

Ab against TNF-a

For IBD, RA, ankylosing spondylitis, psoriasis

146
Q

Natalizumab (mechanism)

A

Ab against alpha4-integrin (leukocyte adhesion impaired)

147
Q

Natalizumab (2 uses)

A

MS, Crohn

148
Q

Natalizumab (side effect)

A

Risk of PML in pts w/ JC virus

149
Q

Denosumab (mechanism and use)

A 
Ab against RANKL
For osteoporosis (inhibits osteoclast maturation by mimicking osteoprotegrin)
150
Q

Omalizumab (mechanism and use)

A

Ab against IgE

For allergic asthma (prevents it from binding to FceRI)

151
Q

Vemurafenib (mechanism and use)

A

BRAF kinase inhibitor

For melanoma w/ BRAF V600E mutation

152
Q

Dexrazoxane (mechanism and use)

A

Iron-chelating agent

Used to prevent doxorubicin cardiotoxicity

153
Q

OKT3 (mechanism and use)

A

Anti-CD3 (so anti T cells)

Used to reduce acute rejection of liver, heart, kidney

154
Q

Argatroban (mechanism and use)

A

Direct thrombin inhibitor

Anti-clotting in pt that you can’t use heparin or warfarin on (for fear of skin necrosis or HIT)

155
Q

Bivalirudin and other hirudin derivatives (mechanism and use)

A

Direct thrombin inhibitor

Anti-clotting in pt that you can’t use heparin or warfarin on (for fear of skin necrosis)

156
Q

Aminocaproic acid (mechanism and 2 uses)

A

Blocks activation of plasminogen

Used as anidote for thrombolytics, and for disorder of fibrinolysis (radical prostatectomy and cirrhosis of liver)

157
Q

Cladribine (2-CDA) (mechanism and use)

A

Purine analog resistant to degradation by adenosine deaminase
Penetrates CNS well, excreted in urine unchanged
DOC for hairy cell leukemia

158
Q

Desmopressin acetate (DDAVP) (mechanism and 2 uses)

A

Stimulates endothelial cells (so release factor VIII and vWF)
Use in vWF disease and mild-moderate hemophilia A

159
Q

Bortezomib (mechanism and 2 uses)

A

Proteasome inhibitor

For MM and Waldenstrom macroglobulinemia

160
Q

Gardos channel blockers (mechanism and use)

A

Ca2+-dependent K+ channel blocker

Prevent intracellular dehydration -> reduces polymerization in sickle cell

161
Q

Fludarabine (mechanism and use)

A

Deamination-resistant purine nucleotide analog

For CLL

162
Q

Lepirudin (mechanism and use)

A

Direct thrombin inhibitor

Anti-clotting in pt that you can’t use heparin or warfarin on (for fear of skin necrosis or HIT)

Pharmacology (12 decks)

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