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)
2
Q
Heparin (antidote)
A
Protamine (chemical inactivation)
3
Q
Heparin (use/placenta crossing)
A
Immediate anticoagulation for DVT, PE, MI
Can use during pregnancy (doesn’t cross placenta)
4
Q
Heparin (side effects)
A
Skin necrosis at injection site
HIT
Bleeding (duh)
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)
6
Q
Warfarin (use/placenta crossing)
A
Chronic anticoagulation
Crosses placenta so don’t use in pregnant women
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)
8
Q
Warfarin (antidotes)
A
Vit K
If severe, fresh frozen plasma
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
10
Q
“-parin” (side effect)
A
No antidote like heparin
11
Q
“-xaban” (mechanism)
A
Apixaban, rivaroxaban
Direct factor Xa inhibitor
12
Q
“-xaban” (3 uses)
A
Tx/prophylaxis of DVT, PE, stroke
13
Q
“-xaban” (side effect)
A
No antidote like heparin or warfarin
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)
15
Q
“-teplase” (3 uses)
A
Early MI
Early ischemic stroke (3-hr window)
Direct thrombolysis of severe PE
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
17
Q
“-teplase” (3 antidotes)
A
Aminocaproic acid (inhibits fibrinolysis)
Fresh frozen plasma
Cryoprecipitate
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)
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
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
21
Q
“-grel” (3 uses)
A
Acute coronary syndrome
Coronary stenting
Reduces thrombotic stroke
22
Q
“-grel” (2 side effects)
A
TTP/HUS
23
Q
Ticlopidine (mechanism)
A
Irreversibly blocking ADP receptor –> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen
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
25
Ticagrelor (mechanism)
Irreversibly blocking ADP receptor --> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen
26
Ticagrelor (3 uses)
Acute coronary syndrome
Coronary stenting
Reduces thrombotic stroke
27
Ticagrelor (2 side effects)
TTP/HUS
28
Cilostazol (mechanism)
Phosphodiesterase III inhibitor --> increases cAMP inplatelets --> inhibits platelet aggregation
ALSO A DIRECT ARTERIAL VASODILATOR
29
Cilostazol (4 uses)
Intermittent claudication -> better than aspirin at peripheral arterial disease
Coronary vasodilation
Prevention of stroke/TIAs (combined w/ aspirin)
Angina prophylaxis
30
Cilostazol (5 side effects)
Flushing, abd pain, hypotension, nausea, headache
31
Dipyridamole (mechanism)
Phosphodiesterase III inhibitor --> increases cAMP inplatelets --> inhibits platelet aggregation
Vasodilator
32
Dipyridamole (4 uses)
Intermittent claudication
Coronary vasodilation
Prevention of stroke/TIAs (combined w/ aspirin)
Angina prophylaxis
33
Dipyridamole (5 side effects)
Flushing, abd pain, hypotension, nausea, headache
34
Abciximab (mechanism)
Monoclonal Ab Fab fragments, analog of fibrinogen
| GP IIb/IIIa (integrin) inhibitor --> inhibits platelet aggregation
35
Abciximab (2 uses)
Unstable angina
| Percutaneous transluminal coronary angioplasty
36
Abciximab (2 side effects)
Thrombocytopenia, bleeding
37
Eptifibatide (mechanism)
Analog of fibrinogen
| GP IIb/IIIa (integrin) inhibitor --> inhibits platelet aggregation
38
Eptifibatide (2 uses)
Unstable angina
| Percutaneous transluminal coronary angioplasty
39
Eptifibatide (2 side effects)
Thrombocytopenia, bleeding
40
Tirofiban (mechanism)
Analog of fibrinogen
| GP IIb/IIIa (integrin) inhibitor --> inhibits platelet aggregation
41
Tirofiban (2 uses)
Unstable angina
| Percutaneous transluminal coronary angioplasty
42
Tirofiban (2 side effects)
Thrombocytopenia, bleeding
43
Streptokinase (mechanism)
Binds free plasminogen to activate it (plasminogen doesn't have to be bound to fibrin clots) --> gets increased plasmin
Nonfibrin-specific (unlike "-teplase")
44
Streptokinase (3 uses)
Acute MI
Stroke
PE
45
Streptokinase (3 side effects)
Loses efficacy after initial administration (sensitized)
Allergic response
Bleeding (duh)
46
Methotrexate (mechanism)
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
47
Methotrexate (3 categories of use)
Cancers: leukemias, lymphomas, choriocarcinoma, sarcoma
Abortion-related: abortion, ectopic pregnancy -> inhibits trophoblast division
Inflammation: RA, psoriasis, IBD
48
Methotrexate (4 side effects)
Myelosuppression (fixed w/ leucovorin rescue)
Hepatotoxicity (macrovesicular fatty change in liver)
Stomatitis (painful mouth ulcers) -> supplement w/ folic acid to prevent this
Teratogenic
49
5-fluorouracil (mechanism)
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)
50
5-fluorouracil (3 uses)
Colon cancer
Pancreatic cancer
Basal cell carcinoma (topical)
51
5-fluorouracil (2 side effects)
Myelosuppression (not reversible w/ leucovorin!)
| Photosensitivity
52
5-fluorouracil (antidote)
Uridine
53
Cytarabine (arabinofuranosyl cytidine) and gemcitabine (mechanism)
Antimetabolite (S-phase specific) - pyrimidine analog inhibiting DNA polymerase
Gemcitabine does the same thing but not S-phase specific and so more toxicity
54
Cytarabine (arabinofuranosyl cytidine) (2 uses)
Leukemias, lymphomas
55
Cytarabine (arabinofuranosyl cytidine) (side effect)
Pancytopenia (leukopenia, thrombocytopenia, megaloblastic anemia)
56
Azathioprine (mechanism)
Azathio"PURINE"
Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis (thus also inhibits lymphocyte proliferation)
Activated by HGPRT
57
Azathioprine (2 categories of use)
Inflammatory: prevents organ rejection, RA, SLE, Crohn, glomerulonephritis
Cancer: leukemia
58
Azathioprine (4 side effects)
```
Bone marrow (pancytopenia), GI, liver
Increased toxicity w/ allopurinol (b/c its metabolism is mediated by xanthine oxidase)
```
59
6-mercaptopurine (mechanism)
Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis
Activated by HGPRT
60
6-mercaptopurine (2 categories of use)
Inflammatory: prevents organ rejection, RA, IBD
Cancer: leukemia
61
6-mercaptopurine (4 side effects)
Bone marrow, GI, liver (abd pain, cirrhosis, cholestasis, jaundice)
Increased toxicity w/ allopurinol (b/c its metabolism is mediated by xanthine oxidase)
62
6-thioguanine (mechanism)
Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis
Activated by HGPRT
63
6-thioguanine (2 categories of use)
Inflammatory: prevents organ rejection, RA, IBD
Cancer: leukemia
64
6-thioguanine (3 side effects)
Bone marrow, GI, liver
65
Dactinomycin (actinomycin D) (mechanism)
Antitumor antibiotics - intercalates in DNA
66
Dactinomycin (actinomycin D) (3 uses)
Children tumors: Wilm tumor, Ewing sarcoma, rhabdomyosarcoma
67
Dactinomycin (actinomycin D) (side effect)
Myelosuppression
68
Doxorubicin (adriamycin) and daunorubicin (mechanism)
Antitumor antibiotics - generates free radicals and breaks DNA (interrupts "proper base pairing and H bond formation")
69
Doxorubicin (adriamycin) and daunorubicin (3 uses)
Solid tumors, leukemias, lymphomas
70
Doxorubicin (adriamycin) and daunorubicin (3 side effects)
Cardiotoxicity (dilated cardiomyopathy; prevented by dexrazoxane which is iron-chelating agent) (think of D being the shape of heart)
Myelosuppression
Alopecia
71
Bleomycin (mechanism)
Antitumor antibiotics - generates free radicals and breaks DNA
G2 phase specific
72
Bleomycin (2 uses)
Testicular cancer
| Hodgkin lymphoma
73
Bleomycin (4 side effects)
Pulmonary fibrosis (think of B being the shape of lungs)
Skin changes
Mucositis
Myelosuppression (minimal)
74
Cyclophosphamide (mechanism)
Alkylating agent - covalently X-linked (interstrand) at guanine N-7
Requires activation by liver P450
75
Cyclophosphamide (4 uses)
Solid tumors
Leukemia
Lymphomas
Some brain cancers
76
Cyclophosphamide (2 side effects)
Hemorrhagic cystitis: prevented by Mesna (binds metabolite acrolein in bladder) (think of C and Y being a bladder and urethra respectively)
Myelosuppression
77
Ifosfamide (mechanism)
Alkylating agent - covalently X-linked (interstrand) at guanine N-7
Requires activation by liver
78
Ifosfamide (4 uses)
Solid tumors
Leukemia
Lymphomas
Some brain cancers
79
Ifosfamide (2 side effects)
```
Hemorrhagic cystitis (C=C): prevented by Mesna (binds metabolite acrolein in bladder)
Myelosuppression
```
80
"-mustine" (mechanism and CNS penetration)
Nitrosoureas: carmustine, lomustine, semustine
Alkylating agent - X-links DNA
Requires bioactivation
Crosses BBB
81
"-mustine" (use)
Brain tumors (incl glioblastoma multiforme)
82
"-mustine" (side effect)
CNS toxicity (convulsions, dizziness, ataxia)
83
Streptozocin (mechanism and CNS penetration)
Nitrosourea too
Alkylating agent - X-links DNA
Requires bioactivation
Crosses BBB
84
Streptozocin (use)
Brain tumors (incl glioblastoma multiforme)
85
Streptozocin (side effect)
CNS toxicity (convulsions, dizziness, ataxia)
86
Busulfan (mechanism)
Alkylating agent - X-links DNA
87
Busulfan (2 uses)
CML
| Ablate bone marrow before transplantation
88
Busulfan (3 side effects)
Severe myelosuppression
Pulmonary fibrosis
Hyperpigmentation
89
"Vin-" (mechanism)
Vincristine, vinblastine
| Inhibits microtubule formation (M-phase specific)
90
"Vin-" (3 uses)
Solid tumors
Leukemias
Lymphomas
91
"Vin-" (3 side effects)
Vincristine: neurotoxicity (think of V being arms and legs and representing peripheral neuropathy), paralytic ileus
Vinblastine: myelosuppression
92
Paclitaxel and other taxols (mechanism)
Inhibits microtubule disassembly (M-phase specific) so anaphase can't occur
93
Paclitaxel and other taxols (2 uses)
Ovarian and breast carcinomas
| Elution of coronary artery stents -> inhibits intimal hyperplasia -> prevents thrombosis and restenosis
94
Paclitaxel and other taxols (3 side effects)
Myelosuppression
Alopecia
Hypersensitivity
95
"-platin" (mechanism)
Cisplatin, carboplatin
| X-link DNA
96
"-platin" (4 uses)
Testicular, bladder, ovary, lung carcinomas
97
"-platin" (2 side effects)
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
"-poside" (mechanism)
Etoposide, teniposide
| Inhibits topoisomerase II (S and G2 phase)
99
"-poside" (3 uses)
Solid tumors (esp testicular and small cell lung cancer)
Leukemias
Lymphomas
100
"-poside" (3 side effects)
Myelosuppression
GI irritation
Alopecia
101
"-tecan" (mechanism)
Irinotecan, topotecan
| Inhibits topoisomerase I
102
"-tecan" (3 uses)
```
Colon cancer (irinotecan)
Ovarian cancer (topotecan)
Small cell lung cancer (topotecan)
```
103
"-tecan" (2 side effects)
Severe myelosuppression
| Diarrhea
104
Hydroxyurea (mechanism)
Inhibits ribonucleotide reductase (S-phase specific)
105
Hydroxyurea (3 uses)
Melanoma
Myeloproliferative disorders: CML, PV (2nd line after phlebotomy)
Sickle cell disease (to increase HbF)
106
Hydroxyurea (2 side effects)
Bone marrow suppression
| GI upset
107
"Predni-" (mechanism)
Prednisone, prednisolone
| Glucocorticoids, trigger apoptosis (work on nondividing cells as well)
108
"Predni-" (2 categories of use)
Cancer (in combination regimen): CLL, non-Hodgkin lymphomas
| Immunosuppression
109
"Predni-" (side effect)
Cushing-like sx (incl psychosis and peptic ulcers)
110
Trastuzumab (mechanism)
Monoclonal Ab against HER-2 (c-erbB2)
111
Trastuzumab (2 uses)
HER-2 positive breast cancer and gastric cancer
112
Trastuzumab (side effect)
Cardiotoxicity ("HEARTceptin" for Herceptin)
113
Imatinib (mechanism and 2 uses)
Tyrosine kinase inhibitor of bcr-abl (CML) and c-kit (GI stromal tumors)
114
Imatinib (side effect)
Fluid retention
115
Rituximab (mechanism)
Monoclonal Ab against CD20
116
Rituximab (3 uses)
Non-Hodgkin lymphoma (follicular lymphoma)
RA (w/ methotrexate)
ITP
117
Rituximab (side effect)
Increased risk of progressive multifocal leukoencephalopathy
118
Vemurafenib (mechanism)
Inhibits B-Raf kinase w/ V600E mutation
119
Vemurafenib (use)
Metastatic melanoma
120
Bevacizumab (mechanism)
Monoclonal Ab against VEGF (so inhibits angiogenesis)
121
Bevacizumab (4use)
Colorectal cancer
Metastatic renal cell carcinoma
Recurrent GBM
Metastatic NSCLC
122
Bevacizumab (2 side effects)
Hemorrhage
| Impaired wound healing
123
Cyclosporin (mechanism)
Calcineurin inhibitor (binds cyclophilin and blocks T cell activation by preventing IL-2 TRANSCRIPTION)
124
Cyclosporin (3 uses)
Transplant rejection prophylaxis
Psoriasis
RA
125
Cyclosporin (side effects)
```
Nephrotoxicity
HTN, HLD, hyperglycemia
Tremor
Hirsutism (difference from tacrolimus)
Gingival hyperplasia (difference from tacrolimus)
```
126
Tacrolimus (mechanism)
Calcineurin inhibitor (binds FKBP and blocks T cell activation by preventing IL-2 TRANSCRIPTION)
127
Tacrolimus (use)
Transplant rejection prophylaxis
128
Tacrolimus (side effects)
Nephrotoxicity
HTN, HLD, hyperglycemia
Tremor
Increased risk of DM and neurotoxicity (difference from cyclosporin)
129
Sirolimus (Rapamycin) (mechanism)
mTOR inhibitor (binds FKBP like tacrolimus, blocks T cell activation and B cell differentiation by preventing IL-2 SIGNAL TRANSDUCTION)
130
Sirolimus (Rapamycin) (use)
Kidney transplant rejection prophylaxis
131
Sirolimus (Rapamycin) (side effects)
```
Not nephrotoxic (like tacrolimus)
Blood counts go down: anemia, thrombocytopenia, leukopenia
Insulin resistance, HLD
```
132
Basiliximab (mechanism)
Monoclonal Ab blocking IL-2R
133
Basiliximab (use)
Kidney transplant rejection prophylaxis
134
Basiliximab (3 side effects)
Edema
HTN
Tremor
135
Glucocorticoids (mechanism)
Inhibits NF-KB (suppresses both B and T fx by decreasing transcription of cytokines)
136
Glucocorticoids (2 uses)
Transplant rejection phophylaxis
| Other autoimmune disorders and inflammation
137
Epoetin alfa (mechanism and use)
Erythropoietin
| For anemia esp in renal failure
138
Oprelvekin (mechanism and use)
IL-11
| For thrombocytopenia
139
Filgrastim (mechanism and use)
GC-SF
| For recovery of bone marrow
140
Sargramostim (mechanism and use)
GMC-SF
| For recovery of bone marrow
141
Aldesleukin (mechanism and 2 uses)
IL-2
| For renal cell carcinoma, metastatic melanoma
142
Alemtuzumab (mechanism and use)
Ab against CD52 -> directly cytotoxic thru complement fixation and Ab-dependent, cell-mediated cytotoxicity
For CLL
143
Cetuximab (mechanism and 4 uses)
Ab against EGFR
| For stage IV colorectal cancer, head and neck cancer, pancreatic cancer, NSCLC
144
Infliximab (mechanism and 4 uses)
Ab against TNF-a
| For IBD, RA, ankylosing spondylitis, psoriasis
145
Adalimumab (mechanism and 4 uses)
Ab against TNF-a
| For IBD, RA, ankylosing spondylitis, psoriasis
146
Natalizumab (mechanism)
Ab against alpha4-integrin (leukocyte adhesion impaired)
147
Natalizumab (2 uses)
MS, Crohn
148
Natalizumab (side effect)
Risk of PML in pts w/ JC virus
149
Denosumab (mechanism and use)
```
Ab against RANKL
For osteoporosis (inhibits osteoclast maturation by mimicking osteoprotegrin)
```
150
Omalizumab (mechanism and use)
Ab against IgE
| For allergic asthma (prevents it from binding to FceRI)
151
Vemurafenib (mechanism and use)
BRAF kinase inhibitor
| For melanoma w/ BRAF V600E mutation
152
Dexrazoxane (mechanism and use)
Iron-chelating agent
| Used to prevent doxorubicin cardiotoxicity
153
OKT3 (mechanism and use)
Anti-CD3 (so anti T cells)
| Used to reduce acute rejection of liver, heart, kidney
154
Argatroban (mechanism and use)
Direct thrombin inhibitor
| Anti-clotting in pt that you can't use heparin or warfarin on (for fear of skin necrosis or HIT)
155
Bivalirudin and other hirudin derivatives (mechanism and use)
Direct thrombin inhibitor
| Anti-clotting in pt that you can't use heparin or warfarin on (for fear of skin necrosis)
156
Aminocaproic acid (mechanism and 2 uses)
Blocks activation of plasminogen
| Used as anidote for thrombolytics, and for disorder of fibrinolysis (radical prostatectomy and cirrhosis of liver)
157
Cladribine (2-CDA) (mechanism and use)
Purine analog resistant to degradation by adenosine deaminase
Penetrates CNS well, excreted in urine unchanged
DOC for hairy cell leukemia
158
Desmopressin acetate (DDAVP) (mechanism and 2 uses)
Stimulates endothelial cells (so release factor VIII and vWF)
Use in vWF disease and mild-moderate hemophilia A
159
Bortezomib (mechanism and 2 uses)
Proteasome inhibitor
| For MM and Waldenstrom macroglobulinemia
160
Gardos channel blockers (mechanism and use)
Ca2+-dependent K+ channel blocker
| Prevent intracellular dehydration -> reduces polymerization in sickle cell
161
Fludarabine (mechanism and use)
Deamination-resistant purine nucleotide analog
| For CLL
162
Lepirudin (mechanism and use)
Direct thrombin inhibitor
| Anti-clotting in pt that you can't use heparin or warfarin on (for fear of skin necrosis or HIT)
