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STEP 1 (2) > Heme Pharm > Flashcards

Heme Pharm Flashcards

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1
Q

How does heparin work?

A

activator of antithrombin, decreasing levels of thrombin and factor Xa (short half-life)

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2
Q

What are the main uses of heparin?

A
  • immediate anticoag for PE, acute coronary syndrome, MI, DVT
  • used during pregnancy

monitor PTT

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3
Q

What are the AEs of heparin?

A

bleeding

thrombocytopenia (HIT)

osteoporosis

DDIs

-monitor PTT

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4
Q

What is the antidote to heparin overdose?

A

protamine sulfate (binds to negatively charged heparin)

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5
Q

What are the advantages of LMWH (like enoxaparin, dalteparin) and fondaparinux?

A

they act more on factor Xa

better bioavailability

2-4x longer half-life

can be administered SubQ and without monitoring

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6
Q

What is heparin-induced thrombocytopenia?

A

development of IgG Abs against heparin-bound platelet factor 4, and the complex activates platelets causing thrombosis and then thrombocytopenia

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7
Q

What are the direct thrombin (factor II) inhibitors?

A
  • argatroban and dabigatran
  • bivalirudin

good alternatives fo anticoag in those with HIT

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8
Q

How does warfarin work?

A

it interferes with y-carboxylation of vitamin-K dependent clotting factors II, VII, IX, X, and proteins C and S

  • affects PT
  • long half-life
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9
Q

The metabolism of warfarin is affected by what?

A

polymorphisms in the gene for vitamin K epoxide reductase complex VKORC1)

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10
Q

What are the uses of warfarin?

A
  • chronic anticoag (e.g. venous TE prophylaxis, and prevention of stroke in a. fib)
  • not used in pregnancy
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11
Q

AEs of warfarin?

A
  • bleeding
  • teratogenic

skin/tissue necrosis

-transient hypercoagulability upon administration because of short half-life of proteins C and S

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12
Q

What is the antidote for warfarin OD?

A

vitamin K, or Fresh frozen plasma for rapid reversal

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13
Q

Describe heparin bridging

A

heparin is frequently used with starting warfarin because heparin’s activation of antithrombin enables anticoag during the initial, transient hypercoag state caused by warfarin

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14
Q

What is the structure of heparin?

A

large, anionic, acidic polymer

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15
Q

How is heparin given?

A

IV/SC

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16
Q

What is the onset of action and DOA of heparin?

A

onset of action- rapid (seconds)

DOA- acute (hours)

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17
Q

What is the structure of warfarin?

A

small, amphipathic molecule

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18
Q

How is warfarin given?

A

PO

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19
Q

What are the direct factor Xa inhibitors?

A

ApiXaban, RivaroXaban

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20
Q

What are the uses of direct factor Xa inhibitors?

A
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21
Q

What are the main plasmin activators?

A

alteplase, reteplase, tenecteplase

streptokinase

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22
Q

What are the AEs of plasmin activators?

A

-bleeding (contraindicated in pts. with active bleeding, hx of intracranial bleeding, recent surgery, or severe HTN)

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23
Q

How can bleeding caused by plasmin activators (or other things) be tx?

A

aminocaproic acid

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24
Q

How does aspirin work?

A

it irreversibly inhibits cyclooxygenase 1/2 by covalent acetylation until the platelet is degraded

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25
How does aspirin affect BT, PT, and PTT?
BT- increased PT/PTT- no effect
26
What are the AEs of aspirin?
gastric ulceration tinnitus (the hearing of sound when no external sound is present- often ringing) renal failure hyperventilation and respiratory alkalosis transitioning to mixed metabolic acidosis-respiratory acidosis
27
What are the ADP receptor inhibitors?
clopidogrel, prasugrel, ticlopidine ticagrelor (reversible)
28
What are the uses of ADP receptor inhibitors?
acute coronary syndrome, coronary stenting
29
What are the AEs of ADP receptor inhibitors?
neutropenia TTP rarely
30
What do cilostazol and dipyridamole do?
phosphodiesterase III inhibitors that cause increased cAMP in platelets, resultng in inhibition of platelet aggregation also act as vasodilators
31
What are the direct GpIIb/IIIa inhibitors?
-abciximab tirofiban -eptigibatide
32
What are the clinical uses of GpIIb/IIIa inhibitors?
unstable angina, percutaneous transluminal coronary angioplasty
33
What phase of the cell cycle do microtubules inhibitors (paclitaxel) and vinca alkaloids (vinblastine; vincristine) work?
Mitosis
34
What phase of the cell cycle do alkylating agents and nitrosoureas (carmustine, cisplatin, lomustine) work?
G1
35
What phase of the cell cycle do antimetabolites (e.g. 5-FU, methotrexate, 6-MP) work?
S
36
What phase of the cell cycle do etoposide and teniposide work?
S and G2
37
What phase of the cell cycle does bleomycin work?
G2
38
How do azathioprine, 6-MP, and 6-thioguanine work?
these are false-purine analogs **activated by HGPRT** that decrease de novo purine synthesis (azathioprine is metabolized to 6-MP)
39
What are the uses of azathioprine, 6-MP, and 6-thioguanine?
preventing organ rejection rheumatoid arthritis IBD SLE used to wean pts off steroids in chronic disease and to treat steroid-refractory chronic disease
40
What are the AEs of azathioprine, 6-MP, and 6-thioguanine??
myelosuppression elevated LFTs GI toxicity azathioprine and 6-MP are metabolized by xanthine xidase, thus both have increased toxicity with allopurinol or febuxostat
41
How does Cladribine (2-CDA) work?
a false purine analog that also inhibits DNA polymerase and causes strand breaks
42
What is the use of 2-CDA?
hairy cell leukemia
43
What are the AEs of 2-CDA?
myelosuppression nephrotixicity, neurotoxicity
44
How does Cyatarabine work?
it is a **false pyrimidine analog** that inhibits DNA polymerase for _tx of leukemias (AML) and lymphomas_
45
What are the AEs of cytarabine?
-leukopenia, thrombocytopenia, megaloblastic anemia
46
How does 5-FU work?
it is a pyrimidine analog bioactivated to 5F-dUMP which covalently complexes with folic acid to **inhibit thymidylate synthase** which converts dUMP to dTP
47
What are the uses of 5-FU?
colon cancer pancreatic cancer basal cell carcinoma
48
How does methotrexate work?
it is a folic acid analog that competitively inhibits dihydrofolate reductase which is needed for conversion of DHF to THF in DNA synthesis
49
What are the main uses of methotrexate?
cancers: leukemia, lymphomas, choriocarcinoma, sarcoma ectopic pregnancy elimination/medical abortion rheumatoid arthrtiis psoriasis IBD vasculitis
50
What are the AEs of methotrexate?
- myelosuppression (reversible with leuocovorin) - hepatotoxicity mucositis (e.g. mouth ulcers)/ skin lesions pulmonary fibrosis
51
How does bleomycin work?
it induces free radical formation to cause DNA stran breaks for tx of testicular cancer and Hodgkin lymphoma
52
What are the AEs of bleomycin?
pulmonary fibrosis skin hyperpigmentation mucositis
53
How does dactinomycin work?
it intercalates with DNA for tx of Wilm's tumor, Ewing sarcoma, and rhabdomyosarcomas (all pediatric tumors)
54
How do doxorubicin and daunorubicin work?
they generate free radicals and intercalate with DNA to form strand breaks
55
What are the AEs of doxo- and daunorubicin?
-cardiotoxicity (dilated cardiomyopathy) myelosuppression alopecia
56
What can be used to prevent the cardiotoxicity of doxo- and daunorubicin?
dexrazoxane
57
What are the main alkylating agents?
- busulfan - cyclophosphamide, ifosfamide - nitrosoureas (carmustine, lomustine, semustine, streptozocin)
58
Busulfan works by cross-linking DNA for tx of CML and to ablate a pt's bone marrow before bone marrow transplant. What are the AEs?
- severe myelosuppression- almost always - pulmonary fibrosis hyperpigmentation
59
How do cyclophosphamide and ifosfamide work?
they are alkylating agents that cross-link DAN at guanine N-7 after being activated in the liver
60
What are the AEs of cyclophosphamide?
- myelosuppression - hemorrhagic cystitis (prevent with **_mesna)_**
61
How do nitrosoureas like carmustine and lomustine work?
they are alkylators that require bioactivation and cross the BBB **for tx of brain tumors** these are the most likely to cause CNS toxicity
62
How do -taxels work?
they hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down and anaphase cannot occur
63
What are the main uses of -taxel drugs?
ovarian and breast carcinomas
64
How do vincristine and vinblastine work?
vinca alkaloids that bind B-tubulin and inhibit its polymerization into microtubules and prevents mitotic spindle formation
65
What are the AEs of vincristine?
neurotoxicity (areflexia, peripheral neuritis) paralytic ileus
66
What are the AEs of vinblastine?
bone marrow suppression
67
How do cisplatin and carboplatin work?
they cross-link DNA for tx of testicular, bladder, ovary, and lung carcinoma
68
What are the AEs of cisplatin and carboplatin?
-nephrotoxicity (prevent with amifostine) and ototoxicity
69
How do etoposide and teniposide work?
they inhibit topoisomerase II
70
What are the AEs of etoposide and teniposide?
myelosuppression GI disturbances alopecia
71
How do irinotecan and topotecan work?
**topo I inhibitor** to prevent DNA unwinding for tx of colon (irinotecan) cancer and ovarian and small cell lung cancer (topotecan)
72
How does hydroxyurea work?
it inhibits ribonucelotide reductase to inhibit DNA synthesis (S phase)
73
What are the uses of hydroxyurea?
- melanoma - CML - sickle cell disease (increased HbF)
74
How do prednisone and prednisolone work?
many mechanisms including altering gene transcription to induce immunosuppression
75
What are the AEs of steroids?
- cushing-like rxn - weight gain and central obesity - muscle breakdown - acne - cataracts - osteoporosis - hyperglycemia
76
How does Bevacizumab work?
it is a VEGF MAb that inhibits angiogenesis for tx of colorectal cancer and renal cell carcinoma
77
How does Erlotinib work?
EGFR tyrosine kianse inhibitor for tx of non-small cell lung cancer (can result in rash)
78
How does Imatinib work? Toxicities?
tyrosine kinase inhibitor of BCR-ABL (Philadelphis fusion gene in CML) and c-kit in GIST tumors may cause fluid retention
79
What is Rituximab?
MAb against CD20, found in most B-cell neoplasms such as Non-hodgkin lymphoma also used to tx CLL, IBD, and rheumatoid arthritis
80
What is a major AE of rituximab?
risk of progressive multifocal leukoencephalopathy
81
How do tamoxifen and raloxifene work?
they are selective estrogen receptor modulators (SERM)- receptor antagonists in breast and agonists in bone blocking the binding of estrogen to ER+ cells
82
What are the main uses of tamoxifen and raloxifene?
breast cancer tx and prevention and raloxifene for osteoporosis prevention
83
What are the AEs of tamoxifen?
agonist of endometrium hot flashes
84
What are the AEs of raloxifene?
no risk of endometrial carcinoma because it is an endometrial antagonist
85
How does Trastuzumab (herceptin) work?
it is a MAb to HER-2, a tyrosine kinase receptor for tx of HER-2+ breast cancer and metastatic gastric cancer
86
What is the major AE of trastuzumab?
Cardiotoxicity
87
What is Vemurafenib?
small molecular inhibitor of BRAF+ melanoma
88

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