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Flashcards in HONC Pharm Deck (37):
1

Heparin
MOA
Uses
ADE
Antidote

activates antithrombin, which decreases the activity of Xa & IIa (thrombin), short t1/2, follow PTT

immediate ac: DVT/PE, MI; can use in pregnancy (no placenta)

HIT, osteoporosis, drug-drug interactions

protamine (+) binds heparin (-)

2

HIT (heparin induced thrombocytopenia)

development of IgG ab's agains PF4 (heparin-bound plt factor 4)
heparin-PF4-ab complex activates plts => thrombosis & thrombocytopenia

3

Low Molecular Weight Heparins
enoxaparin, dalteparin

fondaparinux

enoxaparin, dalteparin
acts predominantly on FXa

acts only on FXa

have better bioavailability 2-4x longer than UFHep
no need for lab monitoring
not easily reversible

4

Direct Thombin Inhibitors
BAD
Bivalirudin, Argatroban, Dabigatran

MOA
ADE & reversal
Use

Bivalirudin, Argatroban, Dabigatran

Directly inhibits activity of free and clot associated FIIa (thrombin), no monitoring

bleeding, dabigatran - idarucizumab
PCC or tranexamic acid (antifibrinolytic)

Afib, venousthromboembolism, HIT

5

Warfarin

MOA
Use
ADE
Reversal

interferes with gamma-carboxylation (epoxide reductase) of vit K factors; monitor with PT/INR

Chronic AC: afib/dvt ppx; DONT USE IN PREG

bleeding, teratogenic, skin/tissue necrosis, drug-drug inter(cyp450 substrate in liver)

vit K, FFP

6

Warfarin Skin Necrosis & Initial risk of hyper-coagulation
Solution?

Protein C has shortest t1/2 of vitk dependent factors thus is depleted before the other factors & results in skin necrosis (2/2 small vessel thrombosis)

Heparin Bridge during initial warfarin therapy

7

Direct FXa Inhibitors
Apixaban, Rivaroxaban
MOA
Use
ADE

Apixaban, Rivaroxaban

bind to and directly inhibit FXa

afib, DVT/PE ppx

bleeding & not easily reversible

8

Thrombolytics
Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA), streptokinase

MOA
USE
ADE
Reversal

Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA), streptokinase

aid conversion of plasminogen to plasmin (FXIII), increased PT and PTT

MI, early ischemic stroke, direct to PE

Bleeding
CI in pts with h/o ICH, recent surgery, severe HTN

Nonspecific anti-fibrinolytics (aminocaproic acid, tranexamic acid), plt, FFP, cyroprecipitate


9

ADP receptor inhibitors
clopidogrel, prasugrel, ticagrelor, ticlopidine

MOA
Use
ADE

clopidogrel, prasugrel, ticagrelor, ticlopidine

Inhibit plt aggregation, irreversibly block ADP(P2Y) receptor => prevent GPIIb/IIIa expression

ACS, coronary stenting, decrease incidence/recurrence stroke

ticlopidine - neutropenia
TTP may be seen

10

Glycoprotein IIb/IIIa receptor inhibitors
Abciximab, eptifibatide, tirofiban

MOA
Use
ADE

Abciximab, eptifibatide, tirofiban

prevent plt aggregation
abciximab = mooclonal ab Fab gragments


Unstable angina, PCI

Bleeding, thrombocytopenia

11

Cancer drugs: inhibit DNA syn

decreased thymidine synthesis
decreased de novo purine synthesis
inhibit ribonucleotide synthesis
Purine analog
Pyrimidine analog

cross link DNA


DNA strand breakage
DNA intercalators
Inhibitor Topoisomerase I
Inhibitor Topoisomerase II

Inhibit MT formation
Inhibit MT diassembly


Methotrexate, 5-fluorouracil
6-mercaptopurine
hydroxyurea
cladribine
cytarabine

alkylating agents (busulfan, cyclophosphamide, ifosfamide, nitrosoureas, procarbazine)
platinum agents (cisplatin, carboplatin)
Bleomycin
Dactinomycin, Doxorubicin
Topotecan, irinotecan
Etoposide, Teniposide

Vincristine, vinblastine
Paclitaxel

12

antimetabolites:
Azathioprine, 6-mecaptopurine
MOA
Use
ADE

block S phase

Purine analog => decrease de novo synthesis
activated by HGPRT, metabolixed by xanthine oxidase

prevent organ rejection, RA, SLE, IBD, steroid wean

myelosuppression, GI, liver toxicity

13

antimetabolites:
Methotrexate
MOA

Use



ADE

block S phase
Folic acid analogue competitively inhibits dihydrofolate reductase --> decreased dTMP --> Decreased DNA syn

leukemia, lymphoma, choriocarcinoma, sarcoma
ectopic preg, medical abortion(w/ misoprostol), RA, IBD, psoriasis, vasculitis

Myelosuppression (leucovorin ~ rescue)
Hepatotoxicity, mucositis, nephrotoxicity, folate def (teratogenic)

14

Antimetabolites
5-fluorouracil
MOA




Use


ADE

block S phase

pyrimidine analogue activated by 5-FdUMP which complexes w/folate & thymidylate synthase
Inhibits thymidylate synthase --> decreased dTMP -->decreased DNA synthesis

Colon CA, pancreatic CA, actinic keratosis, basal cell CA
enhanced with leucovorin

Myelosuppression
Hand-Foot Syndrome (palmar-plantar erythrodysesthesia)

15

Antimetabolites
Cladribine
MOA

Use

ADE

Block S phase

purine analog --> DNA pol inhibitor etc

Hairy Cell Leukemia

Myelosuppression, nephrotoxicity, neurotoxicity

16

Antimetabolites
Cytarabine

MOA

Uses

ADE

Block S phase


Pyrimidine analog --> DNA chain termination (inhibits DNA pol)
Leukemias (AML), lymphoma

myelosuppression w/ megaloblastic anemia, pancytopenia

17

Topoisomerase Inhibitors
Etoposide, tenipopside
MOA
Use
ADE

MOA: inhibit topoisomerase II => increase DNA degrad (S & G2 phase)

USE: solid tumors, lymphomas, leukemias

ADE: myelosuppression, alopecia

18

Antitumor Abx
Bleomycin
MOA
Use
ADE

MOA: induce free radical formation -> DNA strand break

Testicular CA, Hodgkin, lymphoma

ADE: pulm fibrosis, skin hyperpigmentation

19

Antitumor Abx = Dactinomycin
MOA
Use
ADE

MOA: intercalate DNA --| RNA synthesis

Wilms tumor, ewing sarcoma, rhabdomyosarcoma

Myelosuppression

20

Antitumor Abx = Doxorubicin
MOA
Use
ADE

MOA:
Generate free radicals
intercalate DNA --> breaks DNA & interferes with Topoisomerase II

solid tumors, lymphomas, leukemia

cardiotoxicity (DCM), myelosuppression, alopecia
use with dexrazoxane to prevent DCM

21

Microtubule Inhibitors
Paclitaxel

MOA
Use
ADE

hyperstabilize polymerized MT in M phase
=> mitotic spindle can't break down, block anaphase

ovarian & breast CA

neuropathy, myelosuppression, hypersensitivity

22

Microtubule Inhibitor
Vincristine/Vinblastine

MOA
Use
ADE

bind beta-tubulin, inhibit mitotic spindle formation
=> M phase arrest

leukemias, solid tumor,
vinblastine - Hodgkin
vincristine - NHL

23

Alkylating agents - cell cycle independent
Busulfan

MOA
Use
ADE

Cross-links DNA

ablate bone marrow before tranplant

severe myelosuppression, pulm fibrosis, hyperpig

24

Alkylating agents - cell cycle independent
Cyclophosphamide, Ifosfomide

MOA
Use
ADE

Cross-links DNA - G
require activation by liver

Solid tumor, lymphoma, leukemia

Myelosuppression, SIADH, hemorrhagic cystitis
prevent with mesna

25

Alkylating agents - cell cycle independent
Nitrosureas

MOA
Use
ADE

Cross-link DNA
requires bioactivation (cross BBB)

Brain tumors including GBM

CNS toxicity - seizures, ataxia, dizziness

26

Alkylating agents - cell cycle independent
Procarbazine

MOA
Use
ADE

MOA not yet defined

brain tumors, hodgkin lymphoma

bome marrow suppression, pulm tox, leukemia

27

Irinotecan, topotecan

MOA
Use
ADE

Inhibit Topoisomerase I, prevent DNA unwinding

Irinotecan - colon CA
Topotecan - ovarian CA, cmall cell lung cancer

Severe myelosuppression, diarrhea

28

Hydroxyurea

MOA
Use
ADE

Inhibits ribonucleotide reductase => decrease DNA syn (S phase)

Sickle cell, myeloproliferative d/o

severe myelosuppression

29

Bevacizumab

MOA
Use
ADE

VEGF monoclonals ab => inhibit angiogensis

solid tumor, (colon, RCC), wet age related macular degeneration

hemorrhage, blood clots, impaired wound healing

30

Erlotinib

MOA
Use
ADE

EGFR tyrosine kinase inhibitor

NSCLC

Rash

31

Cetuximab

MOA
Use
ADE

EGFR monoclonal ab

Stage IV colorectal CA, Head & neck CA

Rash, diarrhea, elevated LFTs

32

Imatinib

MOA
Use
ADE

c-kit and BCR-ABL RTK inhibitor

CML, GIST

fluid retension

33

Rituximab

MOA
Use
ADE

CD20 monoclonal ab

NHL, CLL, ITP, RA

increase risk progressive multifocal leukoencephalopathy

34

Bortezomib, Carfilzomib

MOA
Use
ADE

Proteasome inhibitor - induce G2-M phase & apoptosis

multiple myeloma, mantle cell lymphoma

Peripheral neuropathy, herpes zoster rxn

35

Tamoxifen, Raloxifene

MOA
Use
ADE

SERM - antagonist - breast; agonist - bone

Tamoxifen - breast, raloxifene - bone (prevent osteoporosis)

Tamoxifen - partial agonist in endometrium increased risk endometrial ca
Raloxifene - er antagonist in endometrial tissue

both increased thromboembolic events

36

Transtuzumab

MOA
Use
ADE

HER-2 RTK monoclonal ab

HER2+ breast or gastric ca

cardiotoxicity

37

Rasburicase

MOA
Use

recombinant uricase: uric acid --> allantoin

prevent & treat TLS