HONC Pharm Flashcards
(37 cards)
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 (-)
HIT (heparin induced thrombocytopenia)
development of IgG ab’s agains PF4 (heparin-bound plt factor 4)
heparin-PF4-ab complex activates plts => thrombosis & thrombocytopenia
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
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
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
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
Direct FXa Inhibitors Apixaban, Rivaroxaban MOA Use ADE
Apixaban, Rivaroxaban
bind to and directly inhibit FXa
afib, DVT/PE ppx
bleeding & not easily reversible
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
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
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
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
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
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)
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)
Antimetabolites
Cladribine
MOA
Use
ADE
Block S phase
purine analog –> DNA pol inhibitor etc
Hairy Cell Leukemia
Myelosuppression, nephrotoxicity, neurotoxicity
Antimetabolites
Cytarabine
MOA
Uses
ADE
Block S phase
Pyrimidine analog –> DNA chain termination (inhibits DNA pol)
Leukemias (AML), lymphoma
myelosuppression w/ megaloblastic anemia, pancytopenia
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
Antitumor Abx Bleomycin MOA Use ADE
MOA: induce free radical formation -> DNA strand break
Testicular CA, Hodgkin, lymphoma
ADE: pulm fibrosis, skin hyperpigmentation
Antitumor Abx = Dactinomycin
MOA
Use
ADE
MOA: intercalate DNA –| RNA synthesis
Wilms tumor, ewing sarcoma, rhabdomyosarcoma
Myelosuppression
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
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
Microtubule Inhibitor
Vincristine/Vinblastine
MOA
Use
ADE
bind beta-tubulin, inhibit mitotic spindle formation
=> M phase arrest
leukemias, solid tumor,
vinblastine - Hodgkin
vincristine - NHL
Alkylating agents - cell cycle independent
Busulfan
MOA
Use
ADE
Cross-links DNA
ablate bone marrow before tranplant
severe myelosuppression, pulm fibrosis, hyperpig
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
