Misc Flashcards
heparin
MOA: Activates antithrombin, which ↓ action of IIa (thrombin) and factor Xa. Short half-life.
Clinical use: Immediate anticoagulation for pulmonary embolism (PE), acute coronary syndrome, MI, deep venous thrombosis (DVT). Used during pregnancy (does not cross placenta). Follow PTT.
Adverse effects: Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal
(antidote) , use protamine sulfate (positively charged molecule that binds negatively charged
heparin) .
Bivalirudin (related to hirudin, the anticoagulant used by leeches), Argatroban, Dabigatran (only
oral agent in class).
Direct thrombin inhibitors
MOA: Directly inhibits activity of free and clot-associated thrombin.
Clinical use: Venous thromboembolism, atrial fibrillation. Can be used in HIT, when heparin is BAD for the
patient. Does not require lab monitoring
Adverse effects: Bleeding; can reverse dabigatran with idarucizumab. Consider PCC and/or antifibrinolytics (eg,
tranexamic acid) if no reversal agent available.
warfarin
MOA: Inhibits epoxide reductase, which interferes
with γ-carboxylation of vitamin K–dependent
clotting factors II, VII, IX, X, and proteins C,
S. Metabolism affected by polymorphisms
in the gene for vitamin K epoxide reductase
complex (VKORC1). In laboratory assay, has
effect on EXtrinsic pathway and ↑PT. Long
half-life.
Clinical use: Chronic anticoagulation (eg, venous
thromboembolism prophylaxis, and prevention
of stroke in atrial fibrillation). Not used in
pregnant women (because warfarin, unlike
heparin, crosses placenta). Follow PT/INR
Adverse effects: Bleeding, teratogenic, skin/tissue necrosis A ,
drug-drug interactions.
Initial risk of hypercoagulation: protein C
has a shorter half-life than factors II and X.
Existing protein C depletes before existing
factors II and X deplete, and before warfarin
can reduce factors II and X production
–> hypercoagulation. Skin/tissue necrosis
within first few days of large doses believed to
be due to small vessel microthrombosis
ApiXaban, rivaroXaban.
Direct factor Xa
inhibitors
MOA: Bind to and directly inhibit factor Xa
Clinical use: Treatment and prophylaxis for DVT and PE; stroke prophylaxis in patients with atrial fibrillation.
Oral agents do not usually require coagulation monitoring
Adverse effects: Bleeding. Not easily reversible.
Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA).
Thrombolytics
MOA: Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin
clots. ↑ PT, ↑ PTT, no change in platelet count
Clinical use: Early MI, early ischemic stroke, direct thrombolysis of severe PE
Adverse effects: Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding,
recent surgery, known bleeding diatheses, or severe hypertension. Nonspecific reversal with
antifibrinolytics (eg, aminocaproic acid, tranexamic acid), platelet transfusions, and factor
corrections (eg, cryoprecipitate, FFP, PCC).
Clopidogrel, prasugrel, ticagrelor (reversible), ticlopidine
ADP receptor inhibitors
MOA: Inhibit platelet aggregation by irreversibly blocking ADP (P2Y12) receptor. Prevent expression of
glycoproteins IIb/IIIa on platelet surface.
Clinical use: Acute coronary syndrome; coronary stenting. ↓ incidence or recurrence of thrombotic stroke
Adverse effects: Neutropenia (ticlopidine). TTP may be seen
Cilostazol, dipyridamole.
Antiplatelet
phosphodiesterase
inhibitors
MOA: ↑ cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators
Clinical use: Intermittent claudication, coronary vasodilation (dipyridamole used for cardiac stress testing),
prevention of stroke or TIAs (combined with aspirin).
Adverse effects: Nausea, headache, facial flushing, hypotension, abdominal pain
Abciximab, eptifibatide, tirofiban
Glycoprotein IIb/IIIa
inhibitors
MOA: Bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. Abciximab
is made from monoclonal antibody Fab fragments
Clinical use: Unstable angina, percutaneous coronary intervention
Adverse effects: Bleeding, thrombocytopenia
Cisplatin, carboplatin, oxaliplatin
MOA: Cross-link DNA.
Clinical use: Testicular, bladder, ovary, GI, and lung carcinomas.
Adverse effects: Nephrotoxicity (including Fanconi syndrome), peripheral neuropathy, ototoxicity. Prevent
nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis
Etoposide, teniposide
MOA: Inhibit topoisomerase II –> ↑ DNA degradation
Clinical use: Solid tumors (particularly testicular and small cell lung cancer), leukemias, lymphomas
Adverse effects: Myelosuppression, alopecia
Irinotecan, topotecan
MOA: Inhibit topoisomerase I and prevent DNA unwinding and replication
Clinical use: Colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan).
Adverse effects: Severe myelosuppression, diarrhea
Hydroxyurea
MOA: Inhibits ribonucleotide reductase –> ↓ DNA Synthesis (S-phase specific).
Clinical use: Myeloproliferative disorders (eg, CML, polycythemia vera), sickle cell (↑ HbF).
Adverse effects: Severe myelosuppression
Bevacizumab
MOA: Monoclonal antibody against VEGF. Inhibits angiogenesis (BeVacizumab inhibits Blood Vessel
formation).
Clinical use: Solid tumors (eg, colorectal cancer, renal cell carcinoma), wet age-related macular degeneration
Adverse effects: Hemorrhage, blood clots, and impaired wound healing
Erlotinib
MOA: EGFR tyrosine kinase inhibitor
Clinical use: Non-small cell lung cancer.
Adverse effects: Rash.
Cetuximab, panitumumab
MOA: Monoclonal antibodies against EGFR
Clinical use: Stage IV colorectal cancer (wild-type KRAS), head and neck cancer
Adverse effects: Rash, elevated LFTs, diarrhea
