Heme Onc Flashcards
Heparin
- Increases binding affinity of antithrombin for factor 2 (thrombin) and 10a
- Causes impaired coagulation, followed with PTT
- Has a short half life and rapid onset of action (IV only)
- Used for quick antiocagulation, also used when warfarin is started to prevent skin necrosis
- Does not cross the placenta and is safe to use in pregnancy
- Overdose can predispose to bleeding and can be treated with protamine sulfate
- LMWH has more effect on factor 10 and has a longer half life
HIT
- IgG antibodies to hapten of heparin and platelet factor 4.
- Causes destruction of platelets leading to thrombocytopenia and also causes thrombosis from platelet fragments in circulation.
- Give direct thombin inhibitors otherwise (lepirudin, bilirudin)
Lepirudin
- Leech protein analog that directly inhibits thormbin
- Used in pts that need anticoagulation that have HIT
Bilirudin
- Leech protein analog that directly inhibits thormbin
- Used in pts that need anticoagulation that have HIT
Agatroban
- Leech protein analog that directly inhibits thormbin
- Used in pts that need anticoagulation that have HIT
Warfarin
- Inhibit vitamin K dependent gamm carboxylation of factors 2, 7, 9, 10, C, S in liver. Epoxide reductase
- Most commonly used for anticoagulation with A fib or DVT prophylaxis
- INR is how you follow it (PT)
- Metabolized by P450 system. Inducers will decrease anti-coagulation effects
- Can cross the placenta and cause teratogenicity including blindness and hydrocephalus
- Causes warfarin induced skin necrosis (C has shorter half life. Always give heparin at first does)
- Overdose treated with vitamin K. If acute need give FFP that contains clotting factors.
Ateleplase
- Activates Plasminogen to Plasmin which cleaves Fibrin, FIbrinogen, and decreases platelet adherence
- Used in ischemic stroke, PE, MI without Cath available
- Contraindicated in any bleeding risk and patients with severe hypertension
- Increase PT and PTT without effecting platelet count
- Overdose treated with aminocaproic acid (anaolog of lysine that inhibits proteases that cleave at lysine sites)
Aspirin
- Covalently acetylates Cox-I and Cox-2 (Suicide inhibition (penicilin also)) irreversible inihbition that requires platelets to be resynthesized to overcome effects (Weeks later)
- Prevents production of TXA2 which prevents vasoconstriction and platelet aggregation
- Prophylaxis in MI and other coagulation risks
- S/E: Tinnitus, GI bleed (PG)
- Intersitial nephritis with longterm use
- Respiratory alkalosis (Depresses breathing center) followed by metabolic acidosis (Salicylic acid)
- Reyes Syndrome with viral infection (flu/VZV) Cirrhosis and mental status changes.
Clopidrogel
- Direct inhibitor of ADP receptor that prevents the expression of Gp2b3a on plateltes and prevents coagulation
- Used commonly post stent
Ticlopodine
- Direct inhibitor of ADP receptor that prevents the expression of Gp2b3a on plateltes and prevents coagulation
- Used commonly post stent
- MAY CAUSE NEUTROPENIA, only one of ADPR inhibitors to do this
Prasugrel
- Direct inhibitor of ADP receptor that prevents the expression of Gp2b3a on plateltes and prevents coagulation
- Used commonly post stent
ticagrelor
- Direct inhibitor of ADP receptor that prevents the expression of Gp2b3a on plateltes and prevents coagulation
- Used commonly post stent
Cilostazol
- Inhibit PDE III leads to decreased cAMP and decreased platelet activation. Also causes vasodilation
- Primarilly indicated in claudication, TIA, Angina
- S/E: Hypotension, headache, nasuea
Dipridamole
- Inhibit PDE III leads to decreased cAMP and decreased platelet activation. Also causes vasodilation
- Primarilly indicated in claudication, TIA, Angina
- S/E: Hypotension, headache, nasuea
Abciximab
- Directly bind to Gp2b3a R and inhibit binding to fibrinogen an platelet aggregation
- Used in angioplasty and acute coronary syndrome
- Risk of thombocytopenia and bleeding
- Fab PORTION OF MAb (only abciximab)
eptifibatide
- Directly bind to Gp2b3a R and inhibit binding to fibrinogen an platelet aggregation
- Used in angioplasty and acute coronary syndrome
- Risk of thombocytopenia and bleeding
Tirofiban
- Directly bind to Gp2b3a R and inhibit binding to fibrinogen an platelet aggregation
- Used in angioplasty and acute coronary syndrome
- Risk of thombocytopenia and bleeding
Rivaroxiban
- Direct factor 10a inhibitor
- Used prophylaxis in A Fib and other clotting disorders
- Oral administration and no checking blood levels (INR)
- Increase risk of bleeding with no reversal
Apcixiban
- Direct factor 10a inhibitor
- Used prophylaxis in A Fib and other clotting disorders
- Oral administration and no checking blood levels (INR)
- Increase risk of bleeding with no reversal
Methotrexate
- Inhibits DHFR leading to impaired TMP synthesis leading to reduced cellular division.
- Functions in S phase
- S/E: Myelosupression, treat with leucoverin (bypass DHFR)
Leucoverin
Treats methotrexate induced myelosuprresion by providing folate that bypasses DHFR
5-FU
- Coverted to 5F-dUMP which Inhibits thymidylate synthesis and reduces TMP production resulting in decreased DNA snythesis
- Used in S phase
- Toxicity: Myelosupression, can’t treat with leucoverin but can be recovered by providing thymidine
6-MP
- Inhibits de novo Purine Synthesis leading to impaired DNA replication
- Activated by HGPRT and metabolized by xanthine oxidase
- Active during S phase
- Metabolism will be impaired with use of allopurinol
Cyterabine
- Pyrimidine analog that inhibits DNA polymerase
- Active in S phase
- Toxicity: Megalolastic Anemia
D-Actinomycin
- Intercalates with DNA
- Works in all phases of cell cylce
- Myelosupression
Doxorubacin
- Intercalates with DNA, inhibits polymerase and causes free radical induced damage
- Works in all stages of cell cycle
- Toxicity: DCM Treatment with Dexrazoxane (Fe Chelator) will reduce risk of DCM
Dexrazoxane
-Given with doxorubicin to reduce risk of DCM
Bleomycin
- Causes free radical damage to DNA and DNA breaks.
- Used in G2 phase
- Toxicity: Pulmonary fibrosis, skin changes. Minimal myelosupression
Cyclophosphamide/ifosphamide
- DNA Alkylating agent
- Effective in all stages of cell cycle
- Toxicity (acrolein) is hemorrhagic cystitis which can be treated with mesna
- Also causes myleosupression
Mesna
-Thiol containing molecule that complexes with acroelin of cyclophophamide to impede hemorrhagic cystitis
Carmustine, lomustine, semustine
- Alkylating agents that can cross the BBB and are effective in brain tumors
- Effective in all stages of cell cycle
- CNS toxicity: ataxia and dizziness
streptozocin
- Alkylating agents that can cross the BBB and are effective in brain tumors
- Effective in all stages of cell cycle
- CNS toxicity: ataxia and dizziness
Busulfan
- Alkylating agent, most commonly used as BM ablating agent before BM transplant
- Works in all stages of cell cycle
- Toxicity: Pulmonary fibrosis and hyperpigmentation
Vincristine
- Binds to tubulin and inhibits polymerization of MT
- Active during M phase
- Cristing causes peripheral neuropathy and paralytic ileus
Vinblastine
- Binds to tubulin and inhibits polymerization of MT
- Active during M phase
- Blastine causes myelosupression
Paclitaxel
- Binds Tubulin in polymerized state and prevents depolymerization and MT dynamics
- Active during M phase
- Toxicity: Myelosupression and may cause female infertility
Cisplatin
- Cross Links DNA
- Toxicity: Nephrotoxicity (prevent with amiphostine) and Acoustic nerve toxicity
Amiphostine
-Scavenges free radicals and reduces nephrotoxicity caused by cisplatin
Etoposide
- Antibiotic that interferes with DNA topoisomerase 2 leading to DNA degredation
- Active during G2 and S phase
Hydroxyurea
- Inhibits ribonucleotide reductase
- Only functions in S phase
- Used in sickle cell to increase HbF production
Prednisone
- Induces apoptosis
- Associated with cataracts, osteoporosis, psychosis and other symptoms
Tamoxifen, Reloxifen
SERM that is partial agonist. Used in breast cancer because acts as an antagonist there.
- Also prevents osteoporosis
- Temoxifen risk of endometrial cancer
- Reloxifen no risk of endometrial cancer
Trastuzumab
Monoclonal antibody to Her2-Neu TK
- Used in Her2 positive breast cancers
- Toxicity: Cardiotoxicity
Imatinib
- Binds BCR-ABL in CML. TKI
- Tox: Fluid retention
Rituximab
- CD20 Ab
- Reduces B cells. NHL and RA
Vemurafenib
- Inhibitor of Braf kinase at V600E mutation
- Used in melanoma
Bevacizumab
-Anti VEGF inhibits angiogenesis