Step 1 - HemeOnc drugs

denniskwinn's version from 2015-04-25 16:02


Question Answer
Heparin MechanismCofactor for the activation of antithrombin, ⇣ thrombin and Xa. Short half-life,
Heparin Clinical use immediate anticoagulation for pulmonary embolism, stroke, acute coronary syndrome. Ml, DVT. Used during pregnancy (does not cross placenta). Follow PTT,
Heparin Toxicity1. Bleeding, 2. thrombocytopenia (HIT), 3. osteoporosis, 4. drug-drug interactions. For rapid reversal of heparinization, use protamine sulfate (positively charged molecule that acts by binding negatively charged heparin).
LMWH(e.g., enoxaparin) act more on Xa. have better bioavailability and 2-4 times longer half-life, Can be administered SubQ and without laboratory monitoring. Not easily reversible.
HIT heparin binds to platelets, causing autoantibody production that destroys platelets and overactivates the remaining ones, resulting in a thrombocytopenic hvpercoagulable state.
Lepirudin, bivalirudin1. Hirudin derivatives 2. Directly inhibit thrombin 3. Used as an alternative to heparin for anticoagulating patients w/HIT
Warfarin mechanisminterferes with normal synthesis of gamma carboxylation of Vit K dependent clotting factors - effect is on extrinsic pathway and ⇡PT. Long half life
Warfarin clinical use1. Chronic anticoagulation 2. Not used in pregnant women (can cross the placenta) 3. Follow PT/INR values
Warfarin toxicites1. Bleeding 2. Teratogenic 3. Skin/tissue necrosis. 4. Drug-drug interactions
Heparin route of adminparenteral (IV, SC)
Warfarin route of adminOral
Heparin site of actionblood [site of action of which anticoagulant]
Warfarin site of actionliver [site of action of which anticoagulant]
Heparin durationAcute (hours) [duration of]
Warfarin durationChronic (days) [duration of]
Inihibitor of coagulation in vitroHeparin is, warfarin is not
Treatment of acute heparin overdoseProtamine sulfate
Treatment of warfarin overdoseIV vitamin K and FFP
Heparin monitoringPTT (intrinsic pathway)
Warfarin monitoringPT/INR (extrinsic pathway)
Thrombolytics list (4)1. Streptokinase 2. Urokinase 3. tPA(alteplase) 4.APSAC (antistreplase)
Thrombolytics mechanism (2) 1. directly or indirectly aid conversion of plasminogen to plasmin ⇢⇡ thrombin and fibrin clots - 2. ⇡PT, ⇡PTT - no change in platelet counts
Thrombolytics clinical useEarly MI, early ischemic stroke
Thrombolytics toxicity1. Bleeding 2. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses or severe HTN. 3. Treat toxicity w/aminocaproic acid = inhibitor of fibrinolysis
Thrombolytics overdose treatementaminocaproic acid - inhibitor of fibrinolysis
Aspirin mechanismacetylates and irreversibly inhibits COX 1 and COX2 - prevents conversion of arachidonic acid to TXA2. 2.⇡bleeding time - no change in PT, PTT
Aspirin clinical use(4)1. Antipyretic 2. Analgesie 3. Anti-inflammatory 4. Anti-platelet drug
Aspirin toxicity(5)1. Gastric ulceration 2. Bleeding 3. Hyperventilation 4. Reye’s syndrome 5. Tinnitus (CNVIII)
Clopidogrel, ticiopidine mechanism(2)1.irreversibly block ADP receptors inhibiting platelet aggregation. 2. Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression
Clopidogrel, ticiopidine clinical use(1. Acute coronary syndrome 2. Coronary stenting - ⇣ incidence or recurrence of thrombotic stroke.
Ticlopidine toxicityNeutropenia [toxicity of which platelet aggregation inhibitor]
Abciximab mechanismmonoclonal antibody that binds to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
Abciximab clinical use1. Acute coronary syndrome 2. Percutaneous transluminal coronary angioplasty
Abciximab toxicity1. Bleeding 2. Thrombocytopenia
Drugs that stop cells in M stage (2)1.Vinca alkaloids 2.taxols
Drugs that stop cell in G2 (2)1.Bleomycin 2. Etoposide
Drugs that stop cell in S (2) 1.Antimetabolites 2. Etoposide
Drugs that stop nucleotide synthesis (2)1.Methotrexate 2. 6-MP
Drugs that stop at DNA stage (5)1. Alklylating agents, 2. cisplatin, 3. Dactinomycin, 4.doxorubicin, 5. Etoposide
Drugs that stop at cellular division (2)1. Vinca alkaloids 2. Paclitaxel


Question Answer
Methotrexate (MTX) Mechanism(antimetabolite) 1. Folic acid analog - inhibits dihydrofolate reductase ⇢⇣dTMP⇢⇣ DNA and ⇣protein synthesis
Methotrexate (MTX) clinical use (8)1. Cancers: Leuk, Lymphomas, choriocarcinoma, sarcomas 2. Nonneoplastic: Abortion, ectopic preg, RA, psoriasis
Methotrexate (MTX) toxicity(4)1. Myelosuppression (reversible w/leucovorin rescue) 2. Macrovesicular fatty change in liver 3. Mucositis 4. Teratogenic
5-FU mechanism(antimetabolite) pyrimidine analog - inhibits thymidylate synthase when bioactivated ⇢⇣dTMP⇢⇣DNA and ⇣protein synth
5-FU clinical use (3)1. Colon cancer and other solid tumors 2. Basal cell carcinoma (topical) 3. Synergy w/MTX
5-FU toxicity1. Myelosuppression (not reversible) 2. Photosensitivity 3. Treat overdose with thymidine
6-MP mechanism(antimetabolite) purine analog ⇢⇣ de novo purine synth - activated by HGPRTase
6-MP clinical use1. Leukemias, lymphomas (not CLL or Hodgkins)
6-MP toxicity1. BM 2. GI 3. Liver 4. Metabolized by xanthine oxidase ⇢⇡toxicity w/allopurinol
6-TG mechanism(antimetabolite) purine analog ⇢⇣ de novo purine synth - activated by HGPRTase
6-TG clinical useAcute lymphoid leukemia
6-TG toxicity1. BM depression 2. Liver toxicity 3. Can be given with allopurinol
Cytarbine (ara-C) mechanism(antimetabolite) Pyrimidine analogue ⇢ inhibition of DNA polymerase
Cytarabine (ara-C) clinical use1. AML 2. ALL 3. High-grade non-hodgkins lymphoma
Cytarabine (ara-C) toxicity1. Leukopenia 2. Thrombocytopenia 3. Megaloblastic anemia
Dactinomycin (actinomycin D) mechanism(antitumor antibiotic) intercalates DNA
Dactinomycin (actinomycin D) toxicitymyelosuppresion
Dactinomycin (actinomycin D) clinical use (3)1. Wilm’s tumor 2. Ewing’s sarcoma 3. Rhabdomyosarcoma 3. Used for childhood tumors
Doxorubicin (adriamycin) daunorubicin mechanism(antitumor antibiotic) generates free radicals - noncovalently intercalate DNA = less replication
Doxorubicin (adriamycin) daunorubicin clinical use (4)1. part of combination regimen for hodgkins lymphomas 2. Myelomas 3. Sarcomas 4. Solid tumors (breast, ovary, lung)
Doxorubicin (adriamycin) daunorubicin toxicity (4)1. Cardiotoxicity 2. myelosuppresion 3. Marked alopecia 4. Toxic to tissue with extravasation
Bleomycin mechanism(antitumor antibiotic) G2 phase - induce formation of free radical which break DNA strands
Bleomycin clinical use1. Testicular cancer 2. Hodgkins lymphoma
Bleomycin toxicity (3)1. Pulm fibrosis 2. Skin changes 3. Minimal myelosuppression
Etoposide, (VP-16), Teniposide mechanism(antitumor antibiotic) Late S to G2 - inhibits topoisomeraseII increasing DNA degradation
Etoposide, (VP-16), Teniposide clinical use1. Small cell carcinoma of lung and prostate 2. Testicular carcinoma
Etoposide, (VP-16), Teniposide toxicity1. Myelosuppression 2. GI irritation 3. Alopecia
Cyclophosphamide, ifosfamide mechanism(alkylating agent) - cross link DNA at guanine N-7 - requires bioactivation by liver
Cyclophosphamide, ifosfamide clinical use1. Non-hodgkins lymphoma 2. Breast and ovarian carcinoma 3. Also as immunosuppression
Cyclophosphamide, ifosfamide toxicity1. Myelosuppression 2. Hemorrhagic cystitis (can be partially prevented with mesna)
Nitrosureas (4)1. Carmustine 2. Lomustine 3. Semustine 4. Streptozocin
Nitrosureas mechanism(alkylating agents) alklyate - require bioactivation - cross the BBB and enter CNS
Nitrosureas clinical use1. Brain tumors (including glioblastoma multiforme)
Nitrosureas toxicityCNS toxicity (dizziness, ataxia)
Bisulfan mechanism(alkylating agent) - alkylates DNA
Busulfan clinical use1. CML 2. Also used for ablating bone marrow in stem cell transplants
Bisulfan toxicity1. Pulm fibrosis 2. Hyperpigmentation


Question Answer
Vincristine, vinblastine mechanism(microtuble inhibitor) - bind to tubulin in M phase and block polymerization - block mitotic spindle formation
Vincristine, vinblastine clinical use (3)1. Hodgkins lymphoma 2. Wilm’s tumor 3. Choriocarcinoma
Vincristine, vinblastine toxicity (3)Vincristine: 1. Neurotoxicity (areflexia, peripheral neuritis 2. Parylitc ileus .. . Vinblatine = Bone marrow suppression
Paclitaxel other Taxols mechanism(microtubule inhibitor) - hyperstabilized polymerized microtubules - spindle can’t break down
Paclitaxel other Taxols clincal useOvarian and breast cancer
Paclitaxel other Taxols toxicity1. Myelosuppresion 2. Hypersensitivity
Cisplatin, carboplatin mechanismcross link DNA
Cisplatin, carboplatin clinical use1. Testicular carcinoma 2. Bladder carcinoma 3. Ovary carcinoma 4. Lung carcinoma
Cisplatin, carboplatin toxicity1. Nephrotoxicity, 2. Acoustic nerve damage
Hydroxyurea mechanism1. Inhibits ribonucleotide reductase
Hydroxyurea clinical use1. Melanoma 2. CML 3. Sickle cell (⇡HbF)
Hydroxyurea toxicity1. BM suppression 2. GI upset
Prednisone mechanism1. May trigger apoptosis - may work in nondividing cells
Prednisone clin use1. Glucocorticoid in cancer chemotherapy 2. CLL and Hodgkins 3. Immunosuppressant in autoimmune diseases
Tamoxifen, Raloxifene mechanismSERMs- receptor antagonists in breast, agonist in bone, block binding of estrogen to ER receptor+ cells
Tamoxifen, raloxifene clinical use1. Breast cancer 2. Osteoporosis prevention
Tamoxifen, raloxifene toxicity1. Tamox increases risk of endometrial cancer - Ralox does not
Trastuzumab (Herceptin) mechanismHER-2 antibody - helps kill breast cancer cells that overexpress HER-2
Trastuzumab (Herceptin) clinical usemetastatic breast cancer
Trastuzumab (Herceptin) toxicityCardiotoxicity
Imatinib (gleevec) mechanismbcr-abl tyrosine kinase inhibitor
Imatinib (gleevec) clinical useCML, GI stromal tumors
Imatinib (gleevec) toxicityfluid retention
Hemoglobin composition4 polypeptide subunits -
T hemoglobintaut form - low affinity for O2
R hemoglobinrelaxed form - exhibits positive cooperativity and negative allostery
Factors that lower Hemoglobin affinity for O2⇡Cl-, H+, 2,3 BPG and temp
Methhemoglobinoxidized form of hemoglobin that does not bind O2 as readily but higher affinity for CN-
Methhemoglobin txMethylene blue [= tx for]
CN poisoning txnitrites - to oxidize hemoglobin to methhemoglobin - binds cyanide
Carboxyhemoglobinform of hemoglobin bound to CO in place of O2 - ⇣oxygen binding capacity with left shift in hemoglobin curve - ⇣oxygen unloading in tissues