| A | B |
|---|
| ALL-Tx | Hoelzer/Linker-based protocol |
| Phase-I-(1-4 weeks) | vincristine; prednisone; daunorubicin & asparaginase |
| Phase-II-(5-8 weeks) | cyclophosphamide; cytarabine & 6-mercaptopurine |
| AML-Tx | cytarabine(Ara-C) |
| 7+3 | 7days Cytarabine days 1-3 daunorubicinor idarubicinor mitoxanthrone |
| HDAC | High-Dose Ara-C (cytarabine) |
| APL-Tx | all-trans-retinoic acid (ATRA) plus daunorubicinor idarubicin |
| APL-2nd-remission-Tx | Arsenic trioxide after ATRA |
| CLL-Tx | fludarabine |
| CML-Tx | imatinibmesylate w/hydroxyurea |
| CML-Tx | allo-SCT |
| HCL-Tx | cladribineandpentostatin |
| HCL | very enlarged spleen |
| ABDV | Doxorubicin (Adriamycin); bleomycin; vinblastine; dacarbazine |
| MOPP | Mechlorethamine; vincristine(Oncovin); procarbazine; prednisone |
| MOPP-or-ABDV | Tx Hodgkin’s Disease or Lymphoma |
| CHOP+Rituximab-regimen | Rituximab cyclophosphamide doxorubicin vincristine prednisone |
| NHL-Tx | Single-agent chlorambucil;fludarabine or rituximab |
| NHL-Tx | CHOP+Rituximab-regimen |
| Multiple-Myeloma-Tx | dexamethasone;thalidomide |
| DVd-regime | vincristine; pegylated liposomal doxorubicin; dexamethasone |
| Multiple-Myeloma-Tx | DVd-regime |
| Multiple-Myeloma-Tx | melphalan or cyclophosphamide & prednisone; transplant |
| vincristine + prednisone | remission induction; pedes lymphocytic leukemia |
| vincristine resistance | MDR, P-glycoprotein, tubulin mutation |
| vincristine toxicity | neurotoxicity; impaired microtubule fnx |
| vincristine side effects | numbness of extremities, loss of deep tendon reflexes |
| vincristine side effects | severe constipation, allopecia, motor weakness |
| vincristine MOA | arrests cell cycle @ mphase |
| vincristine MOA | prevents alpha-beta tubulin dimerization |
| daunorubicin | red color to urine |
| daunorubicin,idarorubicin | acute leukemia |
| doxirubicin | solid tumors, Kaposi's, breat cancer |
| anthracycline antibiotics MOA | tripartite complex w/topoisomerase II and DNA |
| anthracycline antibiotics | daunorubicin,idarorubicin,doxorubicin |
| prevents re-ligation of broken DNA strands | anthracycline antibiotics |
| free radical intermediates | anthracycline quinone group |
| protect against anthracycline free radical damage | vitamin E, iron chelator, dexrazoxane |
| iron + doxorubicin = | increased free radical production |
| anthracycline resistance | increased glutathione peroxidase activity, , MRP, P-glycoprotein |
| enhanced DBS repair; topo II mutation | anthracycline resistance |
| daunorubicin/idarubicin + Ara-c | acute myeliod leukemia |
| doxorubicin long-term toxicity | cardiomyopathy--congestive heart failure unresp. to digitalis |
| daunorubicin/idarubicin toxicity | myelosprssn,stomatitis, allopecia, GI, dermatological |
| adriamycin flare | erythematous streaking @ site of doxorubicin infusion |
| cardiac toxicity, tachycardia, dyspnea...CHF | daunorubicin/idarubicin toxicity |
| l-asparaginase | inhibits protein synthesis in malignant cells |
| l-asparaginase toxicity | hypersensitivity; inhibition of protein synthesis |
| l-asparaginase resistance | induction of asp. synthetase in tumor cells |
| tumor sensitivity to l-asparaginase | hyperdiploid ALL cells |
| hydroxyurea cytotoxicity | inhibits ribonucleoside diphosphate reductase |
| hydroxyurea MOA | destroys iron binding tyrosyl free radical in hRRM2 |
| nucleotide reduction | iron is a key mediator; provides an electron |
| HU cell cycle specificity | S-phase, arrest @ G1-S; both p53 and other mech. |
| reduces vasoocclusive events in sickle cell disease | HYDROXYUREA via NO, HbF, DNREG. L-SELECTIN, PMNs |
| HU resistance | increased synthesis of hRRM2 |
| red. freq /painful acute chest syndrm & 2' stroke | hydroxyurea |
| hydroxyurea benefits | accl. loss of methotrexate double minits |
| potentiates anti-proliferative effects of anti-DNA drugs | hydroxyurea benefits |
| HU + irradation synergistic toxicity | cell sensitivity to irradiation @ G1-S BOUNDRY |
| myelosuppressive agent (CML, polycythemia vera,ess. thrombocytosis) | primary use of HU |
| HU is drug of choice for | thrombocythemia |
| HU toxicity | hematopoietic depression,leukopenia,mglbstc anemia |
| teratogen in animals, desquamative interstitial pneumonitis | HU toxicity |
| 2' HU toxicity | GI disturbance, mild derm. rxns ..stomatitis, allopecia, neuro |
| sickle cell disease tx | hydroxyurea-HU (DROXIA) |
| APL RAR-alpha, RXR dimer | needs ATRA to displace differentiation repressor |
| resitance to ATRA | loss or mutation of t(15,17) fusion gene |
| ATRA (retionoid) toxicity | RAS, dry skin, cheilitis, rev. hepatic enz. abnorm., bone tenderness, hyperlipidemia |
| retinioc acid syndrome | respiratory distress, ,pleuralpericardial effusions, mental status changes, death |
| ATRA + anthracyclines = | >70% relapse free remission APL |
| imatinib inhibits proliferation of | myeloid cells exprssing ABL, v-ABL, ABL-BCR |
| cells dependent on PDGFR, KIT | imatinib inhibits proliferation of |
| CMML-chronic myelomonocytic leukemia | ETV6-PDGFR FUSION (SUBSET) |
| IMATINIB primary resistance | unknown mech failure to acheive desired response |
| IMATINIB acquired resistance | mutations: ABL kinase domain of BCR-ABL |
| IMATINIB peak plasma | 2-4 hours |
| IMATINIB bioavailability; half life | 98%, 8-40 hrs |
| IMATINIB doseage for inhibition of BCR-ABL cells | 400-600mg daily |
| IMATINIB metabolism | CYP3A4; + KETOCONAZOLE, - RIMFAMPIN |
| IMATINIB toxicity | nausea, vomiting, edema, cramps, neutropenia, thrombocytopenia (in Lkmia pt) |
| IMATINIB | protein tyrosine kinase inhibitor |
| vincristine doseage | 2mg/sq.m body s.a weekly w/ 40 mg prednisone q |
| doxorubicine plasma disappearance curve | multi-phasic half-lifes 3 and 30 hrs |
| anthracyclines metabolically converted to | active alcohol intermediate |
| idarubicin half-life; metabolite; half life | 15 hrs.; idarubicinol; 40hrs |
| anthracyclines | rapid uptake into liver, heart, kidneys, don't X bb barrier |
| dauno-,doxo-,idarubicin | administered by IV, cleared by liver, biliary extretion |
| abolish asparagine in blood stream | .03IU/ml in plasma (6-10,000 IU/ 3days) |
| Elspar hypersensitivity rxn alt | Erwinia enzyme prep.; pegasapaginase |
| hydroxyurea bioavailability; peak plasma | 80-100%(oral or IV); 1-1.5 hrs |
| HU doseage, half life | 15-80mg/kg; 3.5-4.5hrs |
| HU absorption | X bloodbrain barrier, breast milk, 40-80% rec. from urine @12hr |
| oral ATRA dose | 45mg.msq./day until remission |
| cetuximab antigen;function | EGFR (ErbB-1); tyrosine kinase |
| rituximab antigen; function | CD20; proliferation, differentiation |
| rituximab tumor type | B-cell lymphoma, CLL |
| alemtuzumab antigen; tumor type | CD52; B-cell CLL and T-cell lymphoma |
| rituximab mechanism | ADCC; CDC; apoptosis |
| improval of event free survival in diffuse large b-cell lymphoma | Rituximab + CHOP synergism |
| dose dependent; half-lives (32-153 hr) | Rituximab pharmacokinetics |
| rituximab toxicity | infusion related w/fever, rash, dyspnea; B-cell depletion, late onset neutropenia |
| rituximab MOA B-cell regulation | transmembrane signals, induction of c-myc and MHC-II; Ca+2 channel |
| CD52 | present on normal PMNs, lymphocytes and many b and T lymphomas |
| alemtuzumab MOA | induces tumor cell death via ADCC and CDC; apoptosis |
| dose dependent; half-life:12 ds, steady state @ 6wks | Alemtuzumab pharmacokinetics |
| mycosis fungoides; t-cell lymphomas | alemtuzumab tx |
| rituximab dose and schedule | 375mg/m sq IV /wk/4wks |
| alemtuzumab dose/schedule | escalation 3,10,30mg/m IV 3x/wk then 30mg/m/wk 4-12 wks |
| alemtuzumab toxicity | infsn rltd, T-cell depltn w/incr. infctn; hematap. spprsn.; pancytopenia: death |
| cetuximab mechanism | inhibition of EGFR; apoptosis;ADCC |
| cetuximab dose/schedule | ld 400mg/kgIV then 2mg/kg /wk |
| cetuximab toxicity | infusion related; skin rash in 75% |
| cetuximab pharmacokinetics | non-linear; mean half life 114hrs |
| gemtuzumab ozogaminicin target | CD33; AML, myelodysplasia |
| gemtuzumab ozogaminicin toxicity | bmarrow supression, serious hepatic-veno-occlusive fatality |
| gemtuzumab ozogaminicin | mcantibody-cytotoxic conjugate |
| CD33 antibody + enediyene antitumor antibiotic | gemtuzumab ozogaminicin |
| mitoxantrone | induce remission in adult non-lymphocytic leukemia |
| doxorubicin analog for AML | mitoxantrone |
| mitoxantrone improvements on doxorubicin | less cardiac and free radical dmg than doxo |
| mitoxantrone toxicity | cardiac, mucositis, acute myelosuppresssion, |
| prednisone induces prompt clinial improvement | acute lymphoblastic or undifferentiated leukemia in children |
| prednisone is a valuble component of curative regimen for | Hodgkin's disease and non-Hodgkin's lymphoma |
| ai hemolytic anemia, and CLL thrombocytopenia | glucocorticoids are very helpful in controlling |
| prednisone oral doseage | initially 60-100mg q, after a few days reduced 20-40mg/day |
| prednisone long term side effects | glucose intolerance, immunosuppression, osteoporosis, psychosis |
| 6-mercaptopurine | Competes with guanine and hypoxanthine for hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) |
| 6-MP | Most common resistance is deficiency or lack of activating enzyme HGPRT |
| thioinosinic acid (T-IMP) | inhibits the first step of de novo purine nucleotide bases |
| converted to thioinosinic acid (T-IMP) | 6-mercaptopurine |
| HGPRT | converts 6-MP to T-IMP |
| 40% hyperbilirubinemia ; >10% myelosupression, leukopenia, thrombocytopenia, anemia | 6-MP |
| RMSF - adults, children | Doxycycline |
| Doxycycline Side effects | low risk of brown teeth |
| RMSF- pregnant women | Chloramphenical |
| aminoglycosides | bind 30s, fixes at start codon |
| streptomycin monosome | 30s-50s- AUG complex |
| aminoglycosides streptomycin monosome | incorp. wrong AA, block translation, cause misreading of mRNA |
| aminoglycosides toxicity | nephrotoxic, ototoxic- damage to sensory cells |
| aminoglycosides neuromuscular blockade | competition w/Ca2+ ->inhibition of ACh release from preganglionic terminal |
| tetracyclines inhibit bacterial protein synthesis | binding to 30s subunit, blocking tRNA binding to A site |
| chloramphenicol binds to the 50s ribosomal subunit | peptidyltransferase site, inhibits transpeptidation rxn |
| clindamycin and macrolide antibiotics | bind 50s near chloramphenicol, drug interaction |
| toxicity of chloramphenicol dose related | anemia, leukopenia, thrombocytopenia |
| toxicity of chloramphenicol idiosyncratic | aplastic anemia which can lead to fatal pancytopenia |
| bac. menningitis, typhoid fever, anaerobic infections | 3rd world countries, chloramphenicol tx |
| doxycycline | fecal elim. give to avoid nephrotoxicity |
| tetraclycline risk of brown teeth | under 5y.o, up to 8 |
| drugs against exoerythocytic (liver) esp. vivax and ovale | primaquine |
| drugs effective againts gametocyte | primaquine |
| drugs against erythrocytic phase | choroquine*, quinine, mefloquine, pyrimethamine,proguanil |
| chloroquin | acculm. in food vacuole |
| chloroquin | inhbt formation of hemozoin--free heme is formed from digested Hb-->cell lysis |
| chloroquin | need primaquin to get extraerythrocytic |
| mefloquine | prophylaxis for travelers |
| atovaquone | interferes w/electron trans in malaria mitochn. |
| primaquine | -->electrophiles |
| ORIENTIA TSUTSUGAMUSHI - | doxycycline or chloramphenicol |
| COXIELLA BURNETII | doxycycline |
| EHRLICHIA CHAFFEENSIS | doxycycline |
| BARTONELLA SP. | azithromycin or erythromycin |
| BABESIA SP. | azithromycin-atovaquone |
| miltephosine | visceral leishmaniasis |
| miltefosine | PKC sphingomyelin biosynthesis, phosphatydiyl chiline biosynthesis |
| sodium stibogluconate | interferes w/trypanathione redox system |
| sodium stibogluconate | pancreaatic, electrocardiogram changes toxicity |
| pentamidine | leishmaniasis, collapses mit. membrane, very toxic |
| Asparaginase | deprives lymphoblastic leukemic cells of Asn by converting it to Asp |
| cladribine pentostatin | 1st choice for hairy cell leukemia |
| inhibits ribonucleotide reductase | hydroxyurea |
| pentostatin | inhibits adenosine deaminase, inhibits DNA synthesis |
| cetuximab | antibody against EGFR, used w.irinotecan |
| rituximab | anti-CD20 |
| aletuzumab | humanized against CD52 on B and T cells tx B-CLL |
