Heme Onc and Immuno Drugs
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- Inhibits calcineurin --> dec'd T-cell differentiation & activation.
- SE's: Nephrotoxicity, lymphomas
- Inhibits cytokine release from T-cells (IL-2). Binds FK-binding protein.
- SE's: Many systems -- nephrotoxicity, pleural effusion, peripheral neuropathy, HTN, hyperglycemia
- Inhibits nucleic acid synthesis, which targets proliferating lymphocytes.
- SE's: bone marrow suppression. Metabolized by xanthine oxidase, so allopurinol may make it toxic.
- Monoclonal Ab that binds CD3 (on all T-cells) --> no signal transduction.
- SE's: Hypersensitivity reaction, cytokine release syndrome
- Blocks T-cell proliferation in response to IL-2, by binding mTOR.
- SE's: leukopenia, thrombocytopenia, hyperlipidemia
Inhibits guanine synthesis --> dec'd lymphocyte production.
Monoclonal Ab against IL-2 receptor on activated T-cells.
Uses for aldesleukin
(IL-2): renal cell carcinoma, metastatic melanoma
G-CSF. SE's: bone pain
GM-CSF. SE's: bone pain, thrombophlebitis at injection site, fever, rash, pleural effusion
Inhibits viral replication; given for Hepatitis B & C, malignant melanoma, leukemias, Kaposi's sarcoma
Try treating malignant melanoma with these 2 cytokines
Alpha-interferon and IL-2
Inhibits viral replication; given for multiple sclerosis
Given for chronic granulomatous disease. (Neutrophils not working due to NADPH oxidase deficiency, so stimulate macrophages?)
- Anti-neoplastic: alkylating agent at guanine N-7 (remember that P bonds exist in DNA, & alkylating agents create bridges between DNA strands).
- SE's: bone marrow suppression, hemorrhagic cystitis (give mesna)
- Use for: NHL, breast, & ovarian cancer
- "Tricks" DHF reductase into thinking it's folic acid --> DHF reductase inhibition --> dec'd thymine synthesis.
- SE's: BM suppression (reverse w/leucovorin), liver fatty change (macrovesicles -- should be micro- since metabolic cause, but this is significant injury)
- Used for: leukemias & lymphomas, choriocarcinomas, sarcomas... also abortion/ectopic pregnancy, RA, psoriasis
- Can be used with methotrexate, but in case some folic acid is still made... 5-F + dUMP + folic acid --> inhibit thymidylate synthase. It's a pyrimidine analog.
- SE's: Bone marrow suppression (thymidine), photosensitivity
- Uses: Solid tumors -- colon, breast, basal cell carcinoma. Not leukemia/lymphoma.
- Inhibits de novo purine nucleotide synthesis (i.e. IMP --> XMP + AMP).
- SE's: bone marrow suppression; liver; metabolized by xanthine oxidase, so allopurinol increases toxicity (just like azathioprine)
Metabolized by xanthine oxidase
Azathioprine, 6-MP (inhib purine synthesis)
- Anti-neoplastic; inhibits DNA polymerase. It's a pyramidine nucleoside analog.
- Uses: AML, ALL, NHL (high-grade, obv)
- SE's: BM suppression (the anemia is megaloblastic)
- Alkylating agent (at guanine N-7), must be activated by liver.
- SE's: BM suppression, nephro- and neurotoxic
Nitrosureas (carmustine, lomustine, semustine, streptozocin)
Alkylating agents (anti-neoplastic). Cross blood-brain barrier, so use for glioblastomas & other brain tumors... but CNS toxicity (dizzy, ataxia), & also renal & hepatic.
- DNA cross-linking (just like an alkylating agent).
- SE's: not BM suppression, but nephro- and neurotoxic, plus CN 8 damage
- Uses: Ovary, testicle, bladder, & lung cancer
- Alkylating agent, used for CML & P.vera.
- SE's: pulm fibrosis, hyperpigmentation
Doxorubicin, daunorubicin, dactinomycin
- Like dogs: take bites out of DNA (i.e. intercalation of DNA).
- Uses: ABVD for Hodgkin's, plus myelomas, & solid tumors
- SE's: BM suppression, bald, cardiotoxic (not true for dactinomycin, which is used to treat Wilms' tumor, Ewing's sarcoma, & rhabdomyosarcoma)
- Free radicals --> DNA strand breaks.
- SE's: Minimal BM toxicity (bleomycin), but pulm fibrosis, skin changes
- Uses: Part of ABVD for Hodgkin's; testicular cancer
- Inhibits ribonucleotide reductase --> dec'd DNA synthesis
- Uses: Melanoma, CML, sickle-cell (to inc fetal hemoglobin)
- SE's: BM suppression, GI
- Inhibits topoisomerase II, inc's DNA degradation. Specific for G2 (right before mitosis).
- Uses: Small-cell of lung & prostate, testicular cancer
- Toxicity: BM suppression, GI, bald
- SERM: agonize estrogen receptors in bone (& endometrium --> endometrial cancer risk), but antagonize those in breast.
- Used to prevent osteoporosis.
- Anti-CD20 monoclonal Ab. For NHL (since most of these = B-cells, except for lymphoblastic lymphoma & some cases of diffuse lymphoma)
- When the drug is an Ab, cells die via complement-mediated lysis.
- TRIBE: anti-HER-2 receptor Ab, so kills breast cancer cells for which HER-2 is upregulated.
- SE's: cardiotoxicity (this tribe doesn't have a heart)
Vincristine & vinblastine
- Bind tubulin, so microtubules can't polymerize --> no mitotic spindle.
- Uses: Hodgkin's (MOPP), Wilms' tumor, choriocarcinoma
- SE's: neurotoxic, paralytic ileus
- Inhibits mitotic spindle disassembly, by hyperstabilizing the polymerized microtubules. (No anaphase.)
- Uses: ovarian & breast cancer (because women like to hang on to relationships & not disassemble)
- SE's: BM suppression, hypersensitivity
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