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Anti-Cancer Drugs 2

Anti-Cancer Drugs 2 ( only 1/2 the lecture)

** The Other Half of This Lec. is in aferdo01's StudyStack ** .
Alkylating agents = ? * Nitrogen mustards and Nitrosoureas
Nitrogen mustards ? * melphalan --- ifosfamide
Nitrosoureas ? * carmustine --- lomustine
Platinum compounds * cisplatin --- carboplatin
*Nitrogen Mustards* .... Melphalan and Ifosfamide uses ? * Melphalan = Ovarian cancer and multiple myeloma...... * Ifosfamide = testicular cancer
Nitrogen Mustard (Mel. and Ifo.) MOA = ? * Alkylate DNA at N7 of guanine (a base) by CROSS-LINKING the cells --> apoptosis... * Unique Thing = Good in both actively dividing and resting cells !
Melphalan SEs = ? * BLACK BOX = Bone marrow suppression (dose limiting) and Hypersensitivity reactions...... * Pulmonary toxicity (cause fibrosis/pneumoitis)
Ifosfamide SEs = ? * BLACK BOX = CNS toxicity, Hemorrhagic cystitis, and Nephrotoxicity (can cause renal failure)...... * TmT of Cystitis = Hydration and MESNA........ * Other tox. = dose limiting BMD, Caridotoxicity, and Pulmonary Toxicity again
*Nitrosoureas*.... Carmustine use ? * UNIQUE: Can cross BBB so REALLY good for BRAIN tumors/cancers
Carmustine MOA = ? * Interferes with DNA & RNA function by alkylation and cross-linking and by carbamylation of amino acids in protein...... * Simple Terms: Alkylates (messes DNA up) and Modifies Proteins (carbamylation)
Lomustine use = ? * Also use in Brain tumors, but also can use for Multiple myeloma, Hodgkin's lymphoma
Lomustine MOA = ? * Inhibits DNA & RNA synthesis by alkylation of DNA and carbamylation of DNA polymerase.... * Simple Terms: Modifies the DNA polymerase
Carmustine and Lomustine SEs = ? * Worst DRUG for BMD ! --> thrombocytopenia and leukopenia..... * The BMD can be delayed,dose related, etc, so need to monitor it ATLEAST 6 months after a dose is given.... * CNS, renal, hepatic & pulmonary toxicity are also dose limiting
*Platinum complexes*.... Cisplatin use = ? * One of the most commonly used drugs ..... * Colon in testicular, ovarian, and bladder
Cisplatin MOA = ? *Water replaces chloride and Creates reactive molecule, which bind to guanine and causes inter- and intra- strand DNA crosslinks ....... * CCNS (kills in all cell cycle stages)
How to prevent Cisplatin toxicity ? * Give Chloride, b/c low Cl creates a favorable environment for the drug to work --> Toxicity
Cisplatin ACUTE SEs = ? * WORST Drug for N/V = High Emetic Frequency ( so give an antiemetic before)...... * BLACK BOX: Hypersensitivity / Anaphylactic-like reactions (need loaded up with -roids, antihists., or epi. before tmt to prevent this)
Cisplatin DELAYED SEs = ? *pop up days --> weeks later..... * BLACK BOX: Nephrotoxicity - One of the most nephrotoxic drugs..... * BLACK BOX: Ototoxicity in KIDS (need to monitor YRS later)
Used to treat DELAYED SEs = ? * Hydration with Chloride...... * Also give Amifostine
Carboplatin use = ? * drug is a 2nd generation analog.....* Ovarian cancer
Carboplatin SEs = ? * Same MOA as Cis..... * SEs = Less TOXIC in everything, except for BMD (dose limiting)
*Antimetabolites*.... Methotrexate Use = ? * LOTS: Treatment of leukemias; lymphomas -- Breast cancer -- Lung cancer -- GVHD (prophylaxis) -- Psoriasis -- Rheumatoid arthritis
MTX MOA = ? * Depletes TMP --> Prevents regenerated folate from being reactivated to be used to make the TMP..... * SIMPLE: inhibits dihydrofolate reductase (DHFR) --> low TMP for DNA synth.
MTX SEs = ? * BLACK BOX: BMD (dose-limiting, GI, Hepatotoxic, Pneumonitis, Derm. issues, and Renal Issues
*Antimetabolites - Pyrimidine analogs*.... 5-Fluorouracil (5-FU) Use = ? * Widely Used agent in the Tmt of Breast Cancer, Topical for Basal Cancer, and for Colorectal Cancer
5-Fluorouracil MOA = ? * Converted in target cells to 5F-dUMP (nucleobase to nucleoside to nucleotide)... * 5F-dUMP covalently binds to thymidylate synthetase with FH4 (reduced folate, which Blocks conversion of dUMP to TMP...* Leads to cell death by depleting TTP
5-FU can also ? * Also converted to FdUTP and FUTP, which Inhibits DNA & RNA synthesis.... * Unique bc this drug can inhibit BOTH RNA and DNA..... * Also, it is a suicide inhibitor = binds permanently
5-FU SEs = ? * Classic Anti-Cancer SEs, nothing major.... * GI, BMD, N/V
Gemcitabine Use = ? * breast, non-small cell lung, pancreatic, ovarian cancer... * Nothing Big stands out
Gemcitabine MOA = ? * Is a Deoxycytidine analog (phosphorylated to mono-, di-, and triphosphate)...... * inhibits ribonucleotide reductase = lowers dNTPs (lowers diphospahtes).... * inhibits DNA polymerase ..... * incorporates into DNA (chain termination)
Gemcitabine SEs = ? * Toxicity – Myelosuppression (neutropenia) (dose limiting)
*Hydroxyurea* Use = ? * Lots.... * Melanoma, chronic myelocytic leukemia (CML), ovarian cancer; management of sickle cell patients
Hydroxyurea MOA = ? * Inhibits ribonucleotide reductase... * Inhibition results in depletion of intracellular dNTP pools leading to inhibition of DNA synthesis
Hydroxyurea SEs = ? * BLACK BOX: Developing a Secondary Malignancy...... * Myelosuppression (dose limiting)..... * Cutaneous Vasculitic issues (look like ulcers on the body)
Created by: thamrick800