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TERMS TO LEARN

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Chronic Myelogenous Leukemia Bone marrow malignancy involving myeloid cells; it is typically seen in older patients and is associated with poor prognosis.
Ewing's Sarcoma Malignancy of the bone; seen in young boys.
Gestational Trophoblastic Neoplasms Group of malignancies stemming from fetal or placental tissue.
Giant Cell Tumors Benign bone tumor.
Hodgkin's Lymphoma Malignancy of the lymph nodes; bimodal age distribution (seen in young and old men); associated with a good prognosis with chemotherapy.
Multiple Myeloma Malignancy of plasma cells; it is characterized by bone pain, "punched out" lytic lesion of the bone, hypercalcemia, and Bence Jones proteinuria.
Neuroblastoma Most common extracranial solid tumor of childhood; malignancy that arises from the neural crest cells that tends to occur in the abdomen and thorax; it secretes catecholamines.
Non-Hodgkin's Lymphoma Malignancy of the lymph nodes; more likely to have extranodal primaries (ie, stomach or thyroid) than Hodgkins lymphoma; it is associated with a poorer prognosis than Hodgkin's lymphoma.
Wilms' Tumor Renal malignancy seen in children; it is associated with hemihypertrophy of the body.

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I. ACTION OF ONCOLOGIC MEDICATIONS

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PHASES OF THE CELL CYCLE

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All cells—normal and neoplastic—must traverse these cell cycle phases before and during cell division. CCS drug actions may not be restricted to a specific phase, but tumor cells are usually most responsive to specific drugs (or drug groups) in the phases indicated. Cell cycle-nonspecific (CCNS) drugs act on tumor cells while they are actively cycling and while they are in the resting phase (G0).

 

Modified from Katzung BG, ed: Basic & Clinical Pharmacology, 8th ed, p 926. Originally published by Appleton & Lange. © 2001 by the McGraw-Hill Companies, Inc.

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II. ALKYLATING DRUGS

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Mechanism of Action: Alkylating agents have a very reactive chemical moiety that binds to the bases of DNA causing damage that is very difficult to repair and sometimes irreparable.

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Resistance Mechanisms: Four resistance mechanisms counteract the effects of alkylating agents:

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  1. Decreased transport in those that are actively transported into the cells

  2. Increased pumping of the drug out of the cell

  3. Increased ability to repair the DNA damage

  4. Increased glutathione levels to get rid of the reactive species

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ALKYLATING DRUG FACTS

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Drug Pharmacokinetics Mechanism of Action Clinical Uses and General Information Side Effects
Mechlorethamine (Mustargen)
  • A: IV or intracavitary

  • M: Rapid hydrolysis and demethylation in plasma

  • E: Parent drug and metabolites excreted in urine

  • Inhibition of DNA and RNA action by various mechanisms resulting in the cross linking of DNA

  • Lymphoma (Hodgkin's and non-Hodgkin's)

  • Malignant effusions

  • More stable and easier to use than nitrogen mustard

  • Bone marrow suppression

  • Headache

  • Injection ...

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