Mechanism of Action: Purine, thiopurine analogue inhibits purine nucleotide synthesis & metabolism. Synthesis and function of RNA/DNA altered. Interferes with nucleotide interconversion and glycoprotein synthesis. To be active, modification by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) required.
Toxicity: myelosuppression, mild gastrointestinal toxicity, Cholestatic jaundice, diarrhea, nausea, vomiting, loss of appetite, stomach/abdominal pain, weakness, skin rash, darkening of the skin, or hair loss, mouth sores, fever, sore throat, easy bruising or bleeding, pinpoint red spots on the skin, yellowing of eyes or skin, dark urine, painful or difficult urination, black or tarry stools (melena), bloody stools and bloody urine.
Symptoms of allergic reaction include rash, itching, swelling, dizziness, trouble breathing, and pancreatitis.
Mechanism of Action: Purine thiopurine analogue, requires modification by HGPRT, inhibit purine biosynthesis. After incorporation into DNA, the thiocarbonyl is methylated, produces a base similar to 6-O-methylguanine. Incorporates into DNA/RNA, resulting in inhibition of syntheses, cell death. Also inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase for purine synthesis
During 2nd round of replication, mismatch repair system recognizes mismatch between methylated base and cytosine. Can't repair since no nucleotides can be matched with methylated base. Leads to 100-200 base single strand breaks. Trigger cell cycle arrest & death. thioguanine and mercaptopurine, although categorized as antimetabolites, functions more like a genotoxic methylating agent,
Toxicity: liver toxicity associated with vascular endothelial damage, leads to veno-occlusive disease (small veins in the liver are blocked leading to weight gain due to fluid retention, increased liver size, and raised levels of bilirubin: sinusoidal obstruction syndrome used if it is a side effect of chemotherapy).
bone marrow suppression, anemia, leukopenia, thrombocytopenia. Mild nausea.
Mechanism of Action: epipodophyllotoxins (semisynthetic derivatives of compounds originally extracted from the mandrake). Inhibit DNA topoisomerase II by formimg ternary complex with DNA and topoisomerase II enzyme, preventing ligation of the DNA strands. This causes errors in DNA synthesis and promotes apoptosis of the cancer cell. DNA cleavage is not repaired and cells stop in S and G2 phase. CELL CYCLE SPECIFIC for cells in S and G2 phases.
Toxicity: fever, hypotension, bronchospasm, low bp, hair loss, pain and/or burning at the IV site, constipation, diarrhea and metallic food taste. Bone marrow suppression is also common, leading to decreased white blood cell counts, anemia, low platelet counts (bruising and bleeding). Leukopenia is a dose-limiting toxicity for etoposide.
secondary leukemias, dose- and schedule-dependent, much lower for the anthracyclines daunorubicin and doxorubicin.
Resistance: Resistant cells demonstrate a) amplification of the mdr-1 gene that encodes P-glycoprotein drug efflux transporter, b) mutation or decreased expression of topoisomerase II, or c) mutations of the p53 tumor suppressor gene, which is a required component of apoptosis.
Mechanism of Action: potent synthetic glucocorticoid. 20 to 30 times more potent than the naturally occurring hormone hydrocortisone and 4 to 5 times more potent than prednisone.
Toxicity: Side-effects common to systemic glucocorticoids may occur including:
Stomach upset leading to ulceration of esophagus, stomach, and duodenum
Increased appetite leading to weight gain
Manifestation of latent diabetes mellitus
Glucose intolerance is worsened in patients with preexisting diabetes.
Fever as a warning symptom is often suppressed
Psychiatric disturbances (personality changes, irritability, euphoria, mania)
Osteoporosis under long term treatment (fractures)
Elevated liver enzymes, fatty liver degeneration (usually reversible)
Cushingoid (facial puffiness and weight gain)
Depression of the adrenal gland
Hypertension, fluid and sodium retention, edema
Dependence with withdrawal syndrome.
Increased intraocular pressure, certain types of glaucoma, cataracts
Dermatologic symptoms including acne, allergic dermatitis, dry scaly skin
ecchymoses and petechiae, erythema, impaired wound-healing, increased
sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria (skin rash notable for dark red, raised, itchy bumps).
Mechanism of Action: Type I IFNs. Allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors. All interferons are important for fighting viral infections.
Toxicity: Flu-like symptoms, Fatigue, Upset stomach, nausea/vomiting, Headache, Irritability, Loss of appetite, Difficulty in controlling blood sugar levels (leading to diabetes), Trouble sleeping, Skin reactions (rash, dry or itchy skin, temporary hair loss, or redness and swelling at the site of injection)
Mechanism of Action: Increases growth and activity of other T cells and B cells. Enhances various T-cell functions and natural killer cell function. Activates lymphokine-activate killer (LAK) cells, which are a type of killer T cell produced when lymphocytes are incubated with IL-2. LAK cells destroy tumor cells and improve the recovery of immune function in certain immunodeficiency states.
Toxicity: a) hypotension, b) ascites formation, b) generalized body edema, c) pulmonary edema, d) chills and fever, e) headache, malaise and flu-like symptoms and f) gastrointestinal effects including nausea, vomiting, loss of appetite, diarrhea, and mucositis. Effect of IL-2 on the kidneys is generally mild but renal failure can result if severe hypotension occurs.
Mechanism of Action: Humanized monoclonal antibody directed against 21-28 kDa cell surface glycoprotein designated CD52, that is expressed by certain types of lymphoma. CD52 is a protein normally expressed on the surface of mature lymphocytes, thymocytes, monocytes, and macrophages.
Toxicity: Increases the risk for opportunistic infections, in particular the reactivation of cytomegalovirus. Infusion-related events including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash. Possible that perturbation of suppressor T cell populations may precipitate autoimmune disease.