Ch 14 - Antineoplastic Agents Flashcards
What are antineoplastic drugs? What do they affect? What are side effects?
Can work by affecting cell survival or by boosting the immune system in its efforts to combat the abnormal cells they are alkylating agents, antimetabolites, antineoplastic modulators, cancer cell-specific agents, protein tyrosine kinase inhibitors and a group that cant be classified elsewhere.
The goal is to limit the offending cells to the degree that the immune system can then respond without causing too much toxicity to the host unfortunately this is difficult as these affect normal rapidly multiplying cells as well.
Adverse effects - exert toxic effects on ova and sperm production, a danger to developing fetus, bone marrow suppression, nausea and vomitting, hair and skin effects
What are alkylating agents? What are their thereapeutic actions and indications, pharmacokinetics, contraindications, adverse effects and drug-to-drug?
These drugs are said to be non-cell cycle specific and are most useful in the treatment of slow-growing cancers.
Chlorambucil
Indications: Palliative treatment of chronic lymphocytic leukaemia, malignant lymphomas, and Hodgkin disease
Actions: Alkylates cellular DNA, interfering with the replication of susceptible cells
Pharmacokinetics: Route oral, onset varies, peak 1h duration 15-20 h
T1/2: 60-90 min metabolized in the liver and excreted in urine.
Adverse effects: Tremors, muscle twitching, confusion, nausea, hepatotoxicity, bone marrow suppression, sterility, cancer. Alopecia
Drug to drug - Are known to cause hepatic or renal toxicity should be used cautiously with any other drugs that have similar effects. Drugs that are toxic to the liver may adversely affect drugs that are metabolized in the liver or that act in the liver - oral anticoagulants.
What are antimetabolites? Therapeutic action, pharamocokinetics, contraindications, adverse effects, drug to drug?
Drugs that have chemical structures similar to those of various natural metabolites that are necessary for the growth and division of rapidly growing neoplastic cells and normal cells
Methotrexate
Indications: Treatment of gestational choriocarcinoma; chorioadenoma destruens; hydatidiform, meningeal leukemia; symptomatic control of severe psoriasis; rheumatoid arthritis; juvenile rheumatoid arthritis.
Actions: Inhibits folic acid reductive, leading to inhibition of DNA synthesis and inhibition of cellular replication; affects the most rapidly dividing cells.
Pharmacokinetics: Route po an iv onset varies and rapid, peak 1-4h and .5-2h.
T1/2: 2 -4 h, excreted unchanged in the urine.
Adverse effects: Fatigue, malaise, rashes, alopecia, ulcerative stomatitis, hepatic toxicity, severe bone marrow suppression, interstitial pneumonia is, chills, fever, anaphylaxis. Nausea, vomitting, diarrhea, anorexia.
Drug-drug cause hepatic or renal toxicity
What are antineoplastic antibiotics? Therapeutic, pharmacokinetics, contraindications, adverse effects, drug-drug?
Although selective for bacterial cells, are also toxic to human cells. These drugs tend to be more toxic to cells that are multiplying rapidly. Some end in rubicin Doxorubicin
Indications: To produce regression in acute lymphoblastic lymphoma, acute myeloblastic leukemia, Wilma tumor, neuroblastoma, soft tissue and bone sarcoma, breast carcinoma, ovarian carcinoma, thyroid carcinoma, hodgkins and non-Hodgkin lymphomas, bronchiole if carcinomas also AIDS related ka poi’s sarcoma.
Actions: Binds to DNA and inhibits DNA synthesis to susceptible cells, causing cell death.
Pharmacokinetics: Route IV Onset Rapid Peak 2h Duration 24-36 h.
T1/2: 12 minutes, then 3.3 h, then 29.6 h: metabolized in the liver and excreted in the bile, feces, and urine.
Adverse Effects: Cardiac toxicity, complete but reversible alopecia, nausea, vomiting, mucositis, red urine, myelosuppression, fever, chills, rash.
Drug-Drug: Cause hepatic or renal toxicity should be used with care with any other drugs known to have same effect. Same with heart and lungs
What are Mitotic Inhibitors? Therapeutic Action, Pharmacokinetics, Adverse Effects, Drug-drug.
Are drugs that kill cells as the process of mitosis begins. These cell cyclespecific agents inhibit DNA synthesis. Affect rapidly multiplying cells, such as bone marrow, gi tract, and skin.
Vincristine
Indications: Acute leukemia, Hodgkin disease, non-Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma, Wilma tumor.
Actions: Arrests mitotic division at the stage of metaphase; the exact mechanism of action is not understood.
Pharmacokinetics: Route IV Onset Varies Peak 15-30 mins.
T1/2: 5 min, then 2.3 h then 85 h; metabolized in the liver and excreted in the feces and urine.
Adverse Effects: Ataxia, cranial nerve manifestations, neuritic pain, muscle wasting, constipation, leukopenia, weight loss, loss of hair, death.
Drug-drug: known to be toxic to the liver or the CNS should be used with care with any other drugs.
What are hormones and hormone modulators? Therapeutic, Pharmocokinetics, adverse effects, drug-drug.
Some cancer, particularly those involving the breast tissue, ovaries, uterus, prostate, and testes are senstive to estrogen stimulation. Estrogen receptor sites on the tumor react with circulating estrogen, and this reaction stimulates the tumor cells to grow and divide. Several antineoplastic agents are used to block or interfere with these receptor sites to prevent growth on the cancer and in some cause cell death. Some are used to block gonadotropic hormones.
Tamoxifen
Indications: Treatment of metastatic breast cancer, reduction of risk of invasive breast cancer in women with Ducati carcinoma in situ, reduction in occurrence of contra lateral breast cancer in patients receiving adjuvant tamoxifen therapy, reduction in incidence of breast cancer in women at high risk for breast cancer, treatment of McCune-Albright syndrome, and treatment of precocious puberty in female patients 2 to 10 yrs of age.
Actions: Competes with estrogen for binding sites in target tissues, such as the breast; a potent antisetogenic agent.
Pharmocokinetics: Route PO Onset Varies Peak 4-7 h
T 1/2: 7-14 days; metabolized in the liver and excreted in the feces.
Adverse Effects: hot flashes, rash, nausea, vomiting, vaginal bleeding, menstrual irregularities, Edelman, pain, cerebrovascular accident, pulmonary emboli.
Drug-drug: if they are taken with oral anticoagulants, inc risk of bleeding. Care is necessary when giving these agents with any drugs that might inc serum lipid levels.
What are cancer cell specific agents? Therapeutic, Pharmcokinetics, Adverse effects, drug-drug.
The goal of research is directed at finding drugs that are cancer cell specific. The drugs would not hurt healthy cells but be effective against particular cancer cells. 1. Protein tyrosine kinase inhibitors act on specific enzymes that are needed for protein building by specific tumor cells. 2. Epidermal growth factor inhibitor it inhibits cell epidermal growth factor receptors. 3. Proteasome inhibitor used after the other two therapies it inhibits proteasome in human cells, a large protein complex that works to maintain cell homeostasis and protein production, without it the cell loses homeostasis and dies.
Imatinib
Indications: Treatment of adults with CML who are in blast crisis, accelerated phase or chronic phase after failure with interferon-alpha therapy. It has since also been approved for use in treatment of patients with CD117 positive unresectable or metastatic gastrointestinal stromatolites tumor (GIST), various myeloproliferative disorders, aggressive system mastectomies, and unreseectable dermatofibrosarcoma protuberant.
Actions: Tyrosine Kinase inhibitor that selectively inhibits the Bcr-Abl tyrosine kinase create by the Philadelphia chromosome abnormality in CML and certain tumor cells present in GIST; blocking this enzyme inhibits proliferation and induces cell division.
Pharmacokinetics: Route PO Onset slow Peak 2-4 h
T1/2: 18-40 h; metabolized in the liver and excreted in the feces.
Adverse effects: Nausea, vomiting, bone marrow suppression, heart failure, headache, dizziness, edema, rash.
Drug-drug: use caution when administering these drugs with other drugs affected by the cytochrome P450 enzyme system. St. John’s wort should be avoided as dec effectiveness of many of these drugs
What are miscellaneous antineoplastics? Therapeutic, pharmcokinetics, adverse effects, drug-drug.
Many other agents that do not fit into one of the other groups are used to cause cell death.
Hydroxyrea
Inhibits enzymes essential for the synthesis of DNA, causing cell death
Actions: treatment for melanoma, ovarian cancer, CML, in combination therapy for primary squamous cell cancers of the head and neck, also used in the treatment of sickle cell anemia.
Adverse effects: cause bone marrow depression, headache, rash, gi toxicity, and renal dysfunction.
What is adjunctive therapy?
Allopurinol
Used to treat tumor lysis syndrome
Is used to dec high blood Uric acid levels. Route PO, IM
Adverse effects: itchiness, rash, IM vomiting and kidney problems can depress the bone Marrow,
Drug-drug: many warfarin, phenytoin, Azathloprine, Didanosine,
