Chemotherapy and Miscellaneous Pharmaceutical Products

Question 1

CA

Answer 1

• cancer
• 2nd leading cause of death in U.S.
• is a neoplasm
  *

Question 2

neoplasm

Answer 2

• an abnormal new growth of tissue

Question 3

tumor

Answer 3

• simply defined without any additional information may or maynot be life threatening
• tumors that are not cancerous and do not metastasize may be classified as benign

Question 4

cancerous tumor

Answer 4

• malignant neoplasm
• treated with antineoplastic agents
  
  • certain antineoplastics are only effective against certain tumor types

Question 5

CA Drug Side Effects

Answer 5

• cancerous growth is achieved through uncontrolled growth
• treating CA typically involves stopping this process by killing dividing cells
  
  • unfortunately – several normal and vital host processes of life also involve dividing cells (controlled growth or replication)
• selective targeting by antineoplastics is not always possible
• lack of selective toxcicity leads to certain side effects
  
  • ex. hair follicles replicate leading to hair growth. cytotoxic drugs also stops the replicaton of hair follicles as well as cancerous growths, leading to hair loss
  • ex. bone marrow continuously divides. when stopped due to cytotoxic drugs leads to a decreased production of blood cells and a state of immunosuppression
• in addition to above general side effects, some drugs have specific side effects
  
  • doxorubicin = cardiotoxicity
  • cisplatin = renal tube failure
    *

Question 6

Chemotherapeutic Drugs

Answer 6

• primary focus is to stop uncontrolled cell growth
• these drugs are used to treat or prevent cancer
• typically delivered intravenously in a hospital setting
• other forms are available in some cases and include:
  
  • oral
  • topical
  • intramuscular injections
• combinations of drugs are often used to combat cancer resistance to chemotherapeutics
• general classifications:
  
  • Cytotoxic - agents that stop or block cell replication
  • Hormonal drugs - treatment of tumors sensitive to hormones
  • Miscellaneous agents that work through a variety of different mechanisms

Question 7

Cancer Immunotherapy

Answer 7

• this form of CA treatment involves the use of the immune system to fight cancer
  
  • since CA cells come from the hosts body they are recognized as “self cells” by the immune system and avoid being attacked.
  • cancer cells have also developed mechanisms to avoid detection by the immune system
• researchers are finding ways to overcome these mechanisms allowing the hosts immune system to attack the cancerous cells
• current drugs in this class help harness the body’s natural defense system to treat cancer
• examples:
  
  • rituximab (Rituxan) - monoclonal antibody
  • trastuzumab (Herceptin)

Question 8

Cytotoxic Drugs

Answer 8

• 3 subclasses:
  
  • Alkylating Agents
  • Antimetabolics
  • Antibiotics

Question 9

Alkylating Agents

Answer 9

• work by adding an alkyl group (a hydrocarbon chain) to DNA, causing damage to the cancer cell’s DNA leading to death
• are not selective agents and will kill other dividing cells the host needs
• classical alkylating agents:
  
  • nitrogen mustards
  • nitrosureas
  • alkly sulfonates
• other alkylator-like agent that also damage cell’s DNA also fall into this category
  
  • cisplatin

Question 10

Antimetabolites

Answer 10

• work by competing for binding sites on enzymes needed for cell growth resulting in cell death
  
  • methotrexate
• also work through incorporation into a growing DNA or RNA strand by mimicing purines and pyrimidines, preventing further growth, resulting in cell death
  
  • cladribine (Leustatin)
  • fluorouracil (Efudex)

Question 11

Antibiotics

Answer 11

• work by disrupting DNA function in cancer cells by binding to DNA in some way, preventing cell division
• Subdivided:
  
  • anthracyclines
  • vinca alkaloids

Question 12

Anthracycline

Answer 12

• name is based on chemical structures that make up this group of drugs
• -rubicin
  
  • daunorubicin
  • doxorubicin
  • epirubicin
• these drugs have cardiac toxicity and should be used with caution

Question 13

Vinca Alkaloids

Answer 13

• bind to tubulin - a protein structure of cells used during reproduction - disrupting cellular formation, stopping growth and division
• 3 most important:
  
  • vincristine
  • vinblastine
  • vinorelbine

Question 14

CA fighting Natural Products

Answer 14

• Paclitaxel
  
  • produced by the Pacific Yew tree
  • works by binding tubulin
• there are a variety of natural products with a variety of mechanisms of action that may be used

Question 15

Antibodies

Answer 15

• proteins generated by the immune system that recognizes a specific molecule called an antigen
• antibodies have been developed to recognize specific antigens present in tumors resulting in a more targeted attack on cancer cells
• the antibody itself is not harmful to the cancer cells so it is often attached to a cytotoxic agent
  
  • gemtuzumab ozogamicin (antibody) is joined with the antitumor antibiotic calicheamicin (cytotoxic agent) that once the antibody finds and binds to the targeted cancer cell, the cytoxic agent is released causing cell death

Question 16

CA Hormonal Agents

Answer 16

• used to treat tumors that are sensitive to hormone levels
• tumors of breast, prostate and uterus often respond to this type of treatment
• this class is not typically cytotoxic so the side effects are related to hormonal changes
• the over-all goal is to reduce specific hormone levels that stimulate the specific cancer growth
• examples:
  
  • aromatase inhibitors - block estrogen formation
  • anastrozole
  • letrozole
  • anamoxifen
  • tamoxifen - competitive inhibitor for estrogen receptor
  • fulvestrant - estrogen receptor antagonist

Question 17

Miscellaneous CA Agents

Answer 17

• kinase inhibitors (-tinib)
  
  • works to modulate the signal transduction cascade necessary for cell replicatioln
  • imatinib (Gleevec)
    
    • one of the first kinase inhibitors developed
    • works by binding to the ATP site on a newly formed kinase enzyme, stopping cell growth
    • does not effect normal cells
  • erlotinib (Tarceva)
    
    • another kinase inhibitor
• bortezomib (Velcade)
  
  • an anticancer compound that works through the inhibition of proteasome - a large complex of proteins responsible for the regulation of protein expression - inhibition leads to cell death
  • malignant cells are more sensitive to proteasome than healthy cells – allows for selective toxcicity