Chemotherapy Flashcards
What is meant by adjuvant chemotherapy?
Used as a neoplastic drug, after surgery or radiation has eradicated the primary tumor, but Used Due to micrometastasis in patients with a history of cancer relapse
What is meant by Neo-adjuvant chemotherapy?
They are anti-neoplastic drugs that are administered prior to surgery to shrink the tumor size and decrease its vascularity
What is meant by primary chemotherapy?
It is the use of antineoplastic alone for metastatic inoperable tumors
What are the modes of action of anti-cancer drugs?
1) Cell cycle-specific drugs (CCS)
2) Cell cycle-nonspecific drugs (CCNS)
- Effective against drugs going through the cell cycle and the ones arrested in G0
How do chemotherapy drugs act and what are their side effects?
They target proliferative/active cells whether cancer or normal, like in hair follicles they cause alopecia, In the GIT they cause severe nausea & vomiting “they inhibit the epithelial renewal of the GIT wall”, in the gonads they cause infertility, in the bone marrow the cause myelosuppression “immunodeficiency”
How does cancer build resistance to drugs?
1) Reduces the uptake of the drug and increases its efflux (via G proteins/glycoproteins)
2) Decreases/deletes the needed enzymes required to activate the drug
3) Produces detoxification substances that detoxify the drug
4) Increases the number of targets to create competition decreasing the effect of the drug
5) Rapidly repairs drug-induced lesions
What are the types of anti-cancer drugs?
1) Action on DNA
- Damages the DNA
- Inhibits the synthesis of the DNA & its function
2) Action on the mitotic spindle
3) Action on steroid/hormone receptors
- Agonist
- Antagonists
How can a drug that acts on the DNA damage the DNA?
1) Alkylation
2) Free radical formation
How can a drug acting on the DNA inhibits its synthesis/function?
1) Antimetabolites
2) Topoisomerase inhibitors
What are some examples of anti-cancer drugs that damage the DNA via alkylating agents?
1) Cyclophosphamide (most imp)
2) Carmistine
3) Busulfan
4) Cisplatin
5) Dacarbazine
- Creates an alkyl group that creates a covalent bond that is very hard to break down
What is the mode of action of phosphorylative anti-cancer drugs?
1) Form a reactive molecular species that alkylated nucleophilic groups on the DNA bases, in particular, guanine positioned in N-7
2) Cross-links bases, abnormally pairs bases & break the DNA strand
3) Cell cycle-nonspecific, but cells are most susceptible to them in late G1 and S phases
- They link 2 DNA strands through a covalent bond instead of a Hydrogen bond that is easier to break when replicating, linking a Guanine to another guanine
How is cyclophosphamide activated (pharmacokinetics)?
Via the hepatic cytochrome-P450, one of the breakdown products is acrolein (causes bladder irritation & hemorrhagic cystitis, treated by administering MESNA “Mercapto-Ethane-Sulfonate”)
What is carmustine mode of action?
- Highly lipophilic, thus it penetrates the CNS easily
- Used to treat Brain tumors
- Can cause CNS toxicity
What is the mode of action of BUSULFAN?
- Used in chronic myelogenous leukemia (CML)
- Associated with pulmonary fibrosis and skin pigmentation
Describe the mode of action of CISPLATIN!
-They are heavy metal drugs that contain platinum, Cisplatin & Carboplatin used in genitourinary cancer like:
- Testicular cancer
- Bladder cancer
- Ovarian Cancer
Describe the use of DACARBAZINE
- Part of the ABVD (Adriamycin “doxorubicin”, bleomycin, vinblastine, and dacarbazine) regimen of Hodgkin’s disease (hodgkins lymphoma (caused by Epstein-Barr virus “EBV”)
What are some examples of anti-cancer drugs that act on inhibiting DNA synthesis/function via antimetabolites?
- All of them are cell cycle-specific acting on the S phase
- Immunosuppressants
Structurally similar and antagonists to:
1) Folic acid (methotrexate)
2) Purine (mercaptopurine)
3) Pyrimidines (5-fluorouracil)
Describe the mechanism of methotrexate (MTX)
It is a substrate and inhibitor of dihydrofolate reductase (DHFR), decreasing the synthesis of thymidylate, nucleotides, and amino acids which interferes with nucleic acid and protein metabolism causing the cell to die
What are the clinical uses of methotrexate?
1) Breast cancer
2) Acute leukemias
3) Non-Hodgkins lymphoma
4) Rheumatoid arthritis
5) Psoriasis
What are the toxicities caused by methotrexate?
1) Mucositis (by all chemo drugs)
- We can decrease the toxic effects by administering folinic acid (leucovorin “leucovorin rescue”)
2) In long-term use it can cause hepatotoxicity, pulmonary infiltrates, and fibrosis
What is the mechanism of action of purine analogs?
6-Mercaptopurine, activated by Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) converts them into toxic metabolites that inhibit enzymes involved in purine metabolism
- By increasing alkaline phosphate (inactivates toxic nucleotides) and decreasing HGPRT levels (stopping the activation of 6-MP) cancer cells develop resistance to it
What is the use of allopurinol?
It treats and prevents hyperuricemia (high level of uric acid in the blood)
