Download Anti- CANCER drugs

Anti- CANCER drugs
Dr. Mohammed Abd-Almoneim
Treatment of Cancer
• Surgery to remove solid tumors
• Radiation to kill cancer cells that have spread to
adjacent local or regional tissues
• Chemotherapy to kill cancer cells located
throughout the body
Treatment of cancer
There are three main approaches to treating established cancer: Surgery, Radiation
therapy, Chemotherapy
Breast cancer
Surgery
Radiation
Chemotherapy
Chemotherapy of cancer presents a difficult problem. In biochemical terms, cancer cells
and normal cells are so similar in most respects that it is more difficult to find differences
between them.
Classifications of Anti- CANCER drugs
According to mechanism:
1-Alkylating agents:
Example: nitrogen mustard and cyclophosphamide.
Mechanism: bind irreversibly to macromolecules in the cell as DNA,
RNA and proteins.
2-Antimetabolites:
Mechanism: these are closely related analogues of normal
components intermediary metabolism or DNA synthesis.
Example:
Methotrexate inhibits folic acid metabolism.
6-mercaptopurine inhibit DNA synthesis.
3-Natural products: A wide range of drugs has been
developed from plants, bacteria, yeasts and fungi.
Examples and mechanisms:
Mitosis inhibitors: as vincristine .
Antibiotics: as actinomycin D.
4-Steroid hormones and antihormones:
Examples: prednisolone, tamoxifen and cyproterone acetate.
5-Others: Several drugs have been identified, Mechanism of
action is not fully established but are thought to interact
with DNA synthesis or replication. They include ,
dacarbazine, and cis-platinum.
Alkylating Agents
• One of the frightening developments of World War I
was the introduction of chemical warfare. The nitrogen
mustards were observed to inhibit cell growth,
especially of bone marrow. Shortly after the war, these
compounds were investigated and shown to inhibit the
growth of cancer cells.
Alkylating Agents
Mechanism of Action
• Nitrogen mustards inhibit cell reproduction by binding
irreversibly with the nucleic acids (DNA).
• The specific type of chemical bonding involved is
alkylation.
• After alkylation, DNA is unable to replicate and
therefore can no longer synthesize proteins and other
essential cell metabolites.
• Consequently, cell reproduction is inhibited and the cell
eventually dies from the inability to maintain its
metabolic functions.
Antimetabolites (Folic Acid Antagonist)
Methotrexate （MTX）
Mechanism of Action：
 The structures of MTX and folic acid are
similar. MTX is actively transported into
mammalian cells and inhibits dihydrofolate
reductase, the enzyme that normally converts
dietary folate to the tetrahydrofolate form
required for thymidine and purine synthesis.
Hormones
• Several types of hormone-dependent cancer (especially
breast, prostate, and endometrial cancer) respond to
treatment with their corresponding hormone antagonists.
• Estrogen antagonists are primarily used in the
treatment of breast cancer (tamoifen) Tamoxifen is
the drug of choice in postmenopausal women with or
recovering from metastatic breast cancer. It is most
effective in patients who have estrogen receptorpositive tumors.
whereas androgen antagonists are used in the treatment
of prostate cancer (cyproterone acetate).
•
Corticosteroids (predinsolone) are particularly useful in
treating lymphocytic leukemias and lymphomas.
Problems With Cancer
Chemotherapy
• Drug Resistance.
• Drug Toxicity.
Adverse effects:
A- general:
Reactions to cancer chemotherapy are
secondary to cell death both in the tumor and
in other rapidly dividing cells of bone marrow,
gastrointestinal tract, germinal epithelium
etc.
1-Nausea and vomiting:
related to the direct actions of cytotoxic drugs on the
chemoreceptor trigger zone or secondary to extensive tissue
damage as occurs in radiation sickness.
Metoclopramide (antiemetics) and the cannabinoid nabilone can be
used to control nausea and vomiting.
2-Alopecia:
is a common adverse effect of cytotoxic drugs. Hair re-grows after
the drugs are withdrawn.
4-Hyperuricaemia:
Very high levels of plasma uric acid with
precipitation of clinical gout or renal failure may
complicate treatment of leukaemias and
Iymphomas.
Allopurinol, the xanthine oxidase inhibitor, may be
used to prevent gout.
5-Diarrhoea and malabsorption:
occur as a result of cytotoxic effects on gut mucosal
cell turnover.
6-Bone marrow depression:
The bone marrow is particularly sensitive to cytotoxic
drugs. Neutropenia or thrombocytopenia is common.
They result in an increased risk of infection and
haemorrhage respectively.
7-Opportunistic infections:
occur as a result of neutropenia and
immunosuppressant therapy, which interfere with
humoral and cell-mediated responses. Unusual
infection with fungi and protozoa in addition to
common pathogenic bacteria and viruses occur.
B. Specific adverse effects
•
•
•
•
Cyclophosphamide :haematuria, cystitis
Doxorubicin : cardiotoxic, alopecia.
Bleomycin : pulmonary fibrosis.
Methotrexate: marrow suppression,
megaloblastic anaemia.
• Vincristine: peripheral neuropathy.
• Cisplatinum: Renal damage.
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