1. Anti- CANCER drugs

2. Classifications of Anti- CANCER drugs
I. According to mechanism:
Alkylating agents:
Example: Including drugs such as nitrogen mustard and cyclophosphamide.
Mechanism: these are highly reactive molecules which bind irreversibly to
macromolecules in the cell, notably DNA, RNA and proteins.
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.
Steroid hormones and antihormones:
Mechanisms: These are widely used in cancer management, not only for the
treatment of malignant disease, but also for the treatment of symptoms such as
anorexia and hypercalcaemia.
Examples: prednisolone, tamoxifen and cyproterone acetate.
Others: Several drugs have been identified, often by random synthesis and
screening, whose, Mechanism of action is not fully established but are thought to
interact with DNA synthesis or replication. They include , dacarbazine, and cis-
platinum.

4. II. According to their effect on the cell
cycle:
• Actively dividing cells pass through several
phases. Mitosis is followed by a gap or delay
(G1) then a synthetic phase (s) a second gap
(G2) and mitosis again (M). Cells may cycle
continuously or enter a quiescent phase (G0).
Some drugs act at all phases of the cell
cycle, others exert effects specifically at
certain phase.

5. Class 1 drugs are non-specific and act on cells whether or
not they are actively dividing, e.g. nitrogen mustard.
Class 2 drugs act only at specific phases of the cell
cycle, e.g. vincristine and methotrexate.
Class 3 drugs act on cells in division and at all phase of
the cycle, e.g. cyclophosphamide and actinomycin, D.
Most cytotoxic drugs act by interfering with the
synthesis and replication of DNA.
•

6. Adverse effects:
•
Reactions to cancer chemotherapy are
secondary to cell death both in the tumour
and in other rapidly dividing cells of bone
marrow, gastrointestinal tract, germinal
epithelium etc. These can be divided into:

7. A. General adverse effects:
Nausea and vomiting:
may be severe and 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.
Alopecia:
is a common adverse effect of cytotoxic drugs. Hair re-grows after the
drugs are withdrawn.

8. 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.
Diarrhoea and malabsorption:
occur as a result of cytotoxic effects on gut mucosal cell
turnover.

9. 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.
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.

10. Drug Adverse effects
Cyclophosphamide Haematuria, Cystitis
Doxorubicin Alopecia, arrhythmias, local tissue necrosis
Bleomycin pulmonary fibrosis, skin rashes
Marrow suppression .Megaloblastic anaemia
Methotrexate
Marrow suppession
Fluorouracil
Peripheral neuropathy
Vincristine
Renal damage, deafness and
Cisplatinum neuropathy

11. Drug Interactions:
With many cytotoxic drugs in use, often in
combination, it is not surprising that adverse
interactions occur.
Methotrexate and salicylates:
As methotrexate is highly protein bound it is readily
displaced from the binding site by aspirin and
other salicylates. This may increase the risk of
adverse effects of methotrexate.

12. 6-Mercaptopurine and allopurinol:
These two drugs are frequently used together.
Allopurinol is a competitive inhibitor of
xanthinc oxidase and also inhibits the
breakdown of 6-mercaptopurine. The dose of
6-mercaptopurine must be reduced by at least
50%.