IMMUNE-PHARMACOLOGY-PART-V-ANTICANCER DRUGS

  ANTI METABOLITES 

These drugs act by inhibiting some enzymes involving in metabolism.

1.Methotrexate:-

It is a folic acid analog and it acts by antagonizing folic acid by preventing its metabolism to tetrahydrofolate by inhibiting the enzyme dihydrofolate reductase. The unavailability of sufficient tetrahydrofolate which is necessary for the synthesis of various components like thymidylate, amino acids, and purine nucleotides which make up DNA and RNA.

Clinical Uses:-

1.Choriocarcinoma-A type of cancer that occurs during the formation of the placenta in the uterus.

2.Lung cancer

3.Acute lymphocytic leukemia

4.Non-Hodkin's lymphoma

5.Breast cancer

6.Psoriasis

7.Rheumatoid arthritis.

Side effects:-

1.Bonemarrow suppression

2.GI hemorrhagic enteritis

3.Neurotoxicity such as seizures, and encephalopathy.

4.Liver damage.

Toxic effects of methotrexate on the healthy normal cells can be minimized or prevented by concomitant administration of Folinic Acid (Leucovorin) which is selectively absorbed by the normal cells and not by the neoplastic cells.

The process is known as Leucovorin Rescue.

2.6-Mercaptopurine:-

6-Mercaptopurine is a purine analog of antimetabolites. This drug competitively enters the target cell and is converted into 6-thioinosinic acid by an enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This active compound then inhibits a number of purine metabolisms to build DNA and RNA by various enzymes.

Clinical Uses:-

1.Acute Lymphocytic Leukemia(ALL)

2.Acute and chronic Granulocytic Leukemia

It can be given orally

Side effects:-

1.Bone Marrow Suppression

2.Liver damage

3.Thioguanine:-

It belongs to the thiopurine family of the drugs. It is an antimetabolite preventing the formation of various purine analogs for the build-up of DNA and RNA by inhibiting the enzyme thiopurine s-methyl transferase which prevents the inactivation of thioguanine and the active thioguanine undergo readily into various cytotoxic metabolites.

Clinical Uses:-

Similar to Mercaptopurine

Side effects:-

Thioguanine is rarely used because of its serious side effects 

1.Leucopenia

2.Neutropenia

3.Thrombocytopenia

4.Anemia

5.Anorexia

6.GI distress

7.Liver damage

4.Pentostatin:-

It is also a purine analog works by inhibiting purine metabolism

Clinical Uses:-

1.Hairy cell leukemia

2.Mycosis Fungoids

3.Chronic lymphocytic leukemia

Side effects:-

1.Cough

2.Fever and chills

3.Lower, side or back pains

4.Painful urination

5.Skin rash

Pyrimidine Analogues

1.Fluorouracil:- 2.Cytarabine:-

It acts as a pyrimidine analog and preventing the synthesis of DNA.

Uses:-

1.Breast cancer

2.Stomach cancer

3.colon,pancreas,ovary,head and neck,urinary bladder cancers

4.Skin lesions

Side effects

1.Myelosuppression

2.marrow suppressions

3.Stomatitis

4.Stomach and oral ulcers