Antimetabolites for cancer treatment

Question 1

What are the indications for antimetabolites in medicine ?

Answer 1

To treat cancer, infections, and autoimmune diseases.

Question 2

What are the pyramidine bases of DNA ?

Answer 2

Cytosine and Thymine

Question 3

What are the purine bases of DNA ?

Answer 3

Adenine and Guanine

Question 4

What are the antimetabolites that mimic purine ?

Answer 4

Azathioprine and Cladribine

Question 5

What are the antimetabolites that mimic pyramidine?

Answer 5

Cytarabine and 5-FU

Question 6

What is the MOA of Azathioprine ?

Answer 6

It is a purine analogue pro-drug that gets converted to 6 Mercapto-purine and 6-Thioguanine by the enzyme Thyopurine S methyletransferease. Both 6-MP and 6-TG get conjugated to ribonucelotides and can mimic neucleotides base pairs of DNA. Incorporation of these neucelotide analogues leads DNA replication arrest.
In addition, the active metabolites of 6MP also inhibits the enzyme PRPP synthatse and AMP deaminase preventing the conversion of PRPP to IMP and AMP to IMP respectively leading to impaired nucleotide synthesis.

Question 7

What are the indications for azathioprine ?

Answer 7

For the Tx of ALL and CML.

Question 8

What are the common side effects of antimetabolites ?

Answer 8

• Pancytopenia and megaloblastic anaemia.

Question 9

What are the specific side effects of azathioprine ?

Answer 9

Hepatotoxicity causing cholistasis and acute pancreatitis. Teratogenicity and GI disturbances.

Question 10

What is the MOA of Cladribine ?

Answer 10

Phosphorelated tri-phosphate form of Cladribine gets inserted into the newly formed DNA strand leading to the arrest of DNA synthesis. It also inhibits DNA polymarase. It is also resistant to adenosine deaminase leading to increased accumulation of the drug intracellularly which reduces the de novo purine synthesis.

Question 11

What is the indication for Cladribine ?

Answer 11

• Hairy cell leukaemia and other forms of leukaemia.

Question 12

What is the MOA of pyrimidine analogue Cytarabine ?

Answer 12

Cytarabine gets phosphorylated to Ara-CTP: a tri-phosphate metabolite that binds and competitively inhibits DNA polymarase arresting DNA synthesis.

Question 13

What is the indication for Cytarabine ?

Answer 13

It is indicated for the Tx of haematological malignancies such as Leukaemia and Lymphoma.

Question 14

What is the MOA of pyrimidine analogue 5-FU?

Answer 14

5-FU interferes with folic acid cycle as it is metabolised to its active form 5-FdUMP which forms a complex with THF. The 5-FdUMP- THF complex inhibits the enzyme thymidylate synthatase which decreases the synthesis of thymidine essential for DNA synthesis. Besides, other active metabolites intercalates into DNA and RNA impairing their synthesis.

Question 15

What is the indication of 5-FU?

Answer 15

For the Tx of all forms of solid tumours and as a topical agent for the Tx of basal cell carcinoma.

Question 16

What is the drug that enhances the effect of 5-FU

Answer 16

Leucovorin also known as Folinic acid which gets converted to folic acid.

Question 17

What are the side effects of 5-FU ?

Answer 17

Side effects include gastrointestinal disturbances like severe diarrhea, mucositis, alopecia, CNS toxicity, cutaneous reactions such as photosensitivity, and palmar-plantar erythrodysesthesia, or hand-foot syndrome.

Question 18

What is the anti-dot for 5-FU overdose ?

Answer 18

Uridine.

Question 19

What is the MOA of Methotrexate ?

Answer 19

It inhibits the DHFR enzyme reducing the levels of THF essential for purine synthesis which leads to inhibition of cell division by decreasing the synthesis of DNA, RNA and proteins.

Question 20

what are the indications of MTX ?

Answer 20

Tx of ALL, Primary CNS and Non-Hodgkins lymphoma, solid tumours of the breast, head and neck , bladder, and Choriocarcinoma.

Question 21

what are the other clinical uses of MTX?

Answer 21

• Abnormal proliferation of the trophoblastic tissue.
• Unruptured ectopic pregnancy and autoimmune diseases.

Question 22

What are the side effects of MTX ?

Answer 22

• Bone marrow suppression which can be reduced by using Lucovorin.
• Megaloblastic anaemia.
• Macro-vascular hepatosteatosis.
  *Pulmonary fibrosis
• teratogenicity, alopecia and mucocitis.