Antimetabolites Drug Class

What is the primary mechanism of action of antimetabolites?

When is the maximal cytotoxic effect of antimetabolites observed?

How can some adverse effects of antimetabolites be prevented or reversed?

What is a notable adverse effect known as 'Hand-foot syndrome' associated with antimetabolites?

What should be done to prevent conjunctivitis when administering high doses of antimetabolites?

What parameter needs adjustment in patients with renal impairment when using antimetabolites?

Which enzyme does methotrexate inhibit?

What is the role of folic acid in cell replication?

How can the inhibition of dihydrofolate reductase by methotrexate be reversed?

Which drug is used to replenish the folate pool when methotrexate inhibits dihydrofolate reductase?

What is the main dietary source of folic acid?

What is the mechanism of action of antifolate agents like pemetrexed and pralatrexate?

Antimetabolites Overview

Antimetabolites primarily act by mimicking normal substrates in biochemical pathways, leading to the disruption of DNA and RNA synthesis.
Maximal cytotoxic effect of antimetabolites is usually observed during the S-phase of the cell cycle when DNA synthesis occurs.

Adverse Effects and Management

Adverse effects such as myelosuppression and nausea can be prevented or reversed using supportive care measures, including hydration and the use of growth factors.
'Hand-foot syndrome' (palmar-plantar erythrodysesthesia) is a notable side effect characterized by redness, swelling, and pain on palms and soles caused by some antimetabolites.

Prevention and Precautions

To prevent conjunctivitis when administering high doses of antimetabolites, co-administration of eye drops or cooling methods is recommended.
Patients with renal impairment require adjustment of antimetabolite dosages to avoid accumulation and toxicity due to impaired clearance.

Specific Mechanisms and Roles

Methotrexate inhibits the enzyme dihydrofolate reductase, which is crucial for the reduction of dihydrofolate to tetrahydrofolate, impacting folate metabolism.
Folic acid plays a significant role in cell replication by providing essential components for nucleic acid synthesis.

Reversal of Inhibition

The inhibition of dihydrofolate reductase by methotrexate can be reversed by administering leucovorin, which restores the folate pool.
The main dietary source of folic acid includes leafy green vegetables, legumes, and fortified grains.

Antifolate Agents Mechanism

Antifolate agents like pemetrexed and pralatrexate function similarly to methotrexate by inhibiting dihydrofolate reductase, disrupting folate-dependent processes vital for cell division and proliferation.

Learn about antimetabolites, a class of drugs that interfere with enzymes necessary for DNA synthesis by competing with normal nucleotide precursors. Discover how they exert their cytotoxic effects in the S phase of the cell cycle.