Alkylating agents

Introduction
Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference

INTRODUCTION

Alkylating agents are a group of chemicals that work by adding an alkyl group (–C₂H₅) to DNA. Before their medical use, alkylating agents like mustard gas were chemical weapons in WWI. Goodman and Gilman began studying nitrogen mustards in 1942, leading to the first cancer chemotherapy trials. Early human tests showed temporary tumor reduction.This process interferes with the DNA’s structure and function, leading to cell death. They are commonly used in cancer treatment because they can stop the growth of rapidly dividing cells.
These agents are considered non-specific to the cell cycle, meaning they can act at any phase, making them effective against a wide range of cancers. However, they also affect normal cells, which can lead to side effects.

Mechanism of acion

1. Alkylation of DNA

Alkylating agents transfer alkyl groups (usually methyl or ethyl groups) to DNA.

The most common site of alkylation is the N7 position of guanine in DNA.

2. DNA Cross-LinkingSome alkylating agents can form cross-links:

Intrastrand cross-links (within the same DNA strand)
Interstrand cross-links (between two DNA strands)

This prevents the DNA strands from separating, which is necessary for replication and transcription.3. DNA Strand Breaks and MisreadingAlkylation can cause abnormal base pairing (e.g., guanine pairing with thymine instead of cytosine).
It can also result in strand breaks during attempted repair by the cell4. Triggering Apoptosis

The DNA damage caused by alkylation is often irreparable.

This triggers cell cycle arrest and activates apoptotic pathways, leading to programmed cell death.

BRAND NAME

Cycram(cyclophosphamide)

Holoxan(Ifosfamide)

Alkeran(Melphalan)

Leukeran(chlorambucil)

Busulfex(busulfan)

BICNU(carmustine)

Gleostine(lomustine)

Carmustine(semustine)

Dacarbazine medac(dacarbazine)

Temodor(temozolomide)

indication

Alkylating agents are medications that are mainly used to treat cancer. They are effective against hematologic malignancies, such as (leukemia, lymphoma, and multiple myeloma), as well as solid tumors like( breast, ovarian, uterus, lung, and bladder cancer).