Platinum Analogs

Platinum Analogs: Cisplatin, Carboplatin, Oxaliplatin

Overview

Mechanism

The platinum analogs do not possess an alkyl group but have the same general effect as the alkylating agents: they form lethal cross-links in DNA, so we lump them in with the alkylating agents.

Side Effects

Mechanism

Alkylation

The alkylating agents comprise a large group of a variety of drugs that interfere with tumor cell DNA replication by forming links within strands of DNA.

The N7 position of guanine has the greatest alkylation affinity – it most readily reacts with alkylating agents.
Alkyl groups are fragments with a vacant attachment site that is highly attractive to a nucleophile, such as the N7 of guanine.
The alkyl group can form both intrastrand linking within a single strand of DNA or it can form interstrand crosslinking between two strands of DNA.
These links and crosslinks interfere with further DNA replication/cell division and, thus, further tumor growth.

Platinum Agents: Cisplatin, Carboplatin, Oxaliplatin

Note that we lump the platinum-containing agents (the platinum coordinating complexes), such as cisplatin, in with the alkylating agents because they form similar links and cross-links within DNA that interfere with DNA replication.
Thus, they have the same antineoplastic effect as the alkylating agents, but they do not actually alkylated the DNA; they form different kinds of chemical bonds (adducts).

Side Effects

Ototoxicity

Ototoxcity stems from injury to cochlear structures, most notably toxicity to the hair cells of the organ of Corti.

Indicate the outer hair cells and inner hair cells.
As a simple heuristic think of the outer hair cells as modulators of sound wave nerve impulses and the inner hair cells as sound wave detectors.

Also indicate that toxicity can occur to the spiral ganglia (especially via demyelination).
Consider that the otoxicity presents with hearing loss without prominent dizziness or vertigo, which highlights that the injury is to the auditory component of the inner ear, rather than the vestibulocochlear nerve, itself.
Note that the toxicity is typically for high frequency range sounds, affects both ears, and is generally irreversible.
To date, there are no clear-cut ways to prevent cisplatin-induced ototoxcity.