Antiviral drug – Chloroquine : How the drug works, Impact of genes & Possible side effects

Antiviral Drug – Chloroquine: How the Drug Works, Impact of Genes & Possible Side Effects

Chloroquine and hydroxychloroquine are antimalarial drugs that gained widespread attention during the COVID-19 pandemic. Understanding how these drugs work — and how your genes influence your response to them — is essential for safe and effective use.

How Chloroquine Works

Chloroquine is a lysosomotropic agent — it accumulates in acidic compartments of cells (lysosomes) and raises their pH. This disrupts the replication of malaria parasites and certain viruses that depend on acidic environments for cell entry and replication. It also has immunomodulatory effects, reducing the production of pro-inflammatory cytokines.

The Role of Genes in Chloroquine Response

Your genetic makeup significantly influences how you metabolise and respond to chloroquine:

• CYP2D6: The primary enzyme responsible for chloroquine metabolism. Poor metabolisers (reduced CYP2D6 activity) accumulate higher drug levels, increasing the risk of toxicity. Ultra-rapid metabolisers may have reduced efficacy.

• CYP3A4/5: Also involved in chloroquine metabolism; variants affect drug clearance rates.

• G6PD deficiency: A common genetic condition in India and Africa — chloroquine can trigger haemolytic anaemia in G6PD-deficient individuals. G6PD testing is recommended before chloroquine use.

Possible Side Effects

• Nausea, vomiting, and abdominal discomfort (most common)

• Headache and dizziness

• Retinal toxicity with long-term use (requires regular eye monitoring)

• QT interval prolongation — risk of cardiac arrhythmia, especially with other QT-prolonging drugs

• Haemolytic anaemia in G6PD-deficient individuals

The Importance of Pharmacogenomic Testing

Knowing your CYP2D6 and G6PD status before starting chloroquine or hydroxychloroquine can prevent serious adverse events and help your doctor select the right dose or alternative treatment.