UPSC MainsMEDICAL-SCIENCE-PAPER-I201112 Marks
Q24.

Classify antimalarial drugs. Discuss the common side effects of chloroquine administration. What are the other therapeutic uses of chloroquine ?

How to Approach

This question requires a structured response covering the classification of antimalarial drugs, the side effects of chloroquine, and its other therapeutic applications. The answer should begin with a brief introduction to malaria and antimalarial drugs. The body should be divided into sections addressing each part of the question systematically. Utilizing a table for drug classification will enhance clarity. Focus on detailing the mechanisms of action where relevant, and providing specific examples of side effects and alternative uses. The conclusion should summarize the key points and highlight the evolving landscape of antimalarial therapy.

Model Answer

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Introduction

Malaria, a mosquito-borne infectious disease caused by parasites of the genus *Plasmodium*, remains a significant global health concern, particularly in tropical and subtropical regions. Antimalarial drugs are crucial for both the treatment and prevention of malaria. These drugs target different stages of the parasite’s life cycle within the human host. The development of resistance to commonly used antimalarials, like chloroquine, has necessitated the continuous search for new and effective therapeutic agents. This answer will classify antimalarial drugs, detail the side effects of chloroquine, and explore its other therapeutic uses.

Classification of Antimalarial Drugs

Antimalarial drugs can be classified based on their chemical structure, mechanism of action, or the stage of the parasite they target. A common classification is as follows:

Class Examples Mechanism of Action
Blood Schizonticides Chloroquine, Amodiaquine, Mefloquine, Lumefantrine Act on the erythrocytic (red blood cell) stage of the parasite, inhibiting heme polymerization and leading to parasite death.
Tissue Schizonticides Primaquine, Tafenoquine Act on the exo-erythrocytic (liver) stage of the parasite, preventing the development of infective forms. Also effective against gametocytes.
Gametocytocides Primaquine, Atovaquone-Proguanil Target the sexual stages of the parasite (gametocytes) in the blood, preventing transmission to mosquitoes.
Fast-Acting Blood Schizonticides Artesunate, Artemether, Arteether Rapidly reduce parasite biomass in the blood, often used in combination therapies.
Combination Therapies Artemisinin-based Combination Therapies (ACTs) – e.g., Artemether-Lumefantrine, Artesunate-Amodiaquine Combine drugs with different mechanisms of action to enhance efficacy and reduce the development of resistance.

Common Side Effects of Chloroquine Administration

Chloroquine, a 4-aminoquinoline, was once the mainstay of malaria treatment. However, its widespread use has led to significant resistance. Even with declining use, understanding its side effects remains crucial.

  • Gastrointestinal Disturbances: Nausea, vomiting, diarrhea, and abdominal pain are common, particularly at the start of treatment.
  • Neurological Effects: Headache, dizziness, blurred vision, and seizures (rare but serious). Prolonged use can lead to retinopathy.
  • Cardiovascular Effects: QT prolongation, potentially leading to arrhythmias, especially in patients with pre-existing heart conditions.
  • Dermatological Effects: Pruritus (itching), skin rash, and rarely, photosensitivity.
  • Ocular Toxicity: Chloroquine retinopathy is a serious, potentially irreversible side effect. Regular ophthalmological monitoring is essential for long-term users.
  • Hematological Effects: Rarely, chloroquine can cause hemolytic anemia, particularly in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

The severity of side effects is dose-dependent and can be mitigated by careful patient selection and monitoring.

Other Therapeutic Uses of Chloroquine

Beyond its antimalarial properties, chloroquine has demonstrated efficacy in treating several other conditions:

  • Amebiasis: Chloroquine is effective against the tissue stages of *Entamoeba histolytica*, the causative agent of amebiasis.
  • Rheumatoid Arthritis: Chloroquine and hydroxychloroquine (a less toxic derivative) are used as disease-modifying antirheumatic drugs (DMARDs) to reduce inflammation and joint damage.
  • Systemic Lupus Erythematosus (SLE): Similar to rheumatoid arthritis, chloroquine/hydroxychloroquine helps manage symptoms and prevent flares in SLE.
  • Porphyria Cutanea Tarda: Chloroquine can improve liver function and reduce skin lesions in this rare metabolic disorder.
  • COVID-19 (Historical Context): During the early stages of the COVID-19 pandemic, chloroquine and hydroxychloroquine were investigated as potential treatments, but subsequent studies demonstrated a lack of efficacy and potential harm. (Knowledge cutoff: 2023)

The mechanisms underlying these therapeutic effects are not fully understood but likely involve immunomodulatory and anti-inflammatory properties.

Conclusion

Antimalarial drugs represent a diverse group of compounds targeting various stages of the *Plasmodium* parasite. While chloroquine remains a valuable drug for certain indications, its use in malaria treatment is limited by widespread resistance. Understanding the classification of these drugs, the potential side effects of chloroquine, and its broader therapeutic applications is crucial for effective patient management. The ongoing development of new antimalarials and combination therapies is essential to combat drug resistance and reduce the global burden of malaria.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Schizont
The stage in the life cycle of a parasitic protozoan, such as *Plasmodium*, in which the nucleus undergoes multiple divisions before the parasite divides into numerous merozoites.
Gametocyte
The sexual stage of the malaria parasite, found in the blood of infected humans, that is taken up by mosquitoes during blood meals, allowing the parasite to continue its life cycle.

Key Statistics

In 2022, there were an estimated 249 million cases of malaria worldwide, leading to 625,000 deaths.

Source: World Health Organization (WHO), World Malaria Report 2023

Approximately 95% of malaria cases and deaths occur in sub-Saharan Africa.

Source: WHO, World Malaria Report 2023 (Knowledge cutoff: 2023)

Examples

Artemisinin-based Combination Therapies (ACTs)

Artemether-Lumefantrine (Coartem) is a widely used ACT, combining a fast-acting artemisinin derivative with a longer-acting partner drug to improve efficacy and prevent resistance.

Frequently Asked Questions

What is the role of G6PD deficiency in chloroquine-induced hemolysis?

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme crucial for protecting red blood cells from oxidative damage. Individuals with G6PD deficiency are more susceptible to hemolysis (destruction of red blood cells) when exposed to oxidative stressors like chloroquine.

Topics Covered

PharmacologyInfectious DiseasesMalariaAntimalarial DrugsPharmacokinetics