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Chloroquine: Uses, Mechanism & Side Effects

Chloroquine is a medication primarily used for the treatment and prevention of malaria. It also has anti-inflammatory properties and is used in certain autoimmune diseases.

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Things worth knowing about "Chloroquine"

Chloroquine is a medication primarily used for the treatment and prevention of malaria. It also has anti-inflammatory properties and is used in certain autoimmune diseases.

What is Chloroquine?

Chloroquine is a synthetic drug belonging to the class of 4-aminoquinolines. Developed in the 1930s, it was for decades one of the most important medications for the treatment and prevention of malaria. Due to its anti-inflammatory properties, chloroquine is also used in autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis.

Indications

Chloroquine is used in the following medical areas:

Malaria treatment and prophylaxis: Particularly effective against Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. Significant resistance exists in many regions for Plasmodium falciparum.
Systemic lupus erythematosus (SLE): For the control of disease flares and as long-term therapy.
Rheumatoid arthritis: As a disease-modifying antirheumatic drug (DMARD).
Other inflammatory conditions: Including certain forms of sarcoidosis and porphyria cutanea tarda.

Mechanism of Action

Chloroquine exerts its effects through several mechanisms:

Antimalarial action: Chloroquine accumulates in the acidic compartments (lysosomes) of the malaria parasite. It inhibits the polymerization of haem (a breakdown product of haemoglobin) into haemozoin, a harmless crystal. This leads to a toxic accumulation of free haem, which kills the parasite.
Immunomodulatory action: By raising the pH within lysosomes, chloroquine impairs antigen processing and the activation of certain immune cells, thereby reducing the production of pro-inflammatory cytokines.

Dosage and Administration

The dosage of chloroquine depends on the indication, the body weight, and the kidney function of the patient. Typical dosages include:

Malaria prophylaxis: Usually 500 mg once weekly, starting 1–2 weeks before travel and continuing for 4 weeks after return.
Malaria treatment: A higher initial dose followed by maintenance doses over several days (exact dosage as prescribed by a physician).
Autoimmune diseases: Lower long-term doses, individually adjusted.

Chloroquine should always be taken as prescribed by a physician. Self-medication is strongly discouraged due to potentially serious side effects.

Side Effects

Chloroquine can cause a range of side effects, from mild to severe:

Common: Nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, skin rash.
Rare but serious:
- Retinopathy: Long-term use can damage the retina, potentially leading to permanent vision loss. Regular ophthalmological examinations are therefore mandatory.
- Cardiomyopathy and cardiac arrhythmias: QT interval prolongation on ECG, increasing the risk of life-threatening heart rhythm disturbances.
- Myopathy and neuropathy: Muscle and nerve damage with long-term therapy.
- Haematotoxicity: Rare blood changes such as haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Contraindications and Interactions

Chloroquine should not be used, or used only under strict supervision, in the following situations:

Known retinopathy or pre-existing eye disease
Severe cardiac arrhythmias or QT prolongation
G6PD deficiency (increased risk of haemolysis)
Epilepsy (chloroquine may lower the seizure threshold)
Pregnancy (only if the benefit outweighs the risk; acceptable for malaria prophylaxis in certain cases)

Important drug interactions exist with other QT-prolonging medications, antacids (which reduce absorption), and certain antiepileptic drugs.

Resistance

In many parts of the world, particularly in sub-Saharan Africa, Southeast Asia, and South America, Plasmodium falciparum strains have developed resistance to chloroquine. In these regions, alternative antimalarials such as artemisinin-based combination therapies (ACT) are preferred.

References

World Health Organization (WHO): Guidelines for the Treatment of Malaria, 3rd edition, 2015. Available at: https://www.who.int/publications/i/item/9789241549127
Brunton LL et al.: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th edition, McGraw-Hill, 2018.
Rainsford KD et al.: Chloroquine and hydroxychloroquine in rheumatology: a review of mechanisms and clinical use. Inflammopharmacology, 2015;23(1):1–12. DOI: 10.1007/s10787-014-0224-0

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