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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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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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