How Chloroquine Works: Biological Action, Medical Uses, and Safety
Chloroquine is a synthetic drug mainly used for the treatment of malaria. Chloroquine was discovered in 1934, it started to practice for the medical needs in the 1940s. It is one of the quinoline derivatives and a member of chemically related antimalarial agents. This chloroquine is tearmed chloroquine phosphate. chloroquine hydrochloride can also use as an intramuscular injection. Chloroquine and hydroxychloroquine are closely related to each other. This is another derivative of quinoline. Hydroxychloroquine can also be used for treating inflammatory rheumatic diseases and malaria.
Chloroquine Chemical Structure
The chemical formula for Chloroquine is C₁₈H₂₆ClN₃. The chloroquine chemical structure 7-chloro-4-(4-diethylamino-1-methyl butyl amino)-quinoline, is formed while 4,7-di chloroquinoline is reacted with 4-diethylamino-1-methyl butylamine at 180 °C.
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This image shows the chloroquine structure and IUPAC name.
Mechanism of Chloroquine
The chloroquine has a lysosomotropic character, which helps to perform as an antimalarial drug. Chloroquine drug concentrates on acidic food vacuole of the parasite and enters into the essential process. The lysosomotropic properties allow it for the use of in vitro experiments pertaining to intracellular lipid-related disease namely apoptosis and autophagy.
The malarial parasite present in the red blood cells undergoes an asexual lifecycle. It starts affecting the hemoglobin to acquire essential amino acids. As the parasite requires to build its own protein and energy metabolism. The digestion of the parasites carries out in a vacuole of the cells. Hemoglobin composed of protein unit and heme unit. The parasite can digest protein units but cannot synthesize heme units. During the digestion process, parasites release the toxic, soluble molecule heme unit. This heme unit consists of the porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, hemozoin is formed by the parasite biocrystallizes heme. Hemozoin gets stored in a digestive vacuole as insoluble crystals.
Chloroquine entering the red blood cells. It inhibits the parasite cell and digestive vacuole for the diffusion process. Chloroquine transfers CQ2+ protons as the digestive vacuole is acidic. So, the parasite cannot go for the diffusion process. Chloroquine covers hemozoin molecules to prevent further biocrystallization of heme thus helps to heme buildup.
The chloroquine join to heme to form the FP-chloroquine complex. This gets high toxic to the cell and disturbs the membrane function. The action of the toxic FP and FP- chloroquine results in cell lysis and supports parasite cell autodigestion. If the parasite does not form hemozoin, then it is resistant to chloroquine.
P. falciparum is a resistant strains of chloroquine. These strains are showing resistant behaviour to chloroquine this is because mainly due to the evolution of species. It was discovered in East and West Africa, Southeast Asia, and South America. The resistant parasites use its transmembrane pump to remove chloroquine from the digestive vacuole. These chloroquine-resistant parasites pump out 40 times more than the chloroquine-sensitive parasites. P. falciparum codes the pump by the chloroquine resistance transporter (PfCRT) gene. The main function of the chloroquine pump is to transport peptides. A Ca²⁺ channel blocker Verapamil has found to restore the ability of chloroquine to treat resistance parasites.
Chloroquine Uses
Chloroquine is an effective agent to act against the susceptible strains of malarial parasites Plasmodium ovale, Plasmodium vivax, and Plasmodium falciparum and some parasitic worms and amoebas. It can also be used for the treatment of inflammatory rheumatic diseases namely rheumatoid arthritis and lupus erythematosus.
Chloroquine Side Effects
Chloroquine tablet uses brings some side effects. The chloroquine side effects vary depends on the individual’s immune power. Chloroquine phosphate uses have mild side effects like abdominal cramps and headache, it is a common effect of all antimalarial drugs. They may also experience tinnitus, skin rashes, nausea, vomiting, muscle weakness, visual impairment, and changes in behaviour. Visual impairment is mainly due to retinal damage. This may occur only due to the long-term chloroquine phosphate uses. This condition of experiencing visual impairment is known as chloroquine retinopathy.
This chloroquine will interact with other medications namely, antibiotics like ampicillin, erythromycin, antacids, antiarrhythmics which increases side effects. Drug-to-drug interactions will alter the chloroquine interaction level in the body. It may block the chloroquine metabolism, which results in toxic chloroquine accumulation in the body. Also, chloroquine has the potential to alter the level of other drugs. This increases the toxicity of the agent and the risk of side effects. A similar derivative of quinoline, hydroxychloroquine has many side effects as chloroquine. But, it is comparatively less toxic.
How to Use Chloroquine Phosphate?
Chloroquine phosphate can intake in the form of tablets. Chloroquine tablet uses for treating malaria and amebiasis. To prevent malaria in adults, can use one dose of the tablet for one week. That should take on the same day of the week. The dosage level must be determined by the doctors. It is preferable to take one dose of chloroquine hydrochloride before 2 weeks or after 8 weeks for travelling to the malaria-affected areas. If a person severely affected by malaria, the physician will prefer to take an extra half a dose after 6 to 8 hours of taking one dose of tablets. For treating or preventing children from malaria, physicians calculate the amount of chloroquine phosphate level based on children’s weight.
For treating amebiasis, it is recommended to take one dose of tablets for 2 days and a half dose of tablets every 2 to 3 weeks. chloroquine tablet can be taken with other amebicides medicine.
FAQs on Chloroquine: Key Concepts, Mechanism & Uses
1. What is the primary medical use of chloroquine?
The primary medical use of chloroquine is for the treatment and prevention of malaria, a disease caused by the parasite Plasmodium. It is effective against the parasite during its life stage within red blood cells. Additionally, chloroquine can be used to treat certain other conditions, such as extraintestinal amebiasis, which is an infection caused by the amoeba Entamoeba histolytica.
2. What are the common side effects associated with chloroquine?
While generally safe when taken as prescribed, chloroquine can cause several side effects. Common, milder effects include nausea, headache, dizziness, and abdominal cramps. However, more serious side effects can occur, especially with long-term or high-dose usage. These can include:
- Retinal damage (chloroquine retinopathy), potentially leading to vision problems.
- Heart rhythm abnormalities (arrhythmias).
- Muscle weakness or damage.
- Hearing difficulties or ringing in the ears (tinnitus).
3. How does chloroquine work to treat malaria?
Chloroquine works by interfering with the malaria parasite's detoxification process inside human red blood cells. The Plasmodium parasite digests haemoglobin for nutrients, which releases a toxic byproduct called heme. To protect itself, the parasite converts this toxic heme into a non-toxic, crystalline form called hemozoin. Chloroquine accumulates in the parasite's food vacuole and blocks this conversion process. The resulting buildup of toxic heme inside the parasite is lethal, effectively killing it.
4. Why is chloroquine resistance a significant problem in malaria control?
Chloroquine resistance is a major challenge because many strains of the malaria parasite, particularly Plasmodium falciparum, have evolved mechanisms to survive the drug. This resistance is primarily due to genetic mutations in the parasite, such as in the pfcrt gene, which allows the parasite to actively pump chloroquine out of its food vacuole. When the drug is expelled, it cannot reach a high enough concentration to be effective. This leads to treatment failure, continued illness, and the spread of drug-resistant malaria in a population, making the disease much harder to control.
5. Is chloroquine a type of steroid or antibiotic?
No, chloroquine is neither a steroid nor an antibiotic. It belongs to a specific class of drugs known as antimalarials, chemically classified as a 4-aminoquinoline. Steroids are compounds that mimic hormones, while antibiotics are substances that kill or inhibit the growth of bacteria. Chloroquine's mechanism is targeted specifically against protozoan parasites like Plasmodium.
6. What is the main difference between chloroquine and hydroxychloroquine?
The main difference lies in their chemical structure and resulting safety profile. Hydroxychloroquine is a derivative of chloroquine, containing an added hydroxyl (-OH) group. This modification makes hydroxychloroquine generally less toxic than chloroquine, particularly regarding the risk of retinal damage with long-term use. While both can treat malaria, hydroxychloroquine's improved safety profile has made it a more common choice for treating autoimmune diseases like lupus and rheumatoid arthritis.
7. As per medical guidelines, is it safe to use chloroquine during pregnancy?
Yes, for women in malaria-endemic regions, chloroquine is generally considered safe for use during pregnancy for both preventing and treating malaria caused by susceptible parasite strains. The health risks posed by a malaria infection to both the mother and the developing foetus are significantly greater than the potential risks of the medication itself. However, its use must always be supervised by a healthcare professional to ensure proper dosage and monitoring.
