Chloroquine is a drug used for the treatment and prophylaxis of malaria and is also used for the therapy of inflammatory rheumatic diseases. However, malaria pathogens have developed resistance to chloroquine in many regions, so that the use of the drug against malaria is limited to certain regions. Taking chloroquine can cause adverse side effects, mainly affecting the gastrointestinal tract and, in rarer cases, leading to retinal and corneal eye disease.
What is chloroquine?
Chloroquine is a drug composed of stereoisomers (enantiomers) similar to quinine. From its chemical molecular formula (C18H26ClN3), it is a chemical compound composed almost entirely of carbon and hydrogen, but with a single chlorine atom attached and three nitrogen atoms. One of the three N atoms forms one corner of each aromatic six-membered ring, while another N atom is attached to two terminal methyl groups (-CH3). The third N atom is part of the hydrogen bond between the two aromatic six-membered rings and the rest of the compound. Because chloroquine is insoluble in water, the water-soluble salts chloroquine diphosphate or chloroquine sulfate are usually used as drugs. The salts also have the advantage of being stable in air. In Switzerland, drugs whose active ingredient consists exclusively of chloroquine (monopreparations) are known under the names Chlorochin and Nivaquine, and in Germany and Austria under Resochin. In Germany, an additional preparation, Weimerquin, is also approved.
Pharmacological action
Chloroquine’s main effect is to inhibit the crystallization of hemozoin, which is formed during the breakdown of heme, the red blood pigment. Plasmodia, the pathogens that cause malaria, occupy red blood cells (erythrocytes) at a certain stage and use their enzymes to break down the hemoglobin they contain. They use the resulting protein fragments in the form of peptides, polypeptides and amino acids of the hemoglobin for their own protein synthesis. The hemozoin of the broken down heme, which is also released, has a toxic effect on the plasmodia. For their own protection, the unicellular pathogens use the enzyme hemopolymerase, which leads to crystallization of the hemozoin, rendering it harmless. Chloroquine inhibits this enzyme and thus prevents the crystallization of hemozoin, which ideally leads to the killing of the plasmodia. What effects the temporary flooding of the body with hemozoin has in the case of simultaneous infection with plasmodia has not yet been adequately researched. However, a worldwide use of drugs based on chloroquine for malaria therapy and prophylaxis have led to the development of resistance in the pathogens. In addition to the specific effect of the drug, there are also anti-inflammatory properties, which are probably based on an inhibition of certain interleukins and other messenger substances. However, it is not sufficiently known what the side effects of the drug are based on, which can lead to discomfort, especially in the gastrointestinal tract. In many cases, deposits of the drug chloroquine have been observed in the retina and cornea of the eyes, so that in rare cases retinopathies or corneal opacities may occur.
Medical use and application
Chloroquine-containing drugs such as Resochin are used primarily for the treatment and prophylaxis of malaria. Until the development of resistance, the active ingredient chloroquine served primarily to control malaria tropica, which is caused by the pathogen Plasmodium falciparum. Malaria tropica is considered the most dangerous of the four major types of malaria. It causes episodes of fever at irregular intervals and is therefore often not diagnosed as malaria at an early stage. From the 1950s to the 1970s, monopreparations with chloroquine as the active ingredient represented the standard means of malaria prophylaxis and treatment. The high half-life of the active ingredient of about 60 days guarantees an effect even after the drug has been discontinued. To establish effective malaria protection in areas where resistance to chloroquine has not been observed, it is necessary to start taking the tablets one week before the planned trip to an endemic area and to continue taking them for up to four weeks after leaving the malaria-prone area.In addition to its main use in malaria prophylaxis, chloroquine is also used in the treatment of rheumatoid arthritis due to its anti-inflammatory properties. In rare cases, chloroquine is also used in the adjunctive treatment of lupus erythematosus to control inflammatory processes. Lupus erythematosus is the name given to a systemic autoimmune disease that progresses in relapses and usually requires both anti-inflammatory measures and long-term immunosuppression to suppress disease progression as much as possible and to attenuate symptoms as much as possible.
Risks and side effects
A number of short-term or long-term side effects may occur after taking chloroquine-containing medications. The most common complaints associated with chloroquine involve the gastrointestinal tract. The complaints noted range from loss of appetite to nausea with vomiting to diarrhea (diarrhea). The complaints may be temporary, lasting until the patient becomes accustomed to the drug, or they may last longer, so that an alternative option for chloroquine must be sought. Particularly with long-term use of chloroquine, because of a permanent stay in endemic malaria regions or if the drug is taken, for example, concomitantly with the therapy of lupus erythematosus, deposits may occur in the cornea and retina of the eyes. The deposits can lead to clouding of the cornea with impaired vision or to retinopathy, a retinal disease. By regularly checking the eyes or after the first appearance of symptoms and objective diagnosis, it is possible to counteract serious eye disease by discontinuing the drug.
