Chloroquine is a medication used primarily to prevent and to treat malaria in areas where that parasitic disease is known to remain sensitive to its effects. A benefit of its use in therapy, when situations allow, is that it can be taken by mouth (versus by injection). Controlled studies of cases involving human pregnancy are lacking, but the drug may be safe for use for such patients.[verification needed] However, the agent is not without the possibility of serious side effects at standard doses, and complicated cases, including infections of certain types or caused by resistant strains, typically require different or additional medication. Chloroquine is also used as a medication for rheumatoid arthritis, lupus erythematosus, and other parasitic infections (e.g., amebiasis occurring outside of the intestines). Beginning in 2020, studies have proceeded on its use as a coronavirus antiviral, in possible treatment of COVID-19.
Chloroquine, otherwise known as chloroquine phosphate, is in the 4-aminoquinoline class of drugs. As an antimalarial, it works against the asexual form of the malaria parasite in the stage of its life cycle within the red blood cell. In its use against rheumatoid arthritis and lupus erythematosus, its activity as a mild immunosuppressive underlies its mechanism. Antiviral activities, established and putative, are attributed to chloroquines inhibition of glycosylation pathways (of host receptor sialylation or virus protein post-translational modification), or to inhibition of virus endocytosis (e.g., via alkalisation of endosomes), or other possible mechanisms. Common side effects resulting from these therapeutic uses, at common doses, include muscle problems,[clarification needed] loss of appetite, diarrhea, and skin rash.[clarification needed] Serious side effects include problems with vision (retinopathy), muscle damage, seizures, and certain anemias.
Chloroquine was discovered in 1934 by Hans Andersag. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is about US$0.04. In the United States, it costs about US$5.30 per dose.
Chloroquine has been used in the treatment and prevention of malaria from Plasmodium vivax, P. ovale, and P. malariae. It is generally not used for Plasmodium falciparum as there is widespread resistance to it.
Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it. In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead. The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations.
In treatment of amoebic liver abscess, chloroquine may be used instead of or in addition to other medications in the event of failure of improvement with metronidazole or another nitroimidazole within 5 days or intolerance to metronidazole or a nitroimidazole.
As it mildly suppresses the immune system, chloroquine is used in some autoimmune disorders, such as rheumatoid arthritis and lupus erythematosus.
Side effects include blurred vision, nausea, vomiting, abdominal cramps, headache, diarrhea, swelling legs/ankles, shortness of breath, pale lips/nails/skin, muscle weakness, easy bruising/bleeding, hearing and mental problems.
- Unwanted/uncontrolled movements (including tongue and face twitching) 
- Deafness or tinnitus.
- Nausea, vomiting, diarrhea, abdominal cramps
- Mental/mood changes (such as confusion, personality changes, unusual thoughts/behavior, depression, feeling being watched, hallucinating)
- Signs of serious infection (such as high fever, severe chills, persistent sore throat)
- Skin itchiness, skin color changes, hair loss, and skin rashes.
- Chloroquine-induced itching is very common among black Africans (70%), but much less common in other races. It increases with age, and is so severe as to stop compliance with drug therapy. It is increased during malaria fever; its severity is correlated to the malaria parasite load in blood. Some evidence indicates it has a genetic basis and is related to chloroquine action with opiate receptors centrally or peripherally.
- Unpleasant metallic taste
- This could be avoided by “taste-masked and controlled release” formulations such as multiple emulsions.
- Chloroquine retinopathy
- Electrocardiographic changes
- This manifests itself as either conduction disturbances (bundle-branch block, atrioventricular block) or Cardiomyopathy – often with hypertrophy, restrictive physiology, and congestive heart failure. The changes may be irreversible. Only two cases have been reported requiring heart transplantation, suggesting this particular risk is very low. Electron microscopy of cardiac biopsies show pathognomonic cytoplasmic inclusion bodies.
- Pancytopenia, aplastic anemia, reversible agranulocytosis, low blood platelets, neutropenia.
Chloroquine has not been shown to have any harmful effects on the fetus when used for malarial prophylaxis. Small amounts of chloroquine are excreted in the breast milk of lactating women. However, this drug can be safely prescribed to infants, the effects are not harmful. Studies with mice show that radioactively tagged chloroquine passed through the placenta rapidly and accumulated in the fetal eyes which remained present five months after the drug was cleared from the rest of the body. Women who are pregnant or planning on getting pregnant are still advised against traveling to malaria-risk regions.
There is not enough evidence to determine whether chloroquine is safe to be given to people aged 65 and older. Since it is cleared by the kidneys, toxicity should be monitored carefully in people with poor kidney functions.
Chloroquine has a number of drug-drug interactions that might be of clinical concern:
- Ampicillin– levels may be reduced by chloroquine;
- Antacids– may reduce absorption of chloroquine;
- Cimetidine– may inhibit metabolism of chloroquine; increasing levels of chloroquine in the body;
- Cyclosporine– levels may be increased by chloroquine; and
- Mefloquine– may increase risk of convulsions.
Chloroquine is very dangerous in overdose. It is rapidly absorbed from the gut. In 1961, a published compilation of case reports contained accounts of three children who took overdoses and died within 2.5 hours of taking the drug. While the amount of the overdose was not stated, the therapeutic index for chloroquine is known to be small. One of the children died after taking 0.75 or 1 gram, or twice a single therapeutic amount for children. Symptoms of overdose include headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, seizures, and sudden respiratory and cardiac arrest.
An analog of chloroquine – hydroxychloroquine – has a long half-life (32–56 days) in blood and a large volume of distribution (580–815 L/kg). The therapeutic, toxic and lethal ranges are usually considered to be 0.03 to 15 mg/l, 3.0 to 26 mg/l and 20 to 104 mg/l, respectively. However, nontoxic cases have been reported up to 39 mg/l, suggesting individual tolerance to this agent may be more variable than previously recognised.
Chloroquine’s absorption of the drug is rapid. It is widely distributed in body tissues. It’s protein binding is 55%.[ It’s metabolism is partially hepatic, giving rise to its main metabolite, desethylchloroquine. It’s excretion os ≥50% as unchanged drug in urine, where acidification of urine increases its elimination It has a very high volume of distribution, as it diffuses into the body’s adipose tissue.
Accumulation of the drug may result in deposits that can lead to blurred vision and blindness. It and related quinines have been associated with cases of retinal toxicity, particularly when provided at higher doses for longer times. With long-term doses, routine visits to an ophthalmologist are recommended.
Chloroquine is also a lysosomotropic agent, meaning it accumulates preferentially in the lysosomes of cells in the body. The pKa for the quinoline nitrogen of chloroquine is 8.5, meaning—in simplified terms, considering only this basic site—it is about 10% deprotonated at physiological pH (per the Henderson-Hasselbalch equation) This decreases to about 0.2% at a lysosomal pH of 4.6.Because the deprotonated form is more membrane-permeable than the protonated form, a quantitative “trapping” of the compound in lysosomes results.
Mechanism of action
The lysosomotropic character of chloroquine is believed to account for much of its antimalarial activity; the drug concentrates in the acidic food vacuole of the parasite and interferes with essential processes. Its lysosomotropic properties further allow for its use for in vitro experiments pertaining to intracellular lipid related diseases, autophagy, and apoptosis.
Inside red blood cells, the malarial parasite, which is then in its asexual lifecycle stage, must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasitic cell.
Hemoglobin is composed of a protein unit (digested by the parasite) and a heme unit (not used by the parasite). During this process, the parasite releases the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a nontoxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.
Chloroquine enters the red blood cell by simple diffusion, inhibiting the parasite cell and digestive vacuole. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form the FP-chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion.  Parasites that do not form hemozoin are therefore resistant to chloroquine.
Resistance in malaria[edit source]
Since the first documentation of P. falciparum chloroquine resistance in the 1950s, resistant strains have appeared throughout East and West Africa, Southeast Asia, and South America. The effectiveness of chloroquine against P. falciparum has declined as resistant strains of the parasite evolved. They effectively neutralize the drug via a mechanism that drains chloroquine away from the digestive vacuole. Chloroquine-resistant cells efflux chloroquine at 40 times the rate of chloroquine-sensitive cells; the related mutations trace back to transmembrane proteins of the digestive vacuole, including sets of critical mutations in the P. falciparum chloroquine resistance transporter (PfCRT) gene. The mutated protein, but not the wild-type transporter, transports chloroquine when expressed in Xenopus oocytes (frog’s eggs) and is thought to mediate chloroquine leak from its site of action in the digestive vacuole. Resistant parasites also frequently have mutated products of the ABC transporter P. falciparum multidrug resistance (PfMDR1) gene, although these mutations are thought to be of secondary importance compared to Pfcrt. Verapamil, a Ca2+ channel blocker, has been found to restore both the chloroquine concentration ability and sensitivity to this drug. Recently, an altered chloroquine-transporter protein CG2 of the parasite has been related to chloroquine resistance, but other mechanisms of resistance also appear to be involved. Research on the mechanism of chloroquine and how the parasite has acquired chloroquine resistance is still ongoing, as other mechanisms of resistance are likely.
Other agents which have been shown to reverse chloroquine resistance in malaria are chlorpheniramine, gefitinib, imatinib, tariquidar and zosuquidar.
Chloroquine has antiviral effects. It increases late endosomal or lysosomal pH, resulting in impaired release of the virus from the endosome or lysosome – release requires a low pH. The virus is therefore unable to release its genetic material into the cell and replicate.
Chloroquine also seems to act as a zinc ionophore, that allows extracellular zinc to enter the cell and inhibit viral RNA-dependent RNA polymerase.
Chloroquine inhibits thiamine uptake. It acts specifically on the transporter SLC19A3.
Against rheumatoid arthritis, it operates by inhibiting lymphocyte proliferation, phospholipase A2, antigen presentation in dendritic cells, release of enzymes from lysosomes, release of reactive oxygen species from macrophages, and production of IL-1.
In Peru the indigenous people extracted the bark of the Cinchona plant trees and used the extract (Chinchona officinalis) to fight chills and fever in the seventeenth century. In 1633 this herbal medicine was introduced in Europe, where it was given the same use and also began to be used against malaria. The quinoline antimalarial drug quinine was isolated from the extract in 1820, and chloroquine is an analogue of this.
Chloroquine was discovered in 1934, by Hans Andersag and coworkers at the Bayer laboratories, who named it “Resochin”. It was ignored for a decade, because it was considered too toxic for human use. During World War II, United States government-sponsored clinical trials for antimalarial drug development showed unequivocally that chloroquine has a significant therapeutic value as an antimalarial drug. It was introduced into clinical practice in 1947 for the prophylactic treatment of malaria.
Society and culture
Chloroquine comes in tablet form as the phosphate, sulfate, and hydrochloride salts. Chloroquine is usually dispensed as the phosphate.
Brand names include Chloroquine FNA, Resochin, Dawaquin, and Lariago.
Chloroquine is used to control the aquarium fish parasite Amyloodinium ocellatum.
In late January 2020 during the 2019–20 coronavirus outbreak, Chinese medical researchers stated that exploratory research into chloroquine and two other medications, remdesivir and lopinavir/ritonavir, seemed to have “fairly good inhibitory effects” on the SARS-CoV-2 virus, which is the virus that causes COVID-19. Requests to start clinical testing were submitted. Chloroquine had been also proposed as a treatment for SARS, with in vitro tests inhibiting the SARS-CoV virus.
Chloroquine has been recommended by Chinese, South Korean and Italian health authorities for the treatment of COVID-19. These agencies noted contraindications for people with heart disease or diabetes. Both chloroquine and hydroxychloroquine were shown to inhibit SARS-CoV-2 in vitro, but a further study concluded that hydroxychloroquine was more potent than chloroquine, with a more tolerable safety profile. Preliminary results from a trial suggested that chloroquine is effective and safe in COVID-19 pneumonia, “improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course.” Self-medication with chloroquine has caused one known fatality.
On 24 March 2020, NBC News reported a fatality due to misuse of a chloroquine product used to control fish parasites.
In October 2004, a group of researchers at the Rega Institute for Medical Research published a report on chloroquine, stating that chloroquine acts as an effective inhibitor of the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro.
Chloroquine was being considered in 2003, in pre-clinical models as a potential agent against chikungunya fever.
The radiosensitizing and chemosensitizing properties of chloroquine are beginning to be exploited in anticancer strategies in humans. In biomedicinal science, chloroquine is used for in vitro experiments to inhibit lysosomal degradation of protein products.
- ^ Jump up to:a b c d e f g h i j k l m n “Aralen Phosphate”. The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 2 December 2015.
- ^ “Chloroquine Use During Pregnancy”. Drugs.com. Archivedfrom the original on 16 April 2019. Retrieved 16 April 2019.
There are no controlled data in human pregnancies.
- ^ Mittra, Robert A.; Mieler, William F. (1 January 2013). Ryan, Stephen J.; Sadda, SriniVas R.; Hinton, David R.; Schachat, Andrew P.; Sadda, SriniVas R.; Wilkinson, C. P.; Wiedemann, Peter; Schachat, Andrew P. (eds.). Retina (Fifth Edition). W.B. Saunders. pp. 1532–1554 – via ScienceDirect.
- ^ Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S (March 2020). “A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19”. Journal of Critical Care. doi:10.1016/j.jcrc.2020.03.005. PMID 32173110.
- ^ Manson P, Cooke G, Zumla A, eds. (2009). Manson’s tropical diseases (22nd ed.). [Edinburgh]: Saunders. p. 1240. ISBN 9781416044703. Archived from the original on 2 November 2018. Retrieved 9 September 2017.
- ^ Bhattacharjee M (2016). Chemistry of Antibiotics and Related Drugs. Springer. p. 184. ISBN 9783319407463. Archived from the original on 1 November 2018. Retrieved 9 September 2017.
- ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ “Chloroquine (Base)”. International Drug Price Indicator Guide. Archived from the original on 27 August 2018. Retrieved 4 December 2015.
- ^ “Frequently Asked Questions (FAQs): If I get malaria, will I have it for the rest of my life?”. US Centers for Disease Control and Prevention. 8 February 2010. Archived from the original on 13 May 2012. Retrieved 14 May 2012.
- ^ Plowe CV (2005). “Antimalarial drug resistance in Africa: strategies for monitoring and deterrence”. Malaria: Drugs, Disease and Post-genomic Biology. Current Topics in Microbiology and Immunology. 295. pp. 55–79. doi:10.1007/3-540-29088-5_3. ISBN 3-540-25363-7. PMID 16265887.
- ^ Uhlemann AC, Krishna S (2005). “Antimalarial multi-drug resistance in Asia: mechanisms and assessment”. Malaria: Drugs, Disease and Post-genomic Biology. Current Topics in Microbiology and Immunology. 295. pp. 39–53. doi:10.1007/3-540-29088-5_2. ISBN 3-540-25363-7. PMID 16265886.
- ^ “Chloroquine phosphate tablet – chloroquine phosphate tablet, coated”. dailymed.nlm.nih.gov. Archived from the original on 8 December 2015. Retrieved 4 November 2015.
- ^ CDC. Health information for international travel 2001–2002. Atlanta, Georgia: U.S. Department of Health and Human Services, Public Health Service, 2001.
- ^ Amebic Hepatic Abscesses~treatment at eMedicine
- ^ Jump up to:a b c d e f “Drugs & Medications”. http://www.webmd.com. Retrieved 22 March 2020.
- ^ Jump up to:a b c d “Chloroquine Side Effects: Common, Severe, Long Term”. Drugs.com. Retrieved 22 March 2020.
- ^ “Chloroquine: MedlinePlus Drug Information”. medlineplus.gov. Retrieved 22 March 2020.
- ^ Ajayi AA (September 2000). “Mechanisms of chloroquine-induced pruritus”. Clinical Pharmacology and Therapeutics. 68 (3): 336. PMID 11014416.
- ^ Vaziri A, Warburton B (1994). “Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions”. Journal of Microencapsulation. 11 (6): 641–8. doi:10.3109/02652049409051114. PMID 7884629.
- ^ Tönnesmann E, Kandolf R, Lewalter T (June 2013). “Chloroquine cardiomyopathy – a review of the literature”. Immunopharmacology and Immunotoxicology. 35 (3): 434–42. doi:10.3109/08923973.2013.780078. PMID 23635029.
- ^ Jump up to:a b c d e f g h i “Aralen Chloroquine Phosphate, USP” (PDF). Archived (PDF) from the original on 25 March 2020. Retrieved 24 March 2020.
- ^ Jump up to:a b “Malaria – Chapter 3 – 2016 Yellow Book”. wwwnc.cdc.gov. Archived from the original on 14 January 2016. Retrieved 11 November 2015.
- ^ Ullberg S, Lindquist NG, Sjòstrand SE (September 1970). “Accumulation of chorio-retinotoxic drugs in the foetal eye”. Nature. 227 (5264): 1257–8. Bibcode:1970Natur.227.1257U. doi:10.1038/2271257a0. PMID 5452818.
- ^ Cann HM, Verhulst HL (January 1961). “Fatal acute chloroquine poisoning in children”. Pediatrics. 27: 95–102. PMID 13690445.
- ^ Jump up to:a b Molina DK (March 2012). “Postmortem hydroxychloroquine concentrations in nontoxic cases”. The American Journal of Forensic Medicine and Pathology. 33 (1): 41–2. doi:10.1097/PAF.0b013e3182186f99. PMID 21464694.
- ^ Chen PM, Gombart ZJ, Chen JW (March 2011). “Chloroquine treatment of ARPE-19 cells leads to lysosome dilation and intracellular lipid accumulation: possible implications of lysosomal dysfunction in macular degeneration”. Cell & Bioscience. 1 (1): 10. doi:10.1186/2045-3701-1-10. PMC 3125200. PMID 21711726.
- ^ Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, et al. (April 2010). “Abeta-mediated NMDA receptor endocytosis in Alzheimer’s disease involves ubiquitination of the tyrosine phosphatase STEP61”. The Journal of Neuroscience. 30(17): 5948–57. doi:10.1523/JNEUROSCI.0157-10.2010. PMC 2868326. PMID 20427654.
- ^ Kim EL, Wüstenberg R, Rübsam A, Schmitz-Salue C, Warnecke G, Bücker EM, et al. (April 2010). “Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells”. Neuro-Oncology. 12 (4): 389–400. doi:10.1093/neuonc/nop046. PMC 2940600. PMID 20308316.
- ^ Hempelmann E (March 2007). “Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors”. Parasitology Research. 100 (4): 671–6. doi:10.1007/s00436-006-0313-x. PMID 17111179.
- ^ Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, et al. (June 2015). “Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance” (PDF). The Journal of Experimental Medicine. 212(6): 893–903. doi:10.1084/jem.20141731. PMC 4451122. PMID 25941254. Archived (PDF) from the original on 22 September 2017. Retrieved 4 November 2018.
- ^ Martin RE, Marchetti RV, Cowan AI, Howitt SM, Bröer S, Kirk K (September 2009). “Chloroquine transport via the malaria parasite’s chloroquine resistance transporter”. Science. 325 (5948): 1680–2. Bibcode:2009Sci…325.1680M. doi:10.1126/science.1175667. PMID 19779197.
- ^ Essentials of medical pharmacology fifth edition 2003, reprint 2004, published by-Jaypee Brothers Medical Publisher Ltd, 2003, KD Tripathi, pages 739,740.
- ^ Alcantara LM, Kim J, Moraes CB, Franco CH, Franzoi KD, Lee S, et al. (June 2013). “Chemosensitization potential of P-glycoprotein inhibitors in malaria parasites”. Experimental Parasitology. 134 (2): 235–43. doi:10.1016/j.exppara.2013.03.022. PMID 23541983.
- ^ Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R (November 2003). “Effects of chloroquine on viral infections: an old drug against today’s diseases?”. The Lancet. Infectious Diseases. 3(11): 722–7. doi:10.1016/s1473-3099(03)00806-5. PMID 14592603.
- ^ Al-Bari MA (February 2017). “Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases”. Pharmacology Research & Perspectives. 5 (1): e00293. doi:10.1002/prp2.293. PMC 5461643. PMID 28596841.
- ^ Fredericksen BL, Wei BL, Yao J, Luo T, Garcia JV (November 2002). “Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus”. Journal of Virology. 76 (22): 11440–6. doi:10.1128/JVI.76.22.11440-11446.2002. PMC 136743. PMID 12388705.
- ^ Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ (1 October 2014). “Chloroquine is a zinc ionophore”. PloS One. 9(10): e109180. doi:10.1371/journal.pone.0109180. PMC 4182877. PMID 25271834.
- ^ te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ (November 2010). “Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture”. PLoS Pathogens. 6 (11): e1001176. doi:10.1371/journal.ppat.1001176. PMC 2973827. PMID 21079686.
- ^ Huang Z, Srinivasan S, Zhang J, Chen K, Li Y, Li W, et al. (2012). “Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy”. PLOS Genetics. 8 (11): e1003083. doi:10.1371/journal.pgen.1003083. PMC 3510038. PMID 23209439.
- ^ Fern, Ken (2010–2020). “Cinchona officinalis – L.” Plans for a Future. Archived from the original on 25 August 2017. Retrieved 2 February 2020.
- ^ V. Kouznetsov, Vladímir (2008). “Antimalarials: construction of molecular hybrids based on chloroquine” (PDF). Universitas Scientiarum: 1. Archived (PDF) from the original on 22 February 2020. Retrieved 22 February 2020 – via scielo.
- ^ Krafts K, Hempelmann E, Skórska-Stania A (July 2012). “From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy”. Parasitology Research. 111 (1): 1–6. doi:10.1007/s00436-012-2886-x. PMID 22411634.
- ^ “The History of Malaria, an Ancient Disease”. Centers for Disease Control. 29 July 2019. Archived from the original on 28 August 2010.
- ^ “Chloroquine”. nih.gov. National Institutes of Health. Retrieved 24 March 2020.
- ^ “Ipca Laboratories: Formulations – Branded”. Archived from the original on 6 April 2019. Retrieved 14 March 2020.
- ^ Francis-Floyd, Ruth; Floyd, Maxine R. “Amyloodinium ocellatum, an Important Parasite of Cultured Marine Fish” (PDF). agrilife.org.
- ^ “Could an old malaria drug help fight the new coronavirus?”. asbmb.org. Archived from the original on 6 February 2020. Retrieved 6 February 2020.
- ^ Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M (October 2004). “In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine”. Biochemical and Biophysical Research Communications. 323 (1): 264–8. doi:10.1016/j.bbrc.2004.08.085. PMID 15351731.
- ^ Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 11:105938. doi:10.1016/j.ijantimicag.2020.105938 PMID 32171740
- ^ “Physicians work out treatment guidelines for coronavirus”. m.koreabiomed.com (in Korean). 13 February 2020. Archivedfrom the original on 17 March 2020. Retrieved 18 March 2020.
- ^ “Azioni intraprese per favorire la ricerca e l’accesso ai nuovi farmaci per il trattamento del COVID-19”. aifa.gov.it (in Italian). Retrieved 18 March 2020.
- ^ “Plaquenil (hydroxychloroquine sulfate) dose, indications, adverse effects, interactions… from PDR.net”. http://www.pdr.net. Archivedfrom the original on 18 March 2020. Retrieved 19 March 2020.
- ^ Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. (March 2020). “In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”. Clinical Infectious Diseases. doi:10.1093/cid/ciaa237. PMID 32150618.
- ^ Gao J, Tian Z, Yang X (February 2020). “Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies”. Bioscience Trends. 14: 72–73. doi:10.5582/bst.2020.01047. PMID 32074550. Archived from the original on 19 March 2020. Retrieved 19 March 2020.
- ^ Edwards, Erika; Hillyard, Vaughn (23 March 2020). “Man dies after ingesting chloroquine in an attempt to prevent coronavirus”. NBC News. Retrieved 24 March 2020.
- ^ “A man died after ingesting a substance he thought would protect him from coronavirus”. NBC News. Retrieved 25 March 2020.
- ^ “Banner Health experts warn against self-medicating to prevent or treat COVID-19”. Banner Health (Press release). 23 March 2020. Retrieved 25 March 2020.
- ^ Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M (October 2004). “In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine”. Biochemical and Biophysical Research Communications. 323 (1): 264–8. doi:10.1016/j.bbrc.2004.08.085. PMID 15351731.
- ^ Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R (November 2003). “Effects of chloroquine on viral infections: an old drug against today’s diseases?”. The Lancet. Infectious Diseases. 3(11): 722–7. doi:10.1016/S1473-3099(03)00806-5. PMID 14592603.
- ^ Savarino A, Lucia MB, Giordano F, Cauda R (October 2006). “Risks and benefits of chloroquine use in anticancer strategies”. The Lancet. Oncology. 7 (10): 792–3. doi:10.1016/S1470-2045(06)70875-0. PMID 17012039.
- ^ Sotelo J, Briceño E, López-González MA (March 2006). “Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial”. Annals of Internal Medicine. 144 (5): 337–43. doi:10.7326/0003-4819-144-5-200603070-00008. PMID 16520474.
“Summaries for patients. Adding chloroquine to conventional chemotherapy and radiotherapy for glioblastoma multiforme”. Annals of Internal Medicine. 144 (5): I31. March 2006. doi:10.7326/0003-4819-144-5-200603070-00004. PMID 16520470.
“Chloroquine”. Drug Information Portal. U.S. National Library of Medicine.
- “Medicines for the Prevention of Malaria While Traveling – Chloroquine (Aralen)” (PDF) (Fact sheet). U.S. Centers for Disease Control and Prevention (CDC).
- The dictionary definition of chloroquine at Wiktionary
|Trade names||Aralen, other|
|Other names||Chloroquine phosphate|
|Elimination half-life||1-2 months|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||319.872 g·mol−1|
|3D model (JSmol)|
//////////////CHLOROQUINE,, クロロキン, ANTIMALARIAL, COVID 19, CORONA VIRUS, Хлорохин , クロロキン , كلوروكين