Hydroxychloroquine may also be used to prevent and treat malaria.
Hydroxychloroquine works by killing the parasite that causes malaria.
CAS Number: 118-42-3
EC Number: 204‑249‑8
IUPAC Name: 2-({4-[(7‑chloroquinolin-4-yl)amino]pentyl}(ethyl)amino)ethan-1-ol
Molecular Formula: C18H26ClN3O
Molar mass: 335.88 g·mol−1
SYNONYMS:
Hydroxychloroquine, 118-42-3, Oxichloroquine, Oxychlorochin, Hidroxicloroquina, oxichlorochine, Polirreumin, Hydroxychloroquinum, 2-((4-((7-Chloro-4-quinolyl)amino)pentyl)ethylamino)ethanol, CHEBI:5801, Dolquine, 7-Chloro-4-(4-(ethyl(2-hydroxyethyl)amino)-1-methylbutylamino)quinoline, 4QWG6N8QKH, 2-(N-(4-(7-Chlor-4-chinolylamino)-4-methylbutyl)ethylamino)ethanol, 7-Chloro-4-(4-(N-ethyl-N-beta-hydroxyethylamino)-1-methylbutylamino)quinoline, NSC4375, 7-Chloro-4-(5-(N-ethyl-N-2-hydroxyethylamino)-2-pentyl)aminoquinoline, (+-)-hydroxychloroquine, Ethanol, 2-((4-((7-chloro-4-quinolinyl)amino)pentyl)ethylamino)-, DTXSID8023135, Hydroxychlorochin, 2-({4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino)ethan-1-ol, Ethanol, 2-[[4-[(7-chloro-4-quinolinyl)amino]pentyl]ethylamino]-, Ethanol, 2-((4-((7-chloro-4-quinolyl)amino)pentyl)ethylamino)-, 2-((4-((7-Chloroquinolin-4-yl)amino)pentyl)(ethyl)amino)ethan-1-ol, 7-chloro-4-[4-(N-ethyl-N-beta-hydroxyethylamino)-1-methylbutylamino]quinoline, 7-chloro-4-[5-(N-ethyl-N-2-hydroxyethylamino)-2-pentyl]aminoquinoline, idroxiclorochina, Ethanol, 2-[[4-[(7-chloro-4-quinolyl)amino]pentyl]ethylamino]-, hidroxychloroquine sulfate, DTXCID403135, P01BA02, 204-249-8, Plaquenil, 2-((4-((7-Chloroquinolin-4-yl)amino)pentyl)(ethyl)amino)ethanol, WIN 1258, 2-[4-[(7-chloroquinolin-4-yl)amino]pentyl-ethylamino]ethanol, 2-[{4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino]ethanol sulfate, Hydroxychloroquine (INN), Oxichlorochinum, MFCD00242707, HCQ, 2-[{4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino]ethanol, 2-[4-[(7-chloroquinolin-4-yl)amino]pentylamino]ethanol, Idrossiclorochina [DCIT], Idrossiclorochina, Oxichlorochine Sulfate, Hidroxicloroquina [INN-Spanish], Hydroxychloroquinum [INN-Latin], HYDROXYCHLOROQUINE [INN], Hydroxychloroquine [INN:BAN], 2-{N-[4-(7-Chloro-4-quinolylamino)pentyl]-N-ethylamino}ethanol, 2-({4-[(7-chloro(4-quinolyl))amino]pentyl}ethylamino)ethan-1-ol, Polirreumin (TN), NCGC00159483-02, EINECS 204-249-8, UNII-4QWG6N8QKH, BRN 0253894, R-Hydroxychloroquine?, Ercoquin (Salt/Mix), Spectrum2_001238, Spectrum5_001697, Z0188, (+/-)-hydroxychloroquine, SCHEMBL8170, CHEMBL1535, 5-22-10-00280 (Beilstein Handbook Reference), (.+/-.)-Hydroxychloroquine, DivK1c_000942, SPBio_001116, HYDROXYCHLOROQUINE [MI], GTPL7198, orb1298213, SCHEMBL29359553, SCHEMBL29430237, HMS502P04, KBio1_000942, HYDROXYCHLOROQUINE [VANDF], Win 1258-2, HYDROXY CHLOROQUINE SULFATE, NINDS_000942, 2-[4-[(7-chloro-4-quinolyl)amino]pentyl-ethyl-amino]ethanol, HYDROXYCHLOROQUINE [WHO-DD], BCP30197, IGA74976, BDBM50247975, BDBM50467780, SBB012559, STL429829, AKOS015997886, AT13123, CCG-208059, DB01611, DT-0016, HY-W031727, SB73036, IDI1_000942, NCGC00159483-03, NCGC00159483-06, DA-74343, ST072188, SY270913, SBI-0052759.P002, CS-0075751, NS00001228, C07043, D08050, EN300-122642, AB00053257_02, Q421094, BRD-A99117172-065-01-6, BRD-A99117172-065-02-4, BRD-A99117172-065-04-0, BRD-A99117172-065-05-7, F2173-0553, 2-((4-(7-chloroquinolin-4-ylamino)pentyl)(ethyl)amino)ethanol, 2-[(4-[(7-Chloro-4-quinolinyl)amino]pentyl)(ethyl)amino]ethanol #, 2-[4-[(7-Chloro-4-quinolyl)amino]pentylamino]ethanol, 7-chloro-4-[4-[ethyl(2-hydroxyethyl)amino]1-methylbutylamino]-quinoline, 7-chloro-4-[4-[ethyl(2-hydroxyethyl)amino]1-methylbutylamino]quinoline, 7-Chloro-4-[4-[ethyl-(2-hydroxyethyl)amino]-1-methylbutylamino]quinoline, (+/-)-2-((4-((7-CHLORO-4-QUINOLYL)AMINO)PENTYL)ETHYLAMINO)ETHANOL, 7-Chloro-4-(4-(N-ethyl-N-beta-hydroxyethylamino)-1-methylbutylamino)quinoline, ETHANOL, 2-((4-((7-CHLORO-4-QUINOLINYL)AMINO)PENTYL)ETHYL)AMINO-, Oxichloroquine;Oxychlorochin;2-[4-[(7-Chloroquinolin-4-yl)amino]pentylamino]ethanol, Hydroxychloroquine, HCQ, (RS)-2‑[(7‑chloroquinolin‑4‑yl)amino]pentylaminoethanol (HCQ)
Hydroxychloroquine is a chemotherapeutic agent that acts against erythrocytic forms of malarial parasites.
Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa.
Hydroxychloroquine inhibits plasmodial heme polymerase.
Hydroxychloroquine is an antimalarial medication used to treat uncomplicated cases of malaria and for chemoprophylaxis in specific regions.
Hydroxychloroquine is a disease-modifying anti-rheumatic drug (DMARD).
Hydroxychloroquine regulates the activity of the immune system, which may be overactive in some conditions.
Hydroxychloroquine can modify the underlying disease process, rather than simply treating the symptoms.
Hydroxychloroquine is a quinoline medicine used to treat or prevent malaria, a disease caused by parasites that enter the body through the bite of a mosquito.
Malaria is common in areas such as Africa, South America, and Southern Asia.
Hydroxychloroquine is not effective against all strains of malaria.
Hydroxychloroquine is not effective against all strains of malaria, or against malaria in areas where the infection has been resistant to a similar drug called chloroquine.
Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine.
Other uses of Hydroxychloroquine include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda.
Hydroxychloroquine is taken by mouth, often in the form of hydroxychloroquine sulfate.
Hydroxychloroquine is in the antimalarial and 4-aminoquinoline families of medication.
Hydroxychloroquine was approved for medical use in the United States in 1955.
Hydroxychloroquine is on the World Health Organization's List of Essential Medicines.
In 2022, Hydroxychloroquine was the 112th most commonly prescribed medication in the United States, with more than 5 million prescriptions.
Hydroxychloroquine has been studied for an ability to prevent and treat coronavirus disease 2019 (COVID-19), but clinical trials found it ineffective for this purpose and a possible risk of dangerous side effects.
Among studies that deemed hydroxychloroquine intake to cause harmful side effects, a publication by The Lancet was retracted due to data flaws.
The speculative use of hydroxychloroquine for COVID-19 threatens its availability for people with established indications.
Hydroxychloroquine is a medicine used to treat rheumatoid arthritis and other inflammatory conditions such as systemic lupus erythematosus (SLE/lupus).
Hydroxychloroquine is also an antimalarial medicine used to prevent and treat malaria and other parasitic infections.
It is not clear how hydroxychloroquine works in inflammatory conditions; however it is thought to have an action on the immune system.
In rheumatoid arthritis this action helps to reduce inflammation and thus reduce pain and swelling.
It also limits damage to the joints and helps to prevent disability in the long term.
Because hydroxychloroquine acts to reduce the damage to the joints, rather than just relieve the pain, it belongs to the group of medicines called disease modifying antirheumatic drugs (DMARDs).
Hydroxychloroquine belongs to the family of medicines called “antimalarials” (AMs), which are also classified as disease-modifying anti-rheumatic drugs, or DMARDs.
These drugs were initially used to prevent and to treat malaria but are no longer used for those purposes; more effective drugs have since been developed.
The antimalarial quinine was first used to treat cutaneous lupus in 1834.
Subsequent reports in 1928 and 1938 showed good results with another quinine-like drug in the treatment of both discoid and subacute cutaneous lupus.
In 1941, discoid lupus patients were treated successfully with Atabrine, a compound developed in Germany in the 1920s.
In the mid-1940s, both Hydroxychloroquine (HCQ) and chloroquine (CQ) had been synthesized.
In 1955 Hydroxychloroquine was shown to be effective for both systemic lupus and rheumatoid arthritis.
Hydroxychloroquine is an aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2.
Hydroxychloroquine is an aminoquinoline, an organochlorine compound, a primary alcohol, a secondary amino compound and a tertiary amino compound.
Hydroxychloroquine is functionally related to a chloroquine.
Hydroxychloroquine is a conjugate base of a hydroxychloroquine(2+).
Hydroxychloroquine is a racemic mixture consisting of an R and S enantiomer.
Hydroxychloroquine is an aminoquinoline like [chloroquine].
Hydroxychloroquine was developed during World War II as a derivative of [quinacrine] with less severe side effects.
Chloroquine and hydroxychloroquine are both being investigated for the treatment of SARS-CoV-2.
The FDA emergency use authorization for hydroxychloroquine and [chloroquine] in the treatment of COVID-19 was revoked on 15 June 2020.
Hydroxychloroquine is an Antirheumatic Agent and Antimalarial.
Hydroxychloroquine is a 4-aminoquinoline with immunosuppressive, antiautophagy, and antimalarial activities.
Although the precise mechanism of action is unknown, hydroxychloroquine may suppress immune function by interfering with the processing and presentation of antigens and the production of cytokines.
As a lysosomotropic agent, hydroxychloroquine raises intralysosomal pH, impairing autophagic protein degradation; hydroxychloroquine-mediated accumulation of ineffective autophagosomes may result in cell death in tumor cells reliant on autophagy for survival.
In addition, Hydroxychloroquine is highly active against the erythrocytic forms of P. vivax and malariae and most strains of P. falciparum but not the gametocytes of P. falciparum.
Hydroxychloroquine is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 1955 and is indicated for malaria and rheumatoid arthritis and has 80 investigational indications.
USES and APPLICATIONS of HYDROXYCHLOROQUINE:
Also a disease modifying anti-rheumatic drug (DMARD) indicated for treatment of rheumatoid arthritis and lupus erythematosus.
Hydroxychloroquine is a racemic mixture consisting of an R and S enantiomer.
Hydroxychloroquine is an aminoquinoline like chloroquine.
Hydroxychloroquine is a commonly prescribed medication in the treatment of uncomplicated malaria, rheumatoid arthritis, chronic discoid lupus erythematosus, and systemic lupus erythematosus.
Hydroxychloroquine is also used for the prophylaxis of malaria in regions where chloroquine resistance is unlikely.
Hydroxychloroquine was developed during World War II as a derivative of quinacrine with less severe side effects.
Chloroquine and hydroxychloroquine are both being investigated for the treatment of SARS-CoV-2.
Hydroxychloroquine is a medication that treats autoimmune conditions like rheumatoid arthritis and lupus.
Hydroxychloroquine slows down your overactive immune system.
Hydroxychloroquine can also prevent and treat malaria by killing the parasite that causes it.
Hydroxychloroquine treats autoimmune conditions, such as rheumatoid arthritis and lupus.
Hydroxychloroquine works by slowing down an overactive immune system.
Hydroxychloroquine may also be used to prevent and treat malaria.
Hydroxychloroquine works by killing the parasite that causes malaria.
Hydroxychloroquine belongs to a group of medications called DMARDs.
Hydroxychloroquine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
Hydroxychloroquine is a disease-modifying anti-rheumatic drug (DMARD).
Hydroxychloroquine can decrease the pain/swelling from arthritis and prevent joint damage.
Hydroxychloroquine was first used to prevent and treat malaria but was found to have benefits in autoimmune diseases, like lupus and other conditions.
The mechanism of action of hydroxychloroquine is not clear, but it is thought to interfere with communication in the immune system.
Hydroxychloroquine is also used to treat symptoms of rheumatoid arthritis and discoid or systemic lupus erythematosus.
Hydroxychloroquine is used in the treatment of arthritis to help relieve inflammation, swelling, stiffness, and joint pain and also to help control the symptoms of lupus erythematosus (lupus; SLE).
Hydroxychloroquine was originally used to prevent and to treat malaria.
An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, Hydroxychloroquine is mainly used as the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions.
Hydroxychloroquine has a role as an antimalarial, an antirheumatic drug, a dermatologic drug and an anticoronaviral agent.
Hydroxychloroquine is a commonly prescribed medication in the treatment of uncomplicated malaria, rheumatoid arthritis, chronic discoid lupus erythematosus, and systemic lupus erythematosus.
Hydroxychloroquine is also used for the prophylaxis of malaria in regions where chloroquine resistance is unlikely.
Hydroxychloroquine is a derivative of chloroquine that has both antimalarial and antiinflammatory activities and is now most often used as an antirheumatologic agent in systemic lupus erythematosis and rheumatoid arthritis.
-Uses of Hydroxychloroquine:
Hydroxychloroquine is used to treat:
*rheumatoid arthritis
*discoid and systemic lupus erythematosus (SLE)
*juvenile idiopathic arthritis (JIA).
Over the long term hydroxychloroquine can reduce pain, swelling and joint stiffness.
If you have lupus, Hydroxychloroquine may also improve the rash.
Hydroxychloroquine may be as long as 12 weeks before you notice the benefits.
Hydroxychloroquine is often taken in combination with other drugs such as methotrexate.
-Medical uses of Hydroxychloroquine:
Hydroxychloroquine treats rheumatic disorders such as systemic lupus erythematosus, rheumatoid arthritis, and porphyria cutanea tarda, and certain infections such as Q fever and certain types of malaria.
Hydroxychloroquine is considered the first-line treatment for systemic lupus erythematosus.
Certain types of malaria, resistant strains, and complicated cases require different or additional medication.
Hydroxychloroquine blocks the effects of some chemicals released in autoimmune diseases, and is used to treat inflammatory conditions.
Hydroxychloroquine is widely used to treat primary Sjögren syndrome but does not appear to be effective.
Hydroxychloroquine is widely used in the treatment of post-Lyme arthritis.
Hydroxychloroquine may have both an anti-spirochete activity and an anti-inflammatory activity, similar to the treatment of rheumatoid arthritis.
COVID-19, HYDROXYCHLOROQUINE:
Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases.
Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19.
Neither drug has been useful to prevent or treat SARS-CoV-2 infection.
Administration of chloroquine or hydroxychloroquine to COVID-19 patients, either as monotherapies or in conjunction with azithromycin, has been associated with deleterious outcomes, such as QT prolongation.
Scientific evidence does not substantiate the efficacy of hydroxychloroquine, with or without the addition of azithromycin, in the therapeutic management of COVID-19.
Cleavage of the SARS-CoV-2 S2 spike protein required for viral entry into cells can be accomplished by proteases TMPRSS2 located on the cell membrane, or by cathepsins (primarily cathepsin L) in endolysosomes.
Hydroxychloroquine inhibits the action of cathepsin L in endolysosomes, but because cathepsin L cleavage is minor compared to TMPRSS2 cleavage, hydroxychloroquine does little to inhibit SARS-CoV-2 infection.
In fall of 2020, the National Institutes of Health issued treatment guidelines recommending against the use of hydroxychloroquine for COVID-19 except as part of a clinical trial.
In 2021, hydroxychloroquine was part of the recommended treatment for mild cases in India.
In 2020, the speculative use of hydroxychloroquine for COVID-19 threatened its availability for people with established indications (malaria and auto-immune diseases).
Hydroxychloroquine is a type of medicine called a disease-modifying anti-rheumatic drug (DMARD).
Hydroxychloroquine works by blocking the effects of the chemicals released when your immune system attacks your body.
Hydroxychloroquine's used to treat inflammatory conditions, including rheumatoid arthritis, juvenile idiopathic arthritis (inflammation of joints in children) and lupus.
Hydroxychloroquine's also used to treat some other skin conditions including sarcoidosis, photosensitive skin disorders (where your skin reacts to sunlight), lichen planus and urticarial vasculitis.
Hydroxychloroquine reduces swelling (inflammation), pain and stiffness of joints, and can improve or clear up some rashes.
Hydroxychloroquine's sometimes used with another DMARD such as methotrexate or a short course of steroids to relieve pain.
Hydroxychloroquine is only available on prescription.
Hydroxychloroquine comes as tablets.
WHAT IS HYDROXYCHLOROQUINE USED FOR?
Hydroxychloroquine is commonly used for the following conditions.
*Prevention and treatment of malaria (an infection from parasites that can lead to death, often from a mosquito bite)
*Treatment of rheumatoid arthritis (a type of arthritis where your immune system damages your joints)
*Treatment of systemic lupus erythematosus (a condition where your immune system attacks your body tissues)
*Treatment of discoid lupus erythematosus (a skin condition with a disc-like rash often on the scalp or face, that can lead to scars, changes in skin color, and hair loss)
Hydroxychloroquine may also be used for other conditions as determined by your healthcare provider.
HOW DOES HYDROXYCHLOROQUINE WORK (MECHANISM OF ACTION)?
Hydroxychloroquine works by calming down your immune system and killing the parasite that causes malaria.
HOW TO TAKE HYDROXYCHLOROQUINE:
Hydroxychloroquine comes in an oral tablet.
Adult dosing for rheumatic diseases ranges, typically, from 200 mg to 400 mg per day (typically 5 mg/kg, maximum 400 mg daily).
It can be taken as a single daily dose or in 2 divided doses.
It is recommended to be taken with food to prevent gastrointestinal side effects.
Symptoms can improve in one to two months, but it can take up to six months for the full benefits of this medication.
BENEFITS of HYDROXYCHLOROQUINE:
Research into the wide-ranging effects of hydroxychloroquine has revealed many important benefits in the treatment of lupus; it must be noted that these benefits may be less effective in people who smoke.
Benefits include:
*Decrease in the number of disease flares.
*Decrease in damage from disease over time.
*Ability to delay absorption of ultraviolet light.
*Reduction in the number of antigen-presenting cells in the skin.
A systematic review published in Annals of Rheumatic Diseases in January 2009 looked at data on the clinical efficacy and side effects of AMs in systemic lupus, from randomized controlled clinical trials and observational studies, in 95 articles published between 1982 and 2007.
The authors found:
*Strong evidence, especially with Hydroxychloroquine, of decreased lupus activity during pregnancy without harm to the fetus.
*Strong evidence of prevention of disease flares.
*Strong evidence of increased long-term survival.
*Moderate evidence of protection against irreversible organ damage, thrombosis (blood clot formation), and bone mass loss.
✅ THERAPEUTIC USES & BENEFITS of HYDROXYCHLOROQUINE:
Malaria treatment and prophylaxis, especially in chloroquine-sensitive strains.
*Autoimmune diseases:
Hydroxychloroquine is afor rheumatoid arthritis, systemic and chronic discoid lupus erythematosus.
*Other clinical uses:
Off-label for porphyria, anticalcification in kidney stones, and certain dermatologic or inflammatory conditions.
*Note:
Extensive clinical trials demonstrated no benefit for COVID‑19, with significant risks—thus emergency use among infected patients has been revoked by FDA and WHO.
CHEMICAL SYNTHESIS of HYDROXYCHLOROQUINE:
The first synthesis of hydroxychloroquine was disclosed in a patent filed by Sterling Drug in 1949.
In the final step, 4,7-dichloroquinoline was reacted with a primary amine which in turn had been made from the chloro-ketone shown:
MANUFACTURING OF HYDROXYCHLOROQUINE
It is frequently sold as a sulfate salt known as hydroxychloroquine sulfate.
In the sulfate salt form, 200 mg is equal to 155 mg of the pure form.
Brand names of hydroxychloroquine include Plaquenil, Hydroquin, Axemal (in India), Dolquine, Quensyl, and Quinoric
HISTORY OF HYDROXYCHLOROQUINE
After World War I, the German government sought alternatives to quinine as an anti-malarial.
Chloroquine, a synthetic analogue with the same mechanism of action was discovered in 1934, by Hans Andersag and coworkers at the Bayer laboratories.
This was introduced into clinical practice in 1947 for the prophylactic treatment of malaria.
Researchers subsequently attempted to discover structural analogs with superior properties and one of these was hydroxychloroquine
HOW DO I TAKE HYDROXYCHLOROQUINE?
Hydroxychloroquine is usually taken twice daily.
The pills are 200-mg. each.
The usual dose is 1 or 2 pills daily.
Hydroxychloroquine should be taken at the same time every day.
Hydroxychloroquine will take 1 to 2 months to begin working.
Follow your doctor’s directions.
Do not take more or less medicine than ordered.
Hydroxychloroquine should be taken with food or milk.
MECHANISM OF ACTION OF HYDROXYCHLOROQUINE
Hydroxychloroquine increases lysosomal pH in antigen-presenting cells by two mechanisms:
As a weak base, it is a proton acceptor and via this chemical interaction, its accumulation in lysozymes raises the intralysosomal pH, but this mechanism does not fully account for the effect of hydroxychloroquine on pH.
Additionally, in parasites that are susceptible to hydroxychloroquine, it interferes with the endocytosis and proteolysis of hemoglobin and inhibits the activity of lysosomal enzymes, thereby raising the lysosomal pH by more than two orders of magnitude over the weak base effect alone.
In 2003, a novel mechanism was described wherein hydroxychloroquine inhibits stimulation of the toll-like receptor (TLR) 9 family receptors.
TLRs are cellular receptors for microbial products that induce inflammatory responses through activation of the innate immune system.
As with other quinoline antimalarial drugs, the antimalarial mechanism of action of quinine has not been fully resolved.
The most accepted model is based on hydrochloroquinine and involves the inhibition of hemozoin biocrystallization, which facilitates the aggregation of cytotoxic heme.
Free cytotoxic heme accumulates in the parasites, causing death.
Hydroxychloroquine increases the risk of low blood sugar through several mechanisms.
These include decreased clearance of the hormone insulin from the blood, increased insulin sensitivity, and increased release of insulin from the pancreas.
PHARMACOLOGY OF HYDROXYCHLOROQUINE:
PHARMACOKINETICS
Hydroxychloroquine has similar pharmacokinetics to chloroquine, with rapid gastrointestinal absorption, large distribution volume, and elimination by the kidneys; T max is 2–4.5 hours.
Cytochrome P450 enzymes (CYP2D6, 2C8, 3A4 and 3A5) metabolize hydroxychloroquine to N-desethylhydroxychloroquine.
Both agents also inhibit CYP2D6 activity and may interact with other medications that depend on this enzyme.
PHARMACODYNAMICS
Antimalarials are lipophilic weak bases and easily pass plasma membranes.
The free base form accumulates in lysosomes (acidic cytoplasmic vesicles) and is then protonated, resulting in concentrations within lysosomes up to 1,000 times higher than in culture media.
This increases the pH of the lysosome from four to six.
Alteration in pH causes inhibition of lysosomal acidic proteases causing a diminished proteolysis effect.
Higher pH within lysosomes causes decreased intracellular processing, glycosylation and secretion of proteins with many immunologic and nonimmunologic consequences.
These effects are believed to be the cause of a decreased immune cell functioning such as chemotaxis, phagocytosis and superoxide production by neutrophils.
Hydroxychloroquine is a weak diprotic base that can pass through the lipid cell membrane and preferentially concentrate in acidic cytoplasmic vesicles.
The higher pH of these vesicles in macrophages or other antigen-presenting cells limits the association of autoantigenic (any) peptides with class II MHC molecules in the compartment for peptide loading and/or the subsequent processing and transport of the peptide-MHC complex to the cell membrane.
OPEN TARGETS OF HYDROXYCHLOROQUINE:
Hydroxychloroquine is only found in individuals that have used or taken this drug.
Hydroxychloroquine is a chemotherapeutic agent that acts against erythrocytic forms of malarial parasites.
Although the exact mechanism of action is unknown, it may be based on ability of hydroxychloroquine to bind to and alter DNA.
Hydroxychloroquine has also has been found to be taken up into the acidic food vacuoles of the parasite in the erythrocyte.
This increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism.
In suppressive treatment, hydroxychloroquine inhibits the erythrocytic stage of development of plasmodia.
In acute attacks of malaria, Hydroxychloroquine interrupts erythrocytic schizogony of the parasite.
Hydroxychloroquine's ability to concentrate in parasitized erythrocytes may account for their selective toxicity against the erythrocytic stages of plasmodial infection.
As an antirheumatic, hydroxychloroquine is thought to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants.
Hydroxychloroquine also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown.
MECHANISM OF ACTION OF HYDROXYCHLOROQUINE:
Originally developed as a quinoline antimalarial, hydroxychloroquine increases lysosomal pH in parasites and immune cells, inhibiting hemozoin formation in malaria and altering antigen presentation in autoimmune diseases by dampening inflammatory cytokine production.