hydroxychloroquine

hydroxychloroquine
IUPAC name	2-image = Hydroxychloroquine structure.svg | tradename = Plaquenil, others | Drugs.com = Monograph | MedlinePlus = a601240 | pregnancy_AU = D | pregnancy_US = N | legal_AU = S4 | legal_UK = POM | legal_US = Rx-only | routes_of_administration = By mouth

hydroxychloroquine is a medication primarily used for the prevention and treatment of certain forms of malaria and for autoimmune conditions such as rheumatoid arthritis and lupus erythematosus. It is a derivative of chloroquine, with a hydroxyl group that reduces its toxicity. The drug gained widespread public attention during the COVID-19 pandemic due to controversial and ultimately disproven claims about its efficacy against the SARS-CoV-2 virus.

Medical uses

Hydroxychloroquine is approved for use against malaria in regions where the parasite remains sensitive, such as certain areas of Central America. For chronic autoimmune diseases, it is a cornerstone therapy for managing symptoms of systemic lupus erythematosus and reducing inflammation in rheumatoid arthritis, often in combination with agents like methotrexate. It is also used in the treatment of Sjögren's syndrome and certain photodermatoses. The World Health Organization includes it on its List of Essential Medicines, and its use is guided by organizations like the American College of Rheumatology.

Adverse effects

Common side effects include gastrointestinal disturbances such as nausea and diarrhea, and skin reactions like pruritus. The most serious risk is dose-related retinopathy, which can lead to irreversible vision loss, necessitoring regular screening with tools like optical coherence tomography. Other significant risks include cardiomyopathy, hypoglycemia, and neuropsychiatric effects. The U.S. Food and Drug Administration has issued a black box warning regarding these cardiac and retinal risks. Overdose can be fatal, with cases reported to agencies like the American Association of Poison Control Centers.

Pharmacology

Hydroxychloroquine is a weak base that accumulates in acidic organelles like lysosomes and endosomes, disrupting processes such as antigen presentation. Its mechanism in autoimmune diseases involves raising the pH within intracellular compartments, interfering with toll-like receptor signaling and inhibiting the production of cytokines like interleukin-1. For malaria, it is thought to inhibit the polymerization of hemozoin in the Plasmodium parasite. The drug is metabolized in the liver by enzymes including CYP2D6 and has a very long half-life, sometimes exceeding 40 days.

History

The compound was first synthesized in 1946 by researchers at the Winthrop Chemical Company, seeking a less toxic analogue of chloroquine, which itself was developed from the ancient Peruvian remedy cinchona bark. It received approval from the U.S. Food and Drug Administration in 1955. Its use expanded beyond antimalarial purposes throughout the latter half of the 20th century, becoming a standard treatment for lupus following studies at institutions like the Johns Hopkins Hospital. The drug's history became intertwined with global events during the COVID-19 pandemic.

Society and culture

Hydroxychloroquine became a major subject of political and media discourse in 2020 after endorsements from public figures like Donald Trump and Jair Bolsonaro. This led to widespread shortages for patients with lupus and rheumatoid arthritis. Regulatory agencies, including the European Medicines Agency and the Therapeutic Goods Administration, issued warnings against its use for COVID-19. The controversy was amplified by studies in journals like The Lancet and The New England Journal of Medicine, which were later retracted, and was a frequent topic on platforms like Fox News.

Research

Ongoing investigation explores its potential in areas like cancer immunotherapy and antiviral therapy, given its effects on autophagy. Historically, it was studied for HIV and Chikungunya virus. The most prominent recent research involved numerous global trials for COVID-19, including the RECOVERY Trial in the United Kingdom and the Solidarity trial coordinated by the World Health Organization, which conclusively found no meaningful clinical benefit. Research into its basic immunomodulatory mechanisms continues at institutions like the National Institutes of Health.

Category:Drugs