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Fact Checked

What is Hydroxychloroquine?

With the number of COVID-19 cases rising rapidly every day around the world, many existing drugs are being researched for potential treatment of this pandemic. Hydroxychloroquine is one drug that has received mass attention as a promising medicine for the treatment of COVID-19. However, it is not currently proven to work in treating this illness yet. In the United States, the Food and Drug Administration (FDA) approved the use of hydroxychloroquine and its related compound, chloroquine, for ‘Emergency Use Authorization’ in COVID-19. This means that these drugs can be used as an emergency resort to treat patients who are hospitalized due to the illness. However, the drug has not been evaluated for its specific effect in treating COVID-19 by clinical trials, so it is not approved for routine treatment of COVID-19 yet. 

Although you may not have heard about hydroxychloroquine before, this drug has been around for almost 70 years as a potent anti-malarial therapy. If you live in the United States, the chance of contracting malaria may not be something that is foremost on your mind. Today, the incidence of malaria is quite rare in the United States, but before the 1950s, malaria was once an endemic in the U.S. After 1951, malaria was considered to be eliminated in the country. According to the Centers for Disease Control and Prevention (CDC), approximately 2000 cases of malaria are diagnosed in the U.S every year. Most of these cases occur in people traveling from countries where malaria is prevalent, like in Africa or South Asia. While most people have heard about the disease, not many people are aware that it is a leading cause of death worldwide. The World Health Organization recorded 228 million cases of malaria in 2018 that resulted in 405,000 deaths. 

Malaria is caused by a parasite that is transmitted to humans by the female Anopheles mosquito. The parasite infects liver cells first and then moves to infect red blood cells. People infected with the parasite become ill with the symptoms of malaria when the parasite moves to the blood and starts reproducing itself there. Malaria is a serious disease which result in fatality. However, it is treatable with certain drugs. The major medications that are used to treat malaria today are chloroquine and hydroxychloroquine. These drugs were initially discovered exclusively for the treatment of malaria, but they were soon recognized for their benefits in other diseases as well. What is Hydroxychloroquine used for? Since its inception, hydroxychloroquine is a first-line drug of treatment for certain of the world where malaria is sensitive to treatment by chloroquine. 

Hydroxychloroquine, like the other anti-malarials in its family, is not a new drug and has been around since 1945. The discovery of its medical potential dates back four centuries before the drug had a name. 

Discovery of the antimalarial drugs 

Chloroquine and hydroxychloroquine are derivatives of a commonly known alkaloid called Quinine. Quinine was discovered in the early 1600s from the powder isolated from the bark of a tree now known as the Cinchona tree. The Incas are credited for recognizing the medical potential of this powder by successfully treating the Countess of Chincon in Peru from a mysterious illness that was later thought to have been malaria. Almost 200 years later, the active alkaloid from this powder was identified to be ‘quinine’ and the tree was named the ‘Cinchona tree’ after the Countess who was cured with its powder. In the 1800s, quinine was used as a medicine for malaria and in many herbal remedies for various medical afflictions. Today, quinine is still used to treat malaria, although it is not the first line drug of choice. It is also well known for its addition to tonic water. 

Until the 1940s, quinine was the major mode of treatment for malaria worldwide. However, during World War II, it was overtaken by a quinine derivative called chloroquine, that belongs to the 4-aminoquinolone group of drugs. During World War II, much research was performed with the goal of finding drugs that are effective against malaria. Chloroquine was discovered by the company Bayer Laboratories, and subsequent testing in clinical trials by the United States proved its therapeutic potential as an anti-malarial drug.  Chloroquine had many undesirable side effects due to its toxicity though. Several years later, scientists founds that the introduction of a hydroxyl group to chloroquine, forming hydroxychloroquine, significantly decreased the toxicity observed with chloroquine but was just as effective in treating patients afflicted with malaria. 

Hydroxychloroquine 

Hydroxychloroquine was FDA-approved for treatment in patients in 1955. Interestingly, during World War II when millions of soldiers were treated with chloroquine, it was observed that there was a decrease in other inflammatory problems like rashes and arthritis in soldiers that were taking this drug. Further benefits of hydroxychloroquine were tested in a clinical trial of its effectiveness in treating the autoimmune disease, Lupus, in 1951. Since then, hydroxychloroquine has been the first-line therapy for Lupus. Estimates report a demonstrated increase in survival of patients with Systemic Lupus Erythematous who take hydroxychloroquine by up to 70%. Over the years, hydroxychloroquine has been consistently effective in treating other autoimmune conditions as well, and it is also FDA-approved for the treatment of Rheumatoid Arthritis.

Hydroxychloroquine is sold under various brand names around the world, with some of the main ones in the United States being Plaquenil and Quineprox. 

How does Hydroxychloroquine work? 

What makes hydroxychloroquine remarkable is that it works for a multitude of diseases.  How exactly the quinolone drugs, including hydroxychloroquine, work as an anti-malarial drug is not entirely clear and multiple mechanisms of action have been postulated for why it is so effective. The major ways in which hydroxychloroquine is thought to work as an anti-malarial is also different than how it works as an anti-inflammatory medication for treating autoimmune diseases.

Anti-Malarial Mechanisms of Hydroxychloroquine

The anti-malarial effect of hydroxychloroquine is widely thought to be due to toxicity to the parasite that causes malaria, making it unable to survive within human cells. When a patient takes hydroxychloroquine, it accumulates inside the food vacuole of the parasite and inhibits proper disposal of ‘hemozoin’, a by-product of the parasite’s digestion of blood, by preventing the conversion of heme from blood into hemozoin. This causes hydroxychloroquine-heme complexes to build up inside the parasite, leading to its toxicity and ultimate death. 

Anti-inflammatory Mechanisms of Hydroxychloroquine

Hydroxychloroquine works as an anti-inflammatory drug by the following established mechanisms: 

  • Increasing the pH of lysosomes in antigen presenting cells

One main way that hydroxychloroquine may work is by decreasing the acidity of components inside cells called the lysosomes. This occurs in special cells of the immune system named ‘antigen presenting cells’. The activity of inflammatory responses of the immune system is lowered overall due to several cellular events that also become altered as a consequence of the reduced acidity of lysosomes. 

  • Interrupting the innate immune system- Certain receptors on immune cells, called Toll-Like Receptors (TLR), are responsible for activating the ‘innate immune system’ of the body that invading microbes normally take advantage of during an infection. This leads to an increase in inflammatory responses in the body. Hydroxychloroquine is thought to reduce the activity of the one type of TLR, named the TLR-9 family, and in this way it can reduce the inflammation that is often seen with autoimmune diseases like Lupus. 
  • Interference of inflammatory cellular pathways- Hydroxychloroquine is also thought to decrease inflammatory responses by interrupting cell-to-cell communication that is necessary for activation of inflammatory responses. These important inflammatory responses are part of pathways in the human cell called the ERK or MAP Kinase pathways. 

How to buy hydroxychloroquine at a discounted price

Purchasing hydroxychloroquine requires a prescription from a doctor. Like any prescription medication, the drug must be taken exactly as prescribed and cannot be purchased without taking your prescription in with you. So far, the major drawback of long-term use of hydroxychloroquine and at high doses is its retinal toxicity. This can be a serious condition, so it is important to only take hydroxychloroquine under the supervision of a physician and according to the prescription. 

Why is hydroxychloroquine so expensive? Hydroxychloroquine is a drug that can be expensive if you have to pay for it out-of-pocket. If you are prescribed hydroxychloroquine for any of the indications it is FDA-approved for, you can find discounts for the drug that may be able to help you save on its cost. For people without health insurance or do not have good prescription drug coverage, a drug discount card is a good option for finding these savings. One excellent option to save on hydroxychloroquine is with the USA Rx discount card that can be signed up for online. The card is completely free and takes just a few minutes to sign up. You can find the estimated cost of the drug at your preferred pharmacy by searching for it. Although hydroxychloroquine has been around for a long time, the costs of this drug is not on the low side, so finding ways to save could be beneficial for you. 

Published April 25th, 2020 by Chris Riley
Fact Checked by Chris Riley

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