Hydroxychloroquine- uses, side effects, interactions & COVID-19

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Last Updated on June 16, 2020 by Sagar Aryal

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Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine

What is hydroxychloroquine?

  • Hydroxychloroquine is a drug that has been used for decades in the treatment of malaria. The brand name for hydroxychloroquine is Plaquenil.
  • It belongs to the group of 4-aminoquinolines and which is listed by the World Health Organisation as one of the most essential drugs, safest and most effective medicines needed in the health care systems.
  • Hydroxychloroquine is the milder form of chloroquine and it is also known as hydroxychloroquine sulfate. Besides being an antimalarial drug it is also used to treat rheumatoid arthritis, lupus and porphyria cutanea tarda.
  • It is taken orally, through the mouth.
Structural diagram of hydroxychloroquine
Figure: Structural diagram of hydroxychloroquine. Source: Wikipedia.

Characteristics of Hydroxychloroquine

  1. It is a lipophilic weak base i.e it can be able to dissolve in fats, oils, non-polar compounds hence they can pass through the plasma membrane with ease.
  2. It is readily absorbed into the gastrointestinal tract and eliminated by the kidney.
  3. They are metabolized by the Cytochrome P450 enzyme into N-desethylhydroxychloroquine.

 Hydroxychloroquine mechanism of action

  • Hydroxychloroquine increases the lysosomal pH of antigen-presenting cells such as dendritic cells.
  • The peripheral lymphoid system has a rare type of immune cell known as the plasmacytoid dendritic cells (pDC) which have toll-like receptors (TLR) such as TLR-9. The pDCs freely circulate in the blood and they have been associated with linking the innate and adaptive immunities. They are also responsible for the secretion of interferon-1(IFN-1) which acts against viral infections. However, they also play a role in worsening Lupus disorder.
  • The Toll-like receptor 9 on the plasma Dendritic Cells, is a protein that recognizes DNA containing immune complexes, activates the production of interferons that cause the dendritic cells to mature and also cause inflammation process. Therefore, the hydroxychloroquine acts by reducing the signaling of the TLRs thus reducing the activation of dendritic cells and hence reducing the inflammatory process.
  • For action against malarial, hydroxychloroquine inhibits hemozoin biocrystallization, an action of the malarial parasites. Malaria parasites (Plasmodium spp) feed on hemoglobin and release free heme protein into the blood which is highly toxic to blood and when it accumulates in the parasite, it causes its death. Therefore the malarial parasite converts it into an insoluble crystalline known as the hemozoin. Hemozoin is also known as the malarial pigment. The role of the hydroxychloroquine is to prevent the crystallization of heme into hemozoin crystalline.

Hydroxychloroquine uses

Hydroxychloroquine is used for treatment:

  1. Certain types of malaria caused by Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale
  2. Systemic lupus erythematous
  3. Rheumatoid disorders such as rheumatoid arthritis
  4. Porphyria cutanea tarda
  5. Q fever caused by Coxiella burnetii
  6. Sjogren syndrome (low effectiveness)
  7. Post-Lyme arthritis

It also has some anti-spirochaete activity and anti-inflammatory activity similar to that of rheumatoid arthritis

Side Effects

The side effects associated with the intake of hydroxychloroquine can be short term or longterm. It is advisable to consult with a physician before taking a prescription to avoid overdosing which can cause the adverse effects of the drug. Some of the side effects include:

  1. Adverse mild effects- this occurs as a result of short-term treatment of acute malaria or overdose
    • Headaches and vomiting
    • Nausea, stomach cramping with mild diarrhea
    • Herat problems
    • reduced appetite
    • Retinopathy due to overdosing
  2. Adverse chronic effects – this occurs after long administration of hydroxychloroquine especially in treating Rheumatoid and lupus disorders
    • The retinopathy associated with impaired vision, difficulty breathing, altered eye pigmentation
    • Prolonged treatment of lupus and/or rheumatoid arthritis effects is associated with acute symptoms of nausea, abdominal cramping, vomit, acne, anemia, fading of hair pigment, mouth, and eye blisters, blood associated disorders, convulsions, impaired vision, diminished body reflexes, the excessive coloring of the skin, impaired hearing, hives, itching, liver problems, liver failure, hair loss, muscle paralysis, muscle weakness and muscle atrophy, emotional effects including having nightmares, psoriasis, skin inflammation, vertigo, skin rashes, skin scaling, weight loss, urinary incontinence.
    • Hydroxychloroquine can worsen existing cases of psoriasis and porphyria.
    • Children may be especially vulnerable to developing adverse effects from hydroxychloroquine.

Hydroxychloroquine contraindications

  • Hydroxychloroquine has adverse effects of inflammation and therefore it should not be administered to people with hypersensitivity for 4-aminoquinolines, because it can cause renal impairments and adverse skin conditions and renal damage.
  • It should be used with caution for persons with eye and ear impairments, psoriasis, vertigo, hepatic disease, alcoholism, gastrointestinal infections like ulcers, myopathic disorders, neurological diseases, pregnant and breast-feeding mothers, diabetes, cardiovascular diseases, hematological diseases, renal diseases, and epilepsy.
  • However some of these disorders are treated with hydroxychloroquine, they should be used on prescription only.

Hydroxychloroquine interactions

Research has shown that Hydroxychloroquine can interact with some forms of medications and therefore, consult with the physician and pharmacists if you are under any medication before getting a prescription. Some of these interactions are as follows.

  • Hydroxychloroquine can transfer into breast milk and it should be used with care for pregnant and breastfeeding mothers.
  • The combination of Hydroxychloroquine with aurothioglucose (Solganal), cimetidine (Tagamet) or digoxin (Lanoxin) can affect liver function. For persons taking penicillamine drug for the treatment of kidney stones, hydroxychloroquine can increase the plasm concentration, leading to severe side effects.
  • Hydroxychloroquine also increases the hypoglycemic effects of insulin and oral hypoglycemic agents, therefore adjusting dosages is recommended to prevent hypoglycemia.
  • Anti-acids may decrease the absorption of hydroxychloroquine.
  • Antagonistic reactions are shown on the interaction of hydroxychloroquine with neostigmine and pyridostigmine.

Some of the drugs listed by the Food and Drug Administration to have interactions with hydroxychloroquine include:

  • Digoxin used to treat cardiac failure can interact with Hydroxychloroquine causing increased serum digoxin levels.
  • Insulin or antidiabetic drugs causing effects of hypoglycemia.
  • Drugs that prolong QT intervals and other arrhythmogenic drugs can interact with Hydroxychloroquine increasing the risk of inducing ventricular arrhythmias if used concurrently.
  • Mefloquine and other drugs that are known to lower the convulsive threshold can interact with this antimalaria and increase convulsions.
  • Antiepileptics used concurrently with hydroxychloroquine may impair the antiepileptic activity.
  • Methotrexate in combination with Hydroxychloroquine may increase the frequency of side effects.
  • Cyclosporin used with Hydroxychloroquine increases the plasma cyclosporin level.

Hydroxychloroquine- uses, side effects, interactions & COVID-19

Treating COVID-19 with Hydroxychloroquine

  • There is no specific antiviral therapy recommended for the disease caused by SARS-CoV-2 (COVID-19).
  • As researchers, practitioners, and clinicians scramble for effective therapies for COVID-19, hydroxychloroquine has been on the front runners-up as a possible therapeutic remedy for the infection.
  • It is however in exploratory studies to show if it can be used for the treatment of COVID-19.
  • COVID-19 which is associated with Acute Respiratory Disease (ARD) coupled with viral pneumonia and multiorgan damage effects in severe cases lacks a specific treatment.
  • The HCQ seems to have anti-viral activity against SARS-CoV-2, the causative agent of COVID-19 however, in vivo shreds of evidence are very few for recommendations.
  • Speculated studies have suggested that hydroxychloroquine interferes with the binding activity of the viral S-proteins with the ACE2 receptors on the respiratory tract host cells.
  • Various trials have started globally with one major one being the RECOVERY trial, the largest randomized Trial, by Oxford University, based in the UK. The trial will cover not only hydroxychloroquine but anti-inflammatory steroids like dexamethasone and HIV drugs such as lopinavir/ritonavir. Other trails are also being conducted in various health care facilities and institutions in the USA.
  • Most of these studies will aim at using low dosages taking into account possible side effects that may affect patient outcomes, identifying the antiviral activities of hydroxychloroquine and its ability to modify the activity of the immune system, with established profiling of risk factors and side effects that might come with its administration.
  • The drug has been known to have specific contraindications and interactions with other diseases and drugs, respectively, and this according to the leaders of various studies will be considered accordingly.
  • The efficacy of combination therapeutic effects of hydroxychloroquine with azithromycin antibiotic is also under trial.
  • According to the study done by Mayla Borba et al., it was suggested that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards.

References

  1. https://www.webmd.com/drugs/2/drug-5482/hydroxychloroquine-oral/details
  2. https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquine-sulfate-1911
  3. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Hydroxychloroquine-Plaquenil
  4. https://www.healthline.com/health/hydroxychloroquine-oral-tablet#important-warnings
  5. https://www.pbs.org/newshour/health/what-you-need-to-know-about-hydroxychloroquine-and-coronavirus

Sources

  • 3% – https://en.wikipedia.org/wiki/Hydroxychloroquine
  • 1% – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221732/
  • 1% – https://www.drugs.com/pro/plaquenil.html
  • 1% – https://en.wikipedia.org/wiki/Plaquenil
  • 1% – https://en.m.wikipedia.org/wiki/Hydroxychloroquine
  • <1% – https://www.sciencedirect.com/topics/medicine-and-dentistry/alcohol-metabolism
  • <1% – https://www.sciencedirect.com/topics/medicine-and-dentistry/plasmacytoid-dendritic-cell
  • <1% – https://www.onlinelibrary.wiley.com/doi/10.1002/bies.201900138
  • <1% – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663072/
  • <1% – https://www.medicinenet.com/penicillamine/article.htm
  • <1% – https://www.medicinenet.com/hydroxychloroquine-oral/article.htm
  • <1% – https://www.healthtap.com/topics/what-does-hydroxychloroquine-do-to-immune-system
  • <1% – https://www.healthline.com/health/administration-of-medication
  • <1% – https://www.drugs.com/sfx/mefloquine-side-effects.html
  • <1% – https://www.cancertreatmentsresearch.com/a-list-of-drugs-and-supplement-to-fight-coronavirus/
  • <1% – https://quizlet.com/122882734/chapter-3-flashcard-review-flash-cards/
  • <1% – https://en.wikipedia.org/wiki/Hemozoin
  • <1% – https://en.m.wikipedia.org/wiki/WHO_Model_List_of_Essential_Medicines
  • <1% – https://en.m.wikipedia.org/wiki/Toll-like_receptor_9
  • <1% – http://www.med.umich.edu/asp/pdf/adult_guidelines/COVID-19-treatment.pdf

1 thought on “Hydroxychloroquine- uses, side effects, interactions & COVID-19”

  1. We emphasize that rational use depends on : restrict its use to be under medical supervision, full knowledge of its pharmacological properties and a careful examination of the patient’s medical history, many of which include liver and kidney functions, a complete picture of blood, and possibly an electrocardiogram. To investigate potential drug –drug interaction and a careful consideration of contraindications
    And we confirm that the effectiveness of the drug depends on early use and at appropriate doses that in view of pharmacokinetic principles likely to be high in the first two or three days ( loading dose ) , then reduce the dose while continuing treatment ( maintenance dose ) for an appropriate period of up to 10 days with follow-up of symptoms and side effects

    Reply

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