HYDROXYCHLOROQUIN

HYDROXYCHLOROQUIN: INTRODUCTION AND INTERACTION IN COVID_19 

Pharmaceuitical MCB

WHAT IS HYDROXYCHOLOROQUIN?

- 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.

CHARACTERISTICS:

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 Ndesethylhydroxychloroquine.

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.

USES:

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

SIDE EFFECTS:

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

- Heart 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.

TREATING COVID-19 WITH HYDROXYCHLOROQUIN:

- 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.

(Extracted)