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[Editor’s Note: In The Hydroxychloroquine Controversy: Part 1, we learned the initial limitations of HCQ. In part we’ll learn the contraindications for HCQ.]

The Cure Worse Than The Disease

The potential risk-benefit ratio of introducing off label prescription drugs for a new, still incompletely understood illness must be carefully considered.

Hydroxychloroquine (HCQ) is a powerful immuno-modulator and immunosuppressant. This is one of the reasons for its use in autoimmune diseases such as arthritis. However, the drug’s immunosuppressive action is still a wild card when it comes to COVID-19. More investigation is warranted before further safety and efficacy claims are made.

Although its precise mechanism of action is unknown, HCQ may suppress the immune system function and potentially create an immune deficiency in a patient who requires an optimally functioning immune system, especially when dealing with an illness such as COVID-19.

The recovery rate for COVID19 is currently estimated at 99.8 percent, which leaves 0.2 percent for mortality. It has been established that 99 percent of the severe and critical cases are people who have between one and three pre-existing co-morbidities. The median age of those affected by COVID-19 is 83.

People with underlying chronic conditions such as cardiovascular diseases, diabetes, COPD, asthma, cancer, and other debilitating illnesses are among the most vulnerable. The risk of contracting any type of infection, including COVID-19 is significantly higher for this immunocompromised slice of the population. They would also be more likely to suffer serious and perhaps fatal adverse reactions when subjected to experimental treatments.  

It is imperative that the drugs approved for the treatment of COVD-19 patients are carefully selected and monitored for contraindications and possible adverse effects that may prove detrimental instead of therapeutic.

Several “in vitro” studies have claimed success in inhibiting viral replication of the SARS-CoV-2 virus with HCQ and Ramdesivir. Ramdesivir has readily been accepted by many without any critical evaluation of what these findings actually mean. Successful “in vitro” inhibition of the virus does not predict clinical efficacy and certainly does not automatically translate into a cure. 

HCQ Contraindications

Myocardiotoxicity

Hydroxychloroquine prolongs the QT interval. The drug may cause severe complications in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances.

In cases where cardiotoxicity is suspected, prompt discontinuation of HCQ may prevent life-threatening cardiac complications. The use of concomitant drugs such as tamoxifen, lopinavir, azithromycin, ciprofloxacin, and risperidone should be considered with caution due to enhancing the risk of QT interval prolongation.

Diabetes

The drug must be used with caution in patients with hypoglycemia or diabetes mellitus. Hydroxychloroquine can cause severe, life-threatening hypoglycemia in patients treated with or without antidiabetic medications.

Monitoring blood glucose and adjusting treatment as necessary is critical in patients presenting with clinical symptoms of hypoglycemia during hydroxychloroquine treatment.

Ocular toxicity

Hydroxychloroquine can cause ocular toxicity. In some cases severe irreversible retinal damage occurs when used in daily doses exceeding 6.5 mg/kg. The risk of contraindications is particularly high in those with pre-existing macular disease. 

Hepatotoxicity

Hydroxychloroquine should be used with caution in patients with hepatic disease, a history of alcoholism, or in conjunction with known hepatotoxic drugs and dosage adjustment should be made accordingly as well as regular bloodwork is done to monitor for potential anomalies.

HCQ-induced Psychosis

HCQ is a powerful drug that may cause significant neuropsychiatric side effects, known as “psychosis after chloroquine” and suicidal ideations – an aspect that must not be overlooked and considered on an individual case basis.

Other Contraindications

Severe reactions to hydroxychloroquine include:

  • hepatic failure
  • suicidal ideation
  • macular degeneration
  • visual impairment
  • retinopathy
  • bronchospasm
  • angioedema
  • ventricular tachycardia
  • ventricular fibrillation
  • AV block
  • and seizures.

The drug may cause some mild to moderate adverse reactions such as photophobia, nausea, vomiting, diarrhea, headaches, tremor, dizziness and fatigue.

Hydroxychloroquine is also contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) due to the risk of hemolysis.

Despite common sense and the plethora of well documented horrific side effects, HCQ is being relentlessly touted as a cure for COVID-19. 

HCQ may also cause serious reactions and complications even in people with no apparent chronic health problems. The most vulnerable populations are those with co-morbidities. Patients with cardiovascular diseases, COPD, and asthma are at the top of the list. 

Individuals with underlying cardiovascular diseases could be at a higher risk of inappropriate blood clot formation observed in COVID-19 patients. This could lead to severe complications, such as pulmonary embolism and even death. 

Hydroxychloroquine known to prolong the QT interval may cause cardiac toxicity and cardiomyopathy. This could further worsen the person’s condition and exacerbate their underlying diseases. 

The risk is even higher due to the fact many of these individuals are on several drugs prescribed for their chronic issues, which could potentially create a problem of drug interactions with HCQ. 

Ideally, patients must be carefully assessed to ensure their pre-existing conditions, as well as their daily medications, do not disagree with the use of HCQ. 

Proclaiming a drug as a cure while it causes proven harm, makes a person more vulnerable and likely to succumb to the illness it is meant to cure, is gravely misleading.

The use of experimental “off label” drugs must always be carefully considered and evaluated for potential contraindications with respect to the disease in question as well as on an individual basis. In other words, in most things, but especially in medicine “one-size-fits-all” almost never works. An individualized approach that takes into account the specific circumstances and needs of the patient is essential for successful treatment outcomes and COVID-19 makes no exception.

Tween80: One Dreaded Vaccine Ingredient

Another point of concern is the presence of polysorbate80 in some of the widespread HCQ formulations. Polysorbate80 (Tween80 detergent) is a common vaccine ingredient.It has been highly controversial due to its solubilizing properties, which causes solvent-mediate disruption and increased permeability of the BBB (blood-brain barrier).

The solvent has been used in drug development for decades as an enhancer of drug delivery to the brain through bypassing the protective BBB. Tween80 also enables the transport of nano-particulates and the accumulation of aluminum in the brain matter, which is a highly problematic issue with aluminum adjuvanted vaccines. This aspect definitely warrants further investigation for potential harm before HCQ is promoted as a viable cure for a disease that may be here to stay. 

HCQ A Potential Nanoparticle Enhancer: Implications For mRNA Vaccines

Another fast-emerging concern about the widespread use of HCQ as a nanoparticle enhancer has to do with the new experimental mRNA COVID19 vaccine and its lipid nanoparticle delivery system. Moderna’s vaccine has been met with much apprehension and resistance by the general population mainly due to the novel application, the lack of proper safety and effectiveness testing as well as the unusually speedy process of developing this new vaccine.

There is a concern over the reactogenicity of the mRNA vaccine and the potential to elicit a powerful immunologic response and potentially a cytokine type of reaction with undesired consequences. This is where HCQ may play the role of a Trojan horse. The drug can efficiently pass through lipid cell membranes and serve as a vector of delivering nanoparticles into cells.

A 2016 study funded by NIH and conducted by Moderna’s co-founder MIT professor Robert Langer looked into efficient ways of mRNA vaccine delivery by way of lipid nanoparticles.HCQ is also an endosomal membrane disrupting agent that can lead to vesicular swelling and membrane permeabilization, which likely facilitates the release of therapeutic agents from lysosomes into the cytoplasm.”

Hydroxychloroquine can also accumulate in endosomes and bind to the minor groove of double-stranded DNA. It can be argued that HCQ could potentially enhance the distribution and action of the mRNA vaccine. Past research demonstrates the potential of modified RNA to alter host DNA. In the case of Moderna’s mRNA COVID-19 vaccine, this can lead to unforeseen side effects and an explosion of vaccine-induced autoimmune, neurological diseases, and cancer epidemics.

Are There Safer Natural Alternatives To HCQ?

Quercetin is a flavonoid found in many plants and foods such as green tea, red wine, apples, berries, Ginkgo biloba, St. John’s wort, and others. Quercetin is most commonly taken orally as an adjunct treatment for cardiovascular diseases, diabetes, arthritis, and as a cancer preventative.

The flavonoid has anti-oxidant and anti-inflammatory effects, but what makes it an exciting safer alternative to HCQ is its ionophore properties. A recent study sheds light on the potential use of quercetin as a potent zinc ionophore and provides insights into the possible application of this natural combo as a potential COVID-19 therapeutic agent. Quercetin appears to be a strong HCQ alternative, free of side effects and appropriate for patients with underlying conditions that contraindicate the use of HCQ.

While the world is desperately racing for cures and vaccines against a disease with a 99.8 percetnt survival rate, it behooves us to pause and consider these therapeutic means and weigh in on the pros and cons before jumping blindly on the most popular bandwagon at the present time. Looking at safe natural alternatives has always been an option that deserves equal attention.

The best way to prevent illness is by way of maintaining health through diet and healthy lifestyle choices. That doesn’t mean you can’t fall ill, but it does give you the advantage of a healthy robust immune system. Aided properly, your. immune system will likely get you through the illness.

There is a lot of excitement around the adoption of HCQ as a cure for COVID-19, but in this day and age, one needs to be cautious about blindly following trends as they may easily get you on the wrong path. A critical examination of the risk-benefit ratio, as well as the potential negative consequences, is warranted.


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