Chloroquine

 

 

 

Used in the treatment or prevention of malaria from Plasmodium vivax, P. ovale, and P. malariae, excluding the malaria parasite Plasmodium falciparum, for it started to develop widespread resistance to it.

 

 

The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations.

 

 

In treatment of amoebic liver abscess, chloroquine may be used instead of or in addition to other medications in the event of failure of improvement with metronidazole or another nitroimidazole within 5 days or intolerance to metronidazole or a nitroimidazole.

 

 

It mildly suppresses the immune system, and isused in some autoimmune disorders, such as rheumatoid arthritis and lupus erythematosus.

 

 

Side effects include: neuromuscular, hearing, gastrointestinal, brain, skin, eye, cardiovascular, blood reactions, seizures

 

deafness or tinnitus,nausea, vomiting, diarrhea, abdominal cramps, and anorexia, transient headache, 

 

itchiness, skin color changes, hair loss, and skin rashes.

 

 

Among black Africans 70% or so experience chloroquine-induced itching, but this is much less common in other races. 

 

 

Associated itching increases with age and may decrease compliance with drug therapy.

 

 

Itching increases during the Larry a fever and it’s severity is correlated to the blood parasite load.

 

 

Itching may have a genetic basis related to receptors centrally or peripherally.

 

 

Chloroquine retinopathy, may be irreversible, and occurs with long-term use over many years or with high doses. 

 

 

For long-term chloroquine therapy patients should be screened at baseline and then annually after five years of use.

 

 

Hypotension and electrocardiographic changes may manifests as conduction disturbances of bundle-branch block, atrioventricular block or cardiomyopathy.

 

 

Cardiovascular changes may be irreversible but the risk is very low.

 

 

Rarely pancytopenia, aplastic anemia, reversible agranulocytosis,  thrombocytopenia and, neutropenia have been reported.

 

 

It has not been shown to have any harmful effects on the fetus when used for malarial prophylaxis.

 

 

Small amounts of the drug are excreted in the breast milk of lactating women. 

 

 

It can be safely prescribed to infants.

 

 

It is cleared by the kidneys and toxicity should be monitored carefully in people with poor kidney functions.

 

 

Drug interactions: 

 

 

Ampicillin- levels may be reduced by chloroquine

 

 

Antacids- may reduce its absorption

 

 

Cimetidine- may inhibit metabolism of and increase levels

 

 

Cyclosporine- levels may be increased by chloroquine

 

 

Kaolin- may reduce absorption 

 

 

Chloroquine  overdose is dangerous, and therapeutic index is known to be small.

 

 

Overdose symptoms include : headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, seizures, and sudden respiratory and cardiac arrest.

 

 

Absorption is rapid and almost complete.

 

 

It is widely distributed into body tissues.

 

 

Protein binding: 55%

 

 

Metabolism is partially hepatic to main metabolite, desethylchloroquine.

 

 

Excretion: Urine 50% as unchanged drug.

 

 

It diffuses into the body’s adipose tissue.

 

 

Associated with cases of retinal toxicity, particularly when provided at higher doses for longer times. 

 

 

Long term use may result in deposits that can lead to blurred vision and blindness. 

 

 

Routine visits to an ophthalmologist are recommended for long-term users.

 

 

It accumulates preferentially in the lysosomes of cells.

 

 

It is its lysosomotropic character believed to account for much of its antimalarial activity.

 

 

The drug concentrates in the acidic food vacuole of the parasite.

 

 

The  malarial parasite inside RBCs in its asexual lifecycle stage, must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. 

 

 

The degradation of hemoglobin is carried out in a vacuole of the parasitic cell.

 

 

During the degradation of hemoglobin by the parasite, the toxic and soluble molecule heme is released..

 

 

The malarial parasite biocrystallizes heme to form hemozoin, a nontoxic molecule. 

 

 

Hemozoin collects in the digestive vacuole of the parasite as insoluble crystals.

 

 

It enters the red blood cell by diffusion, and inhibits the parasite cell and digestive vacuole. 

 

 

Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. 

 

 

Chloroquine binds to heme to form a chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. 

 

 

The complex results in cell lysis and ultimately parasite cell autodigestion. 

 

 

Parasites that do not form hemozoin are therefore resistant to chloroquine.

 

 

Chloroquine effectiveness against P. falciparum has declined as resistant strains of the parasite neutralize the drug via a mechanism that drains chloroquine away from the digestive vacuole. 

 

 

Cells resistant to chloroquine efflux the drug at 40 times the rate of chloroquine-sensitive cells.

 

 

A Ca2+ channel blocker verapamil has been found to restore both the chloroquine concentration ability and sensitivity to this drug. 

 

 

Additional drugs  that can reverse chloroquine resistance in malaria are chlorpheniramine, gefitinib, imatinib, tariquidar and zosuquidar.

 

 

Chloroquine has antiviral effects, which work by increasing endosomal pH resulting in impaired virus/cell fusion that requires a low pH, and  acts as a zinc ionophore, thereby allowing extra cellular zinc to enter inside the cell and inhibit viral RNA dependant RNA polymerase.

 

 

It inhibits thiamine uptake.

 

 

In  rheumatoid arthritis, it inhibits lymphocyte proliferation, phospholipase A2, antigen presentation in dendritic cells, release of enzymes from lysosomes, release of reactive oxygen species from macrophages, and production of IL-1.

 

 

Chloroquine appears to have inhibitory effects on the 2019 novel coronavirus.

 

 

Preliminary results found that chloroquine may be effective and safe in treating COVID-19 associated pneumonia.

 

 

A further study concluded that hydroxychloroquine was more potent than chloroquine, with a more tolerable safety profile.