What is Chloroquine Phosphate mainly used for?

Chloroquine Phosphate is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication.Chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus.While it has not been formally studied in pregnancy, it appears safe.It is also being studied to treat COVID-19 as of 2020.It is taken by mouth.

chloroquine phosphate

Common side effects include muscle problems, loss of appetite, diarrhea, and skin rash.Serious side effects include problems with vision, muscle damage, seizures, and low blood cell levels.Chloroquine is a member of the drug class 4-aminoquinoline.As an antimalarial, it works against the asexual form of the malaria parasite in the stage of its life cycle within the red blood cell.How it works in rheumatoid arthritis and lupus erythematosus is unclear.

Chloroquine was discovered in 1934 by Hans Andersag.It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.It is available as a generic medication.The wholesale cost in the developing world is about US$0.04.In the United States, it costs about US$5.30 per dose.

Medical Uses Of Chloroquine Phosphate

Malaria

Chloroquine has been used in the treatment and prevention of malaria from Plasmodium vivax, P. ovale, and P. malariae. It is generally not used for Plasmodium falciparum as there is widespread resistance to it.

Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it.In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead. The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations.

Amebiasis

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.

Rheumatic disease

As it mildly suppresses the immune system, chloroquine is used in some autoimmune disorders, such as rheumatoid arthritis and lupus erythematosus.

SARS-CoV

Chloroquine had been also proposed as a treatment for SARS, with in vitro tests inhibiting the SARS-CoV virus.In October 2004, a group of researchers at the Rega Institute for Medical Research published a report on chloroquine, stating that chloroquine acts as an effective inhibitor of the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro

Side effects Of Chloroquine

Side effects include blurred vision, nausea, vomiting, abdominal cramps, headache, diarrhea, swelling legs/ankles, shortness of breath, pale lips/nails/skin, muscle weakness, easy bruising/bleeding, hearing and mental problems.

• Unwanted/uncontrolled movements (including tongue and face twitching).
• Deafness or tinnitus.
• Nausea, vomiting, diarrhea, abdominal cramps.
• Headache.
• Mental/mood changes (such as confusion, personality changes, unusual thoughts/behavior, depression, feeling being watched, hallucinating)
• Signs of serious infection (such as high fever, severe chills, persistent sore throat)
• Skin itchiness, skin color changes, hair loss, and skin rashes.
  • Chloroquine-induced itching is very common among black Africans (70%), but much less common in other races. It increases with age, and is so severe as to stop compliance with drug therapy. It is increased during malaria fever; its severity is correlated to the malaria parasite load in blood. Some evidence indicates it has a genetic basis and is related to chloroquine action with opiate receptors centrally or peripherally.
• Unpleasant metallic taste
  • This could be avoided by “taste-masked and controlled release” formulations such as multiple emulsions.
• Chloroquine retinopathy.
• Electrocardiographic changes..
  • This manifests itself as either conduction disturbances (bundle-branch block, atrioventricular block) or Cardiomyopathy – often with hypertrophy, restrictive physiology, and congestive heart failure. The changes may be irreversible. Only two cases have been reported requiring heart transplantation, suggesting this particular risk is very low. Electron microscopy of cardiac biopsies show pathognomonic cytoplasmic inclusion bodies.
• Pancytopenia, aplastic anemia, reversible agranulocytosis, low blood platelets, neutropenia.

Pregnancy

Chloroquine has not been shown to have any harmful effects on the fetus when used in the recommended doses for malarial prophylaxis.Small amounts of chloroquine are excreted in the breast milk of lactating women. However, this drug can be safely prescribed to infants, the effects are not harmful. Studies with mice show that radioactively tagged chloroquine passed through the placenta rapidly and accumulated in the fetal eyes which remained present five months after the drug was cleared from the rest of the body.Women who are pregnant or planning on getting pregnant are still advised against traveling to malaria-risk regions.

Elderly

There is not enough evidence to determine whether chloroquine is safe to be given to people aged 65 and older. Since it is cleared by the kidneys, toxicity should be monitored carefully in people with poor kidney functions.

Overdose Of Chloroquine

Chloroquine is very dangerous in overdose. It is rapidly absorbed from the gut. In 1961, a published compilation of case reports contained accounts of three children who took overdoses and died within 2.5 hours of taking the drug. While the amount of the overdose was not stated, the therapeutic index for chloroquine is known to be small.One of the children died after taking 0.75 or 1 gram, or twice a single therapeutic amount for children. Symptoms of overdose include headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, seizures, and sudden respiratory and cardiac arrest.

An analog of chloroquine – hydroxychloroquine – has a long half-life (32–56 days) in blood and a large volume of distribution (580–815 L/kg).^[25] The therapeutic, toxic and lethal ranges are usually considered to be 0.03 to 15 mg/l, 3.0 to 26 mg/l and 20 to 104 mg/l, respectively. However, nontoxic cases have been reported up to 39 mg/l, suggesting individual tolerance to this agent may be more variable than previously recognised.

Pharmacology

Chloroquine’s absorption of the drug is rapid.It is widely distributed in body tissues.Its protein binding is 55%.Its metabolism is partially hepatic, giving rise to its main metabolite, desethylchloroquine.Its excretion is ≥50% as unchanged drug in urine, where acidification of urine increases its elimination.It has a very high volume of distribution, as it diffuses into the body’s adipose tissue.

Accumulation of the drug may result in deposits that can lead to blurred vision and blindness.It and related quinines have been associated with cases of retinal toxicity, particularly when provided at higher doses for longer times.With long-term doses, routine visits to an ophthalmologist are recommended.

Chloroquine is also a lysosomotropic agent, meaning it accumulates preferentially in the lysosomes of cells in the body.The pK_a for the quinoline nitrogen of chloroquine is 8.5, meaning it is about 10% deprotonated at physiological pH (per the Henderson-Hasselbalch equation).This decreases to about 0.2% at a lysosomal pH of 4.6.Because the deprotonated form is more membrane-permeable than the protonated form, a quantitative “trapping” of the compound in lysosomes results.

Formulations

Chloroquine comes in tablet form as the phosphate, sulfate, and hydrochloride salts. Chloroquine is usually dispensed as the phosphate.

History

In Peru, the indigenous people extracted the bark of the Cinchona tree (Cinchona officinalis) and used the extract to fight chills and fever in the seventeenth century. In 1633 this herbal medicine was introduced in Europe, where it was given the same use and also began to be used against malaria.The quinoline antimalarial drug quinine was isolated from the extract in 1820, and chloroquine is an analogue of this.

Chloroquine was discovered in 1934, by Hans Andersag and coworkers at the Bayer laboratories, who named it Resochin.It was ignored for a decade, because it was considered too toxic for human use. Instead, the DAK used the chloroquine analogue 3-methyl-chloroquine, known as Sontochin. After Allied forces arrived in Tunis, Sontochin fell into the hands of Americans, who sent the material back to the United States for analysis, leading to renewed interest in chloroquine.United States government-sponsored clinical trials for antimalarial drug development showed unequivocally that chloroquine has a significant therapeutic value as an antimalarial drug. It was introduced into clinical practice in 1947 for the prophylactic treatment of malaria.

Credit:

https://en.wikipedia.org/wiki/Chloroquine