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What is Hydroxychloroquine (HCQ) ?
What is Hydroxychloroquine (HCQ) ?
The Origin
The Origin
Chloroquine was researched around 1943 by German scientists in relation to antimalarial research, but they determined it was too toxic for use in humans so trials were discontinued1.
Later on in 1955, hydroxychloroquine (brand name Plaquenil) was synthesised by adding a hydroxyl group to chloroquine - this was found to have minimal/no effect on the efficacy of the drug, but significantly reduced the toxicity1.
Hydroxychloroquine is a synthetic derivative of quinine, which is a natural compound found in the bark of Cinchona plants, native to South America2.
Uses
Uses
Although initially developed for the treatment of malaria, it is currently used in the treatment of several diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Hydroxychloroquine is therefore classed as a disease-modifying anti-rheumatic drug (DMARD)3.
Chloroquine and hydroxychloroquine were both approved by the FDA as treatments for COVID-19 in 2020, but approval was revoked due to the potentially serious adverse effects4.
Administration
Administration
Hydroxychloroquine is administered as a sulfate1.
It is administered orally, in tablet form. Patients should take less than 5mg/kg body weight daily, or less than 400mg daily1.
Hydroxychloroquine has a bioavailability of 70%1.
How Does it Work?
How Does it Work?
At a molecular level, hydoxychloroquine accumulates in lysosomes5,6.
It interferes with lysosomal activity, disrupts the membrane and causes variation in the signalling pathways and transcription6.
Hydroxychloroquine dampens the immune response via inhibition of the toll-like receptor signalling and reducing cytokine production6.
It also reduces the expression of the protein CD154 in T cells6.
Schematic of the mechanism of action of hydroxychloroquine (HCQ). Adapted from: https://link.springer.com/content/pdf/10.1007/s00296-021-04868-6.pdf
Contraindications
Contraindications
Hydroxychloroquine should not be used in patients with known glucose-6-dehydrogenase deficiency, due to its potential to cause haemolytic anaemia1.
It is also contraindicated in people with a known allergy / sensitivity to hydroxychloroquine derivatives, and those with pre-existing maculopathy1.
Caution is needed if either chloroquine or hydroxychloroquine is given to patients with psychotic or neuromuscular disorders (e.g. myasthenia gravis)7-8.
Explore Further...
Explore Further...
References:
1. Ben-Zvi I, Kivity S, Langevitz P, & Shoenfeld Y. Hydroxychloroquine: from Malaria to Autoimmunity. Clinical reviews in Allergy & Immunology. 2012, 42, pp145-153.
2. Bell, JS, Bell JA, Creek DJ. Off-label prescribing in the midst of a pandemic: The case of hydroxychloroquine. Australian Journal of General Practice. 2020; 49.
3. Della Porta A, Bornstein K, Coye A, Montrief T, Long B, Parris MA. Acute chloroquine and hydroxychloroquine toxicity: A review for emergency clinicians. American Journal of Emergency Medicine. 2020; 38(10): 2209-2217.
4. Kowalska M, Fijałkowski Ł, & Nowaczyk A. Detailed comparison between the safety profiles of Chloroquine and Hydroxychloroquine. Paper presented at: ECB 2021; 31/05/2021; Poland.
5. Muller R. Systemic toxicity of chloroquine and hydroxychloroquine: prevalence, mechanisms, risk factors, prognostic and screening possibilities. Rheumatology International. 2020; 41: 1189-1202.
6. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nature Reviews Rheumatology. 2020;16(3):155-66.
7. Ilowite N & Laxer R. PHARMACOLOGY AND DRUG THERAPY. In: Cassidy J, Laxer R, Petty R, & Lindsley C. eds. Textbook of Pediatric Rheumatology. Philadelphia. Saunders Elvesier, 2010, pp 76-126.
8. Ali S & Jones H. 23. An adverse neuropsychiatric reaction following treatment with Hydroxychloroquine: a case report. Rheumatology Advances in Practice. 2018, 2(1), pp i16-i17.
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