• Clinical science

Chloroquine and hydroxychloroquine

Summary

Chloroquine and hydroxychloroquine are drugs derived from the quinoline molecule. Both are used as antimalarial blood schizonticides, and hydroxychloroquine is also frequently used as an antirheumatic. Their mechanism of action is not entirely understood. Despite their varying therapeutic dosage and toxicity, both drugs have similar clinical indications and side effects. One of their most serious side effects is retinal toxicity, referred to as 4AQ retinopathy or chloroquine retinopathy, which must be screened for in all cases of long-term use.

Pharmacodynamics

The precise mechanisms of action are unknown, but the following are the most widely accepted hypotheses:

  • Antimalarial action: drug accumulation in the parasite's food vacuole: → inhibition of heme polymerization (and thus, detoxification) into hemozoin and formation of highly toxic heme-chloroquine complexes → lysis of membranes and death of the parasites [1]
  • Antirheumatoid action: interference with antigen processing in macrophages and other APCs ↓ formation of peptide-MHC protein complexes → ↓ immune response against autoantigenic peptides [2]

Adverse effects

Patients using long-term chloroquine/hydroxyhloroquine should have regular ophthalmological examinations.

We list the most important adverse effects. The selection is not exhaustive.

Indications

Mechanism of resistance

  • Attributed to the development of membrane efflux pumps, which decrease the intracellular concentration of the drug.
  • Occurs especially in P. falciparum
  • 1. Chong CR, Sullivan DJ. Inhibition of heme crystal growth by antimalarials and other compounds: implications for drug discovery. Biochem Pharmacol. 2003; 66(11): pp. 2201–2212. pmid: 14609745.
  • 2. Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum. 1993; 23(2 Suppl 1): pp. 82–91. pmid: 8278823.
  • 3. UpToDate. Chloroquine: Drug Information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/chloroquine-drug-information. Last updated January 1, 2017. Accessed April 9, 2017.
  • 4. UpToDate. Hydroxychloroquine: Drug Information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/hydroxychloroquine-drug-information. Last updated January 1, 2017. Accessed April 9, 2017.
  • 5. Aghahowa S, Obianwu H, Isah A, Arhewoh I. Chloroquine-induced Pruritus. Indian J Pharm Sci. 2010; 72(3): p. 283. doi: 10.4103/0250-474x.70471.
  • 6. Lior Jankelson, Giorgio Karam, Matthijs L. Becker, Larry A. Chinitz, and Meng-Chiao Tsai. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211688/.
last updated 09/09/2020
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