- Clinical science
Chloroquine and hydroxychloroquine are drugs derived from 4-aminoquinoline (4AQ), a chemical compound with the amino group at the 4-position of 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. However, 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.
- Widely-accepted mechanisms of action
- Anti-malarial action: the drugs stabilize the lysosomes of the schizonts and reach a high concentration in the vacuoles → their alkaline nature raises the internal pH → bind to heme to form the heme-chloroquine complex, which is highly toxic to the schizont → the parasite perishes
- Anti-rheumatoid action: these drugs interfere with "antigen processing" in macrophages and other antigen-presenting cells → decrease the formation of peptide-MHC protein complexes → down-regulate the immune response against autoantigenic peptides
Visual disturbances: in cases of long-term use, regular ophthalmological exams are recommended
- Irreversible retinopathy: key funduscopic feature is
- Reversible corneal opacity
- Blurred vision
- Gastrointestinal (e.g., most commonly nausea with cramps; anorexia; vomiting)
- Neurologic (e.g., sensorineural deafness, tinnitus, cranial nerve palsies, and myasthenia-like muscle weakness)
- Dermatologic (e.g., photosensitivity, pruritus, alopecia, bleaching of hair)
- Hematologic (e.g., thrombocytopenia, leukopenia)
- Worsening of preexisting conditions: epilepsy, psoriasis, porphyria and preexisting retinal damage
Initially, visual acuity remains excellent despite difficulty reading or performing tasks requiring fine visual motor skills (due to central or paracentral scotomas).
We list the most important adverse effects. The selection is not exhaustive.