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.
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 
- Antirheumatoid action: interference with antigen processing in macrophages and other APCs → ↓ formation of peptide-MHC protein complexes → ↓ immune response against autoantigenic peptides 
- Nausea with cramps (most common)
- Visual disturbances
- Cardiac: torsades de pointes (due to possible QT prolongation), can cause sudden death 
- Hematologic: e.g., thrombocytopenia, leukopenia
- Worsening of preexisting conditions: epilepsy, psoriasis, porphyria and preexisting retinal damage
Patients using long-term chloroquine/hydroxyhloroquine should have regular ophthalmological examinations.
We list the most important adverse effects. The selection is not exhaustive.
- Definition: a type of toxic retinopathy caused by long-term chloroquine and hydroxychloroquine use
- Pathogenesis: long-term chloroquine and hydroxychloroquine use ; (threshold dose ∼ 300 mg/d) → irreversible changes in the retinal pigment epithelium; often bilateral
- Decrease in visual acuity
- Impaired color perception
- Differential diagnosis: In advanced stage, symptoms are similar to those of retinitis pigmentosa.
Mechanism of resistance
- Attributed to the development of membrane efflux pumps, which decrease the intracellular concentration of the drug.
- Occurs especially in P. falciparum