Chloroquine and hydroxychloroquine

Amodiaquin is also a structural analog of chloroquine and hydroxychloroquine, and it does not express any vital differences in terms of activity. Therefore it is used less often than the drugs described above. Synonyms of this drug are flavoquine and camoquin. 

Malaria is the cause for approximately 20% of child deaths in Africa and for more than 1 million deaths around the world each year. The appearance and spread of drug resistance of the Plasmodium falciparum parasites to common antimalarial drugs, such as chloroquine and hydroxychloroquine, have posed the urgent challenge of developing effective, safe and affordable antimalarial drugs. 

Chloroquine and hydroxychloroquine are used mainly in malaria (see Chapter 52) and in the rheumatic diseases. The mechanism of the antiinflammatory action of these drugs in rheumatic diseases is unclear. The following mechanisms have been proposed suppression of T-lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis, and the trapping of free radicals. 

When severe psychosis following treatment with chloroquine and hydroxychloroquine occurs it is usually during treatment for malaria, but it can follow treatment for connective tissue disorders. Hallucinations have been reported after hydroxychloroquine treatment for erosive lichen planus (152). 

Chloroquine and hydroxychloroquine Whorl-like epithelial opacities (also termed vortex keratopathy... 

Chloroquine and hydroxychloroquine are quinoline drugs used for the chronic management of rheumatoid arthritis, discoid and systemic lupus erythematosus, and other collagen diseases. Because chloroquine is rapidly absorbed and becomes highly concentrated in various tissues due to melanin and protein binding, it is now used only for malaria prophylaxis. Hydroxychloroquine has replaced it primarily because of its superior safety profile. 

Long-term chloroquine can cause cardiac comphca-tions, such as conduction disorders and cardiomyopathy (restrictive or hypertrophic), by structural alteration of the interventricular septum (4). Thirteen cases of cardiac toxicity associated with long-term chloroquine and hydroxychloroquine have been reported in patients with systemic autoimmune diseases. The cumulative doses were 600-2281 g for chloroquine and 292-4380 g for hydroxychloroquine. 

Shroyer NF, Lewis RA, Lupski JR. Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease Am J Ophthalmol 2001 131(6) 761-6. 

Answer C. Ocular toxicity is characteristic of chloroquine and hydroxychloroquine. Corneal deposits are reversible, but retinal pigmentation can ultimately lead to blindness. Patients will complain about GI distress, visual dysfunction, ringing in the ears (note that tinnitus aiso occurs in salicylism), and itchy skin. Hydroxychloroquine also promotes oxidative stress that can lead to hemolysis in G6PD deficiency. DMARDs include gold salts (e.g., auranofin), methotrexate, and etanercept, but thioridazine is a phenothiazine used as an antipsychotic it lacks anti-inflammatory effect, but does cause retinal pigmentation. 

Photodegradation studies have been carried out for several antimalarial compounds (Kristensen et al., 1993 Nord et al., 1991 Tpnnesen et al., 1988 Tpnnesen and Grislingaas, 1990). The main degradation products of chloroquine and hydroxychloroquine correspond to their in vivo metabolites. These degradation products are also demonstrated to be photolabile (unpublished results). Some of the photodegradation products of hydroxychloroquine seem to be more potent as photosensitizers than the parent drug (Kristensen et al., 1994a). 

Quinacrine, which is tricyclic and highly lipophilic, will easily penetrate cell membranes but hardly diffuse through the hydrophilic vitreous cavity. It also forms a stable complex with melanin and will therefore be retained in the RPE. Quinacrine must be considered a potent photosensitizer in the retina due to the absorption maximum of this drug in the visible region of the spectrum (Table 10.1). The more hydrophilic compounds chloroquine and hydroxychloroquine will more easily be transported to the lens. They are known to accumulate in the eye and induce toxic reactions. Primaquine is not likely to be distributed to the eye to any extent due to low distribution volume and fast elimination. 

Nord, K., Karlsen, J., and Tpnnesen, H.H. (1994) Photochemical stability of biologically active compounds. IX. Characterization of the spectroscopic properties of the 4-aminoquinolones, chloroquine and hydroxychloroquine, and of selected metabolites by absorption, fluorescence and phosphorescence measurements, Photochem. Photobiol., 60, 427 -31. 

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