Chloroquine toxicity

The eye may be a target organ as a result of its external position in the organism and direct exposure, but also from systemic exposure. Thus, the various components of the eye may be specifically damaged. The presence of pigments in the eye such as melanin has been suggested as the cause of chloroquine toxicity to the retina. 

Figure 35-8 Characteristic bull s eye maculopathy associated with chloroquine toxicity.

Figure 35-10 Peripheral retinal pigment epithelial hyperplasia characteristic of pseudoretinitis pigmentosa in 42-year-old man with chloroquine toxicity.

Bentsi-Enchill KO. Pigmentary skin changes associated with ocular chloroquine toxicity in Ghana. Trop Geogr Med 1980 32(3) 216-20. 

The presence of pigments in the eye such as melanin has been suggested as the cause of chloroquine toxicity to the retina. 

Taken in proper doses, chloroquine is an extraordinarily safe drug however, its safety margin is narrow, and a single dose of 30 mg/kg may be fatal. Acute chloroquine toxicity is encountered most frequently with too rapid administration of parenteral doses. Cardiovascular effects include hypotension, vasodilation, depressed myocardial function, cardiac arrhythmias, and cardiac arrest. Confusion, convulsions, and coma denote central nervous system (CNS) dysfunction. Chloroquine doses of >5 g given parenterally usually are fatal. Prompt treatment with mechanical ventilation, epinephrine, and diazepam may be lifesaving. 

Malaria affects an estimated 270 million people and causes 2—3 million deaths annually, approximately one million of which occur in children under the age of five. While primarily an affliction of the tropics and subtropics, it has occurred as far north as the Arctic Circle. The disease essentially has been eradicated in most temperate-zone countries, but some 1100 cases of malaria in U.S. citizens returning from abroad were reported to the Centers for Disease Control during 1990. Malaria is seen today in Southeast Asia, Africa, and Central and South America. It is on the increase in Afghanistan, Brazil, China, India, Mexico, the Philippines, Sri Lanka, Thailand, and Vietnam. Escalation of the disease is because of the discontinued use of the insecticide DDT which effectively kills mosquito larvae, but has been found to be toxic to Hvestock and wildlife. Also, chloroquine (6), a reUable dmg for the prophylaxis and treatment of falcipamm malaria, is ineffective in many parts of the world because of the spread of dmg-resistant strains. 

Chagas disease is caused by a kinetoplastid trypanosoma parasite and affects millions of people in Latin America. The disease is currently incurable. Chemotherapy is based mainly on nitrofuran and nitroimidazole compounds and sterol biosynthesis inhibitors such as ketoconazole (337). Toxicity and high doses are the major problems for these organic drugs. Urbina et al. (338, 339) have found that com-plexation of antiparasitic organic agents such as chloroquine (78)... 

Chalcones are one of the classes of flavonoids well known for their antiplasmodial properties. Licochalcone A (65), isolated from Chinese licorice roots, was shown to display strong in vitro activity against both chloroquine-susceptible (3D7) and chloroquine-resistant (Dd2) P. falciparum strains it also displayed a strong in vivo acitivity in mice infected with P. yoelii, when administered intraperitoneally or orally for 3 to 6 days. The compound appeared to inhibit the growth of the parasites at all stages (rings, trophozoites, and schizonts). Although licochalcone and some derivatives interred the clinical trials as anti-malarials, none of them have ever made it to the market due to severe toxicity observed in phase II clinical trials. 

Chloroquine is a rapidly acting blood schizonti-cide with some gametocytocidal activity. It is used with primaquine for Plasmodium vivax and Plasmodium ovale infections. It has been widely used prophylactically by traveler s to endemic areas. Its mechanism of action is unclear. It is believed to hinder the metabolism of hemoglobin in the parasite. Presumably chloroquine prevents the formation in the plasmodia of polymers out of free heme which then builds up and becomes toxic. Resistance occurs as a consequence of the expression of a membrane phospho-glycoprotein pump in the plasmodia which is able to expel chloroquine from the parasite. Plasmodium falciparum is the most likely to become resistant. 

Eye. Several drugs have an affinity for the retinal pigment melanin and thus may accumulate in the eye. Chlorpromazine and other phe-nothiazines bind to melanin and accumulate in the uveal tract, where they may cause retino-toxicity. Chloroquine concentration in the eye can be approximately 100 times that found in the liver. 

Although dapsone (Avlosulfon) was once used in the treatment and prophylaxis of chloroquine-resistant P. falciparum malaria, the toxicities associated with its administration (e.g., agranulocytosis, methemoglobinemia, hemolytic anemia) have severely reduced its use. 

Chloroquine 4mL/kg freshly squeezed GFJ (study performed in chicken) Cloroquine concentration (7-37%) No overt signs of toxicity were observed (123)... 

Chloroquine probably acts by concentrating in parasite food vacuoles, preventing the biocrystallization of the hemoglobin breakdown product, heme, into hemozoin, and thus eliciting parasite toxicity due to the buildup of free heme. 

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