Tags: Chloroquine

Non-falciparum Malaria (P Vivax, P Ovale, P Malariae)

Patients with nonfalciparum malaria invariably develop fever and chills that may become cyclic. Initially, patients experience chills, which are followed by fever (Box 1). Patients with malaria often manifest many nonspecific symptoms such as weakness, malaise, headache, and myalgias. As the disease progresses, signs of anemia, such as pale conjunctiva, may be seen.

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Syncope occurred in a hypertensive 48-year-old man who took oral chloroquine sulfate (total 600 mg base) while also taking amlodipine 5 mg/day. Chloroquine and amlodipine both cause vasodilatation, perhaps by release of nitric oxide, and the syncope in this case was probably due to a synergistic mechanism. Malaria itself can also provoke orthostatic reactions, which may be why syncope is not a reported adverse effect of chloroquine.

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Chloroquine has a bitter taste, which can deter children from taking it, so a sweet effervescent formulation of chloroquine phosphate has been compared with chloroquine tablets in a pharmacodynamic study. However, sweet-tasting medications carry a risk of accidental overdose in children. If given intravenously, chloroquine should be diluted and infused slowly, since rapid injection causes toxic concentrations.

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Electrocardiographic changes, comprising altered T waves and prolongation of the QT interval, are not uncommon during high-dose treatment with chloroquine. The clinical significance of this is uncertain. With chronic intoxication, a varying degree of atrioventricular block can be seen; first-degree right bundle branch block and total atrioventricular block have been described.

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The most common dermatological adverse event associated with chloroquine is skin discomfort (often called pruritus). It is much more common in people with darker skins and has been ascribed to chloroquine binding to increased melanin concentrations in the skin. In a pharmacokinetic study, the ratio of AUCo-48 for chloroquine and its major metabolite desethylchloroquine was significantly higher in the plasma and urine of 18 patients with chloroquine-induced pruritus than in that of 18 patients without. These results imply that differences in metabolism and higher chloroquine concentrations may be partly responsible for chloroquine-induced pruritus.

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Chloroquine and its congeners can cause two typical effects in the eye, a keratopathy and a specific retinopathy. Both of these effects are associated with the administration of the drug over longer periods of time. Chloroquine-induced keratopathy is limited to the corneal epithelium, where high concentrations of the drug are readily demonstrable. Slit lamp examination shows a series of punctate opacities scattered diffusely over the cornea; these are sometimes seen as lines just below the center of the cornea, while thicker yellow lines may be seen in the stroma.

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Mefloquine, a fluorinated derivative of 4-quinoline methanol, is a product of the US Army’s antimalarial research program. It is active against chloroquine-resistant Plasmodium falciparum, and has an excellent schizonticidal effect in the blood in experimentally induced Plasmodium vivax infections in volunteers.

Amebiasis

Amebiasis is caused by the intestinal protozoan, Entamoeba histolytica. Infection results from ingestion of fecally contaminated food, such as garden vegetables or by direct fecal-oral transmission. Most persons are asymptomatic or have minimal diarrheal symptoms. In a few patients, invasive intestinal or extraintestinal (e.g., liver, and less commonly kidney, bladder, male or female genitalia, skin, lung, brain) infection results.