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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. Chloroquine was rapidly absorbed after either intramuscular or subcutaneous administration (5 mg of base per kilogram every 12 hours), producing high peak blood concentrations but transient hypotension in 5 of 18 patients (28 percent). Intermittent intravenous infusion (5 mg of base per kilogram over 4 hours, repeated every 12 hours) also produced wide fluctuations in chloroquine levels, suggesting incomplete distribution from a small central compartment. Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.
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PMID:Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations. 305 58

Chloroquine (25 mg/kg over 3 d) was compared to quinine (10 mg/kg 3 times daily for 5 d) in 20 adult Filipino males with uncomplicated Plasmodium falciparum malaria in a double-blind, randomized trial. Asexual parasitaemia was cleared in all patients, with no statistically significant difference (P = 0.13) in the rate of clearance between the chloroquine-treated patients (76.1 +/- 29.3 h) and those receiving quinine (60.3 +/- 12.5 h). The duration of fever was also comparable (chloroquine 46.3 +/- 24.7 h; quinine 43.2 +/- 20.0 h; P = 0.76) and 40% of patients in each treatment group experienced mild side effects. Chloroquine, however, is cheaper and easier to administer. In vitro results were strikingly different. P. falciparum parasites from 4 quinine-treated patients were all sensitive to this compound in vitro, whereas 4 of the 5 isolates from the chloroquine group were resistant. Further comparisons of these two antimalarials are indicated, especially in cerebral malaria, and drug use policies should be based on clinical and parasitological response to treatment.
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PMID:Chloroquine and quinine: a randomized, double-blind comparison of efficacy and side effects in the treatment of Plasmodium falciparum malaria in the Philippines. 305 54

This review of methods for determining antimalarial drugs in biological fluids has focused on the various analytical techniques for the assay of chloroquine, quinine, amodiaquine, mefloquine, proguanil, pyrimethamine, sulphadoxine, primaquine and some of their metabolites. The methods for determining antimalarials and their metabolites in biological samples have changed rapidly during the last eight to ten years with the increased use of chromatographic techniques. Chloroquine is still the most used antimalarial drug, and various methods of different complexity exist for the determination of chloroquine and its metabolites in biological fluids. The pharmacokinetics of chloroquine and other antimalarials have been updated using these new methods. The various analytical techniques have been discussed, from simple colorimetric methods of intermediate selectivity and sensitivity to highly sophisticated, selective and sensitive chromatographic methods applied in a modern analytical laboratory. Knowledge concerning the method for a particular study is determined by the type of application and the facilities, equipment and personnel available. Often is it useful to apply various methods when conducting a clinical study in malaria-endemic areas. Field-adapted methods for the analysis of urine samples can be applied at the study site for screening, and corresponding blood samples can be preserved for subsequent analysis in the laboratory. Selecting samples for laboratory analysis is based on clinical, parasitological and field-assay data. The wide array of methods available for chloroquine permit carefully tailored approaches to acquire the necessary analytical information in clinical field studies concerning the use of this drug. The development of additional field-adapted and field-interfaced methods for other commonly used antimalarials will provide similar flexibility in field studies of these drugs.
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PMID:Detection and determination of antimalarial drugs and their metabolites in body fluids. 307 44

A 24 year old Zambian female presented with falciparum malaria when 27 weeks pregnant. She had recently travelled to the copperbelt from Solwezi in the North-West Province of Zambia. Oral chloroquine in a dose of 29 mg/kg failed to clear the parasitaemia. Chloroquine resistance was confirmed by testing in vitro and in vivo. In addition, Fansidar (2 courses), amodiaquine, quinine and quinine plus erythromycin failed to achieve radical cure. Quinine resistance was confirmed in vitro and in vivo. She was eventually cured by 10 d of quinine plus clindamycin, which was greatly assisted by the spontaneous delivery of a live normal infant at 37 weeks gestation. The baby's birth weight was 2.68 kg and its blood slide was negative for malaria.
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PMID:Multiple drug resistant Plasmodium falciparum malaria in a pregnant indigenous Zambian woman. 307 12

Representatives of 200 urban and 200 rural households were interviewed to determine the extent and appropriateness of the use of chloroquine obtained over-the-counter for malaria prophylaxis. Malaria prophylaxis was taken by 38 urban and 65 rural respondents. Chloroquine was the only drug used and was found in 7 urban and 40 rural households. The presence of chloroquine was detected in 4/130 urban and 11/136 rural urine samples tested. Knowledge about chloroquine was unsatisfactory with 6 urban and 10 rural respondents aware that chloroquine could have harmful adverse effects. The doses of chloroquine taken for prophylaxis varied widely, and of the 103 respondents who took prophylaxis only 16% (urban) and 31% (rural) were taking the correct dose. Self-medication accounts for a substantial, little acknowledged, portion of chloroquine use. To limit appropriate use of a powerful, potentially dangerous antimalarial drug and perhaps extend the useful therapeutic life of chloroquine clear recommendations and population education are needed.
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PMID:Self-medication with chloroquine for malaria prophylaxis in urban and rural Zimbabweans. 318 20

This study concerns the in vitro interaction with human polymorphonuclear neutrophils (PMNs) of amodiaquine, chloroquine, and mefloquine, three antimalarial drugs currently in use for the treatment and prophylaxis of malaria. It was found that mefloquine (100 and 50 micrograms/ml) significantly altered PMN viability while the other two drugs did not. Neutrophil chemotaxis was impaired by chloroquine (100 micrograms/ml) and mefloquine (greater than 10 micrograms/ml) but not by amodiaquine. Phagocytosis was decreased by about 50% in the presence of chloroquine (100 micrograms/ml) or mefloquine (10 micrograms/ml). The three antimalarial drugs altered neutrophil oxidative metabolism as assessed by luminol-amplified chemiluminescence. The strongest effect was observed with mefloquine, which abolished almost completely the neutrophil burst at concentrations of greater than 10 micrograms/ml whatever the stimulus used. This effect was not reversed by washing. Chloroquine and amodiaquine also impaired this PMN response by approximately 80 and 50%, respectively, but only at the highest concentration used (100 micrograms/ml). In the case of amodiaquine, the neutrophil response was restored by washing, except for stimulation with opsonized particles. After washing, the depressive effect of chloroquine was reversed completely in the case of phorbol myristate acetate stimulation and partly in the case of opsonized particle stimulation, but the formylmethionyl-leucyl-phenylalanine-induced response was not restored. These data show that although they are structurally related, amodiaquine and chloroquine exhibit qualitatively and quantitatively different depressive effects on PMN function and probably interfere at different points of cell activation, although the precise mechanisms are as yet unresolved.
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PMID:Effects of amodiaquine, chloroquine, and mefloquine on human polymorphonuclear neutrophil function in vitro. 326 35

1. Chloroquine diphosphate (15 mg base kg-1) was given by constant rate intravenous infusion to two groups of Thai subjects. Eleven were patients with malaria (10 with Plasmodium vivax and one case with Plasmodium malariae) and 10 were healthy normal volunteers. 2. Plasma and packed red-cell concentrations of chloroquine, electrocardiographic intervals, arterial blood pressure and pulse were measured at frequent intervals. 3. Peak plasma concentrations at the end of the infusion ranged from 979 to 2,900 ng ml-1 in the malaria patients. In the group of healthy subjects the range was 550-2,200 ng ml-1. Values for terminal elimination rate constant, (lambda z) plasma clearance (CL), initial volume of distribution (V1) and volume of distribution at steady state (Vss) were calculated. For the healthy subjects, mean estimates of these parameters were lambda z = 0.062 +/- 0.030 day-1, CL = 597 +/- 238 ml min-1, V1 = 0.66 +/- 0.71 l kg-1 and Vss = 132 +/- 50 l.kg-1 For the group of malaria patients, the corresponding values were lambda z = 0.055 +/- 0.032 day-1, CL = 535 +/- 246 ml min-1, V1 = 0.74 +/- 0.75 l kg-1 and Vss = 136 +/- 64 l kg-1 There was no statistically significant difference in the estimates for any parameter between groups (P less than or equal to 0.05). 4. Chloroquine concentrations in packed red blood cells consistently exceeded those in plasma and showed no consistent change with time throughout the period of study in either group. The median value for the red cell to plasma ratio was between 3 and 4 in each group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics of chloroquine in Thais: plasma and red-cell concentrations following an intravenous infusion to healthy subjects and patients with Plasmodium vivax malaria. 328 1

During the period of June to October 1985, a study in vivo was made on 162 patients suffering from malaria by P. falciparum, in order to evaluate the sensitivity of the parasite to the drugs: Chloroquine, Amodiaquine and Pyrimethamine-Sulfadoxine (Fansidar). As an alternative treatment, in the resistant cases, Quinine with Fansidar or Quinine with Tetracycline was given. The following cases of resistance were found: 17 cases to Chloroquine (5-RI, 9-RII, 3-RIII), 7 cases to Amodiaquine (5-RI, 2-RII) and 2 cases to Fansidar (1-RI, 1-RII). It is recommended that the epidemiologic studies of the resistance by P. falciparum to the anti-malarials be increased, following up the evolution of its scope, and the organization of a program to fight against malaria. Also the use of Fansidar is recommended as the principal medicine against P. falciparum in malaria without complications, in the zones where there is strong resistance to the 4-amino-quinoleines. In case of multi-resistance in malaria by P. falciparum, the use of Quinine is recommended. At a prophylactic level we do not advise the use of Chloroquine as the only medicine, nor the use of Fansidar because of its potential toxic effects.
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PMID:[Pharmacoresistance of Plasmodium falciparum in Rwanda: an in vivo study]. 331 Nov 92

Individual chemoprophylaxis against malaria remains mandatory for all trips of brief or intermediate duration in endemic areas. The selected anti-malarial drug must be taken regularly from the beginning of the stay, during the stay and for the 30 days after return (The 30 days following the departure from regions at risk). Presently the following drugs are available: amino-4-quinolines, quinine, antifolinic agents, the association antifolinic-antifolic agents and mefloquine. Specific advantages, side-effects and adverse reactions, as well as dosage used for prophylaxis are given for each drug. The risk of agranulocytosis and severe hepatitis related to amodiaquine forbids its use until more information has become available. The association sulfadoxine + pyrimethamine is no longer recommended for prophylaxis by the French authorities and recently by the W.H.O., because of its potential, although seldom, risk of severe muco-cutaneous disorders. Detailed schemes of prophylaxis are given; they rely on sensitivity or resistance of Plasmodia strains, the length of the stay in at risk areas, and the local situation concerning the hazard of infection and drug resistance of Plasmodia. Chloroquine must be used in priority in areas characterized by sensitivity or low grade resistance to chloroquine. In order to avoid resistance to mefloquine, its administration has to be limited to prophylaxis for short stays and to the treatment of attacks resulting from infections acquired in areas known for resistance against the other drugs. Today, indeed, mefloquine is the single agent efficient in case of multiresistance to Plasmodium falciparum. The treatment of suspected or proved cases of malaria attacks occurring in temporary or permanent expatriates or in local, semi-immune residents, has become strongly advisable. In areas of resistance to chloroquine, either quinine (repeated injections), sulfadoxine-pyrimethamine (per os or unique parenteral injection) or if possible, mefloquine (full dose during 1 day) are to be used for the therapy of acute attacks. Continuous chemoprophylaxis is no longer encouraged for populations living in holoendemic areas. Treatment of suspected or overt malaria crises is, however, mandatory. The limitation to curative therapy is opening the way to more specific prophylaxis: pregnancy, delivery, intercurrent pathological events, such as surgery, trauma, infection... It is hoped that, until the forthcoming of anti-malaria immunoprophylaxis, these newly adjusted designs for chemotherapy will help to keep the progress of malaria and the development of plasmodial resistance under control.
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PMID:[Malaria prevention today and tomorrow]. 331 65

A 30-year-old woman underwent laparotomy and was placed on a seven-day course of metronidazole and ampicillin postoperatively. Chloroquine therapy for malaria was instituted on the sixth day and the patient developed acute dystonic reactions after a single dose. Diphenhydramine therapy before chloroquine administration did not prevent the development of the dystonic reactions. The extrapyramidal symptoms subsided upon diazepam administration and chloroquine withdrawal even though metronidazole therapy was continued. The mechanism of this adverse drug reaction based on the pharmacodynamic interaction between chloroquine and metronidazole is discussed. It is suggested that the combination of pyrimethamine and sulfadoxine be used in place of chloroquine for malaria chemotherapy in patients on metronidazole therapy.
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PMID:Chloroquine-induced acute dystonic reactions in the presence of metronidazole. 337 Nov 93


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