Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of agranulocytosis due to dapsone administered for the treatment of acne vulgaris is described. Agranulocytosis has previously been reported after administration of dapsone for other dermatological disorders, leprosy, and prophylaxis against falciparum malaria. The frequency of agranulocytoses when dapsone was used for malaria prophylaxis in United States servicemen in Vietnam was sufficient to result in its withdrawal from use for this purpose. Caution should therefore be exercised in the administration of dapsone for conditions for which less toxic agents are available.
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PMID:Agranulocytosis due to dapsone. 90

A specific enzyme-linked immunosorbent assay (ELISA) was developed for the detection and characterisation of antibodies directed against amodiaquine (AQ), an anti-malarial drug associated with agranulocytosis and liver damage in man. The assay incorporated an antigen which was produced by the reaction of amodiaquine quinone imine (AQQI), a protein reactive product produced from AQ by silver oxide oxidation, and metallothionein. The protein-conjugate (AQ-MT) had a ratio of AQ to protein of 5.2:1. Specific anti-drug antibody was defined as the differential binding to AQ-MT and unconjugated MT which was inhibitable by AQ-mercapturate (5 microM). Following administration of AQ (0.27 mmol/kg; for 4 days) to male Wistar rats there was a significant increase in the IgG anti-AQ activity on day 18 (P less than 0.05, 0.596 +/- 0.410, N = 7) compared to pre-injection levels (0.111 +/- 0.074, N = 7). This activity was shown to be specific for the AQ determinant by hapten inhibition with AQ (IC50 250 nM) and AQ-mercapturate (IC50 310 nM). Following administration of AQQI (27 mumol/kg; i.m.; 4 days) there was a significant increase in IgG anti-AQ antibody activities on day 18 (0.584 +/- 0.161, N = 7) compared to pre-injection levels (0.078 +/- 0.048, N = 7). This activity was inhibited by AQ (IC50 150 nM) and AQ-mercapturate (IC50 180 nM). In addition IgG anti-AQ antibodies were detected in four patients who exhibited agranulocytosis and one patient who exhibited hepatitis (range 0.017-0.842) whilst receiving AQ at a dose of 400 mg weekly for several weeks, but not in individuals who had not received the drug (-0.014 +/- 0.022, N = 7). There was no increase in IgG anti-AQ antibody activities in patients who had not exhibited an adverse reaction whilst receiving the drug for the treatment of malaria (-0.059 +/- 0.074 on day 0 and -0.053 +/- 0.068 on day 7, N = 13). Thus, we have shown that AQ is immunogenic in the rat and that the formation of a chemically reactive metabolite (AQQI) is involved in the generation of the antibody response. Furthermore, drug-specific antibodies were detected in sera from five patients with severe adverse reactions to the drug.
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PMID:Drug-protein conjugates--XVIII. Detection of antibodies towards the antimalarial amodiaquine and its quinone imine metabolite in man and the rat. 247 Mar 78

Seven cases of agranulocytosis and two of liver damage that were probably due to amodiaquine treatment were studied. In five cases agranulocytosis was combined with liver damage, and in one case of primary liver damage moderate neutropenia was present. Three patients died. High total doses or prolonged duration of treatment, or both, appear to favour the occurrence of these reactions. The clustering of five of the seven cases of agranulocytosis within six months in one medical centre indicates that the risk to benefit ratio of amodiaquine for malaria prophylaxis should be re-evaluated.
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PMID:Amodiaquine induced agranulocytosis and liver damage. 308 10

The toxicities of antimalarial drugs vary because of the differences in the chemical structures of these compounds. Quinine, the oldest antimalarial, has been used for 300 years. Of the 200 to 300 compounds synthesised since the first synthetic antimalarial, primaquine in 1926, 15 to 20 are currently used for malaria treatment, most of which are quinoline derivatives. Quinoline derivatives, particularly quinine and chloroquine, are highly toxic in overdose. The toxic effects are related to their quinidine-like actions on the heart and include circulatory arrest, cardiogenic shock, conduction disturbances and ventricular arrhythmias. Additional clinical features are obnubilation, coma, convulsions, respiratory depression. Blindness is a frequent complication in quinine overdose. Hypokalaemia is consistently present, although apparently self-correcting, in severe chloroquine poisoning and is a good index of severity. Recent toxicokinetic studies of quinine and chloroquine showed good correlations between dose ingested, serum concentrations and clinical features, and confirmed the inefficacy of haemodialysis, haemoperfusion and peritoneal dialysis for enhancing drug removal. The other quinoline derivatives appear to be less toxic. Amodiaquine may induce side effects such as gastrointestinal symptoms, agranulocytosis and hepatitis. The main feature of primaquine overdose is methaemoglobinaemia. No cases of mefloquine and piperaquine overdose have been reported. Overdose with quinacrine, an acridine derivative, may result in nausea, vomiting, confusion, convulsion and acute psychosis. The dehydrofolate reductase inhibitors used in malaria treatment are sulfadoxine, dapsone, proguanil (chloroguanide), trimethoprim and pyrimethamine. Most of these drugs are given in combination. Proguanil is one of the safest antimalarials. Convulsion, coma and blindness have been reported in pyrimethamine overdose. Sulfadoxine can induce Lyell and Stevens-Johnson syndromes. The main feature of dapsone poisoning is severe methaemoglobinaemia which is related to dapsone and to its metabolites. Recent toxicokinetic studies confirmed the efficacy of oral activated charcoal, haemodialysis and haemoperfusion in enhancing removal of dapsone and its metabolites. No overdose has been reported with artemesinine, a new antimalarial tested in the People's Republic of China. The general management of antimalarial overdose include gastric lavage and symptomatic treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical features and management of poisoning due to antimalarial drugs. 330 66

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

Two patients are presented who during malaria prophylaxis with amodiaquine developed a hepatitis associated with granulocytopenia of short duration. The suspicion that this could be an adverse reaction to amodiaquine was confirmed by a reexposure to the drug.
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PMID:[Amodiaquine-induced hepatitis with leukopenia]. 376 79

A case of agranulocytosis during malaria prophylaxis with Maloprim (pyrimethamine and dapsone) is described. At the recommended dose of one tablet weekly this is apparently a rare occurrence but highlights one of the hazards in a changing climate of malarial prophylaxis in which the use of Maloprim is increasing.
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PMID:Agranulocytosis during malaria prophylaxis with Maloprim (pyrimethamine and dapsone). 647 41

A patient is presented who developed agranulocytosis while taking amodiaquine for suppressive therapy of malaria. An amodiaquine-dependent granulocytotoxic antibody could be demonstrated in the patient's serum on day 1 after stopping amodiaquine medication. Granulocyte transfusion was ineffective on days 6 and 7, possibly due to the slow elimination of the drug.
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PMID:[Amodiaquine-induced agranulocytosis in malaria prevention: demonstration of an amodiaquine-induced cytotoxic antibody against granulocytes]. 666 34

Various drugs are widely used in the prophylaxis and treatment of malaria. In the prevention of malaria in travellers, a careful risk-benefit analysis is required to balance the risk of acquiring potentially serious malaria against the risk of harm from the prophylactic agent. Unfortunately, the information needed to perform accurate analyses of this type is not available for most antimalarials. In the prophylaxis of malaria, chloroquine and proguanil have an excellent safety record, being very rarely associated with severe adverse reactions in the recommended dosages. However, in many parts of the world they are no longer effective prophylactic agents. Pyrimethamine-dapsone (Maloprim) is associated with agranulocytosis, especially if the recommended dose is exceeded, and should be reserved as a second-line agent for travellers to high risk areas. Pyrimethamine-sulfadoxine (Fansidar) and amodiaquine are associated with a relatively high incidence of potentially fatal reactions, and are no longer recommended for prophylaxis. Mefloquine, a relative newcomer, may provoke severe neuropsychiatric reactions with a frequency of 1 in 15,000 to 20,000 users at the prophylactic dosage. In the treatment of Plasmodium falciparum malaria, which has a high mortality if untreated, a greater risk of adverse reactions to antimalarial drugs is acceptable. As chloroquine resistance has become widespread, alternative agents including quinine, mefloquine, pyrimethamine-sulfadoxine, tetracyclines, halofantrine and artemisinin (qinghaosu) and its derivatives may be used in treatment regimens. The therapeutic ratios for chloroquine, quinine and mefloquine are narrow and toxicity is frequent when recommended treatment dosages are exceeded; parenteral administration above the recommended dose range is especially associated with the hazards of cardiac and neurological toxicity.
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PMID:Adverse effects of antimalarials. An update. 848 Dec 16

Assessment of peripheral blood counts and blood film analysis are frequently performed as diagnostic procedures in emergency medicine. Far fewer situations exist, however, in which these analyses are the main clue in establishing an emergency diagnosis. Artifacts can lead to wrong diagnosis, e.g. pseudo-thrombocytopenia, which is defined as a low platelet count resulting from a laboratory artifact. Severe neutropenia (agranulocytosis) and extreme hyperleukocytosis, as well as suspicion of acute leukemia, require a rapid diagnostic work-up. A newly detected anemia should not necessarily be treated by packed red cell transfusions. The decision whether an anemic patient ought to receive transfusions should be based on the speed with which the anemia has developed, as well as on clinical judgement. As a rule a chronic anemia patient with hemoglobin above 70 g/l does not need transfusions. An uncritical transfusion policy can even cause emergencies, e.g. in patients with megaloblastic anemia or in anemic multiple myeloma patients with a hyperviscosity syndrome. An elevated hematocrit requires prompt further investigations. This is of utmost importance if one considers the diagnosis of polycythemia vera rubra, a disease in which patients are particularly prone to thrombotic complications. Fragmented red cells (schistocytes) on peripheral blood smears constitute a cardinal diagnostic clue for the detection of microangiopathic hemolytic anemias (MAHA), in particular for the diagnosis of the life-threatening thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Malaria is another example for a chief role of blood smears examination in achieving a rapid diagnosis. If one encounters an unexpected severe thrombocytopenia, a marrow examination reveals whether it is due to rapid peripheral destruction, or due to a marrow failure. Furthermore, in any patients with an unanticipated thrombocytopenia, a disseminated intravascular coagulation and a MAHA should be ruled out. Heparin-induced thrombocytopenia is a rare, but possibly fatal complication of therapy with heparins.
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PMID:[Emergency blood picture]. 848 74


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