Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02448 (Fansidar)
 243 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of antimalarial treatment on the blood oxygen-transporting properties and on the tissue hypoxia were investigated in severe murine malaria, using mice infected with Plasmodium berghei (NK65). Five week old male ddY mice were inoculated intraperitoneally with 1 X 10(7) of P. berghei-infected red blood cells and treated with Fansidar (20 mg/kg body weight sulfadoxine and 1 mg/kg body weight pyrimethamine orally) on day 5 after inoculation. Parasitemia in these mice decreased rapidly on day 1 after treatment. Blood hemoglobin concentration, however, decreased on days 1 and 2 of treatment, then began to increase. The actual oxygen equilibrium curve (OEC) in vivo (actual pH; actual Pco2; 36.5 degrees C) was calculated from the measured OEC and the results of blood gas analysis. Looking from arterial and venous Po2 of each group, blood oxygen-transporting properties decreased markedly on day 2 of treatment. This decrease resulted mainly from the decrease of hemoglobin concentration and also partly from the raised hemoglobin affinity for oxygen. Adenosine triphosphate concentration in liver tissues, however, began to increase on day 1 of treatment. Adenylate energy charge of liver tissues also recovered on day 1. Blood glucose concentration began to increase and blood lactate concentration began to decrease simultaneously on day 1 of treatment. Glucose concentration in liver tissues, in contrast, decreased on days 1 and 2 of inoculation. Lactate concentration in liver tissue decreased earlier on day 1. These data indicate that tissue hypoxia was removed on day 1 following antimalarial treatment although blood oxygen-transporting properties decreased on days 1 and 2 after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Trends of tissue hypoxia following chemotherapy of acute malaria in mice]. 178

Toxoplasmosis-retinochorioiditis is the second most frequent opportunistic infection of the eye among our series of AIDS patients. Between 1985 and 1990 we diagnosed 7 cases in 261 AIDS patients (Walter Reed classification 6); prevalence = 2.7%). The incidence has been increasing over the years. In four cases, toxoplasmosis was restricted to the eye, in three cases, ocular disease occurred combined with toxoplasmosis of the central nervous system. Since serological findings are not very reliable in AIDS-patients, the most important element in the differential diagnosis against retinitis of different etiology is ophthalmoscopy. There are a number of findings which allow differentiation of toxoplasmosis from other forms of retinitis, especially cytomegalovirus retinitis. Toxoplasmosis-retinitis was stopped in all cases by administering a specific therapy of pyrimethamine combined with clindamycin, a sulfonamide or spiramycin. Stable scar formation was achieved after 2-3 weeks therapy. Subsequent maintenance therapy with Fansidar (pyrimethamine + sulfadoxine) protected 4/4 patients from a relapse, while maintenance therapy with pyrimethamine alone allowed a relapse in 1/2 patients.
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PMID:[Prevalence, morphology and therapy of toxoplasmosis chorioretinitis in AIDS]. 179 94

Paludism can occur quite easily in pregnant women in endemic zones, above all those who are primiparous or in their 2nd or 3rd terms. The onset of paludal attacks can be serious for both the mother and the child. That is to say, besides the obviously imperative therapeutic action, a prophylaxis is also a necessity. The use of antipaludial substances at our disposal has been complicated during the last few years as a result of chloroquine-resistance extension. Besides a few nuances of kinetic nature observed in pregnant women, a good knowledge of teratogenous or embryotoxic effects is necessary. But this remains fragmentary. Among the principal antipaludial medications is quinine (Q), reported to be abortifacient but in reality it is not: it is often poorly tolerated by the mother (hypoglycemia), but is not responsible for abnormalities in children, except under large doses. Chloroquine (CQ), considered to be without harmful effects, can be used in women without large restrictions, even if toxic effects have been observed in animals. The pyrimethamine-sulfanilamide (P-S) combination contains two substances which are a potential risk. Nevertheless, experiments have never showed harmful effects in pregnant women, particularly when under cover of a joint prescription of folinic acid. Proguanil is without doubt the only molecule which can be used without restriction. Two new medications, quinoline methanol, Mefloquine (MQ) and Halofantrine (HF) are contra-indicated for lack of experimentation and because of some abnormalities observed at high doses in animals. Artemisinine and amino-8-quinoline are contra-indicated, and cyclines are strongly inadvised. From the practical point of view, the present use of antipaludial medication in pregnancy should take into account the surrounding risk, namely that of paludism and of treatments. Curatively, Q remains a serious treatment in any form. In CQ-sensitive zones CQ is usable unreservedly in simple attacks. In CQ resistance zones the use of Q seems preferable to that of Fansidar proposed by certain people. MQ and HF, although contra-indicated, have already been employed without inconvenience. By way of prevention, it is important first of all to avoid all leisure stays in endemic zones. If travel is unavoidable or for indigenous people, a chemoprophylaxis, judged according to the local risk of impaludation, is desirable: CQ in sensitive zones, PG+CQ in resistant zones, P-S, as proposed by some people, is normally contra-indicated; MQ and HF are contra-indicated. Protection against nocturnal mosquito bites is still strongly applied (Mosquito net, repellents, insecticides).
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PMID:[Antimalarials and pregnancy]. 181 22

Between 1987 and 1990, susceptibility of Plasmodium falciparum to chloroquine and to Fansidar was measured in vivo in 151 volunteers using the standard 7-day test. All volunteers lived in Arso PIR, Irian Jaya. A 25 mg/kg dose of chloroquine base was administered over a three-day period to 92 volunteers positive for P. falciparum rings (greater than 10 rings/200 white blood cells). Fifty volunteers (54%) showed results consistent with resistance. Twenty-nine were classified RII, and 21 RIII. In November 1989, a single curative dose of Fansidar was administered to 59 volunteers divided among three groups with 18 months, four years, and life-long exposure to endemic malaria. The proportion of volunteers in each group still positive for P. falciparum on day 7 of followup was 54%, 0%, and 14%, respectively. Thus, immune status profoundly effected clinically response to Fansidar. Standard in vitro microtests were also performed on parasites from 11 volunteers against chloroquine, amodiaquine, quinine, pyrimethamine/sulfadoxine, and and mefloquine. Nine of ten isolates showed in vitro growth consistent with resistance to chloroquine. Tests with other drugs showed few isolates with results considered indicative of susceptibility. Arso PIR has a severe drug resistance problem.
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PMID:Resistance to antimalarials by Plasmodium falciparum in Arso PIR, Irian Jaya, Indonesia. 185 67

Studies were conducted to examine the effect of activated charcoal on the disposition kinetics of sulphadoxine after Fansidar administration. Activated charcoal caused a significant reduction in ka, half-life and AUC0-48hr from 1.4 to 0.7 hr, 256 to 117 hr and 2533 to 1346 mg/l/hr, respectively. Activated charcoal absorbed sulphadoxine effectively in vitro. Sulphadoxine, at a simulated highly toxic dose of 5 mg/ml, showed adsorption percentages of 23.06, 28.66, 41.24, 64 and 100 to amounts of activated charcoal of 12.5, 25, 50, 100 and 250 mg, respectively. The results show that activated charcoal effectively adsorbs sulphadoxine both in vitro and in vivo.
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PMID:Effect of activated charcoal on the disposition of sulphadoxine. 188 27

From July 1983 to March 1984 a randomized double blind prophylactic trial in Thai gem miners working across the border in Cambodia was conducted to determine the prophylactic efficacy of 3 drug regimens against P. falciparum and P. vivax malaria along the Thai-Cambodian border. Gem miners have a high incidence of malaria. Maximum duration of individual participation was 14 weeks. Of 334 participants in this study who were seen every 2 weeks, 145 received mefloquine 500 mg fortnightly, 112 received chloroquine 300 mg base weekly plus Fansidar (1000 mg sulfadoxine and 50 mg pyrimethamine) fortnightly and 77 received chloroquine as 300 mg base weekly. The significant reduction of vivax malaria in study subjects (compared to background incidence) implied good compliance with self administration of chloroquine in the intervening weeks between scheduled appointments. The attack rate in each prophylactic regimen was 2188 cases/1000/year with mefloquine, 8338 cases/1000/year with chloroquine-Fansidar and 10,207 cases/1000/year receiving chloroquine alone. There was a 79% prophylactic efficacy for mefloquine and 18% efficacy for the chloroquine plus Fansidar regimen compared to chloroquine. Using life table analysis, 56% of the mefloquine group, 6% of the chloroquine-Fansidar group and 4% of the chloroquine group were malaria free at the end of the 14 weeks study. The chloroquine plus sulfadoxine-pyrimethamine regimen prescribed for prophylaxis is no longer effective for multidrug resistant strains of P. falciparum in the study area. This study also seriously questions the efficacy of mefloquine prophylaxis.
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PMID:Comparison of mefloquine, chloroquine plus pyrimethamine-sulfadoxine (Fansidar), and chloroquine as malarial prophylaxis in eastern Thailand. 194 77

Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium falciparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prevalence of this mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. falciparum strains from a wide section of the Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrimethamine resistance, four samples contained only the wild-type Ser-108 codon AGC, and none contained the Thr-108 codon ACC found in cycloguanil-resistant pyrimethamine-sensitive strains. These findings indicate that a very high incidence of the Asn-108 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are consistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine.
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PMID:Prevalence of the dihydrofolate reductase Asn-108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the Brazilian Amazon. 195 58

We reported a rare case of Plasmodium vivax malaria who showed findings of disseminated intravascular coagulation (DIC). A 50-year-old Japanese male was sent to our hospital with the diagnosis of Plasmodium vivax malaria on the 26th of April, 1990. He had stayed in the Solomon Islands from Oct. 1987 to Dec. 1989, and had febrile episodes during his stay in the island. On April 18, 1990, he complained of a high fever with chills, and showed the same episodes on the 20th, 22th and was diagnosed as malaria. He was treated successfully with the sulfadoxine 500 mg and pyrimethamine 25mg (Fansidar), following the normal temperature on the 4th day and disappearance of malarial parasites in the peripheral blood smear on the 6th day. Interestingly, he had thrombocytopenia and a high titer serum level of fibrin degradation product (FDP) supporting the questionable diagnosis of DIC. Even on the 12th day after improved thrombocytopenia by treatment with Gabexate (FOY), the serum level of FDP, D-dimer and thrombin-nati-thrombin (TAT)III complex still remained at high titer levels. One month later he was readmitted for a relapse of Plasmodium vivax malaria, when he showed thrombocytopenia but the serum level of FDP, D-dimer, TAT III complex and PM.alpha 2 PI complex were normal levels. We concluded that the thrombocytopenia and the high titer of FDP at his first admission was a manifestation of DIC.
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PMID:[A case of Plasmodium vivax malaria with findings of DIC]. 207 64

88 asymptomatic Tanzanian schoolchildren with Plasmodium falciparum parasitaemia were given all, half or quarter of the recommended standard therapeutic dose of sulfadoxine-pyrimethamine (Fansidar). All children cleared the parasites by day 3 and all remained negative during 28-42 days of follow-up. All 32 successful in vitro micro-tests showed full sensitivity. High performance liquid chromatographic methods were applied for drug determinations. Using 100 microliter capillary blood dried on filter paper for sulfadoxine determination the inter-individual variation during follow-up of the standard dose group was 2-4 fold and the median half life was 8.9 d. Sulfadoxine concentrations in the half and quarter dose groups were roughly proportional to those in the standard dose group. The median whole blood to plasma concentration ratio for sulfadoxine was 0.72 and the correlation coefficient 0.95. There was only a weak correlation (r=0.46) between plasma concentrations of sulfadoxine and pyrimethamine. The uniform efficacy of sulfadoxine-pyrimethamine in vivo, even when reduced doses were used, makes this combination a good alternative for treatment of P. falciparum in Tanzania.
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PMID:Standard and reduced doses of sulfadoxine-pyrimethamine for treatment of Plasmodium falciparum in Tanzania, with determination of drug concentrations and susceptibility in vitro. 209 29

All reports of adverse reactions with pyrimethamine-sulphadoxine (Fansidar), pyrimethamine-dapsone (Maloprim), and amodiaquine spontaneously reported through the UK national post-marketing system were reviewed. Retrospective reporting rates of serious reactions associated with these drugs were analysed using prescription data from the Department of Health, derived from the Prescription Pricing Authority, and relevant pharmaceutical companies. Whilst interpretation of these data requires caution, they allowed comparison with reporting rates from other studies. The reported rate for all serious reactions to pyrimethamine-sulphadoxine was 1:2100 prescriptions, and for cutaneous reactions was 1:4900 prescriptions, with a fatality rate of 1:11,100. The reported rate for serious reactions to pyrimethamine-dapsone was 1:9100 prescriptions, and for blood dyscrasias was 1:20,000 prescriptions, with a fatality rate of 1:75,000. The reported rate of blood dyscrasias associated with amodiaquine was 1:2100 users with a fatality rate of 1:31,000. Serious hepatic disorders occurred in 1:11 1000 pyrimethamine-sulphadoxine prescriptions, 1:75,200 pyrimethamine-dapsone prescriptions, and in 1:15,650 amodiaquine users. 35% of cases received these drugs needlessly as they were not exposed to drug resistant strains of Plasmodium falciparum. Since few serious reactions have been reported to chloroquine plus proguanil, these data support guidelines which restrict the use of reviewed drugs for those at greatest risk of infection. Dosage data indicated that fatalities had taken higher doses and continued prophylaxis after onset of symptoms. Two thirds of serious reactions to the compound antimalarials were reported in females.
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PMID:Serious adverse drug reactions to pyrimethamine-sulphadoxine, pyrimethamine-dapsone and to amodiaquine in Britain. 221 17


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