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

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

The A.A. weight present criteria of choice in order to set right a correct and effective anti-malarial prophylaxis. In the last ten years, a progressive increase of tropical diseases has been observed. This is due to the considerable growth of intercontinental traffic and of the number of persons moving to or from tropical areas where such diseases are endemic. Among these, malaria represent the most alarming problem, both because of the incidence cases and the difficulties related to the efficacy of pharmacological remedies for the chemoprophylaxis. In particular, three are now various pharmacological possibilities for malarial prophylaxis. Undoubtedly Chloroquine is the most efficacious even if there are many Plasmodium falciparum species resistant to Chloroquine and to other available medicines (multi-resistance). Most authors recommend to associate Chloroquine to others pharmacological substances to avoid pharmaco-resistance phenomena. Among the most famous pharmacological products used elsewhere are Fansidar, Maloprim, Paludrine and Lapudrine, not all are available in Italy. In China, for the therapy of resistant forms of malaria, the Qinghaosu a "schizont-killer" acting on multiresistant plasmodium falciparum has been utilizing for years. The Qinghaosu is not responsible for the crossing-reactions with other anti-malarial medicines. Various substances with Ca-antagonist action (Verapamil) are being experimented. It is supposed that Verapamil associated with Chloroquine can stop the flow of chlorine from plasmodium cells. The same mechanism is expected to be valid also for Desipramine, an experimental tricyclic anti-depressive when associated to Chloroquine. To the people moving to endemic areas, the A.A., at the end, suggest a series of practical norms to prevent infection and, therefore, the incidence of imported cases, still increasing at the moment, due to the absence of efficacious vaccine.
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PMID:[A current problem: the prevention of malaria]. 248 2

In the treatment of severe Plasmodium falciparum infection antimalarial drugs should, ideally, be given by controlled rate intravenous infusion until the patient is able to swallow tablets. In cases where infection has been acquired in a chloroquine resistant area, and where it has broken through chloroquine prophylaxis or where the geographical origin or species are uncertain, quinine is the treatment of choice. When access to parenteral quinine is likely to be delayed, parenteral quinidine is an effective alternative. A loading dose of quinine is recommended in order to achieve therapeutic plasma concentrations as quickly as possible. In the case of chloroquine sensitive P. falciparum infection, chloroquine, which can be given safely by slow intravenous infusion, may be more rapidly effective and has fewer toxic effects than quinine. There is limited experience with parenteral administration of pyrimethamine sulphonamide combinations such as Fansidar, and resistance to these drugs has developed in South East Asia and elsewhere. Mefloquine and halofantrine cannot be given parenterally. Qinghaosu derivatives are not readily available and have not been adequately tested outside China. Supportive treatment includes the prevention or early detection and treatment of complications, strict attention to fluid balance, provision of adequate nursing for unconscious patients and avoidance of harmful ancillary treatments. Anaemia is inevitable and out of proportion to detectable parasitaemia. Hypotension and shock ('algid malaria') are often attributable to secondary gram-negative septicaemia requiring appropriate antimicrobial therapy and haemodynamic resuscitation. Many patients with severe falciparum malaria are hypovolaemic on admission to hospital and require cautious fluid replacement. Failure to rehydrate these patients may lead to circulatory collapse, lactic acidosis, renal failure and severe hyponatraemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of severe malaria. 269 26

The most recent acquisitions on chemotherapy and chemoprophylaxis of malaria are reviewed. With regard to chemotherapy, candidate antimalarial compounds have been divided into four groups, according to their stages of development. Mefloquine and the combination of mefloquine with sulfadoxine/pyrimethamine belong to the first group: they have completed clinical trials and have been registered in several countries for routine clinical use. The second group is characterized by chemical compounds which are in an advanced stage of development, including clinical trials. The compounds considered in this group are: a) the 9-phenanthrenemethanols, among which halofantrine is the most promising one; b) the sesquiterpene lactones such as Qinghaosu, artemether, artesunate, artesunic acid and arteether which must be further tested in order to find more effective drug regimens capable of eliminating recrudescences and for the completion of toxicity studies; c) pyronaridine, which appears to be a promising antimalarial, effective also against chloroquine-resistant P. falciparum, but still requiring further investigations on resistance and cross-resistance, as well as its pharmacokinetics, tolerability and bioavailability; d) enpiroline, another promising compound, which needs to be further studied in Phase II and Phase III investigations with naturally acquired malaria. The third group is composed of seven chemical classes of compounds that are in an advanced pre-clinical development, namely: the 4-aminoquinolines, such as dabechin, piperaquine, hydroxypiperaquine, tripiperaquine, dichlor-quinazine and the Mannich base compounds, the 8-aminoquinolines, the 4-quinolinemethanols, the quinolones, the naphthoquinones, the quinazolines and the dihydrotriazines. Among the many antimalarial compounds of interest, which can be considered at the moment as leads for further studies, only the acridandione derivatives such as floxacrine, the antibiotics, antifungal agents or their metabolites, plant substances such as Yingzhaosu A and quassinoids have been mentioned. Malaria chemoprophylaxis, especially in chloroquine-resistant P. falciparum areas, has become a real problem. The attempts to secure protection under these circumstances with the utilization of amodiaquine, the combination of sulfadoxine/pyrimethamine (Fansidar), sulfalene/pyrimethamine (Metakelfin), of pyrimethamine/dapsone (Maloprim), with or without chloroquine, had to be abandoned or to be used with caution in view of the severe complications following the weekly administration of these drugs. The combination of chloroquine with proguanil or chlorproguanil, which could be recommended on theoretical bases, did not meet the expectations when tested in the field. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recent acquisitions on chemotherapy and chemoprophylaxis of malaria. 269 8

A prospective trial in 80 patients randomly allocated to four antimalarial treatment regimens--mefloquine plus pyrimethamine-sulfadoxine ('Fansidar'); mefloquine plus qinghaosu; mefloquine, fansidar, and qinghaosu; and qinghaosu alone--was carried out on Hainan Island, China, in patients with chloroquine-resistant falciparum malaria. A radical cure with slight side-effects was obtained with mefloquine plus fansidar; the addition of qinghaosu greatly increased the rate of parasite clearance with no additional side-effects. Qinghaosu alone had a rapid rate of parasite clearance, no side-effects, but a high recrudescence rate. These antimalarial drugs seem to act at different stages of the asexual parasite cycle and their most efficient use may depend on when in the course of the disease they are given. Because of the continuing appearance of drug-resistant strains of Plasmodium falciparum combination drug therapy is now indicated, but which drugs and how best they should be used remains to be decided.
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PMID:Randomised comparative study of mefloquine, qinghaosu, and pyrimethamine-sulfadoxine in patients with falciparum malaria. 615 Mar 65

In the absence of a suitable malaria case definition, reliable surveillance data on the impact of malaria are not available. Determinants of case loads, including population movements, environmental changes, lack of political commitment and resources, and resistance to antimalarials and residual insecticides, work towards global deterioration. Some 90% of the Plasmodium falciparum burden is carried by Africa south of the Sahara. There, in 1992, the number of children under five years of age and exposed to high risk was about 106 million. Assuming a malaria attack rate of 0.5-1.5 per child per year, and a case fatality rate of 2%, annual clinical cases and malaria deaths in this population alone come to 53-160 million and 1-3 million, respectively. Roche, a pharmaceutical company with major research efforts in tropical medicine, in collaboration with research centers and international institutions, has recently set up a tropical medicine unit that coordinates and concentrates corporate efforts in this field. The unit aims to make affordable and innovative products available which are effective against major tropical diseases. A commercial product of the unit is Lariam, a major antimalarial used alone or in simultaneous or sequential combinations. The single dose combination of Lariam plus Fansidar (Fansimef) is particularly useful for stand-by or emergency oral therapy. Artemisinine, or its derivatives, followed by one to two doses of Lariam are effective against severe and multiresistant P. falciparum malaria. A new Roche peroxide antimalarial is currently in phase II clinical trials. The unit is also involved in research and development of malaria sporozoite and asexual blood stage vaccine candidates.
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PMID:Commitment of Roche in malaria and other tropical diseases. 825 5