El nacimiento de la especialidad farmacéutica / Birth of the pharmaceutical specialty

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On the history of Cinchona bark in the treatment of Malaria.

How and when the medical value of Cinchona bark was discovered is obscure, but it is said that the powder was given to a European for malaria for the first time in the 1630s. The bark was brought to Europe by Spanish missionaries and it was recommended by the cardinal Juan de Lugo. In the 1660s, the use of Cinchona bark became known in England - and in Denmark by Thomas Bartholin. It was used for the treatment of malaria, but several debates on its value continued up to the 1730s. However, successful treatment of malaria was obtained by Thomas Sydenham, Robert Tabor and Francesco Torti. Sydenham emphasized a modern view that Cinchona bark was a unique specific drug for the treatment of malaria, and the treatment was fully accepted when Torti's Therapeutice specialis appeared. In the early 18th century, botanical expeditions were arranged in search of the most valuable Cinchona species for cultivation. The content of quinine was impor- tant, and determination of quinine was realized when Pierre Pelletier and Joseph Caventou isolated the alkaloid from the bark in 1820. Dutch plantations and quinine industry dominated the market, but the supply of quinine came to an end when the Japanese occupied Indonesia in 1942, cutting off the rest of the world from the main supplies of Cinchona. Synthetic antimalarials were developed and chloroquine became the drug of choice, but the intensive use of these drugs caused drug resistance. Chloroquine-resistant strains of P. falciparum are now treated with other drugs as artemisinin and artemether.

Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance.

The emergence and spread of antimalarial resistance has been a major liability for malaria control. The spread of chloroquine-resistant Plasmodium falciparum strains had catastrophic consequences for people in malaria-endemic regions, particularly in sub-Saharan Africa. The recent emergence of artemisinin-resistant P. falciparum strains is of highest concern. Current efforts to contain artemisinin resistance have yet to show success. In the absence of more promising plans, it has been suggested to eliminate falciparum malaria from foci of artemisinin resistance using a multipronged approach, including mass drug administrations. The use of mass drug administrations is controversial as it increases drug pressure. Based on current knowledge it is difficult to conceptualize how targeted malaria elimination could contribute to artemisinin resistance, provided a full treatment course is ensured.

A resistência à cloroquina e a busca de antimalariais entre as décadas de 1960 e 1980 / Chloroquine resistance and the search for antimalarial drugs from the 1960s to 1980s

Em 1961, a Organização Mundial de Saúde (OMS) reconheceu a resistência de cepas de Plasmodium à cloroquina, o que estimulou programas de pesquisa e desenvolvimento de novas drogas sintéticas que pudessem substituí-la no combate à malária. Analiso o processo de pesquisa científica relativo à produção de antimalariais nos contextos nacional e internacional, em especial nos EUA e na China, entre as décadas de 1960 e 1980. Pontos de convergência e distanciamento são marcados pelas dinâmicas próprias de cada país e pelos interesses envolvidos nas relações internacionais, em relação aos quais fica evidente o papel central da OMS.(AU)

A resistência à cloroquina e a busca de antimalariais entre as décadas de 1960 e 1980 / Chloroquine resistance and the search for antimalarial drugs from the 1960s to 1980s

Em 1961, a Organização Mundial de Saúde (OMS) reconheceu a resistência de cepas de Plasmodium à cloroquina, o que estimulou programas de pesquisa e desenvolvimento de novas drogas sintéticas que pudessem substituí-la no combate à malária. Analiso o processo de pesquisa científica relativo à produção de antimalariais nos contextos nacional e internacional, em especial nos EUA e na China, entre as décadas de 1960 e 1980. Pontos de convergência e distanciamento são marcados pelas dinâmicas próprias de cada país e pelos interesses envolvidos nas relações internacionais, em relação aos quais fica evidente o papel central da OMS.

Seventy-five years of Resochin in the fight against malaria.

The four different forms of human malaria have threatened humanity since time immemorial and to this day, they exact a death toll of one to three million people annually. Synthetic anti-malarial agents have been in development since early 1900. Perhaps the most successful and widely used drug, Resochin (chloroquine), was discovered 75 years ago; for a long time, it was the drug of choice and to this day, it is still used in many regions of the world as a reliable treatment against simpler forms of malaria. In regions where it has not been in use against malaria tropica for quite some time due to the development of resistances, it has regained some of its efficacy. This review traces the discovery and the mechanism of action of this substance, illustrates the significance of malaria today, and underlines the need for controlled and reliable therapeutic measures.

Parasites and progress: ethical decision-making and the Santee-Cooper Malaria study, 1944-1949.

As part of a mid-1940s malaria research program, U.S. Public Health Service researchers working in South Carolina chose to withhold treatment from a group of subjects while testing the efficacy of a new insecticide. Research during World War II had generated new tools to fight malaria, including the insecticide DDT and the medication chloroquine. The choices made about how to conduct research in one of the last pockets of endemic malaria in the United States reveal much about prevailing attitudes and assumptions with regard to malaria control. We describe this research and explore the ethical choices inherent in the tension between environmentally based interventions and the individual health needs of the population living within the study domain. The singular focus on the mosquito and its lifecycle led some researchers to view the humans in their study area as little more than parasite reservoirs, an attitude fueled by the frustrating disappearance of malaria just when the scientists were on the verge of establishing the efficacy of a powerful new agent in the fight against malaria. This analysis of their choices has relevance to broader questions in public health ethics.

History and importance of antimalarial drug resistance.

The emergence of Plasmodium falciparum resistance to widely used antimalarial drugs such as chloroquine (CQ) has made malaria control and treatment much more difficult. This is particularly dramatic for Africa, as few affordable alternatives are available. Drug pressure has been identified as one of the key factors for the emergence and spread of resistance. The contribution of the extensive use and misuse of antimalarial drugs to the selection of resistant parasites became particularly evident during the Global Malaria Eradication campaign, launched by World Health Organization (WHO) in 1955. The first reports confirming P. falciparum resistance to CQ came almost simultaneously in the early 1960s from South America and South-East Asia, where direct or indirect (through use of medicated cooking salt) mass drug administration (MDA) had been implemented. Similar approaches were very limited in Africa, where P. falciparum resistance to CQ was first reported from the eastern region in the late 1970s and spread progressively west. Most African countries still rely heavily on CQ as first-line treatment despite various levels of resistance, although some states have changed to sulphadoxine-pyrimethamine (SP) as the first-line drug. Unfortunately, the predicted SP useful therapeutic life might be very short, probably because of its prolonged half-life, causing a higher probability of selecting resistant strains and a consequent fast development of resistance. CQ resistance is not evenly distributed and important differences can be found within and between countries. It seems to have spread more rapidly in East than in West Africa. Considering the high level of CQ use in West Africa, other factors such as intensity of transmission, population immunity or population movements should be considered when explaining the different levels of resistance. Understanding such factors may help us in devising strategies to contain the spread of drug resistance.

From chloroquine to antineoplastic drugs? the story of antibacterial quinolones.

Chemotherapy has not only proved valuable in treating many diseases but the history of discovery of some drugs makes exciting reading. The aim of this article is to outline one such story.

Localized permanent epidemics: the genesis of chloroquine resistance in Plasmodium falciparum.

Localized permanent epidemics occur when, for an indefinite period of time, there is a temporary but continuous introduction of unprotected non-immunes into the same locality of a hyperendemic area. The main epidemiological factors involved in the genesis of localized permanent epidemics were encountered in Pailin (Cambodia) the epicenter of drug resistance in Southeast Asia: a very efficient vector, Anopheles dirus, exophilic and of limited distribution with, therefore, adjacent hyperendemic and non-endemic areas; a permanent pole of attraction in the hyperendemic area: Pailin's sapphires and rubies; a temporary but continuous influx of non-immunes into the pole of attraction: continuous influx of non-immunes into the Pailin gem mining area. In the gem-mining Pailin village drug pressure was considerable: mass drug administration, a medicated salt project and permanent self-medication with very high doses, much higher doses being required to cure non-immunes with heavy infections and severe clinical attacks in epidemic situations. It appears, therefore, that the emergence of chloroquine resistance in Southeast Asia was the consequence of the localized permanent epidemics in Païlin. High level resistance was the result of continuous and intensive serial passages of P. falciparum in the non-immune subjects, large numbers of parasites being exposed to a high level of drug pressure at each passage. Similar epidemiological conditions are encountered in some parts of South America where the exophilic vector is An. nuneztovari. In Colombia, whose eastern mountains bordering Venezuela yield the most highly prized emeralds in the world, chloroquine resistance was detected at about the same time as in Southeast Asia.(ABSTRACT TRUNCATED AT 250 WORDS)