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Wikipedia

Quinine

January 12, 2023

Not to be confused with quinidine, quinone, quinoline, or chloroquine.
For the Nine album, see Quinine (album).

Quinine is a medication used to treat malaria and babesiosis.[4] This includes the treatment of malaria due to Plasmodium falciparum that is resistant to chloroquine when artesunate is not available.[4][5] While sometimes used for nocturnal leg cramps, quinine is not recommended for this purpose due to the risk of serious side effects.[4] It can be taken by mouth or intravenously.[4] Malaria resistance to quinine occurs in certain areas of the world.[4] Quinine is also used as an ingredient in tonic water to impart a bitter taste.[6]

Quinine
Clinical data
PronunciationUS: /ˈkwaɪnaɪn/, /kwɪˈniːn/ or UK: /ˈkwɪniːn/ KWIN-een
Trade namesQualaquin, Quinbisul, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa682322
License data
Pregnancy
category
Routes of
administration		By mouth, intramuscular, intravenous, rectal
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding70–95%[3]
MetabolismLiver (mostly CYP3A4 and CYP2C19-mediated)
Elimination half-life8–14 hours (adults), 6–12 hours (children)[3]
ExcretionKidney (20%)
Identifiers
  • (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol
CAS Number
  • 130-95-0 Y
PubChem CID
  • 8549
IUPHAR/BPS
  • 2510
DrugBank
  • DB00468 Y
ChemSpider
  • 84989 Y
UNII
  • A7V27PHC7A
KEGG
  • D08460 Y
ChEBI
  • CHEBI:15854 N
ChEMBL
  • ChEMBL170 Y
CompTox Dashboard (EPA)
  • DTXSID0044280
ECHA InfoCard100.004.550
Chemical and physical data
FormulaC20H24N2O2
Molar mass324.424 g·mol−1
3D model (JSmol)
  • Interactive image
Melting point177 °C (351 °F)
  • [H][C@@]1([C@@H](C2=CC=NC3=CC=C(C=C23)OC)O)C[C@@H]4CC[N@]1C[C@@H]4C=C
  • InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19-,20+/m0/s1 Y
  • Key:LOUPRKONTZGTKE-WZBLMQSHSA-N Y
 NY (what is this?)  (verify)

Common side effects include headache, ringing in the ears, vision issues, and sweating.[4] More severe side effects include deafness, low blood platelets, and an irregular heartbeat.[4] Use can make one more prone to sunburn.[4] While it is unclear if use during pregnancy causes harm to the baby, treating malaria during pregnancy with quinine when appropriate is still recommended.[4] Quinine is an alkaloid, a naturally occurring chemical compound.[4] How it works as a medicine is not entirely clear.[4]

Quinine was first isolated in 1820 from the bark of a cinchona tree, which is native to Peru,[4][7][8] and its molecular formula was determined by Strecker in 1854.[9] The class of chemical compounds to which it belongs is thus called the cinchona alkaloids. Bark extracts had been used to treat malaria since at least 1632 and it was introduced to Spain as early as 1636 by Jesuit missionaries returning from the New World.[10] It is on the World Health Organization's List of Essential Medicines.[11][12] Treatment of malaria with quinine marks the first known use of a chemical compound to treat an infectious disease.[13]

Uses

Medical

As of 2006, quinine is no longer recommended by the World Health Organization (WHO) as a first-line treatment for malaria, because there are other substances that are equally effective with fewer side effects. They recommend that it be used only when artemisinins are not available.[14][15][16][17] Quinine is also used to treat lupus and arthritis.

Quinine was frequently prescribed as an off-label treatment for leg cramps at night, but this has become less common due to a warning from the US Food and Drug Administration (FDA) that such practice is associated with life-threatening side effects.[18][19][20] Quinine can also act as a competitive inhibitor of monoamine oxidase (MAO), an enzyme that removes neurotransmitters from the brain. As an MAO inhibitor, it has potential to serve as a treatment for individuals with psychological disorders similar to antidepressants that inhibit MAO.[21]

Available forms

Quinine is a basic amine and is usually provided as a salt. Various existing preparations include the hydrochloride, dihydrochloride, sulfate, bisulfate and gluconate. In the United States, quinine sulfate is commercially available in 324-mg tablets under the brand name Qualaquin.

All quinine salts may be given orally or intravenously (IV); quinine gluconate may also be given intramuscularly (IM) or rectally (PR).[22][23] The main problem with the rectal route is that the dose can be expelled before it is completely absorbed; in practice, this is corrected by giving a further half dose. No injectable preparation of quinine is licensed in the US; quinidine is used instead.[24][25]

Quinine base in various salts
Name Quinine base equivalence
Quinine base 100 mg
Quinine bisulfate 169 mg
Quinine dihydrochloride 122 mg
Quinine gluconate 160 mg
Quinine hydrochloride 111 mg
Quinine sulfate dihydrate [(quinine)2H2SO4∙2H2O] 121 mg

Beverages

See also: Tonic water
 
Tonic water, in normal light and ultraviolet "black light". The quinine content of tonic water causes it to fluoresce under black light.

Quinine is a flavor component of tonic water and bitter lemon drink mixers. On the soda gun behind many bars, tonic water is designated by the letter "Q" representing quinine.[26]

Tonic water was initially marketed as a means of delivering quinine to consumers in order to offer anti-malarial protection. According to tradition, because of the bitter taste of anti-malarial quinine tonic, British colonials in India mixed it with gin to make it more palatable, thus creating the gin and tonic cocktail, which is still popular today.[27] While it is possible to drink enough tonic water to temporarily achieve quinine levels that offer anti-malarial protection, it is not a sustainable long-term means of protection.[28]

In France, quinine is an ingredient of an apéritif known as quinquina, or "Cap Corse," and the wine-based apéritif Dubonnet. In Spain, quinine (also known as "Peruvian bark" for its origin from the native cinchona tree) is sometimes blended into sweet Malaga wine, which is then called "Malaga Quina". In Italy, the traditional flavoured wine Barolo Chinato is infused with quinine and local herbs, and is served as a digestif. In Scotland, the company A.G. Barr uses quinine as an ingredient in the carbonated and caffeinated beverage Irn-Bru. In Uruguay and Argentina, quinine is an ingredient of a PepsiCo tonic water named Paso de los Toros. In Denmark, it is used as an ingredient in the carbonated sports drink Faxe Kondi made by Royal Unibrew.

As a flavouring agent in drinks, quinine is limited to less than 83 parts per million in the United States, and 100 mg⁄l in the European Union.[29][30][31]

Scientific

Quinine (and quinidine) are used as the chiral moiety for the ligands used in Sharpless asymmetric dihydroxylation as well as for numerous other chiral catalyst backbones. Because of its relatively constant and well-known fluorescence quantum yield, quinine is used in photochemistry as a common fluorescence standard.[32][33]

Contraindications

Because of the narrow difference between its therapeutic and toxic effects, quinine is a common cause of drug-induced disorders, including thrombocytopenia and thrombotic microangiopathy.[34] Even from minor levels occurring in common beverages, quinine can have severe adverse effects involving multiple organ systems, among which are immune system effects and fever, hypotension, hemolytic anemia, acute kidney injury, liver toxicity, and blindness.[34] In people with atrial fibrillation, conduction defects, or heart block, quinine can cause heart arrhythmias, and should be avoided.[35]

Quinine can cause hemolysis in G6PD deficiency (an inherited deficiency), but this risk is small and the physician should not hesitate to use quinine in people with G6PD deficiency when there is no alternative.[36]

Adverse effects

Quinine can cause unpredictable serious and life-threatening blood and cardiovascular reactions including low platelet count and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), long QT syndrome and other serious cardiac arrhythmias including torsades de pointes, blackwater fever, disseminated intravascular coagulation, leukopenia, and neutropenia.[4] Some people who have developed TTP due to quinine have gone on to develop kidney failure.[4][36] It can also cause serious hypersensitivity reactions including anaphylactic shock, urticaria, serious skin rashes, including Stevens–Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, granulomatous hepatitis, and itchiness.[4][36]

The most common adverse effects involve a group of symptoms called cinchonism, which can include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception.[4][34][36] More severe cinchonism includes vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in heart rhythms.[36] Cinchonism is much less common when quinine is given by mouth, but oral quinine is not well tolerated (quinine is exceedingly bitter and many people will vomit after ingesting quinine tablets).[4] Other drugs, such as Fansidar (sulfadoxine with pyrimethamine) or Malarone (proguanil with atovaquone), are often used when oral therapy is required. Quinine ethyl carbonate is tasteless and odourless,[37] but is available commercially only in Japan. Blood glucose, electrolyte and cardiac monitoring are not necessary when quinine is given by mouth.

Quinine has diverse unwanted interactions with numerous prescription drugs, such as potentiating the anticoagulant effects of warfarin.[4]

Mechanism of action

Quinine is used for its toxicity to the malarial pathogen, Plasmodium falciparum, by interfering with its ability to dissolve and metabolize hemoglobin.[4][38] As with other quinoline antimalarial drugs, the precise mechanism of action of quinine has not been fully resolved, although in vitro studies indicate it inhibits nucleic acid and protein synthesis, and inhibits glycolysis in P. falciparum.[4] The most widely accepted hypothesis of its action is based on the well-studied and closely related quinoline drug, chloroquine. This model involves the inhibition of hemozoin biocrystallization in the heme detoxification pathway, which facilitates the aggregation of cytotoxic heme.[medical citation needed] Free cytotoxic heme accumulates in the parasites, causing their deaths.[39] Quinine may target the malaria purine nucleoside phosphorylase enzyme.[40]

Chemistry

The UV absorption of quinine peaks around 350 nm (in UVA). Fluorescent emission peaks at around 460 nm (bright blue/cyan hue).[41] Quinine is highly fluorescent (quantum yield ~0.58) in 0.1 M sulfuric acid solution.[32][33]

Synthesis

Main article: Quinine total synthesis

Cinchona trees remain the only economically practical source of quinine. However, under wartime pressure during World War II, research towards its synthetic production was undertaken. A formal chemical synthesis was accomplished in 1944 by American chemists R.B. Woodward and W.E. Doering.[42] Since then, several more efficient quinine total syntheses have been achieved,[43] but none of them can compete in economic terms with isolation of the alkaloid from natural sources. The first synthetic organic dye, mauveine, was discovered by William Henry Perkin in 1856 while he was attempting to synthesize quinine.

Biosynthesis

 
Quinine biosynthesis

In the first step of quinine biosynthesis, the enzyme strictosidine synthase catalyzes a stereoselective Pictet–Spengler reaction between tryptamine and secologanin to yield strictosidine.[44][45] Suitable modification of strictosidine leads to an aldehyde. Hydrolysis and decarboxylation would initially remove one carbon from the iridoid portion and produce corynantheal. Then the tryptamine side-chain were cleaved adjacent to the nitrogen, and this nitrogen was then bonded to the acetaldehyde function to yield cinchonaminal. Ring opening in the indole heterocyclic ring could generate new amine and keto functions. The new quinoline heterocycle would then be formed by combining this amine with the aldehyde produced in the tryptamine side-chain cleavage, giving cinchonidinone. For the last step, hydroxylation and methylation gives quinine.[46][47]

Catalysis

Quinine and other Cinchona alkaloids can be used as catalysts for stereoselective reactions in organic synthesis.[48]: Table 3B Plate 560  For example, the quinine-catalyzed Michael addition of a malononitrile to α,β-enones gives a high degree of sterechemical control.[48]

History

See also: History of malaria
 
19th-century illustration of Cinchona calisaya

Quinine was used as a muscle relaxant by the Quechua people, who are indigenous to Peru, Bolivia and Ecuador, to halt shivering.[49] The Quechua would mix the ground bark of cinchona trees with sweetened water to offset the bark's bitter taste, thus producing something similar to tonic water.[50]

Spanish Jesuit missionaries were the first to bring cinchona to Europe. The Spanish had observed the Quechua's use of cinchona and were aware of the medicinal properties of cinchona bark by the 1570s or earlier: Nicolás Monardes (1571) and Juan Fragoso (1572) both described a tree, which was subsequently identified as the cinchona tree, whose bark was used to produce a drink to treat diarrhea.[51] Quinine has been used in unextracted form by Europeans since at least the early 17th century.[52]

A popular story of how it was brought to Europe by the Countess of Chinchon was debunked by medical historian Alec Haggis around 1941.[53] During the 17th century, malaria was endemic to the swamps and marshes surrounding the city of Rome. It had caused the deaths of several popes, many cardinals and countless common Roman citizens. Most of the Catholic priests trained in Rome had seen malaria patients and were familiar with the shivering brought on by the febrile phase of the disease.

The Jesuit Agostino Salumbrino (1564–1642),[54] an apothecary by training who lived in Lima (now in present-day Peru), observed the Quechua using the bark of the cinchona tree to treat such shivering. While its effect in treating malaria (and malaria-induced shivering) was unrelated to its effect in controlling shivering from rigors, it was a successful medicine against malaria. At the first opportunity, Salumbrino sent a small quantity to Rome for testing as a malaria treatment.[55] In the years that followed, cinchona bark, known as Jesuit's bark or Peruvian bark, became one of the most valuable commodities shipped from Peru to Europe. When King Charles II was cured of malaria at the end of the 17th Century with quinine, it became popular in London.[56] It remained the antimalarial drug of choice until the 1940s, when other drugs took over.[57]

The form of quinine most effective in treating malaria was found by Charles Marie de La Condamine in 1737.[58][59] In 1820, French researchers Pierre Joseph Pelletier and Joseph Bienaimé Caventou first isolated quinine from the bark of a tree in the genus Cinchona – probably Cinchona pubescens – and subsequently named the substance.[60] The name was derived from the original Quechua (Inca) word for the cinchona tree bark, quina or quina-quina, which means "bark of bark" or "holy bark". Prior to 1820, the bark was dried, ground to a fine powder, and mixed into a liquid (commonly wine) in order to be drunk. Large-scale use of quinine as a malaria prophylaxis started around 1850. In 1853 Paul Briquet published a brief history and discussion of the literature on "quinquina".[61]

Quinine played a significant role in the colonization of Africa by Europeans. The availability of quinine for treatment had been said to be the prime reason Africa ceased to be known as the "white man's grave". A historian said, "it was quinine's efficacy that gave colonists fresh opportunities to swarm into the Gold Coast, Nigeria and other parts of west Africa".[62]

To maintain their monopoly on cinchona bark, Peru and surrounding countries began outlawing the export of cinchona seeds and saplings in the early 19th century. In 1865, Manuel Incra Mamani collected seeds from a plant particularly high in quinine and provided them to Charles Ledger. Ledger sent them to his brother, who sold them to the Dutch government. Mamani was arrested on a seed collecting trip in 1871, and beaten so severely, likely because of providing the seeds to foreigners, that he died soon afterwards.[63]

By the late 19th century the Dutch grew the plants in Indonesian plantations. Soon they became the main suppliers of the tree. In 1913 they set up the Kina Bureau, a cartel of cinchona producers charged with controlling price and production.[64] By the 1930s Dutch plantations in Java were producing 22 million pounds of cinchona bark, or 97% of the world's quinine production.[62] U.S. attempts to prosecute the Kina Bureau proved unsuccessful.[64]

During World War II, Allied powers were cut off from their supply of quinine when Germany conquered the Netherlands, and Japan controlled the Philippines and Indonesia. The US had obtained four million cinchona seeds from the Philippines and began operating cinchona plantations in Costa Rica. Additionally, they began harvesting wild cinchona bark during the Cinchona Missions. Such supplies came too late. Tens of thousands of US troops in Africa and the South Pacific died of malaria due to the lack of quinine.[62] Despite controlling the supply, the Japanese did not make effective use of quinine, and thousands of Japanese troops in the southwest Pacific died as a result.[65][66][67][68]

Quinine remained the antimalarial drug of choice until after World War II. Since then, other drugs that have fewer side effects, such as chloroquine, have largely replaced it.[69]

Bromo Quinine were brand name cold tablets containing quinine, manufactured by Grove Laboratories. They were first marketed in 1889 and available until at least the 1960s.[70]

Conducting research in central Missouri, John S. Sappington independently developed an anti-malaria pill from quinine. Sappington began importing cinchona bark from Peru in 1820. In 1832, using quinine derived from the cinchona bark, Sappington developed a pill to treat a variety of fevers, such as scarlet fever, yellow fever, and influenza in addition to malaria. These illnesses were widespread in the Missouri and Mississippi valleys. He manufactured and sold "Dr. Sappington's Anti-Fever Pills" across Missouri. Demand became so great that within three years, Sappington founded a company known as Sappington and Sons to sell his pills nationwide.[71]

Society and culture

Natural occurrence

The bark of Remijia contains 0.5–2% of quinine. The bark is cheaper than bark of Cinchona. As it has an intense taste, it is used for making tonic water.[72]

Regulation in the US

From 1969, to 1992, the US Food and Drug Administration (FDA) received 157 reports of health problems related to quinine use, including 23 which had resulted in death.[73] In 1994, the FDA banned the marketing of over-the-counter quinine as a treatment for nocturnal leg cramps. Pfizer Pharmaceuticals had been selling the brand name Legatrin for this purpose. Also sold as a Softgel (by SmithKlineBeecham) as Q-vel.[citation needed] Doctors may still prescribe quinine, but the FDA has ordered firms to stop marketing unapproved drug products containing quinine. The FDA is also cautioning consumers about off-label use of quinine to treat leg cramps.[18][19] Quinine is approved for treatment of malaria, but was also commonly prescribed to treat leg cramps and similar conditions. Because malaria is life-threatening, the risks associated with quinine use are considered acceptable when used to treat that condition.[74]

Though Legatrin was banned by the FDA for the treatment of leg cramps, the drug manufacturer URL Mutual has branded a quinine-containing drug named Qualaquin. It is marketed as a treatment for malaria and is sold in the United States only by prescription. In 2004, the CDC reported only 1,347 confirmed cases of malaria in the United States.[75]

Cutting agent

Quinine is sometimes detected as a cutting agent in street drugs such as cocaine and heroin.[76]

Other animals

Quinine is used as a treatment for Cryptocaryon irritans (commonly referred to as white spot, crypto or marine ich) infection of marine aquarium fish.[77]

References

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  47. ^ O'Connor SE, Maresh JJ (August 2006). "Chemistry and biology of monoterpene indole alkaloid biosynthesis". Natural Product Reports. 23 (4): 532–547. doi:10.1039/b512615k. PMID 16874388.
  48. ^ a b Reyes E, Uria U, Vicario JL, Carrillo L (13 September 2016), "The Catalytic, Enantioselective Michael Reaction", Organic Reactions, Hoboken, NJ, USA: John Wiley & Sons, Inc., pp. 1–898, doi:10.1002/0471264180.or090.01, ISBN 978-0-471-26418-7
  49. ^ Flückiger FA, Hanbury D (1874). "Cortex Cinchonæ". Pharmacographia: A History of the Principal Drugs of Vegetable Origin, Met with in Great Britain and British India. London: Macmillan and Co. pp. 302–331.
  50. ^ Hobbs K, West D (2020). The Story of Trees : and how they changed the way we live. illustrated by Thibaud Hérem. London: Laurence King. p. 148. ISBN 978-1-7862-7522-6.
  51. ^ See:
    • Ortiz Crespo FI (1995). "Fragoso, Monardes and pre-Chinchonian knowledge of Cinchona". Archives of Natural History. 22 (2): 169–181. doi:10.3366/anh.1995.22.2.169. ISSN 0260-9541.
    • Stuart DC (2004). Dangerous Garden: The Quest for Plants to Change Our Lives. Cambridge, MA: Harvard University Press. p. 28. ISBN 978-0-674-01104-5.
    • Monardes N (1580). Primera y segunda y tercera partes de la Historia medicinal, de las cosas que se traen de nuestras Indias Occidentales, que sirven en Medicina (in Spanish). Seville, Spain: Fernando Díaz. pp. 74–75. Del nuevo Reyno, traen una corteza, que dizen ser de un arbol, que es de mucha grandeza: el qual dizen que lleva unas hojas en forma de coraçon, y que no lleva fruto. Este arbol tiene una corteza gruessa, muy solida y dura, que en esto y en el color parece mucho a la corteza del palo que llaman Guayacan: en la superficie tiene una pelicula delgada blanquisca, quebrada por toda ella: tiene la corteza mas de un dedo de gruesso, solida y pesada: la qual gustada tiene notable amargor, como el de la Genciana: tiene en el gusto notable astriction, con alguna aromaticidad, porque al fin de mascar la respica della buen olor. Tienen los Indios esta corteza en mucho, y usan della en todo genero de camaras, que sean con sangre, o sin ella. Los Españoles fatigados de aquesta enfermedad, por aviso de los Indios, han usado de aquesta corteza y han sanado muchos dellos con ella.
      Toman della tanto como una haba pequeña hecha polvos, tomase en vino tinto, o en agua apropiada, como tienen la calentura, o mal: hase de tomar por la mañana en ayunas, tres o quatro vezes: usando en lo demas, la orden y regimiento que conviene a los que tienen camaras.       [From the new kingdom, there is brought a bark, which is said to be from a tree, which is very large: it is said that it bears leaves in the form of a heart, and that it bears no fruit. This tree has a thick bark, very solid and hard, that in this and in its color looks much like the bark of the tree that is called guayacán: on the surface, it has a thin, discontinuous whitish film throughout it: it has bark more than one finger thick, solid and heavy: which, when tasted, has a considerable bitterness, like that of the gentian: it has in its taste a considerable astringency, with some aromaticity, because at the end of chewing it, one breathes with a sweet odor. The Indians hold this bark in high regard, and use it for all sorts of diarrhea, that are with blood [i.e., bloody] and without it. The Spanish [who are] tired of this disease, on the advice of the Indians, have used this bark and have healed many of those with it. They take as much as a small bean, make [it into] powder, take it in red wine or in appropriate water, if they have fever or illness: it must be taken in the morning on an empty stomach, three or four times: otherwise, using the order and regimen that suits those who have diarrhea.]
    • Fragoso J (1572). Discursos de las cosas aromaticas, arboles y frutales, y de otras muchas medicinas simples que se traen de la India Oriental y que sirven al uso de medicina [Discourse on fragrant things, trees and fruits, as well as many other ordinary medicines that have been brought from India and the Orient and are of use to medicine] (in Spanish). Madrid, Spain: Francisco Sánchez. p. 35. En el nuevo mundo ay un grande arbol que lleva las hojas a forma de coraçon, y carece de fruto. Tiene dos cortezas, la una gruessa muy solida y dura, que assi en la sustancia como en el color es muy semejante al Guayacan: la otra es mas delgada y blanquezina, la qual es amarga con alguna estipticidad: y demas desto es aromatica. Tienenla en mucho nuestros Indios, porque la usan contra qualesquier camaras, tomando del polvo peso de una drama o poco mas, desatado en agua azerada, o vino tinto. [In the new world, there is a big tree that bears leaves in the form of a heart, and lacks fruit. It has two barks, one [is] thick, very solid, [and] hard, which in substance as well as in color is much like guayacan [i.e., lignum vitae]: the other is thinner and whitish, which is bitter with some styptic [i.e., astringent] quality: and besides this, it is aromatic. Our Indians regard it highly, because they use it against any diarrheas, taking a weight of a dram or a bit more of the powder, mixing it in mineral water, or red wine.]
  52. ^ Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, et al. (May 2011). "Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria". Malaria Journal. 10: 144. doi:10.1186/1475-2875-10-144. PMC 3121651. PMID 21609473.
  53. ^ Pain S (15 September 2001). "The Countess and the cure". New Scientist.
  54. ^ de Andrade A (3 August 1642). "Vida del Devoto Hermano Agustin Salumbrino" [The life of the devout Brother Agustin Salumbrino]. Varones ilustres en santidad, letras y zelo de las almas de la Compañía de Jesús [Illustrious men in holiness, letters, and zeal for souls of the Society of Jesus]. Varones ilustres de la Compañía de Jesús (in Spanish). Vol. 5. Original series by Juan Eusebio Nieremberg. Madrid, Spain: José Fernandez de Buendía (published 1666). pp. 612–628. p. 612: Naciò el Hermano Agustin Salumbrino el año de mil y quinientos y sesenta y quatro en la Ciudad de Fḷọṛi en la Romania […] [Brother Agustino Salumbrino was born in the year 1564 in the city of Forlì in Romagna]
  55. ^ See:
    • Medina Rodríguez F, Aceves Ávila FJ, Moreno Rodríguez J (2007). "Precisions on the History of Quinine". Reumatología Clínica. Letters to the Editor. 3 (4): 194–196. doi:10.1016/S2173-5743(07)70246-0. ISSN 2173-5743. In fact, though the last wordon this has not yet been spoken, there are Jesuit texts thatmention that quinine reached Rome in 1632, with theprovincial of the Jesuit missions in Peru, father AlonsoMessia Venegas, as its introducer, when he brought asample of the bark to present it as a primacy, and whohad left Lima 2 years earlier, because evidence of his stayin Seville 1632 has been registered, publishing one of hisbooks there and following his way to Rome as a procurator.
    • Torres Saldamando E (June 1882). "El P. Diego de Torres Vazquez". Los antiguos jesuitas del Perú (in Spanish). Lima, Peru: Imprenta Liberal. pp. 180–181. p. 181: Al siguiente año se dirigieron á Europa los Procuradores P. Alonso Messía Venegas y P. Hernando de Leon Garavito, llevando gran cantidad de la corteza de la quina, cuyo conocimiento extendieron por el mundo los jesuitas. [In the following year [i.e., 1631] there went to Europe the procurators Father Alonso Messia Venegas and Father Hernando de Leon Garavito, taking a great quantity of cinchona bark, knowledge of which the Jesuits spread throughout the world.]
    • Bailetti A. "Capítulo 10: La Condesa de Chinchón". LA MISIÓN DEL JESUITA AGUSTÍN SALUMBRINO, la malaria y el árbol de quina. A últimas horas de la tarde del treinta y uno de mayo de 1631 se hizo a la vela la Armada Real con dirección a Panamá llevando el precioso cargamento de oro y plata.
      En una de las naves viajaban los procuradores jesuitas padres Alonso Messia y Hernando León Garavito custodiando los fardos con la corteza de quina en polvo preparados por Salumbrino. Después de casi veinte días de navegación el inapreciable medicamento llegó a la ciudad de Panamá, donde fue descargado para cruzar en mulas el agreste camino del itsmo palúdico hasta Portobelo para seguir a Cartagena y la Habana, cruzar el Atlántico y llegar a Sanlúcar de Barrameda en Sevilla. […] Finalmente siguió su camino a Roma y a su destino final el Hospital del Espíritu Santo.       [Late in the afternoon of 31 May 1631, the royal armada set sail in the direction of Panama, carrying its multimillion [dollar] cargo of gold and silver.
      On one of the ships traveled the Jesuit procurators Fathers Alonso Messia and Hernando León Garavito, guarding the cases of powdered cinchona bark, prepared by Salumbrino. After almost 20 days of sailing, medicine arrived in the city of Panama, where it was transloaded onto mules. It then traveled the malarial isthmus as far as Portobelo, thence to Cartagena [in Colombia] and Havana. It then traveled to Sanlúcar de Barrameda in Seville, [Spain]. […] Finally it followed the road to Rome and to its final destination, the Hospital of the Holy Spirit]
  56. ^ Rocco F (2004). Quinine: malaria and the quest for a cure that changed the world. New York, NY: Perennial.
  57. ^ Humphrey L (2000). Quinine and Quarantine. Columbia, Missouri: University of Missouri Press.
  58. ^ Charles Marie de la Condamine (29 May 1737). "Sur l'arbre du quinquina". Histoire de l'Académie royale des sciences. Imprimerie Royale (published 1740). pp. 226–243.
  59. ^ De Jussieu accompanied de la Condamine on the latter's expedition to Peru: de Jussieu J (1737). Description de l'arbre à quinquina. Paris: Société du traitement des quinquinas (published 1934).
  60. ^ Pelletier PJ, Caventou JB (1820). "Recherches Chimiques sur les Quinquinas" [Continuation: Chemical Research on Quinquinas]. Annales de Chimie et de Physique (in French). Crochard. 15: 337–365. The authors name quinine on page 348: " …, nous avons cru devoir la nommer quinine, pour la distinguer de la cinchonine par un nom qui indique également son origine." ( …, we thought that we should name it "quinine" in order to distinguish it from cinchonine by means of a name that also indicates its origin.)
  61. ^ Briquet P (1853). Traité thérapeutique du quinone et de ses préparations (in French). Paris: L. Martinet.
  62. ^ a b c Conner CD (2005). A People's History of Science: Miners, Midwives, and 'Low Mechanicks'. New York: Nation Books. pp. 95–96. ISBN 978-1-56025-748-6. Also cites Porter R (1998). The Greatest Benefit to Mankind: A Medical History of Humanity. New York: W. W. Norton. pp. 465–466. ISBN 978-0-393-04634-2.
  63. ^ Canales NA (7 April 2022). "Hunting lost plants in botanical collections". Wellcome Collection. Retrieved 9 May 2022.
  64. ^ a b Shah S (2010). The Fever: How Malaria Has Ruled Humankind for 500,000 Years. Farrar, Straus and Giroux. p. 94.
  65. ^ Louis Morton (1953). "29". The Fall of the Philippines. Washington, D.C.: United States Army. p. 524. from the original on 25 May 2017.
  66. ^ Alan Hawk. "Remembering the war in New Guinea: Japanese Medical Corps – malaria". from the original on 22 November 2011.
  67. ^ Lt. Gen. Leonard D. Heaton, ed. (1963). "8". Preventive Medicine in World War II: Volume VI, Communicable Diseases: Malaria. Washington, D.C.: Department of the Army. pp. 401 and 434. from the original on 29 January 2012.
  68. ^ "Notes on Japanese Medical Services". Tactical and Technical Trends (36). 1943. from the original on 14 October 2011.
  69. ^ Shah S (2010). The Fever: How Malaria Has Ruled Humankind for 500,000 Years. Farrar, Straus and Giroux. p. 102.
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  71. ^ "John. S Sappington". Historic Missourians. State Historical Society of Missouri.
  72. ^ Hobhouse H (2004). Šest rostlin, které změnily svět (in Czech). Prague: Akademie věd České republiky. p. 59. ISBN 978-80-200-1179-4.
  73. ^ . FDA Consumer Magazine. U.S. Food and Drug Administration (FDA). July–August 1995. Archived from the original on 15 January 2008. Retrieved 31 July 2009.
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  75. ^ Skarbinski J, James EM, Causer LM, Barber AM, Mali S, Nguyen-Dinh P, et al. (May 2006). "Malaria surveillance--United States, 2004" (PDF). Morbidity and Mortality Weekly Report. Surveillance Summaries. 55 (4): 23–37. PMID 16723971.
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Further reading

  • Schroeder-Lein G (2008). The encyclopedia of Civil War medicine. Armonk, NY: Sharpe, Inc.
  • Hobhouse H (2005) [1986]. Seeds of Change: Six Plants That Transformed Mankind. Berkeley, CA: Counterpoint. ISBN 978-1-59376-049-6.
  • Stockwell JR (October 1982). "Aeromedical considerations of malaria prophylaxis with mefloquine hydrochloride". Aviation, Space, and Environmental Medicine. 53 (10): 1011–1013. PMID 6983345.
  • Wolff RS, Wirtschafter D, Adkinson C (June 1997). . Undersea & Hyperbaric Medicine. 24 (2): 131–134. PMID 9171472. Archived from the original on 11 August 2011. Retrieved 13 August 2008.{{cite journal}}: CS1 maint: unfit URL (link)
  • Slater L (2009). War and disease : biomedical research on malaria in the twentieth century. New Brunswick, NJ: Rutgers University Press.
  • Lloyd HD (June 1884). "Lords of Industry". The North American Review. University of Northern Iowa. 138 (331): 535–553. ISSN 0029-2397. JSTOR 25118388.
  • World Health Organization (2015). Guidelines for the treatment of malaria, 3rd ed (3rd ed.). World Health Organization (WHO). hdl:10665/162441. ISBN 9789241549127.

External links

 
Look up quinine in Wiktionary, the free dictionary.
  • Quinine at the Drug Information Portal
  • Quinine at the International Programme on Chemical Safety
  • "Quinine". Resource Center. Chemwatch.

January 12, 2023
quinine, confused, with, quinidine, quinone, quinoline, chloroquine, nine, album, album, medication, used, treat, malaria, babesiosis, this, includes, treatment, malaria, plasmodium, falciparum, that, resistant, chloroquine, when, artesunate, available, while,. Not to be confused with quinidine quinone quinoline or chloroquine For the Nine album see Quinine album Quinine is a medication used to treat malaria and babesiosis 4 This includes the treatment of malaria due to Plasmodium falciparum that is resistant to chloroquine when artesunate is not available 4 5 While sometimes used for nocturnal leg cramps quinine is not recommended for this purpose due to the risk of serious side effects 4 It can be taken by mouth or intravenously 4 Malaria resistance to quinine occurs in certain areas of the world 4 Quinine is also used as an ingredient in tonic water to impart a bitter taste 6 QuinineClinical dataPronunciationUS ˈ k w aɪ n aɪ n k w ɪ ˈ n iː n or UK ˈ k w ɪ n iː n KWIN eenTrade namesQualaquin Quinbisul others 1 AHFS Drugs comMonographMedlinePlusa682322License dataUS DailyMed Quinine US FDA QuininePregnancycategoryAU D 2 Routes ofadministrationBy mouth intramuscular intravenous rectalATC codeM09AA01 WHO P01BC01 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US onlyPharmacokinetic dataProtein binding70 95 3 MetabolismLiver mostly CYP3A4 and CYP2C19 mediated Elimination half life8 14 hours adults 6 12 hours children 3 ExcretionKidney 20 IdentifiersIUPAC name R 6 Methoxyquinolin 4 yl 1S 2S 4S 5R 5 vinylquinuclidin 2 yl methanolCAS Number130 95 0 YPubChem CID8549IUPHAR BPS2510DrugBankDB00468 YChemSpider84989 YUNIIA7V27PHC7AKEGGD08460 YChEBICHEBI 15854 NChEMBLChEMBL170 YCompTox Dashboard EPA DTXSID0044280ECHA InfoCard100 004 550Chemical and physical dataFormulaC 20H 24N 2O 2Molar mass324 424 g mol 13D model JSmol Interactive imageMelting point177 C 351 F SMILES H C 1 C H C2 CC NC3 CC C C C23 OC O C C H 4CC N 1C C H 4C CInChI InChI 1S C20H24N2O2 c1 3 13 12 22 9 7 14 13 10 19 22 20 23 16 6 8 21 18 5 4 15 24 2 11 17 16 18 h3 6 8 11 13 14 19 20 23H 1 7 9 10 12H2 2H3 t13 14 19 20 m0 s1 YKey LOUPRKONTZGTKE WZBLMQSHSA N Y N Y what is this verify Common side effects include headache ringing in the ears vision issues and sweating 4 More severe side effects include deafness low blood platelets and an irregular heartbeat 4 Use can make one more prone to sunburn 4 While it is unclear if use during pregnancy causes harm to the baby treating malaria during pregnancy with quinine when appropriate is still recommended 4 Quinine is an alkaloid a naturally occurring chemical compound 4 How it works as a medicine is not entirely clear 4 Quinine was first isolated in 1820 from the bark of a cinchona tree which is native to Peru 4 7 8 and its molecular formula was determined by Strecker in 1854 9 The class of chemical compounds to which it belongs is thus called the cinchona alkaloids Bark extracts had been used to treat malaria since at least 1632 and it was introduced to Spain as early as 1636 by Jesuit missionaries returning from the New World 10 It is on the World Health Organization s List of Essential Medicines 11 12 Treatment of malaria with quinine marks the first known use of a chemical compound to treat an infectious disease 13 Contents 1 Uses 1 1 Medical 1 1 1 Available forms 1 2 Beverages 1 3 Scientific 2 Contraindications 3 Adverse effects 4 Mechanism of action 5 Chemistry 5 1 Synthesis 5 2 Biosynthesis 5 3 Catalysis 6 History 7 Society and culture 7 1 Natural occurrence 7 2 Regulation in the US 7 3 Cutting agent 8 Other animals 9 References 10 Further reading 11 External linksUses EditMedical Edit As of 2006 quinine is no longer recommended by the World Health Organization WHO as a first line treatment for malaria because there are other substances that are equally effective with fewer side effects They recommend that it be used only when artemisinins are not available 14 15 16 17 Quinine is also used to treat lupus and arthritis Quinine was frequently prescribed as an off label treatment for leg cramps at night but this has become less common due to a warning from the US Food and Drug Administration FDA that such practice is associated with life threatening side effects 18 19 20 Quinine can also act as a competitive inhibitor of monoamine oxidase MAO an enzyme that removes neurotransmitters from the brain As an MAO inhibitor it has potential to serve as a treatment for individuals with psychological disorders similar to antidepressants that inhibit MAO 21 Available forms Edit Quinine is a basic amine and is usually provided as a salt Various existing preparations include the hydrochloride dihydrochloride sulfate bisulfate and gluconate In the United States quinine sulfate is commercially available in 324 mg tablets under the brand name Qualaquin All quinine salts may be given orally or intravenously IV quinine gluconate may also be given intramuscularly IM or rectally PR 22 23 The main problem with the rectal route is that the dose can be expelled before it is completely absorbed in practice this is corrected by giving a further half dose No injectable preparation of quinine is licensed in the US quinidine is used instead 24 25 Quinine base in various salts Name Quinine base equivalenceQuinine base 100 mgQuinine bisulfate 169 mgQuinine dihydrochloride 122 mgQuinine gluconate 160 mgQuinine hydrochloride 111 mgQuinine sulfate dihydrate quinine 2H2SO4 2H2O 121 mgBeverages Edit See also Tonic water Tonic water in normal light and ultraviolet black light The quinine content of tonic water causes it to fluoresce under black light Quinine is a flavor component of tonic water and bitter lemon drink mixers On the soda gun behind many bars tonic water is designated by the letter Q representing quinine 26 Tonic water was initially marketed as a means of delivering quinine to consumers in order to offer anti malarial protection According to tradition because of the bitter taste of anti malarial quinine tonic British colonials in India mixed it with gin to make it more palatable thus creating the gin and tonic cocktail which is still popular today 27 While it is possible to drink enough tonic water to temporarily achieve quinine levels that offer anti malarial protection it is not a sustainable long term means of protection 28 In France quinine is an ingredient of an aperitif known as quinquina or Cap Corse and the wine based aperitif Dubonnet In Spain quinine also known as Peruvian bark for its origin from the native cinchona tree is sometimes blended into sweet Malaga wine which is then called Malaga Quina In Italy the traditional flavoured wine Barolo Chinato is infused with quinine and local herbs and is served as a digestif In Scotland the company A G Barr uses quinine as an ingredient in the carbonated and caffeinated beverage Irn Bru In Uruguay and Argentina quinine is an ingredient of a PepsiCo tonic water named Paso de los Toros In Denmark it is used as an ingredient in the carbonated sports drink Faxe Kondi made by Royal Unibrew As a flavouring agent in drinks quinine is limited to less than 83 parts per million in the United States and 100 mg l in the European Union 29 30 31 Scientific Edit Quinine and quinidine are used as the chiral moiety for the ligands used in Sharpless asymmetric dihydroxylation as well as for numerous other chiral catalyst backbones Because of its relatively constant and well known fluorescence quantum yield quinine is used in photochemistry as a common fluorescence standard 32 33 Contraindications EditBecause of the narrow difference between its therapeutic and toxic effects quinine is a common cause of drug induced disorders including thrombocytopenia and thrombotic microangiopathy 34 Even from minor levels occurring in common beverages quinine can have severe adverse effects involving multiple organ systems among which are immune system effects and fever hypotension hemolytic anemia acute kidney injury liver toxicity and blindness 34 In people with atrial fibrillation conduction defects or heart block quinine can cause heart arrhythmias and should be avoided 35 Quinine can cause hemolysis in G6PD deficiency an inherited deficiency but this risk is small and the physician should not hesitate to use quinine in people with G6PD deficiency when there is no alternative 36 Adverse effects EditQuinine can cause unpredictable serious and life threatening blood and cardiovascular reactions including low platelet count and hemolytic uremic syndrome thrombotic thrombocytopenic purpura HUS TTP long QT syndrome and other serious cardiac arrhythmias including torsades de pointes blackwater fever disseminated intravascular coagulation leukopenia and neutropenia 4 Some people who have developed TTP due to quinine have gone on to develop kidney failure 4 36 It can also cause serious hypersensitivity reactions including anaphylactic shock urticaria serious skin rashes including Stevens Johnson syndrome and toxic epidermal necrolysis angioedema facial edema bronchospasm granulomatous hepatitis and itchiness 4 36 The most common adverse effects involve a group of symptoms called cinchonism which can include headache vasodilation and sweating nausea tinnitus hearing impairment vertigo or dizziness blurred vision and disturbance in color perception 4 34 36 More severe cinchonism includes vomiting diarrhea abdominal pain deafness blindness and disturbances in heart rhythms 36 Cinchonism is much less common when quinine is given by mouth but oral quinine is not well tolerated quinine is exceedingly bitter and many people will vomit after ingesting quinine tablets 4 Other drugs such as Fansidar sulfadoxine with pyrimethamine or Malarone proguanil with atovaquone are often used when oral therapy is required Quinine ethyl carbonate is tasteless and odourless 37 but is available commercially only in Japan Blood glucose electrolyte and cardiac monitoring are not necessary when quinine is given by mouth Quinine has diverse unwanted interactions with numerous prescription drugs such as potentiating the anticoagulant effects of warfarin 4 Mechanism of action EditThis section is missing information about cramp mechanism MAOI action aforementioned Please expand the section to include this information Further details may exist on the talk page December 2022 Quinine is used for its toxicity to the malarial pathogen Plasmodium falciparum by interfering with its ability to dissolve and metabolize hemoglobin 4 38 As with other quinoline antimalarial drugs the precise mechanism of action of quinine has not been fully resolved although in vitro studies indicate it inhibits nucleic acid and protein synthesis and inhibits glycolysis in P falciparum 4 The most widely accepted hypothesis of its action is based on the well studied and closely related quinoline drug chloroquine This model involves the inhibition of hemozoin biocrystallization in the heme detoxification pathway which facilitates the aggregation of cytotoxic heme medical citation needed Free cytotoxic heme accumulates in the parasites causing their deaths 39 Quinine may target the malaria purine nucleoside phosphorylase enzyme 40 Chemistry EditThe UV absorption of quinine peaks around 350 nm in UVA Fluorescent emission peaks at around 460 nm bright blue cyan hue 41 Quinine is highly fluorescent quantum yield 0 58 in 0 1 M sulfuric acid solution 32 33 Synthesis Edit Main article Quinine total synthesis Cinchona trees remain the only economically practical source of quinine However under wartime pressure during World War II research towards its synthetic production was undertaken A formal chemical synthesis was accomplished in 1944 by American chemists R B Woodward and W E Doering 42 Since then several more efficient quinine total syntheses have been achieved 43 but none of them can compete in economic terms with isolation of the alkaloid from natural sources The first synthetic organic dye mauveine was discovered by William Henry Perkin in 1856 while he was attempting to synthesize quinine Biosynthesis Edit Quinine biosynthesis In the first step of quinine biosynthesis the enzyme strictosidine synthase catalyzes a stereoselective Pictet Spengler reaction between tryptamine and secologanin to yield strictosidine 44 45 Suitable modification of strictosidine leads to an aldehyde Hydrolysis and decarboxylation would initially remove one carbon from the iridoid portion and produce corynantheal Then the tryptamine side chain were cleaved adjacent to the nitrogen and this nitrogen was then bonded to the acetaldehyde function to yield cinchonaminal Ring opening in the indole heterocyclic ring could generate new amine and keto functions The new quinoline heterocycle would then be formed by combining this amine with the aldehyde produced in the tryptamine side chain cleavage giving cinchonidinone For the last step hydroxylation and methylation gives quinine 46 47 Catalysis Edit Quinine and other Cinchona alkaloids can be used as catalysts for stereoselective reactions in organic synthesis 48 Table 3B Plate 560 For example the quinine catalyzed Michael addition of a malononitrile to a b enones gives a high degree of sterechemical control 48 History EditSee also History of malaria 19th century illustration of Cinchona calisaya Quinine was used as a muscle relaxant by the Quechua people who are indigenous to Peru Bolivia and Ecuador to halt shivering 49 The Quechua would mix the ground bark of cinchona trees with sweetened water to offset the bark s bitter taste thus producing something similar to tonic water 50 Spanish Jesuit missionaries were the first to bring cinchona to Europe The Spanish had observed the Quechua s use of cinchona and were aware of the medicinal properties of cinchona bark by the 1570s or earlier Nicolas Monardes 1571 and Juan Fragoso 1572 both described a tree which was subsequently identified as the cinchona tree whose bark was used to produce a drink to treat diarrhea 51 Quinine has been used in unextracted form by Europeans since at least the early 17th century 52 A popular story of how it was brought to Europe by the Countess of Chinchon was debunked by medical historian Alec Haggis around 1941 53 During the 17th century malaria was endemic to the swamps and marshes surrounding the city of Rome It had caused the deaths of several popes many cardinals and countless common Roman citizens Most of the Catholic priests trained in Rome had seen malaria patients and were familiar with the shivering brought on by the febrile phase of the disease The Jesuit Agostino Salumbrino 1564 1642 54 an apothecary by training who lived in Lima now in present day Peru observed the Quechua using the bark of the cinchona tree to treat such shivering While its effect in treating malaria and malaria induced shivering was unrelated to its effect in controlling shivering from rigors it was a successful medicine against malaria At the first opportunity Salumbrino sent a small quantity to Rome for testing as a malaria treatment 55 In the years that followed cinchona bark known as Jesuit s bark or Peruvian bark became one of the most valuable commodities shipped from Peru to Europe When King Charles II was cured of malaria at the end of the 17th Century with quinine it became popular in London 56 It remained the antimalarial drug of choice until the 1940s when other drugs took over 57 The form of quinine most effective in treating malaria was found by Charles Marie de La Condamine in 1737 58 59 In 1820 French researchers Pierre Joseph Pelletier and Joseph Bienaime Caventou first isolated quinine from the bark of a tree in the genus Cinchona probably Cinchona pubescens and subsequently named the substance 60 The name was derived from the original Quechua Inca word for the cinchona tree bark quina or quina quina which means bark of bark or holy bark Prior to 1820 the bark was dried ground to a fine powder and mixed into a liquid commonly wine in order to be drunk Large scale use of quinine as a malaria prophylaxis started around 1850 In 1853 Paul Briquet published a brief history and discussion of the literature on quinquina 61 Quinine played a significant role in the colonization of Africa by Europeans The availability of quinine for treatment had been said to be the prime reason Africa ceased to be known as the white man s grave A historian said it was quinine s efficacy that gave colonists fresh opportunities to swarm into the Gold Coast Nigeria and other parts of west Africa 62 To maintain their monopoly on cinchona bark Peru and surrounding countries began outlawing the export of cinchona seeds and saplings in the early 19th century In 1865 Manuel Incra Mamani collected seeds from a plant particularly high in quinine and provided them to Charles Ledger Ledger sent them to his brother who sold them to the Dutch government Mamani was arrested on a seed collecting trip in 1871 and beaten so severely likely because of providing the seeds to foreigners that he died soon afterwards 63 By the late 19th century the Dutch grew the plants in Indonesian plantations Soon they became the main suppliers of the tree In 1913 they set up the Kina Bureau a cartel of cinchona producers charged with controlling price and production 64 By the 1930s Dutch plantations in Java were producing 22 million pounds of cinchona bark or 97 of the world s quinine production 62 U S attempts to prosecute the Kina Bureau proved unsuccessful 64 During World War II Allied powers were cut off from their supply of quinine when Germany conquered the Netherlands and Japan controlled the Philippines and Indonesia The US had obtained four million cinchona seeds from the Philippines and began operating cinchona plantations in Costa Rica Additionally they began harvesting wild cinchona bark during the Cinchona Missions Such supplies came too late Tens of thousands of US troops in Africa and the South Pacific died of malaria due to the lack of quinine 62 Despite controlling the supply the Japanese did not make effective use of quinine and thousands of Japanese troops in the southwest Pacific died as a result 65 66 67 68 Quinine remained the antimalarial drug of choice until after World War II Since then other drugs that have fewer side effects such as chloroquine have largely replaced it 69 Bromo Quinine were brand name cold tablets containing quinine manufactured by Grove Laboratories They were first marketed in 1889 and available until at least the 1960s 70 Conducting research in central Missouri John S Sappington independently developed an anti malaria pill from quinine Sappington began importing cinchona bark from Peru in 1820 In 1832 using quinine derived from the cinchona bark Sappington developed a pill to treat a variety of fevers such as scarlet fever yellow fever and influenza in addition to malaria These illnesses were widespread in the Missouri and Mississippi valleys He manufactured and sold Dr Sappington s Anti Fever Pills across Missouri Demand became so great that within three years Sappington founded a company known as Sappington and Sons to sell his pills nationwide 71 Society and culture EditNatural occurrence Edit The bark of Remijia contains 0 5 2 of quinine The bark is cheaper than bark of Cinchona As it has an intense taste it is used for making tonic water 72 Regulation in the US Edit From 1969 to 1992 the US Food and Drug Administration FDA received 157 reports of health problems related to quinine use including 23 which had resulted in death 73 In 1994 the FDA banned the marketing of over the counter quinine as a treatment for nocturnal leg cramps Pfizer Pharmaceuticals had been selling the brand name Legatrin for this purpose Also sold as a Softgel by SmithKlineBeecham as Q vel citation needed Doctors may still prescribe quinine but the FDA has ordered firms to stop marketing unapproved drug products containing quinine The FDA is also cautioning consumers about off label use of quinine to treat leg cramps 18 19 Quinine is approved for treatment of malaria but was also commonly prescribed to treat leg cramps and similar conditions Because malaria is life threatening the risks associated with quinine use are considered acceptable when used to treat that condition 74 Though Legatrin was banned by the FDA for the treatment of leg cramps the drug manufacturer URL Mutual has branded a quinine containing drug named Qualaquin It is marketed as a treatment for malaria and is sold in the United States only by prescription In 2004 the CDC reported only 1 347 confirmed cases of malaria in the United States 75 Cutting agent Edit Quinine is sometimes detected as a cutting agent in street drugs such as cocaine and heroin 76 Other animals EditQuinine is used as a treatment for Cryptocaryon irritans commonly referred to as white spot crypto or marine ich infection of marine aquarium fish 77 References Edit Quinine International Drugs com 2 November 2020 Retrieved 8 November 2020 a b Quinine Use During Pregnancy Drugs com 25 March 2020 Retrieved 13 August 2020 a b Qualaquin quinine dosing indications interactions adverse effects and more Medscape Reference WebMD Archived from the original on 2 February 2014 Retrieved 29 January 2014 a b c d e f g h i j k l m n o p q r s t Quinine sulfate Drugs com 20 February 2020 Retrieved 14 May 2020 Esu EB Effa EE Opie ON Meremikwu MM June 2019 Artemether for severe malaria The Cochrane Database of Systematic Reviews 6 6 CD010678 doi 10 1002 14651858 CD010678 pub3 PMC 6580442 PMID 31210357 Olmsted J Williams GM 1997 Chemistry The Molecular Science Jones amp Bartlett Learning p 137 ISBN 978 0 815 18450 8 Archived from the original on 15 September 2016 Willcox M 28 June 2004 Traditional Medicinal Plants and Malaria CRC Press p 231 ISBN 9780203502327 Cechinel Filho V 2012 Plant bioactives and drug discovery principles practice and perspectives Hoboken N J John Wiley amp Sons p 2 ISBN 9780470582268 Archived from the original on 4 March 2016 Strecker A 1854 Ueber einen neuen aus Aldehyd Ammoniak und Blausaure entstehenden Korper Liebigs Ann Chem 91 3 349 351 doi 10 1002 jlac 18540910309 Staines HM Krishna S 2011 Treatment and Prevention of Malaria Antimalarial Drug Chemistry Action and Use S l Springer Verlag p 45 ISBN 9783034604796 World Health Organization 2019 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO World Health Organization 2021 World Health Organization model list of essential medicines 22nd list 2021 Geneva World Health Organization hdl 10665 345533 WHO MHP HPS EML 2021 02 Quinine Encyclopedia Britannica Retrieved 12 November 2021 World Health Organization 2006 Guidelines for the treatment of malaria PDF World Health Organization Archived from the original PDF on 5 August 2009 Retrieved 10 August 2009 Dondorp A Nosten F Stepniewska K Day N White N 2005 Artesunate versus quinine for treatment of severe falciparum malaria a randomised trial Lancet 366 9487 717 725 doi 10 1016 S0140 6736 05 67176 0 PMID 16125588 S2CID 173027 Reyburn H Mtove G Hendriksen I von Seidlein L July 2009 Oral quinine for the treatment of uncomplicated malaria PDF BMJ 339 b2066 doi 10 1136 bmj b2066 PMID 19622550 S2CID 206891479 Achan J Tibenderana JK Kyabayinze D Wabwire Mangen F Kamya MR Dorsey G et al July 2009 Effectiveness of quinine versus artemether lumefantrine for treating uncomplicated falciparum malaria in Ugandan children randomised trial BMJ 339 b2763 doi 10 1136 bmj b2763 PMC 2714631 PMID 19622553 a b FDA Drug Safety Communication New risk management plan and patient Medication Guide for Qualaquin quinine sulfate U S Food and Drug Administration FDA 7 August 2010 Archived from the original on 19 February 2011 Retrieved 21 February 2011 a b Serious risks associated with using Quinine to prevent or treat nocturnal leg cramps September 2012 U S Food and Drug Administration FDA 31 August 2012 Archived from the original on 22 October 2016 Retrieved 19 January 2020 Quinine for Night Time Leg Cramps Consumer Reports Retrieved 20 January 2020 Mitsui N Noro T Kuroyanagi M Miyase T Umehara K Ueno A February 1989 Monoamine oxidase inhibitors from Cinchonae Cortex Chemical amp Pharmaceutical Bulletin 37 2 363 366 doi 10 1248 cpb 37 363 PMID 2743481 Barennes H Pussard E Mahaman Sani A Clavier F Kahiatani F Granic G et al May 1996 Efficacy and pharmacokinetics of a new intrarectal quinine formulation in children with Plasmodium falciparum malaria British Journal of Clinical Pharmacology 41 5 389 395 doi 10 1046 j 1365 2125 1996 03246 x PMC 2042609 PMID 8735679 Barennes H Balima Koussoube T Nagot N Charpentier JC Pussard E May 2006 Safety and efficacy of rectal compared with intramuscular quinine for the early treatment of moderately severe malaria in children randomised clinical trial BMJ 332 7549 1055 1059 doi 10 1136 bmj 332 7549 1055 PMC 1458599 PMID 16675812 Centers for Disease Control and Prevention April 1991 Treatment with quinidine gluconate of persons with severe Plasmodium falciparum infection discontinuation of parenteral quinine from CDC Drug Service MMWR Recommendations and Reports 40 RR 4 21 23 PMID 1850497 Magill A Panosian C July 2005 Making antimalarial agents available in the United States The New England Journal of Medicine 353 4 335 337 doi 10 1056 NEJMp058167 PMID 16000347 Charming C 2006 Miss Charming s Guide for Hip Bartenders and Wayout Wannabes USA Sourcebooks Inc p 189 ISBN 978 1 4022 0804 1 Gin and Tonic The fascinating story behind the invention of the classic English cocktail India com 17 March 2017 Retrieved 8 June 2019 Meyer CG Marks F May J December 2004 Editorial Gin tonic revisited Tropical Medicine amp International Health 9 12 1239 1240 doi 10 1111 j 1365 3156 2004 01357 x PMID 15598254 S2CID 24261782 Ballestero JA Plazas PV Kracun S Gomez Casati ME Taranda J Rothlin CV et al September 2005 Effects of quinine quinidine and chloroquine on alpha9alpha10 nicotinic cholinergic receptors Molecular Pharmacology 68 3 822 829 doi 10 1124 mol 105 014431 PMID 15955868 S2CID 26907917 Food Additive Status List U S Food and Drug Administration U S Department of Health and Human Services Retrieved 9 October 2017 COMMISSION IMPLEMENTING REGULATION EU No 872 2012 EUR Lex Official Journal of the European Union Retrieved 9 October 2017 a b Lakowicz JR 2006 2 Instrumentation for Fluorescence Spectroscopy Principles of Fluorescence Spectroscopy 3rd ed Springer Science amp Business Media p 54 ISBN 978 0 387 46312 4 a b Prahl S Quinine sulfate OMLC Retrieved 16 August 2013 a b c Liles NW Page EE Liles AL Vesely SK Raskob GE George JN May 2016 Diversity and severity of adverse reactions to quinine A systematic review American Journal of Hematology 91 5 461 466 doi 10 1002 ajh 24314 PMID 26822544 Off label use of sildenafil in valvular heart disease should be avoided Clinical Pharmacist 2017 doi 10 1211 cp 2017 20203778 ISSN 2053 6178 a b c d e US label quinine sulfate PDF FDA April 2013 Archived PDF from the original on 20 January 2017 Jamaludin A Mohamad M Navaratnam V Selliah K Tan SC Wernsdorfer WH Yuen KH February 1988 Relative bioavailability of the hydrochloride sulphate and ethyl carbonate salts of quinine British Journal of Clinical Pharmacology 25 2 261 263 doi 10 1111 j 1365 2125 1988 tb03299 x PMC 1386482 PMID 3358888 Wishart DS Djombou Feunang Y Guo AC Lo EJ Marcu A Grant JR Sajed T Johnson D Li C Sayeeda Z Assempour N Iynkkaran I Liu Y Maciejewski A Gale N Wilson A Chin L Cummings R Le D Pon A Knox C Wilson M Quinine DrugBank Online DrugBank 5 0 Foley M Tilley L February 1997 Quinoline antimalarials mechanisms of action and resistance International Journal for Parasitology 27 2 231 240 doi 10 1016 s0020 7519 96 00152 x PMID 9088993 Lowe D 22 January 2019 Quinine s Target Science Retrieved 28 January 2019 Basic Concepts in Fluorescence Archived from the original on 13 September 2012 Woodward R Doering W 1944 The Total Synthesis of Quinine J Am Chem Soc 66 849 849 doi 10 1021 ja01233a516 Kaufman TS Ruveda EA 2005 Die Jagd auf Chinin Etappenerfolge und Gesamtsiege Angewandte Chemie International Edition in German 117 6 876 907 Bibcode 2005AngCh 117 876K doi 10 1002 ange 200400663 Treimer JF Zenk MH November 1979 Purification and properties of strictosidine synthase the key enzyme in indole alkaloid formation European Journal of Biochemistry 101 1 225 233 doi 10 1111 j 1432 1033 1979 tb04235 x PMID 510306 Mizukami H Nordlov H Lee SL Scott AI August 1979 Purification and properties of strictosidine synthetase an enzyme condensing tryptamine and secologanin from Catharanthus roseus cultured cells Biochemistry 18 17 3760 3763 doi 10 1021 bi00584a018 PMID 476085 Medicinal natural products a biosynthetic approach 3rdition ed Wiley pp 380 381 ISBN 9780470742761 O Connor SE Maresh JJ August 2006 Chemistry and biology of monoterpene indole alkaloid biosynthesis Natural Product Reports 23 4 532 547 doi 10 1039 b512615k PMID 16874388 a b Reyes E Uria U Vicario JL Carrillo L 13 September 2016 The Catalytic Enantioselective Michael Reaction Organic Reactions Hoboken NJ USA John Wiley amp Sons Inc pp 1 898 doi 10 1002 0471264180 or090 01 ISBN 978 0 471 26418 7 Fluckiger FA Hanbury D 1874 Cortex Cinchonae Pharmacographia A History of the Principal Drugs of Vegetable Origin Met with in Great Britain and British India London Macmillan and Co pp 302 331 Hobbs K West D 2020 The Story of Trees and how they changed the way we live illustrated by Thibaud Herem London Laurence King p 148 ISBN 978 1 7862 7522 6 See Ortiz Crespo FI 1995 Fragoso Monardes and pre Chinchonian knowledge of Cinchona Archives of Natural History 22 2 169 181 doi 10 3366 anh 1995 22 2 169 ISSN 0260 9541 Stuart DC 2004 Dangerous Garden The Quest for Plants to Change Our Lives Cambridge MA Harvard University Press p 28 ISBN 978 0 674 01104 5 Monardes N 1580 Primera y segunda y tercera partes de la Historia medicinal de las cosas que se traen de nuestras Indias Occidentales que sirven en Medicina in Spanish Seville Spain Fernando Diaz pp 74 75 Del nuevo Reyno traen una corteza que dizen ser de un arbol que es de mucha grandeza el qual dizen que lleva unas hojas en forma de coracon y que no lleva fruto Este arbol tiene una corteza gruessa muy solida y dura que en esto y en el color parece mucho a la corteza del palo que llaman Guayacan en la superficie tiene una pelicula delgada blanquisca quebrada por toda ella tiene la corteza mas de un dedo de gruesso solida y pesada la qual gustada tiene notable amargor como el de la Genciana tiene en el gusto notable astriction con alguna aromaticidad porque al fin de mascar la respica della buen olor Tienen los Indios esta corteza en mucho y usan della en todo genero de camaras que sean con sangre o sin ella Los Espanoles fatigados de aquesta enfermedad por aviso de los Indios han usado de aquesta corteza y han sanado muchos dellos con ella Toman della tanto como una haba pequena hecha polvos tomase en vino tinto o en agua apropiada como tienen la calentura o mal hase de tomar por la manana en ayunas tres o quatro vezes usando en lo demas la orden y regimiento que conviene a los que tienen camaras From the new kingdom there is brought a bark which is said to be from a tree which is very large it is said that it bears leaves in the form of a heart and that it bears no fruit This tree has a thick bark very solid and hard that in this and in its color looks much like the bark of the tree that is called guayacan on the surface it has a thin discontinuous whitish film throughout it it has bark more than one finger thick solid and heavy which when tasted has a considerable bitterness like that of the gentian it has in its taste a considerable astringency with some aromaticity because at the end of chewing it one breathes with a sweet odor The Indians hold this bark in high regard and use it for all sorts of diarrhea that are with blood i e bloody and without it The Spanish who are tired of this disease on the advice of the Indians have used this bark and have healed many of those with it They take as much as a small bean make it into powder take it in red wine or in appropriate water if they have fever or illness it must be taken in the morning on an empty stomach three or four times otherwise using the order and regimen that suits those who have diarrhea Fragoso J 1572 Discursos de las cosas aromaticas arboles y frutales y de otras muchas medicinas simples que se traen de la India Oriental y que sirven al uso de medicina Discourse on fragrant things trees and fruits as well as many other ordinary medicines that have been brought from India and the Orient and are of use to medicine in Spanish Madrid Spain Francisco Sanchez p 35 En el nuevo mundo ay un grande arbol que lleva las hojas a forma de coracon y carece de fruto Tiene dos cortezas la una gruessa muy solida y dura que assi en la sustancia como en el color es muy semejante al Guayacan la otra es mas delgada y blanquezina la qual es amarga con alguna estipticidad y demas desto es aromatica Tienenla en mucho nuestros Indios porque la usan contra qualesquier camaras tomando del polvo peso de una drama o poco mas desatado en agua azerada o vino tinto In the new world there is a big tree that bears leaves in the form of a heart and lacks fruit It has two barks one is thick very solid and hard which in substance as well as in color is much like guayacan i e lignum vitae the other is thinner and whitish which is bitter with some styptic i e astringent quality and besides this it is aromatic Our Indians regard it highly because they use it against any diarrheas taking a weight of a dram or a bit more of the powder mixing it in mineral water or red wine Achan J Talisuna AO Erhart A Yeka A Tibenderana JK Baliraine FN et al May 2011 Quinine an old anti malarial drug in a modern world role in the treatment of malaria Malaria Journal 10 144 doi 10 1186 1475 2875 10 144 PMC 3121651 PMID 21609473 Pain S 15 September 2001 The Countess and the cure New Scientist de Andrade A 3 August 1642 Vida del Devoto Hermano Agustin Salumbrino The life of the devout Brother Agustin Salumbrino Varones ilustres en santidad letras y zelo de las almas de la Compania de Jesus Illustrious men in holiness letters and zeal for souls of the Society of Jesus Varones ilustres de la Compania de Jesus in Spanish Vol 5 Original series by Juan Eusebio Nieremberg Madrid Spain Jose Fernandez de Buendia published 1666 pp 612 628 p 612 Nacio el Hermano Agustin Salumbrino el ano de mil y quinientos y sesenta y quatro en la Ciudad de Fḷọṛi en la Romania Brother Agustino Salumbrino was born in the year 1564 in the city of Forli in Romagna See Medina Rodriguez F Aceves Avila FJ Moreno Rodriguez J 2007 Precisions on the History of Quinine Reumatologia Clinica Letters to the Editor 3 4 194 196 doi 10 1016 S2173 5743 07 70246 0 ISSN 2173 5743 In fact though the last wordon this has not yet been spoken there are Jesuit texts thatmention that quinine reached Rome in 1632 with theprovincial of the Jesuit missions in Peru father AlonsoMessia Venegas as its introducer when he brought asample of the bark to present it as a primacy and whohad left Lima 2 years earlier because evidence of his stayin Seville 1632 has been registered publishing one of hisbooks there and following his way to Rome as a procurator Torres Saldamando E June 1882 El P Diego de Torres Vazquez Los antiguos jesuitas del Peru in Spanish Lima Peru Imprenta Liberal pp 180 181 p 181 Al siguiente ano se dirigieron a Europa los Procuradores P Alonso Messia Venegas y P Hernando de Leon Garavito llevando gran cantidad de la corteza de la quina cuyo conocimiento extendieron por el mundo los jesuitas In the following year i e 1631 there went to Europe the procurators Father Alonso Messia Venegas and Father Hernando de Leon Garavito taking a great quantity of cinchona bark knowledge of which the Jesuits spread throughout the world Bailetti A Capitulo 10 La Condesa de Chinchon LA MISIoN DEL JESUITA AGUSTIN SALUMBRINO la malaria y el arbol de quina A ultimas horas de la tarde del treinta y uno de mayo de 1631 se hizo a la vela la Armada Real con direccion a Panama llevando el precioso cargamento de oro y plata En una de las naves viajaban los procuradores jesuitas padres Alonso Messia y Hernando Leon Garavito custodiando los fardos con la corteza de quina en polvo preparados por Salumbrino Despues de casi veinte dias de navegacion el inapreciable medicamento llego a la ciudad de Panama donde fue descargado para cruzar en mulas el agreste camino del itsmo paludico hasta Portobelo para seguir a Cartagena y la Habana cruzar el Atlantico y llegar a Sanlucar de Barrameda en Sevilla Finalmente siguio su camino a Roma y a su destino final el Hospital del Espiritu Santo Late in the afternoon of 31 May 1631 the royal armada set sail in the direction of Panama carrying its multimillion dollar cargo of gold and silver On one of the ships traveled the Jesuit procurators Fathers Alonso Messia and Hernando Leon Garavito guarding the cases of powdered cinchona bark prepared by Salumbrino After almost 20 days of sailing medicine arrived in the city of Panama where it was transloaded onto mules It then traveled the malarial isthmus as far as Portobelo thence to Cartagena in Colombia and Havana It then traveled to Sanlucar de Barrameda in Seville Spain Finally it followed the road to Rome and to its final destination the Hospital of the Holy Spirit Rocco F 2004 Quinine malaria and the quest for a cure that changed the world New York NY Perennial Humphrey L 2000 Quinine and Quarantine Columbia Missouri University of Missouri Press Charles Marie de la Condamine 29 May 1737 Sur l arbre du quinquina Histoire de l Academie royale des sciences Imprimerie Royale published 1740 pp 226 243 De Jussieu accompanied de la Condamine on the latter s expedition to Peru de Jussieu J 1737 Description de l arbre a quinquina Paris Societe du traitement des quinquinas published 1934 Pelletier PJ Caventou JB 1820 Recherches Chimiques sur les Quinquinas Continuation Chemical Research on Quinquinas Annales de Chimie et de Physique in French Crochard 15 337 365 The authors name quinine on page 348 nous avons cru devoir la nommerquinine pour la distinguer de la cinchonine par un nom qui indique egalement son origine we thought that we should name it quinine in order to distinguish it from cinchonine by means of a name that also indicates its origin Briquet P 1853 Traite therapeutique du quinone et de ses preparations in French Paris L Martinet a b c Conner CD 2005 A People s History of Science Miners Midwives and Low Mechanicks New York Nation Books pp 95 96 ISBN 978 1 56025 748 6 Also cites Porter R 1998 The Greatest Benefit to Mankind A Medical History of Humanity New York W W Norton pp 465 466 ISBN 978 0 393 04634 2 Canales NA 7 April 2022 Hunting lost plants in botanical collections Wellcome Collection Retrieved 9 May 2022 a b Shah S 2010 The Fever How Malaria Has Ruled Humankind for 500 000 Years Farrar Straus and Giroux p 94 Louis Morton 1953 29 The Fall of the Philippines Washington D C United States Army p 524 Archived from the original on 25 May 2017 Alan Hawk Remembering the war in New Guinea Japanese Medical Corps malaria Archived from the original on 22 November 2011 Lt Gen Leonard D Heaton ed 1963 8 Preventive Medicine in World War II Volume VI Communicable Diseases Malaria Washington D C Department of the Army pp 401 and 434 Archived from the original on 29 January 2012 Notes on Japanese Medical Services Tactical and Technical Trends 36 1943 Archived from the original on 14 October 2011 Shah S 2010 The Fever How Malaria Has Ruled Humankind for 500 000 Years Farrar Straus and Giroux p 102 Medicine What s Good for a Cold Time 22 February 1960 Archived from the original on 26 July 2010 Retrieved 27 April 2010 John S Sappington Historic Missourians State Historical Society of Missouri Hobhouse H 2004 Sest rostlin ktere zmenily svet in Czech Prague Akademie ved Ceske republiky p 59 ISBN 978 80 200 1179 4 FDA Orders Stop to Marketing of Quinine for Night Leg Cramps FDA Consumer Magazine U S Food and Drug Administration FDA July August 1995 Archived from the original on 15 January 2008 Retrieved 31 July 2009 FDA Orders Unapproved Quinine Drugs from the Market and Cautions Consumers About Off Label Use of Quinine to Treat Leg Cramps Press release U S Food and Drug Administration FDA 11 December 2006 Archived from the original on 28 July 2009 Retrieved 31 July 2009 Skarbinski J James EM Causer LM Barber AM Mali S Nguyen Dinh P et al May 2006 Malaria surveillance United States 2004 PDF Morbidity and Mortality Weekly Report Surveillance Summaries 55 4 23 37 PMID 16723971 Microgram Bulletin DIMETHYLTRYPTAMINE AND ECSTASY MIMIC TABLETS ACTUALLY CONTAINING 5 METHOXY METHYLISOPROPYLTRYPTAMINE IN OREGON PDF U S Department of Justice Drug Enforcement Administration October 2009 p 79 Archived from the original PDF on 17 October 2012 Retrieved 22 September 2012 Porritt M Cryptocaryon irritans Reef Culture Magazine 1 ed Archived from the original on 24 October 2009 Retrieved 9 July 2009 Further reading EditSchroeder Lein G 2008 The encyclopedia of Civil War medicine Armonk NY Sharpe Inc Hobhouse H 2005 1986 Seeds of Change Six Plants That Transformed Mankind Berkeley CA Counterpoint ISBN 978 1 59376 049 6 Stockwell JR October 1982 Aeromedical considerations of malaria prophylaxis with mefloquine hydrochloride Aviation Space and Environmental Medicine 53 10 1011 1013 PMID 6983345 Wolff RS Wirtschafter D Adkinson C June 1997 Ocular quinine toxicity treated with hyperbaric oxygen Undersea amp Hyperbaric Medicine 24 2 131 134 PMID 9171472 Archived from the original on 11 August 2011 Retrieved 13 August 2008 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint unfit URL link Slater L 2009 War and disease biomedical research on malaria in the twentieth century New Brunswick NJ Rutgers University Press Lloyd HD June 1884 Lords of Industry The North American Review University of Northern Iowa 138 331 535 553 ISSN 0029 2397 JSTOR 25118388 World Health Organization 2015 Guidelines for the treatment of malaria 3rd ed 3rd ed World Health Organization WHO hdl 10665 162441 ISBN 9789241549127 External links Edit Look up quinine in Wiktionary the free dictionary Quinine at the Drug Information Portal Quinine at the International Programme on Chemical Safety Quinine Resource Center Chemwatch Portal Medicine Retrieved from https en wikipedia org w index php title Quinine amp oldid 1129571582, wikipedia, wiki, book, books, library,

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