|
|
| Line 1: |
Line 1: |
| {{drugbox
| | __NOTOC__ |
| | IUPAC_name = (2-ethenyl-4-azabicyclo[2.2.2]oct-5-yl)- (6-methoxyquinolin-4-yl)-methanol
| | {{quinine}} |
| | image = Quinine-2D-skeletal.png
| | {{CMG}}; {{AE}} {{chetan}} |
| | image2 = Quinine-3D-balls.png
| |
| | size = 250px
| |
| | CAS_number = 130-95-0
| |
| | ATC_prefix = M09
| |
| | ATC_suffix = AA01
| |
| | ATC_supplemental = {{ATC|P01|BC01}}
| |
| | PubChem = 8549
| |
| | DrugBank = APRD00563
| |
| | C = 20 |H = 24 |N = 2 |O = 2
| |
| | molecular_weight = 324.417 [[Gram|g]]/[[Mole (unit)|mol]]
| |
| | bioavailability = 76 to 88%
| |
| | protein_bound = ~70%
| |
| | metabolism = [[Liver|Hepatic]] (mostly [[CYP3A4]] and [[CYP2C19]]-mediated)
| |
| | elimination_half-life = ~18 hours
| |
| | excretion = [[Kidney|Renal]] (20%)
| |
| | pregnancy_category = X <small>([[United States of America|USA]])</small>, D <small>([[Australia|Au]])</small>
| |
| | legal_status =
| |
| | routes_of_administration = Oral, [[intravenous therapy|intravenous]]
| |
| | melting_point = 177
| |
| }} | |
| {{SI}} | |
| {{CMG}} | |
|
| |
|
| | ==Overview== |
|
| |
|
| | ==Category== |
|
| |
|
| ==[http://www.wikidoc.org/index.php?title=Quinine_(Patient_information)&action=edit click here for Quinine patient information]== | | ==US Brand Names== |
|
| |
|
| '''Quinine''' ({{IPAEng|ˈkwaɪnaɪn, kwɪˈniːn, ˈkwiːniːn}}) is a natural white [[crystal]]line [[alkaloid]] having [[antipyretic]] (fever-reducing), anti-smallpox, [[analgesic]] (painkilling), and [[anti-inflammatory]] properties and a bitter taste. It is a [[stereoisomer]] of [[quinidine]].
| | ==FDA Package Insert== |
|
| |
|
| Quinine was the first effective treatment for [[malaria]] caused by [[Plasmodium falciparum|P falciparum]], appearing in therapeutics in the 17th century. It remained the antimalarial drug of choice until the 1940s, when other drugs took over. Since then, many effective antimalarials have been introduced, although quinine is still used to treat the disease in certain critical situations. Quinine is available with a prescription in the [[United States of America|United States]]. Quinine is also used to treat [[Cramps#Nocturnal leg cramps|nocturnal leg cramps]] and [[arthritis]], and there have been attempts (with limited success) to treat [[prion]] diseases. It was once a popular [[heroin]] [[adulterant]].
| | ''' [[quinine description|Description]]''' |
| | '''| [[quinine clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[quinine microbiology|Microbiology]]''' |
| | '''| [[quinine indications and usage|Indications and Usage]]''' |
| | '''| [[quinine contraindications|Contraindications]]''' |
| | '''| [[quinine warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[quinine adverse reactions|Adverse Reactions]]''' |
| | '''| [[quinine drug interactions|Drug Interactions]]''' |
| | '''| [[quinine overdosage|Overdosage]]''' |
| | '''| [[quinine clinical studies|Clinical Studies]]''' |
| | '''| [[quinine dosage and administration|Dosage and Administration]]''' |
| | '''| [[quinine how supplied|How Supplied]]''' |
| | '''| [[quinine labels and packages|Labels and Packages]]''' |
|
| |
|
| ==Mechanism of action== | | ==Mechanism of Action== |
| The [[theory|theorized]] mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the [[malaria]] [[Wiktionary:parasite|parasite]]. Specifically, the drugs interfere with the parasite's ability to break down and digest [[hemoglobin]]. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself.
| |
| | |
| ==Sources of quinine==
| |
| Quinine was extracted from the bark of the [[South America]]n [[cinchona]] tree and was isolated and named in [[1817]] by French researchers [[Pierre Joseph Pelletier]] and [[Joseph Bienaimé Caventou]]. The name was derived from the original [[Quechua]] (Inca) word for the cinchona tree bark, "Quina" or "Quina-Quina", which roughly means "bark of bark" or "holy bark". Prior to 1820, the bark was first dried, ground to a fine powder and then mixed into a liquid (commonly wine) which was then drunk.
| |
| | |
| Large scale use of quinine as a prophylaxis started around [[1850]], although it had been used in un-extracted form by Europeans since at least the early [[1600s]]. Quinine was first used to treat malaria in Rome in 1631. During the 1600s, malaria was endemic to the [[swamp]]s and [[marsh]]es surrounding the city of [[Rome]]. Over time, malaria was responsible for the death of several [[Pope]]s, many [[Cardinal (Catholicism)|Cardinal]]s and countless common citizens of Rome. Most of the [[priest]]s trained in Rome had seen malaria victims and were familiar with the [[shivering]] brought on by the cold phase of the disease. In addition to its anti-malarial properties, quinine is an effective muscle relaxant, long used by the [[Quechua]] Indians of [[Peru]] to halt shivering brought on by cold temperatures. The [[Jesuit]] Brother Agostino Salumbrino (1561-1642), an [[apothecary]] by training and who lived in [[Lima]], observed the Quechua using the quinine-containing bark of the [[cinchona]] tree for that purpose. While its effect in treating malaria (and hence malaria-induced shivering) was entirely unrelated to its effect in controlling shivering from cold, it was still the correct medicine for malaria. At the first opportunity, he sent a small quantity to Rome to test in treating malaria. In the years that followed, cinchona bark became one of the most valuable commodities shipped from Peru to Europe.
| |
| | |
| Quinine also played a significant role in the colonization of Africa by Europeans. As the dawn of modern pharmacology, Quinine was the prime reason why Africa ceased to be the white man's grave. According to Clifford D. Conner in "A People's History of Science", "It was quinine's efficacy that gave colonist fresh opportunities to swarm into the Gold Coast, Nigeria and other parts of west Africa and seize fertile agricultural lands, introduce new livestock and crops, build roads and railways, drive natives into mines, and introduce all the disruptions to traditional lifestyles that cash economies brought."(Conner pp 95-96) also cites Porter, "The Greatest Benefit to Mankind, pp. 465-466)
| |
| | |
| ===Synthetic quinine===
| |
| :''Main article: [[quinine total synthesis]]''
| |
| Cinchona trees remain the only practical source of quinine. However, under wartime pressure, research towards its artificial production was undertaken. A formal chemical synthesis was accomplished in [[1944]] by American chemists [[Robert Burns Woodward|R.B. Woodward]] and [[W.E. Doering]].<ref name="Woodward1944">
| |
| {{cite journal | author = Woodward R, Doering W | title = The Total Synthesis of Quinine | journal = [[Journal of the American Chemical Society|J Am Chem Soc]] | volume = 66 | issue = 849 | year = 1944}}</ref> Since then, several more efficient [[quinine total synthesis|quinine total syntheses]] have been achieved <ref>see review article in Angewandte Chemie, Int. Ed., 2005, 44, p. 854 ff</ref> , but none of them can compete in economic terms with isolation of the alkaloid from natural sources.
| |
| | |
| ==Dosing==
| |
| Quinine is a basic amine and is therefore always presented as a salt. Various preparations that exist include the [[hydrochloride]], dihydrochloride, [[sulfate]], bisulfate and [[gluconate]]. This makes quinine dosing very complicated, because each of the salts has a different weight.
| |
| | |
| The following amounts of each form are equal:
| |
| | |
| * quinine base 100 mg
| |
| * quinine bisulfate 169 mg
| |
| * quinine dihydrochloride 122 mg
| |
| * quinine hydrochloride 122 mg
| |
| * quinine sulfate 121 mg
| |
| * quinine gluconate 160 mg.
| |
| | |
| All quinine salts may be given orally or [[Intravenous therapy|intravenous]]ly (IV); quinine gluconate may also be given [[intramuscular injection|intramuscular]]ly (IM) or rectally (PR).<ref name="Barennes1996">{{cite journal | author=Barennes H, ''et al.'' | title=Efficacy and pharmacokinetics of a new intrarectal quinine formulation in children with Plasmodium falciparum malaria | journal=Brit J Clin Pharmacol | volume=41 | pages=389 | year=1996
| |
| | doi=10.1046/j.1365-2125.1996.03246.x | issue=5 }}</ref><ref name="Barennes2006">{{cite journal | Barennes H, Balima-Koussoubé T, Nagot N, Charpentier J-C, Pussard E | title=Safety and efficacy of rectal compared with intramuscular quinine for the early treatment of moderately sever malaria in children: randomised clinical trial | journal=Brit Med J | volume=332 | issue=7549 | pages=1055–57 }}</ref> The main problem with the rectal route is that the dose can be expelled before it is completely absorbed, but this can be rectified by giving half dose again.
| |
| | |
| The IV dose of quinine is 8 mg/kg of quinine base every eight hours; the IM dose is 12.8 mg/kg of quinine base twice daily; the PR dose is 20 mg/kg of quinine base twice daily. Treatment should be given for seven days.
| |
| | |
| The preparations available in the UK are quinine sulfate (200 mg or 300 mg tablets) and quinine hydrochloride (300 mg/ml for injection). Quinine is not licensed for IM or PR use in the [[United Kingdom|UK]]. The adult dose in the UK is 600 mg quinine dihydrochloride IV or 600 mg quinine sulfate orally every eight hours.
| |
| | |
| In the United States quinine sulfate is available as 324 mg tablets under the brand name Qualaquin; the adult dose is two tablets every eight hours. There is no injectable preparation of quinine licensed in the U.S.: [[quinidine]] is used instead.<ref>{{cite journal | author=Center for Disease Control | title=Treatment with Quinidine Gluconate of Persons with Severe ''Plasmodium falciparum'' Infection: Discontinuation of Parenteral Quinine | journal=Morb Mort Weekly Rep | year=1991 | volume=40 | issue=RR-4 | pages=21–23 | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/00043932.htm | accessdate=2006-05-06 }}</ref><ref>{{cite journal | journal=New Engl J Med | volume=353 | pages=335–337 | year=2005 | issue=4 | title=Making Antimalarial Agents Available in the United States | author=Magill A, Panosian C }}</ref>
| |
| | |
| Quinine is not recommended for malaria prevention ([[Wiktionary:prophylaxis|prophylaxis]]) because of its side effects and poor tolerability, not because it is ineffective. When used for prophylaxis, the dose of quinine sulphate is 300–324mg once daily, starting one week prior to travel and continuing for four weeks after returning.
| |
| | |
| ==Side effects==
| |
| :''See: [[cinchonism]]''
| |
| It is usual for quinine in therapeutic doses to cause [[cinchonism]]; in rare cases, it may even cause death (usually by [[pulmonary edema]]). The development of mild cinchonism is not a reason for stopping or interrupting quinine therapy and the patient should be reassured. Blood glucose levels and electrolyte concentrations must be monitored when quinine is given by injection; the patient should also ideally be in cardiac monitoring when the first quinine injection is given (these precautions are often unavailable in developing countries where malaria is most a problem).
| |
| | |
| Cinchonism is much less common when quinine is given by mouth, but oral quinine is not well tolerated (quinine is exceedingly bitter and many patients will vomit up quinine tablets): other drugs such as Fansidar® ([[sulfadoxine]] (sulfonamide antibiotic) with [[pyrimethamine]]) or Malarone® ([[proguanil]] with [[atovaquone]]) are often used when oral therapy is required. Blood glucose, electrolyte and cardiac monitoring are not necessary when quinine is given by mouth.
| |
| | |
| In [[1994]], the [[USA|U.S.]] [[Food and Drug Administration]] (FDA), banned the use of [[Over-the-counter drug|over-the-counter]] (OTC) quinine as a treatment for nocturnal leg cramps. [[Pfizer]] [[Pharmaceuticals]] had been selling the brand name Legatrin® for this purpose. This soon followed disallowing even [[Medical prescription|prescription]] quinine for leg cramps, and all OTC sales of the drug for malaria. From [[1969]] to [[1992]], the FDA received 157 reports of health problems related to quinine use, including 23 which had resulted in death.[http://www.fda.gov/fdac/departs/695_updates.html]
| |
|
| |
| Quinine can cause paralysis if accidentally injected into a nerve. It is extremely toxic in overdose and the advice of a [[toxicology|poisons specialist]] should be sought immediately.
| |
| | |
| ===Quinine and pregnancy===
| |
| In very large doses, quinine also acts as an [[abortifacient]]; in the United States quinine is classed as a Category X [[teratogen]] by the Food and Drug Administration, meaning that it can cause [[birth defect]]s (especially [[deafness]]) if taken by a woman during [[pregnancy]]. In the UK, the recommendation is that pregnancy is ''not'' a contra-indication to quinine therapy for [[Plasmodium falciparum|falciparum]] malaria (which directly contradicts the US recommendation), although it should be used with caution; the reason for this is that the risks to the pregnancy are small and theoretical, as opposed to the very real risk of death from falciparum malaria. Futher research, conducted in Sweden's Consug University hospital, has found a weak but significant correlation between dosage increase in pregnancy and Klebs-Loeffler bacillus infections in neonates.
| |
| | |
| ===Quinine and interactions with other diseases===
| |
| Quinine can cause [[hemolysis]] in [[G6PD deficiency]], but again this risk is small and the physician should not hesitate to use quinine in patients with [[G6PD deficiency]] when there is no alternative. Quinine can also cause [[drug-induced]] [[immune thrombocytopenic purpura]] (ITP).
| |
| | |
| Quinine can cause abnormal heart rhythms and should be avoided if possible in patients with [[atrial fibrillation]], [[conduction defects]] or [[heart block]].
| |
| | |
| Quinine must not be used in patients with [[hemoglobinuria]], [[myasthenia gravis]] or [[optic neuritis]], because it worsens these conditions.
| |
| | |
| ===Quinine and hearing impairment===
| |
| Some studies have related the use of quinine and [[hearing impairment]], which can cause some high-frequency loss, but it has not been conclusively established whether such impairment is temporary or permanent.<ref>{{cite journal | author=Department of Clinical Pharmacology, Huddinge University Hospital, Sweden | title=The concentration-effect relationship of quinine-induced hearing impairment | journal=Clin Pharmacol Ther | year=1994 | volume=55 | issue=3 | pages=317–323 | pmid = 8143397 | accessdate=2006-05-06 }}</ref>
| |
| | |
| ==Non-medical uses of quinine==
| |
| [[Image:Tonic water uv.jpg|thumb|left|Tonic water, in normal light and UV.]]
| |
| Quinine is a flavour component of [[tonic water]], [[bitter lemon]], and [[vermouth]]. According to tradition, the bitter taste of anti-malarial quinine tonic led British colonials in [[India]] to mix it with [[gin]], thus creating the [[gin and tonic]] cocktail, which is still popular today in both India and [[United Kingdom]], and in many English speaking countries.
| |
| | |
| In the [[United States]], the [[Food and Drug Administration]] limits tonic water quinine to 83 [[parts per million]], which is one-half to one-quarter the concentration used in therapeutic tonic.
| |
| | |
| In [[France]], quinine is an ingredient of an [[apéritif]] known as [[Quinquina]].
| |
| | |
| Quinine is often added to street drugs [[cocaine]] or [[ketamine]] in order to "[[cutting agent|cut]]" the product and make more profit.
| |
| | |
| Because of its relatively constant and well-known [[fluorescence]] quantum yield, quinine is also used in photochemistry as a common fluorescence standard.
| |
| | |
| In the United States, quinine is an ingredient in the [[Howling monkey energy drink]].
| |
| | |
| In Canada, quinine is an ingredient in the carbonated [[chinotto]] beverage called Brio.
| |
| | |
| In the United Kingdom, quinine is an ingredient in the carbonated and caffeinated beverage, [[Irn-Bru]].
| |
| | |
| In South Africa and Europe, quinine is an ingredient in the carbonated beverage called [[Schweppes]].
| |
|
| |
|
| ==References== | | ==References== |
| <references/>
| | {{Reflist|2}} |
| | |
| ==See also==
| |
| *[[Pharmacology]]
| |
| *[[Luis Jerónimo Fernández de Cabrera]] and [[Jesuit's bark]], for the story of its introduction into Europe
| |
| Jeffrey I. Seeman, ''The Woodward-Doering/Rabe-Kindler Total Synthesis of Quinine: Setting the Record Straight'' ''Angew. Chem. Int. Ed. Eng''. '''2007''', ''9'', 1373.
| |
| | |
| ==External links==
| |
| * [http://www.companymagazine.org/v144/powder.html Jesuits' Powder]
| |
| * [http://www.intox.org/databank/documents/pharm/quinine/ukpid13.htm From intox databank]
| |
| * [http://www.inchem.org/documents/pims/pharm/pim464.htm From inchem]
| |
| * [http://www.rain-tree.com/quinine.htm Database file on Quinine from rain-tree.com]
| |
| * [http://www.organic-chemistry.org/Highlights/2004/01November.shtm Catalytic Asymmetric Synthesis of Quinine and Quinidine]
| |
| * [http://pubs.acs.org/cen/coverstory/83/8325/8325quinine.html Summary article on history of Quinine in Chemical and Engineering News]
| |
| * [http://historyofalcoholanddrugs.typepad.com/alcohol_and_drugs_history/quinine/index.html Quinine news page] - [[Alcohol and Drugs History Society]]
| |
| | |
| {{Antimalarials}} | |
| [[ca:Quinina]]
| |
| [[cs:Chinin]]
| |
| [[da:Kinin]]
| |
| [[de:Chinin]]
| |
| [[es:Quinina]]
| |
| [[eo:Kinino]]
| |
| [[fr:Quinine]]
| |
| [[ko:퀴닌]]
| |
| [[it:Chinino]]
| |
| [[he:כינין]]
| |
| [[nl:Kinine]]
| |
| [[ja:キニーネ]]
| |
| [[no:Kinin]]
| |
| [[pt:Quinina]]
| |
| [[ru:Хинин]]
| |
| [[sk:Chinín]]
| |
| [[fi:Kiniini]]
| |
| [[sv:Kinin]]
| |
| [[zh:奎寧]]
| |
| | |
| | |
| [[Category:Ethers]]
| |
| [[Category:Nitrogen heterocycles]]
| |
| [[Category:Quinine]]
| |
| [[Category:Teratogens]]
| |
| [[Category:Antimalarial agents]]
| |
| [[Category:Quinolines]]
| |
| [[Category:Drugs]]
| |
| | |
| [[pl:Chinina]]
| |
| [[tr:Kinin]]
| |
|
| |
|
| {{jb1}}
| | [[Category:Antibiotics]] |
| {{WH}}
| | [[Category:Wikinfect]] |
| {{WikiDoc Sources}}
| |