Quinine
Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to Plasmodium falciparum that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg cramps, quinine is not recommended for this purpose due to the risk of serious side effects. It can be taken by mouth or intravenously. Malaria resistance to quinine occurs in certain areas of the world. Quinine is also used as an ingredient in tonic water and other beverages to impart a bitter taste.
Common side effects include headache, ringing in the ears, vision issues, and sweating. More severe side effects include deafness, low blood platelets, and an irregular heartbeat. Use can make one more prone to sunburn. While it is unclear if use during pregnancy carries potential for fetal harm, treating malaria during pregnancy with quinine when appropriate is still recommended. Quinine is an alkaloid, a naturally occurring chemical compound. It possesses a quinoline functional group.
Quinine was first isolated in 1820 from the bark of a cinchona tree, which is native to Peru, and its molecular formula was determined by Adolph Strecker in 1854. 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. It is on the World Health Organization's List of Essential Medicines. Treatment of malaria with quinine marks the first known use of a chemical compound to treat an infectious disease.
Uses
Medical
As of 2006, quinine is no longer recommended by the World Health Organization 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. 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 since 2010 due to a warning from the US Food and Drug Administration that such practice is associated with life-threatening side effects. Quinine can also act as a competitive inhibitor of monoamine oxidase, 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.
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 ; quinine gluconate may also be given intramuscularly or rectally. The main problem with rectal administration 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.
| Name | Amount equivalent to 100 mg quinine base |
| Quinine base | 100 mg |
| Quinine bisulfate | 169 mg |
| Quinine dihydrochloride | 122 mg |
| Quinine gluconate | 160 mg |
| Quinine hydrochloride | 111 mg |
| Quinine sulfate dihydrate | 121 mg |
Beverages
Quinine is a flavor component of tonic water and bitter lemon soft drinks. On the soda gun behind many bars, tonic water is designated by the letter "Q" representing quinine.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. 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.
In France, quinine is an ingredient of an apéritif known as quinquina, or "Cap Corse", and the wine-based apéritif Dubonnet. In Spain, quinine 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 Britain, 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 83 ppm in the United States, to 85 mg/L in Taiwan, and to 100 mg/L in the European Union.
Direct use of cinchona bark in beverages is also allowed in the US, with a maximum allowed total cinchona alkaloid level of 83 ppm in the finished beverage.
Scientific
Quinine 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.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. 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. In people with atrial fibrillation, conduction defects, or heart block, quinine can cause heart arrhythmias, and should be avoided.Quinine can cause hemolysis in G6PD 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.
While not necessarily an absolute contraindication, concomitant administration of quinine with drugs primarily metabolized by CYP2D6 may lead to higher than expected plasma concentrations of the drug, due to quinine's strong inhibition of the enzyme.
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, long QT syndrome and other serious cardiac arrhythmias including torsades de pointes, blackwater fever, disseminated intravascular coagulation, leukopenia, and neutropenia. Some people who have developed TTP due to quinine have gone on to develop kidney failure. 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.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. More severe cinchonism includes vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in heart rhythms. Cinchonism is much less common when quinine is given by mouth, but oral quinine is not well tolerated. Other drugs, such as Fansidar or Malarone, are often used when oral therapy is required. Quinine ethyl carbonate is tasteless and odourless, 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. It is a strong inhibitor of CYP2D6, an enzyme involved in the metabolism of many drugs.