Quinine is a natural white
crystalA crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is crystallography...
line
alkaloidAlkaloids are naturally occurring chemical compounds containing basic nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of...
having
antipyreticAntipyretics are drugs that reduce body temperature in situations such as fever. However, they will not affect the normal body temperature if one does not have a fever....
(fever-reducing),
antimalarialAntimalarial drugs are designed to prevent or cure malaria. Some antimalarial agents, particularly chloroquine and hydroxychloroquine, are also used in the treatment of rheumatoid arthritis and lupus associated arthritis. There are many of these drugs currently on the market...
,
analgesicAn analgesic is any member of the diverse group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos...
(painkilling), and
anti-inflammatoryAnti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids which affect the brain.-Medications:...
properties and a bitter taste. It is a stereoisomer of
quinidineQuinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
.
The bark of the
cinchonaCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
tree is used to make quinine. The medicinal properties of the cinchona tree were originally discovered by the
QuechuaQuechua is a Native American language family spoken primarily in the Andes of South America, derived from an original common ancestor language, Proto-Quechua. It is the most widely spoken language family of the indigenous peoples of the Americas, with a total of probably some 6 to 8 million speakers...
Indians of
PeruPeru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean.Peruvian territory was home to the Norte Chico...
and
BoliviaBolivia, officially Plurinational State of Bolivia , is a landlocked country in central South America. It is bordered by Brazil to the north and east, Paraguay and Argentina to the south, and Chile and Peru to the west....
; later, the Jesuits were the first to bring the cinchona to Europe.
Quinine was the first effective treatment for
malariaMalaria is a vector-borne infectious disease caused by a eukaryotic protist of the genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria, killing between one and...
caused by
Plasmodium falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
, appearing in therapeutics in the 17th century. It remained the antimalarial drug of choice until the 1940s, when other drugs replaced it. 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 and over-the-counter, in very small quantities, in
tonic waterTonic water is a carbonated soft drink flavoured with quinine, which gives it a distinctively bitter taste.The drink has garnered its name effects of this bitter flavouring...
. Quinine is also used to treat
lupusSystemic lupus erythematosus is a chronic autoimmune connective tissue disease that can affect any part of the body...
, nocturnal leg cramps and
arthritisArthritis is a group of conditions involving damage to the joints of the body....
.
Chemical structure
Quinine contains two major fused-ring systems: The aromatic
quinolineQuinoline is a heterocyclic aromatic organic compound. It has the formula C
9H
7N and is a colourless hygroscopic liquid with a strong odour. Aged samples, if exposed to light, become yellow and later brown...
and the bicyclic
quinuclidineQuinuclidine is an organic compound and a bicyclic amine and used as a catalyst and a chemical building block. It is a strong base with pKa of the conjugate acid of 11.0. This is due to greater availability of the nitrogen lone pair...
.
Mechanism of action against P. falciparum
As with other quinoline anti-malarial drugs, the action of quinine has not been fully resolved. The most widely accepted hypothesis of quinine action is based on the well-studied and closely related quinoline drug,
chloroquineChloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-Uses:* It has long been used in the treatment or prevention of malaria. After the malaria parasite Plasmodium falciparum started to develop widespread resistance to chloroquine, new potential utilisations of...
. This model involves the inhibition of
hemozoinHemozoin is a disposal product formed from the digestion of blood by some blood-feeding parasites. These hematophagous organisms such as Malaria parasites , Rhodnius and Schistosoma digest hemoglobin and release high quantities of free heme, which is the non-protein component of hemoglobin...
biocrystallizationBiocrystallization is the formation of crystals from organic macromolecules by living organisms. This may be a stress response, a normal part of metabolism such as processes that dispose of waste compounds, or a pathology. Template mediated crystallization is qualitatively different from in vitro...
, which facilitates the aggregation of cytotoxic
hemeA heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin...
. Toxic free heme accumulates in the parasites, leading to their death.
History
Quinine is an effective muscle relaxant, long used by the
QuechuaQuechua is a Native American language family spoken primarily in the Andes of South America, derived from an original common ancestor language, Proto-Quechua. It is the most widely spoken language family of the indigenous peoples of the Americas, with a total of probably some 6 to 8 million speakers...
Indians of
PeruPeru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean.Peruvian territory was home to the Norte Chico...
to halt shivering due to low temperatures. The Peruvians would mix the ground bark of
cinchonaCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
trees with sweetened water to offset the bark's bitter taste, thus producing
tonic waterTonic water is a carbonated soft drink flavoured with quinine, which gives it a distinctively bitter taste.The drink has garnered its name effects of this bitter flavouring...
.
Quinine has 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
swampA swamp is a wetland featuring temporary or permanent inundation of large areas of land by shallow bodies of water. A swamp generally has a substantial number of hammocks, or dry-land protrusions, covered by aquatic vegetation, or vegetation that tolerates periodical inundation. The two main types...
s and
marshIn geography, a marsh, or morass, is a type of wetland which is subject to frequent or continuous flood. Typically the water is shallow and features grasses, rushes, reeds, typhas, sedges, and other herbaceous plants. Woody plants will be low-growing shrubs. A marsh is different from a swamp,...
es surrounding the city of
RomeRome is the capital of Italy and the country's largest and most populated municipality , with over 2.7 million residents in , while the population of the urban area is estimated by Eurostat to be 3.46 million. The metropolitan area of Rome is estimated by OECD to have a population of 3.7 million...
. Malaria was responsible for the death of several
popeThe pope is the Bishop of Rome and, as such, is leader of the worldwide Catholic Church...
s, many
cardinalA cardinal is a senior ecclesiastical official, usually a bishop, of the Catholic Church. They are collectively known as the College of Cardinals, which as a body elects a new pope. The duties of the cardinals include attending the meetings of the College and making themselves available...
s and countless common Roman citizens. Most of the
priestA priest or priestess is a person having the authority or power to administer religious rites; in particular, rites of sacrifice to, and propitiation of, a deity or deities. Their office or position is the priesthood, a term which may also apply to such persons collectively.Priests and priestesses...
s trained in Rome had seen malaria victims and were familiar with the
shiveringShivering is a bodily function in response to early hypothermia in warm-blooded animals. When the core body temperature drops, the shivering reflex is triggered. Muscle groups around the vital organs begin to shake in small movements in an attempt to create warmth by expending energy...
brought on by the cold phase of the disease. The Jesuit brother Agostino Salumbrino (1561-1642), an
apothecaryApothecary is a historical name for a medical professional who formulates and dispenses materia medica to physicians, surgeons and patients — a role now served by a pharmacist ....
by training who lived in
LimaLima is the capital and largest city of Peru. It is located in the valleys of the Chillón, Rímac and Lurín rivers, on a coast overlooking the Pacific Ocean. It forms a contiguous urban area with the seaport of Callao...
, observed the Quechua using the bark of the
cinchonaCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
tree for that purpose. While its effect in treating malaria (and hence malaria-induced shivering) was unrelated to its effect in controlling shivering from cold, it was still a successful 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 was known as
Jesuit's barkJesuit's Bark, also called Peruvian Bark, is the historical name of the most celebrated specific remedy for all forms of malaria. It is so named because it was obtained from the bark of several species of the genus Cinchona, of the order Rubiaceae, that have been discovered at different times and...
and became one of the most valuable commodities shipped from Peru to Europe.
The form of quinine most effective in treating malaria was found by
Charles Marie de La CondamineCharles Marie de La Condamine was a French explorer, geographer, and mathematician.La Condamine was born in Paris. He was trained for the military profession, but turned his attention to science and geographical exploration...
in 1737. Quinine was isolated and named in 1817 by French researchers
Pierre Joseph PelletierPierre-Joseph Pelletier was a French chemist who did notable research on vegetable alkaloids, and was the co-discoverer of quinine and strychnine....
and
Joseph Bienaimé CaventouJoseph Bienaimé Caventou was a French chemist.He was a professor at the École de Pharmacie in Paris. He collaborated with Pierre-Joseph Pelletier in a Parisian laboratory located behind an apothecary. He was a pioneer in the use of mild solvents to isolate a number of active ingredients from...
. The name was derived from the original
QuechuaQuechua is a Native American language family spoken primarily in the Andes of South America, derived from an original common ancestor language, Proto-Quechua. It is the most widely spoken language family of the indigenous peoples of the Americas, with a total of probably some 6 to 8 million speakers...
(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.
Quinine also played a significant role in the colonization of Africa by Europeans. The harbinger of modern pharmacology, quinine was the prime reason Africa ceased to be known as the white man's grave. A historian has stated that "it was quinine's efficacy that gave colonists fresh opportunities to swarm into the
Gold CoastThe Gold Coast was the region of West Africa which is now the nation of Ghana. Early uses of the term refer literally to the coast and not the interior. It is not until the 19th century that the term comes to refer to areas that are far from the coast...
,
NigeriaNigeria , officially the Federal Republic of Nigeria, is a federal constitutional republic comprising thirty-six states and one Federal Capital Territory. The country is located in West Africa and shares land borders with the Republic of Benin in the west, Chad and Cameroon in the east, and Niger...
and other parts of west Africa".
To maintain their monopoly on cinchona bark, Peru and surrounding countries began outlawing the export of cinchona seeds and saplings beginning in the early 19th century. The
DutchThe Netherlands is a country in Northwestern Europe, constituting the major portion of the Kingdom of the Netherlands. It is a parliamentary democratic constitutional monarchy. The Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east...
government persisted in their attempts to smuggle the seeds, and by the 1930s Dutch plantations in
JavaJava is an island of Indonesia and the site of its capital city, Jakarta. Once the centre of powerful Hindu-Buddhist kingdoms, Islamic sultanates, and the core of the colonial Dutch East Indies, Java now plays a dominant role in the economic and political life of Indonesia...
were producing 22 million pounds of cinchona bark, or 97% of the world's quinine production. During
World War IIWorld War II, or the Second World War , was a global military conflict which involved a majority of the world's nations, including all great powers, organized into two opposing military alliances: the Allies and the Axis...
, Allied powers were cut off from their supply of quinine when the Germans conquered Holland and the Japanese controlled the
PhilippinesThe Philippines officially known as the Republic of the Philippines, is a country in Southeast Asia with Manila as its capital city. It comprises 7,107 islands in the western Pacific Ocean....
and
IndonesiaThe Republic of Indonesia is a country in Southeast Asia and Oceania. Indonesia comprises 17,508 islands. With an estimated population of around 237 million people, it is the world's fourth most populous country, with the world's largest population of Muslims.Indonesia is a republic, with an...
. The
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
, however, had managed to obtain four million cinchona seeds from the Philippines and begin operation of cinchona plantations in
Costa RicaCosta Rica, officially the Republic of Costa Rica is a country in Central America, bordered by Nicaragua to the north, Panama to the east and south, the Pacific Ocean to the west and south and the Caribbean Sea to the east.Costa Rica, which translates literally as "Rich Coast", constitutionally...
. It came too late, and an estimated 60,000 US troops in Africa and the South Pacific died due to the lack of quinine.
Synthetic quinine
Cinchona treesCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
remain the only practical source of quinine. However, under wartime pressure, research towards its synthetic production was undertaken. A formal chemical synthesis was accomplished in 1944 by American chemists
R.B. WoodwardRobert Burns Woodward was an American organic chemist. He made many significant contributions to modern organic chemistry, especially in the synthesis and structure determination of complex natural products, and worked closely with Roald Hoffmann on theoretical studies of chemical reactions...
and W.E. Doering. Since then, several more efficient
quinine total synthesesIn total synthesis, the Quinine total synthesis describes the efforts in synthesis of quinine over a 150 year period. The development of synthetic quinine is considered a milestone in organic chemistry although it has never been produced industrially as a substitute for natural occurring quinine...
have been achieved, but none of them can compete in economic terms with isolation of the alkaloid from natural sources. The first synthetic
organicOrganic chemistry is a discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation of chemical compounds that contain carbon...
dyeA dye can generally be described as a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and may require a mordant to improve the fastness of the dye on the fiber....
,
mauveineMauveine, also known as aniline purple and Perkin's mauve, was the first synthetic organic dye.Its chemical name is3-amino-2,±9-dimethyl-5-phenyl-7-phenazinium acetate...
, was discovered by William Henry Perkin in 1856 while he was attempting to synthesize quinine.
Dosing and indication
As of 2006, quinine is no longer recommended by the WHO as first line treatment for malaria and should only be used when artemesinins are not available.
Quinine is a basic
amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
and is therefore always presented as a salt. Various preparations that exist include the
hydrochlorideIn chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base...
, dihydrochloride,
sulfateIn inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
, bisulfate and gluconate. This makes quinine dosing complicated since 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 111 mg
- quinine sulfate (actually (quinine)2H2SO4∙2H2O) 121 mg
- quinine gluconate 160 mg.
All quinine salts may be given orally or
intravenousIntravenous therapy or IV therapy is the giving of liquid substances directly into a vein. It can be intermittent or continuous; continuous administration is called an intravenous drip. The word intravenous simply means "within a vein", but is most commonly used to refer to IV therapy...
ly (IV); quinine gluconate may also be given
intramuscularIntramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
ly (IM) or rectally (PR). The main problem with the rectal route is that the dose can be expelled before it is completely absorbed; this can be corrected by giving a 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
UKThe United Kingdom of Great Britain and Northern Ireland is a sovereign state located off the northwestern coast of continental Europe. It is an island country, spanning an archipelago including Great Britain, the northeastern part of Ireland, and many small islands...
. The adult dose in the UK is 600 mg quinine dihydrochloride IV or 600 mg quinine sulfate orally every eight hours. For nocturnal leg cramps, the dosage is 200-300 mg at night.
In the United States, quinine sulfate is commercially available in 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.:
quinidineQuinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
is used instead.
Quinine is not recommended for malaria prevention (prophylaxis) because of its side-effects and poor tolerability, not because it is ineffective. When used for prophylaxis, the dose of quinine sulfate is 300–324 mg once daily, starting one week prior to travel and continuing for four weeks after returning.
Side-effects
- See: cinchonism
Cinchonism or quinism is a pathological condition in humans caused by an overdose of quinine or its natural source, cinchona bark. Quinine is medically used to treat malaria. In much smaller amounts, quinine is an ingredient of tonic drinks, acting as a bittering agent...
It is usual for quinine in therapeutic doses to cause
cinchonismCinchonism or quinism is a pathological condition in humans caused by an overdose of quinine or its natural source, cinchona bark. Quinine is medically used to treat malaria. In much smaller amounts, quinine is an ingredient of tonic drinks, acting as a bittering agent...
; in rare cases, it may even cause death (usually by
pulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the lungs. It leads to impaired gas exchange and may cause respiratory failure. It is due to either failure of the heart to remove fluid from the lung circulation or a direct injury to the lung parenchyma...
). 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 ideally be in cardiac monitoring when the first quinine injection is given (these precautions are often unavailable in developing countries where malaria is endemic).
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 after ingesting quinine tablets): Other drugs such as Fansidar (
sulfadoxineSulfadoxine is an ultra-long-lasting sulfonamide often used in combination with pyrimethamine to treat or prevent malaria....
(sulfonamide antibiotic) with
pyrimethaminePyrimethamine is a medication used for protozoal infections. It is commonly used as an antimalarial drug , and is also used in the treatment of Toxoplasma gondii infections in immunocompromised patients, such as HIV-positive individuals.-Mechanism of action:Pyrimethamine interferes with...
) or Malarone (
proguanilProguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
with
atovaquoneAtovaquone is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about US$2.13 per standard 250 mg. tablet...
) are often used when oral therapy is required. Quinine ethyl carbonate is tasteless and odourless, but is only commercially available in Japan. Blood glucose, electrolyte and cardiac monitoring are not necessary when quinine is given by mouth.
Quinine can cause paralysis if accidentally injected into a nerve. It is extremely toxic in overdose, and the advice of a
poisons specialistToxicology is the study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people.-History:...
should be sought immediately.
Quinine in some cases can lead to constipation, erectile dysfunction, and a loose stool or in rare cases many loose stools.
The New York Times Magazine described a case, presenting with
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
,
hypotensionIn physiology and medicine, hypotension refers to an abnormally low blood pressure. This is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the opposite of hypertension, which is high blood...
, and blood abnormalities mimicking
septic shockSeptic shock is a serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...
.
Abortifacient
Despite popular belief, quinine is an ineffective
abortifacientAn abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots.Common abortifacients used in performing medical abortions include mifepristone, which is typically used in conjunction with misoprostol in a two-step approach...
(in the US, quinine is listed as
Pregnancy categoryThe pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does not include any risks conferred by pharmaceutical agents or their metabolites that are present in breast...
C
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=8546). Pregnant women who take toxic doses of quinine will suffer from
renal failureRenal failure or kidney failure is a situation in which the kidneys fail to function adequately. It is divided into acute and chronic forms; either form may be due to a large number of other medical problems....
before experiencing any kind of quinine-induced abortion. Indeed, quinine is the only drug recommended by the WHO as firstline treatment for uncomplicated malaria in pregnancy.
Disease interactions
Quinine can cause
hemolysisHemolysis —from the Greek Hemo-, Greek meaning blood, -lysis, meaning to break open—is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid ....
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 fibrillationAtrial fibrillation is the most common cardiac arrhythmia and involves the two upper chambers of the heart. Its name comes from the fibrillating of the heart muscles of the atria, instead of a coordinated contraction...
, conduction defects or
heart blockA heart block is a disease in the electrical system of the heart. This is opposed to coronary artery disease, which is disease of the blood vessels of the heart...
.
Quinine can worsen
hemoglobinuriaIn medicine, hemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free plasma hemoglobin...
,
myasthenia gravisMyasthenia gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
and
optic neuritisOptic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...
.
Hearing impairment
Some studies have related the use of quinine and
hearing impairmentA hearing impairment or deafness is a full or partial decrease in the ability to detect or understand sounds. Caused by a wide range of biological and environmental factors, loss of hearing can happen to any organism that perceives sound...
, in particular high-frequency loss, but it has not been conclusively established whether such impairment is temporary or permanent.
Regulation by the United States Food and Drug Administration
From 1969 to 1992, the U.S.
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
(FDA) received 157 reports of health problems related to quinine use, including 23 which had resulted in death. In 1994, the FDA banned the use of
over-the-counterOver-the-counter drugs are medicines that may be sold to a customer without a prescription from a health care professional, as compared to prescription drugs, which may only be sold to customers possessing a valid prescription...
(OTC) quinine as a treatment for nocturnal leg cramps.
PfizerPfizer Incorporated is a pharmaceutical company, ranking number one in sales in the world. The company is based in New York City, with its research headquarters in Groton, Connecticut...
Pharmaceuticals had been selling the brand name Legatrin for this purpose. 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. Quinine is approved for treatment of malaria, but is 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 affliction.
Non-medical uses of quinine
Quinine is a flavor component of
tonic waterTonic water is a carbonated soft drink flavoured with quinine, which gives it a distinctively bitter taste.The drink has garnered its name effects of this bitter flavouring...
and
bitter lemonBitter lemon is a carbonated soft drink flavoured with quinine and lemon, the former giving it a bitter taste. The principal difference between tonic water and bitter lemon is the addition of lemon juice and rind....
. According to tradition, the bitter taste of anti-malarial quinine tonic led British colonials in
IndiaIndia, officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the south, the Arabian Sea on the west, and the Bay of Bengal...
to mix it with
ginGin is a spirit flavoured primarily with juniper berries. Distilled gin is made by redistilling white grain spirit which has been flavoured with juniper berries. Compound gin is made by flavouring neutral grain spirit with juniper berries without redistilling.The most common style of gin,...
, thus creating the
gin and tonicA gin and tonic is a highball cocktail made with gin and tonic water, usually garnished with a slice of lime or lemon and often served over ice...
cocktail, which is still popular today in many parts of the world, especially the U.K.,
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
,
CanadaCanada is a country occupying most of northern North America, extending from the Atlantic Ocean in the east to the Pacific Ocean in the west and northward into the Arctic Ocean...
, parts of
AustraliaAustralia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the continental mainland , the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans...
and
LhasaLhasa, and sometimes spelled Lasa, is the administrative capital of the Tibet Autonomous Region in the People's Republic of China. It is located at the foot of Mount Gephel....
,
TibetTibet is a plateau region in Asia, north of the Himalayas. It is home to the indigenous Tibetan people, and to some other ethnic groups such as Monpas and Lhobas, and is now also inhabited by considerable numbers of Han Chinese people. Tibet is the highest region on earth, with an average...
.
Bark of
RemijiaRemijia is a genus in tribe Cinchoneae in the Rubiaceae and is native to Peru and Brazil. Bark of Remijia contains 0,5 - 2 % of quinine. The bark is cheaper than bark of Cinchona and it has an intensive taste so it is used for making of tonic water.-Species:36 species* Remijia asperula* Remijia...
contains 0.5 - 2 % of quinine. The bark is cheaper than bark of
CinchonaCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
and as it has an intense taste, it is used for making
tonic waterTonic water is a carbonated soft drink flavoured with quinine, which gives it a distinctively bitter taste.The drink has garnered its name effects of this bitter flavouring...
.
In some areas, non-medical use of quinine is regulated. For example, in the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
and in
GermanyGermany , officially the Federal Republic of Germany , is a country in Central Europe. It is bordered to the north by the North Sea, Denmark, and the Baltic Sea; to the east by Poland and the Czech Republic; to the south by Austria and Switzerland; and to the west by France, Luxembourg, Belgium,...
, quinine is limited to between 83-85 parts per million.
In
FranceFrance , officially the French Republic , is a country located in Western Europe, with several overseas islands and territories located on other continents. Metropolitan France extends from the Mediterranean Sea to the English Channel and the North Sea, and from the Rhine to the Atlantic Ocean...
, quinine is an ingredient of an
apéritifAn apéritif is an alcoholic drink that is usually served to stimulate the appetite before a meal, contrasting with digestifs, which are served after meals....
known as
QuinquinaIn France, Quinquina is a collective name for alcoholic bitters having quinine as one of their main ingredients. Quinquina is also known as Peruvian Bark.It originates from South America...
or "Cap Corse".
Because of its relatively constant and well-known
fluorescenceFluorescence is the emission of visible light by a substance that has absorbed light of a differing, usually invisible, wavelength. Absorption of a photon triggers the emission of a photon with a longer wavelength. A shorter wavelength emission is sometimes observed from multiple photon absorption...
quantum yieldThe quantum yield of a radiation-induced process is the number of times that a defined event occurs per photon absorbed by the system. Thus, the quantum yield is a measure of the efficiency with which absorbed light produces some effect....
, quinine is also used in
photochemistryPhotochemistry, a sub-discipline of chemistry, is the study of the interactions between atoms, small molecules, and light...
as a common fluorescence
standardA technical standard is an established norm or requirement. It is usually a formal document that establishes uniform engineering or technical criteria, methods, processes and practices....
.
Quinine (and quinidine) are used as the chiral moiety for the ligands used in
Sharpless asymmetric dihydroxylationSharpless asymmetric dihydroxylation is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol....
.
In
CanadaCanada is a country occupying most of northern North America, extending from the Atlantic Ocean in the east to the Pacific Ocean in the west and northward into the Arctic Ocean...
, quinine is an ingredient in the carbonated
chinottoThe chinotto is a small, bitter citrus fruit that grows on the chinotto tree, which is also called the "myrtle-leaved orange tree"...
beverage called Brio.
In the
United KingdomThe United Kingdom of Great Britain and Northern Ireland is a sovereign state located off the northwestern coast of continental Europe. It is an island country, spanning an archipelago including Great Britain, the northeastern part of Ireland, and many small islands...
, Scottish company
A.G. BarrA.G. Barr plc is a Scottish soft drinks manufacturer, based in Cumbernauld, North Lanarkshire, Scotland. It is particularly notable for the manufacture of the popular Scottish drink, Irn-Bru. A.G. Barr is the largest manufacturer of soft drinks in the United Kingdom...
's uses quinine as an
ingredientAn ingredient is a substance that forms part of a mixture . For example, in cooking, recipes specify which ingredients are used to prepare a specific dish. Many commercial products contain a secret ingredient that is purported to make them better than competing products...
in the carbonated and caffeinated beverage
Irn-BruIrn-bru is a popular carbonated soft drink produced in Cumbernauld, Scotland where it has been made by A.G. Barr of Glasgow since moving out of their original Denniston factory in the mid 90s and at a second manufacturing site in Mansfield, England...
.
In the
United KingdomThe United Kingdom of Great Britain and Northern Ireland is a sovereign state located off the northwestern coast of continental Europe. It is an island country, spanning an archipelago including Great Britain, the northeastern part of Ireland, and many small islands...
,
AustraliaAustralia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the continental mainland , the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans...
,
New ZealandNew Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses , and numerous smaller islands, most notably Stewart Island/Rakiura and the Chatham Islands. The indigenous Māori named New Zealand Aotearoa, commonly translated as The Land of the Long White Cloud...
and
EgyptEgypt , officially the Arab Republic of Egypt, is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Western Asia...
, quinine is an ingredient in Schweppes and other Indian tonic waters, at a concentration of 0.4 mg/l.
In
UruguayUruguay , is a country located in the southeastern part of South America. It is home to 3.46 million people, of whom 1.1 million live in the capital Montevideo and its metropolitan area. An estimated 88–94% of the population are of mostly European and/or mixed descent.Uruguay's only land border is...
and
ArgentinaArgentina, officially the Argentine Republic , is the second largest country in South America, constituted as a federation of 23 provinces and an autonomous city, Buenos Aires. It is the eighth largest country in the world by land area and the largest among Spanish-speaking nations, though Mexico,...
, quinine is an ingredient of a
PepsicoPepsiCo, Incorporated is a Fortune 500, American multinational corporation headquartered in Purchase, NY with interests in manufacturing and marketing a wide variety of carbonated and non-carbonated beverages, as well as salty, sweet and grain-based snacks, and other foods...
Inc.
Tonic waterTonic water is a carbonated soft drink flavoured with quinine, which gives it a distinctively bitter taste.The drink has garnered its name effects of this bitter flavouring...
named Paso de los Toros.
In
South AfricaThe Republic of South Africa is a country located at the southern tip of Africa, with a coastline on the Atlantic and Indian Oceans. To the north lie Namibia, Botswana and Zimbabwe, to the east are Mozambique and Swaziland, while Lesotho is an independent country surrounded by South Africa.Modern...
, quinine is an ingredient of a Clifton Instant Drink named Chikree produced by Tiger Food Brands.
As a treatment for
Cryptocaryon irritans (commonly referred to as white spot, crypto or marine ich) infection of
marine aquariumA marine aquarium is an aquarium that keeps marine plants and animals in a contained environment. Marine aquaria are further subdivided by hobbyists into fish only , fish only with live rock , and reef aquaria...
fish.
Quinine is sometimes used as a
cutting agentA cutting agent is a chemical used to "cut" illicit drugs with something less expensive than the drug itself.-Overview:The classical model of drug cutting refers to the way that illicit drugs were diluted at each stage of the chain of distribution. The rationale for such cutting is greed...
in
street drugsThe illegal drug trade is a global black market consisting of the cultivation, manufacture, distribution and sale of illegal controlled drugs. Most jurisdictions prohibit trade, except under license, of many types of drugs by drug control laws...
such as
cocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system and an appetite suppressant...
and
heroinHeroin, or diacetylmorphine , also known as diamorphine , is a semi-synthetic opioid drug synthesized from morphine, a derivative of the opium poppy. It is the 3,6-diacetyl ester of morphine...
.
See also
- Pharmacology
Pharmacology is the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals...
- Luis Jerónimo de Cabrera, 4th Count of Chinchón and Jesuit's bark
Jesuit's Bark, also called Peruvian Bark, is the historical name of the most celebrated specific remedy for all forms of malaria. It is so named because it was obtained from the bark of several species of the genus Cinchona, of the order Rubiaceae, that have been discovered at different times and...
, for the story of its introduction into Europe
- Stockwell JR. Aeromedical considerations of malaria prophylaxis
Malaria prophylaxis is the prevention of malaria. Malaria is thought to be one of the oldest infectious diseases, evolving around 10,000 years ago. The development of virulence in the parasite has been demonstrated using genomic mapping of samples from this period, confirming the emergence of genes...
with mefloquine hydrochloride. Aviation, Space, and Environmental MedicineAviation, Space, and Environmental Medicine is a peer-reviewed scientific journal in the field of aviation / aerospace medicine.Aviation, Space, and Environmental Medicine was founded as the Journal of Aviation Medicine in 1930 by Louis H...
1982; 3(10):1011-3
Additional reading
- Hobhouse, Henry - Seeds of Change Six Plants that Transformed Mankind C2005 ISBN(10) 1-59376-049-3
External links