CHINCHONA OFFICINALIS - A Medicine For Malaria

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Synthetic quinine



Cinchona trees 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. Woodward and W.E. Doering.

Since then, several more efficient quinine total syntheses have been achieved, 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.

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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 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 intravenously (IV); quinine gluconate may also be given intramuscularly (IM) or rectally (PR).[4][5] 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 UK. 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 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.

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.

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Side-effects - 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 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 (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.

Quinine can cause paralysis if accidentally injected into a nerve. It is extremely toxic in overdose, and the advice of a poisons specialist 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.[citation needed]

The New York Times Magazine described a case, presenting with fever, hypotension, and blood abnormalities mimicking septic shock

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Abortifacient



Despite popular belief, quinine is an ineffective abortifacient (in the US, quinine is listed as Pregnancy category C.

Pregnant women who take toxic doses of quinine will suffer from renal failure 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 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 can worsen hemoglobinuria, myasthenia gravis and optic neuritis.





Hearing impairment



Some studies have related the use of quinine and hearing impairment, in particular high-frequency loss, but it has not been conclusively established whether such impairment is temporary or permanent

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Regulation by the United States Food and Drug Administration



From 1969 to 1992, the U.S. Food and Drug Administration (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-counter (OTC) quinine as a treatment for nocturnal leg cramps. Pfizer 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.

As of 2008, pharmacists will not sell quinine even if the patient has used a prescription for it in the past.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.

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Non-medical uses of quinine
 


Quinine is a flavor component of tonic water and bitter lemon. 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 many parts of the world, especially the U.K., United States, southern Canada, parts of Australia and Lhasa, Tibet.

Bark of Remijia contains 0.5 - 2 % of quinine. The bark is cheaper than bark of Cinchona and as it has an intense taste, it is used for making tonic water.

In some areas, non-medical use of quinine is regulated. For example, in the United States and in Germany, quinine is limited to between 83-85 parts per million.

In France, quinine is an ingredient of an apéritif known as Quinquina or "Cap Corse".

Because of its relatively constant and well-known fluorescence quantum yield, quinine is also used in photochemistry as a common fluorescence standard.

Quinine (and quinidine) are used as the chiral moiety for the ligands used in Sharpless asymmetric dihydroxylation.

Quinine is sometimes added to ****, heroin and others to "cut" the product and increase profits. Heroin dealers mostly those in Baltimore, Maryland have long known the benefit of mixing Quinine and heroin not only to increase profits but due to its synergistic effect's of intensifying the rush accompanied with injecting it. Heroin cut with quinine is referred to as Scramble; it has become attractive over the last decade or so among dealers and junkies alike as a cheaper alternative to raw heroin.

In Canada, quinine is an ingredient in the carbonated chinotto beverage called Brio.

In the United Kingdom, Scottish company A.G. Barr's uses quinine as an ingredient in the carbonated and caffeinated beverage Irn-Bru.

In the United Kingdom, Australia, New Zealand and Egypt, quinine is an ingredient in Schweppes and other Indian tonic waters, at a concentration of 0.4 mg/l.

In Uruguay and Argentina, quinine is an ingredient of a Pepsico Inc. Tonic water named Paso de los Toros.

In South Africa, 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 aquarium fish.



RETRIEVED FROM:

WIKIPEDIA.ORG

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Tonic water was never intended as a cure or preventive for malaria, but malaria is the reason the quinine is in there. Quinine has a bitter taste. To make the stuff palatable when used as an antidote for fevers, legend has it, British colonials in India mixed quinine with gin and lemon or lime. Over time they learned to love the godawful stuff. (You can see this principle at work in a lot of British cuisine.) Tonic water was granted an English patent in 1858, Schweppes brought it to the United States in 1953, and to this day it remains an essential component of Anglo-American mixology. Quinine is also used, along with other herbs, to flavor vermouth.

It's only fitting that we toast quinine (well, toast with quinine). Few drugs have been such a boon to humanity. Quinine comes from the bark of the cinchona tree, which grows in the rain forest on the eastern slopes of the Andes. (One begins to comprehend the importance of preserving rain forests.) The Spanish first heard about the medicinal properties of the bark of the "fever tree" from the natives in the early 17th century. According to tradition, the stuff was used in 1638 to cure Countess Anna del Chinchon, wife of the viceroy of Peru, an event commemorated a century later when botanists named the plant. The viceroy shipped a boatload of it to Europe in 1640, and the Jesuits began using it in their missionary work, whence it acquired the nickname "Jesuit's powder." For a time religious and national rivalries kept quinine from being universally adopted, but eventually everybody began using it, and many historians today say it permitted the European conquest of the tropics.

Quinine was the only effective treatment for malaria for 300 years.

After World War II, however, it was largely supplanted by synthetic drugs such as chloroquine that were safer, more effective, and easier to make. (Though quinine kills malarial parasites in red blood cells and alleviates fever, it doesn't completely destroy malaria in the body, allowing relapses to occur if quinine therapy is halted.)

But some strains of the malarial parasite Plasmodium falciparum became resistant to the synthetic drugs--one reason the global malaria eradication program launched by the World Health Organization in 1955 was declared a failure in 1976--and in some parts of the world quinine has again become the antimalarial drug of choice.



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