Daniel in The Lion's Den | 929: Mosquitoes and Malaria XIX – Quinine: Origin / History / Synthesis / Derivatives / Dosage

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929: Mosquitoes and Malaria XIX – Quinine: Origin / History / Synthesis / Derivatives / Dosage

04 November, 2009

Gleaned from various sources…quoted as and when…

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Quinine was first brought to Europe by Jesuits and it was used to cure King Louis XIV. The drug inhibits hemozoin bio-crystallization in the plasmodium and facilitates aggregations of cytotoxic hemes. Toxic-free hemes then accumulate in the parasites, leading to their death.

Msn-Encarta

Cytotoxic: describes a drug that prevents cell division or a type of cell in the immune system that destroys other cells

Heme: the deep red, non-protein portion of hemoglobin that contains iron

Quinine was derived from the original Quechua, Inca word for the cinchona tree bark: Quina or Quina-Quina, which roughly means bark of bark. Prior to 1820, the bark was first dried, ground to a fine powder, and then mixed into a liquid, usually wine, which was then drunk.

Large scale use of quinine as a prophylactic began 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 swamps and marshes surrounding the city of Rome. Over time, malaria was responsible for the deaths of several Popes, many Cardinals, and countless common citizens of Rome. Most of the priests 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 the shivering in cold temperatures.

A Jesuit apothecary observed the Quechua Indians using the quinine-containing bark of the cinchona tree for that purpose. While its effect in treating malaria and 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.

Msn-Encarta

Apothecary: a historical name for a medical person who formulates, prepares, and dispenses materia medica to physicians, surgeons and patients; and also offers general medical advice and a range of services – a position now served by a pharmacist and performed solely by other specialist practitioners

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 known as the white man's grave. It was quinine's efficacy that gave colonists fresh hope and opportunities to swarm into the Gold Coast, now Ghana, Nigeria, and other parts of West Africa.

Synthetic quinine; main article: quinine total synthesis

The Cinchona tree remains the only practical source of quinine. However, under wartime pressure, research towards synthetic-quinine 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 effective and economic terms with the isolation of the alkaloid from natural sources.

Quinine is a basic amine – any organic derivative of ammonia formed by the replacement of hydrogen with one or more alkyl (alkaloid) groups – and is therefore always presented as a salt. Various preparations that exist include hydrochloride, dihydrochloride, sulfate, bisulfate and gluconate. This makes quinine dosage very complicated, because each of the salts has a different weight.

The following amounts of each form are equal: Quinine base 100mg = Quinine hydrochloride 122mg; Quinine dihydrochloride 122mg = Quinine sulfate 121mg = Quinine bisulfate 169mg = Quinine gluconate 160mg.

All quinine salts may be given orally or intravenously; quinine gluconate may also be given intramuscularly or rectally. 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-a-dose again.

The intra-venous dose of quinine is 8mg of quinine base every eight hours; the intra-muscular dose is 12.8mg of quinine base twice daily; the par PR dose is 20mg/kg of quinine base twice daily. Treatment should be maintained for seven days.

The preparations available in the UK are quinine sulfate 200mg or 300mg tablets and quinine hydrochloride 300mg/ml for injection. Quinine is not licensed for IM or PR use in the UK. The adult dose in the UK is 600mg of quinine dihydrochloride IV or 600mg of quinine sulfate orally every eight hours.

In the US, quinine sulfate is available as 324mg tablets under the brand name Qualaquin; the adult dose is two tablets every eight hours. There are no licensed inject-able preparations of quinine in the US. Quinidine is used instead.

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Synthetic quinine; main article: quinine total synthesis

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