Cinchona Bark

Chinchonæ Flavæ Cortex or ‘the yellow bark of the cinchona tree’ has historically been used in medicine throughout the world. Cinchona is a flowering plant belonging to the Rubiaceae family. Cinchona was said to have gotten its name from the Countess of Chinchon, the wife of a Spanish viceroy of Peru who contracted malaria and was cured by the bark. Cinchona is native to the Andes Mountain range in South America, especially found in Peru, Ecuador, Columbia and Bolivia. There are between 23 and 29 species of Cinchona with some of key species of medicinal importance being:

1. Cinchona Officinalis - ‘Peruvian Bark’ - the ‘official’ medicinal species

2. Cinchona Calisaya - yellow cortex - rich in quinine

3. Cinchona Pubescens - red bark

4. Cinchona ledgeriana

The different species largely contain the same active ingredients, but vary in ratios and concentration.

The sample of Cinchona found in the historical medicinal collection in the Department of Pharmacology in Trinity College Dublin, based in St. James’s University Hospital, is labelled as “Flavæ Cortex” meaning Yellow Bark in Latin. Therefore, we assume our sample to be Cinchona Calisaya. The specimen was obtained from the Royal College of Physicians in Ireland in 1867, when they presented their Materia Medica collection to the School of Physic in Trinity College. The sample, which was first documented in the “Catalogue of the Museum of the King and Queen’s College of Physicians in Ireland” printed in 1864, describes the Cinchona Bark as being quilled. This same sample was obtained by the RCPI from ‘Messers. Allen and Hanbury, London.’ a British Pharmaceutical Manufacturer and was displayed in the International Exhibition in 1862 in a glass jar, twenty-one inches in height, the same jar in which it resides today.

Active Ingredients:
Cinchona bark contains 4 alkaloids contributing to its pharmacological effect. Total alkaloid content is between 5-10%, depending on species. Quinine is the dominant compound of Cinchona Calisaya.

Traditional and Historical Use:

• In Pre-Colonial South America, Cinchona was used as an antipyretic. “The bark of Cinchona was known to Indigenous Andeans for its fever-reducing qualities. It was administered in powdered form, typically in water or fermented beverages.” - "New World Objects of Knowledge" – UCL Press (2021)

• When the Jesuits learned of this use in Peru in the 17th century, they began using it themselves and it became known in Europe as ‘Jesuit’s Bark’ for the treatment of Malaria.

• In 1820, French chemists Pierre Pelletier and Joseph Caventou isolated the quinine alkaloid from the bark and quinine became the first effective treatment of Malaria. Quinine became critical for colonial expansion in malaria prone areas of Africa and India and for military campaigns

Mechanism of Action of Quinine and Quinidine:

Quinine:

• Quinine utilises ion trapping to kill Plasmodium species, the parasite causing malaria. 

• Quinine is a weak base and so it gets absorbed into the parasites food vacuole

• It becomes protonated and ion trapped due to the low pH environment.

• Quinine accumulates and disrupts the haemoglobin digestion pathway causing death of the Plasmodium parasite

Quinidine:

• Quinidine is a Class IA antiarrhythmic drug - Sodium channel blocker that prolongs action potential duration

• Quinidine exerts a moderate block on open Na+ channels - decreasing phase 0 upstroke velocity, decreasing conduction through the myocardium

• Quinidine also blocks K+ channels and reduces efflux responsible for repolarisation of the membrane. This prolongation of repolarisation increases the effective refractory period of the cells

• The decreased conduction velocity and increased effective refractory period decreases re-entry arrhythmias

Pharmacokinetics:

Both Quinine and Quinidine have a high oral bioavailability but are administered by Intravenous injection. They are both excreted renally and are metabolised by hepatic CYP450 Enzymes.

Side Effects of Cinchona Bark:
Cinchonism (Quinine or Quinidine toxicity syndrome) can cause blurred vision, tinnitus, heachaches and psychosis.

Torsades de pointes and other arrhythmias may result from Quinidine.

Contradictions:

• Don’t take if pregnant

• Don’t take with previous heart rhythm disorders

Drug-Drug Interactions:

Cinchona alkaloids, particularly quinine affect the cytochrome P450 system, potentially interacting with drugs such as Digoxin and Warfarin. 

Sample #18/43