3. quinine or peruvian bark

Question 1

which genus

Answer 1

cinchona

Question 2

genus cinchona

Answer 2

includes a number of closely related tree species, 15-20m in height, native to the tropical andean highlands of south america and north into central america.
-it is uncertain whether cinchona was used medicinally by the indigenous ppls of South america prior to the 17th century; while quinine bark was used by early Peruvian herbalists as a fever remedy, there are no records of its use by earlier inca civilizations

Question 3

europeans firs became aware of the antimalarial properties of cinchona bark in ..

Answer 3

1630, probably from Indigenous Peruvians

Question 4

popularized by

Answer 4

spanish jesuit cardinal john de lugo, and as a result it became known in Europe as “jesuits powder” or “lugos powder”

Question 5

mistrust and strong anti-catholic rhetoric at the time

Answer 5

limited the use of jesuits powder in non-catholic europe, despite the prevalence of malaria throughout the continent.

Question 6

Robert talbor

Answer 6

• 1660s he began treating malaria with a secret recipe
• he became rich and famous after curing England’s king charles II of malaria
• he then traveled to france where he treated successfully a number of famous and important people.
• talbor was rewarded handsomely for his efforts and entered into an agreement with king louis XIV of france whereby the secret recipe remained sealed in an envelope to be opened on on Talbor’s death

Question 7

talbors death 1681

Answer 7

the secret cure proved to be powered quinine bark administered at the correct does
the revelation that talbors secret cure and jesuits powder were one and the same resulted in its subsequent widespread use: this was helped, no doubt, by a simultaneous waning of anti-catholic sentiment in northern europe

Question 8

huge shipments of quinine from the rain forests of ____ and _____ were subsequently sent to europe for processing

Answer 8

peru and bolivia

the trade was so profitable that attempts were made by various european nations to corner the market in Peruvian bark.

Question 9

quinine named after quina (the native name for quinine bark) was isolated by ..

Answer 9

french chemists in 1820

-isolation of the drug allowed for standardization of dosages, further spurring demand for the drug

Question 10

whole sale stripping of bark

Answer 10

-killed the tress, so that by the mid 1800s a severe shortage of high quality cinchona bark developed

Question 11

quinine yields from tree bark vary widely,

Answer 11

with the highest quality trees being found in eastern bolivia and peru

Question 12

when these high yielding trees were extirpated,

Answer 12

harvesters moved deeper into the rain forests of south america in a desperate search for bark to meet the insatiable demand. This supply problem led to the dutch establishing extensive cinchona plantations in java (present day indonesia, southeast asia) beginning in 1854
-their initial effort was unsuccessful; only 75 of 500saplings survived the long journey from south america and quinine yields proved very low.

Question 13

in the 1860s the british (under the direction of sir clements markham) spent considerable time doing what?

Answer 13

establishing cinchona plantations in india and sri Lanka
-this effort was a huge failure, however , since quinine yields from the plantation trees were far too low to be of commercial value. We now know that relatively few cinchona species contain commercially viable concentrations of quinine (greater than 3%) and both the dutch and british had planted low yielding varieties of C. puberscens

Question 14

charles ledger

Answer 14

-befriended manuel incra mamani, a native Bolivian who knew where very high yielding cinchona trees occurred.

Question 15

maneul incra mamani

Answer 15

-sold fourteen pounds of cinchona seed to ledger, later died in jail for breaking a bolivian law forbidding the collection of cinchona seed for export.

Question 16

ledger tried to sell his purchased seed to the british government

Answer 16

but the failure of sir markham’s india plantations had made the government wary

Question 17

dutch

Answer 17

• he was finally able to sell a single pound of seed to the dutch for $20 usd (a considerable sum at the time). although the dutch were somewhat skeptical of the quality of ledgers seedlot, they carefully nurtured the seedlings at their java plantation and eventually raised 12,000 samplings. a few years later, tests on the bark revealed quinine concentrations of 8-13%. initially, many of the low yielding trees from previous plantation efforts were removed to prevent them from hybridizing with high yielding ledger variety. The ledger trees proved to have a weak root system, however, and were subsequently grafted onto the stronger rootstock from the earlier low yielding trees.
• the dutch were able to maintain a virtual monopoly on quinine production until the early 1940’s

Question 18

wild populations in south america had been harvested to near extinction, and efforts to establish plantations by…

Answer 18

americans, french, british and belgians proved unsuccessful

Question 19

the kina bureau

Answer 19

• kina is dutch for quinine
• set global quotas and prices for quinine, resulting in huge profits for the dutch monopoly
• the americans viewed this monopoly with disdain.

Question 20

a number of factors contributed to the eventual breakup of the dutch quinine monopoly in the mid 20th century:

Answer 20

• introduction of the insecticide DDT, which greatly reduced malaria in the US and europe.
• development of synthetic anti-malarial drugs
• independence of the dutch colony of java
• in addition, the japanese invasion and occupation of java cut off the supply of quinine to allied forces during world war II, prompting the US to establish cinchona plantations in both South america and africa.

Question 21

malaria is a a debilitating and potentially deadly disease caused by

Answer 21

parasitic protozoans of the genus plasmodium.

Question 22

where does malaria originate from

Answer 22

africa, and some researchers have speculated that it was not present in the americas until introduced by europeans in the early 1500s

Question 23

There are four main species of plasmodium:

Answer 23

P. malariae, P. vivax, P. ovale, P. falciparum.
-all except P. malariae exclusively parasitize humans, making malaria a very human disease.
-P vivax is the most common, occurring in both temperate and tropical climates.
-P. falciparum which occurs only in the tropics, is the most pathogenic
-malaria is transmitted to the human bloodstream by female anopheles mosquitoes.
of the 380 or so species of anopheles, only about 60 transmit malaria

Question 24

life cycle of the the malaria parasite (complex)

Answer 24

1. a malaria infected female anopheles mosquito injects plasmodium sporozoites into the bloodstream
2. the sporozoites find their way to the liver, where they invade liver cells and divide
3. the liver cells rupture, releasing merozoites into the bloodstream that invade RBC and divide again
4. the invaded RBCs rupture and the merozoites invade other RBCs-gametocytes are produced
5. a mosquito biting an infected individual carries the parasite to another host: both male and female gametocytes must be present in the mosquito to complete the cycle
   - the release of of merozoites at regular intervals (every 12-60 hours, depending on the strain of plasmodium) produces alternating bouts of fevers, chills and sweating. the liver and spleen become swollen and tender and anemia may occur.

Question 25

malaria is often a self limiting disease,

Answer 25

with complete recovery occurring after the primary attack or (more commonly) over an extended period of time. Severe malaria progresses rapidly, however, and death often occurs within days or even hours. the prognosis is poor if plasmodium invades the CNS. death is generally attributable to failure of the immune system

Question 26

malaria has adversely affected…

Answer 26

virtually every human civilization and culture
-although now considered a tropical disease, malaria was common in both europe and north america as recently as the early 20th century.

Question 27

Rome was considered a “pestilence city” because of malaria:

Answer 27

mal aria is italian for bad air, reflecting the mistaken belief that the disease is caused by march gases.

Question 28

malaria often affected the course of human history

Answer 28

both alexander the great and oliver cromwell died of a malignant form of malaria, and many european royalty and famous artists were affected by the disease

Question 29

malaria has been eradicated from..

Answer 29

temperate regions of the world through a combo of wetland drainage and the use of powerful insecticides
-the disease continues to rage across the tropics and subtropics, however with an estimated 300-500 million new infections new infections annually

Question 30

in 1980 how many deaths estimated ?
1980-2000?
in 2010?

Answer 30

one million
20 million
600,00 (mostly children in africa)
-the continued high rate of mortality from malaria reflects the increased prevalence of plasmodium strains resistant to standard anit-malarial drugs

Question 31

cinchona bark contains a number of quinoline alkaloids

Answer 31

the most important of which is the anti-malarial drug is quinine

Question 32

quinidine

Answer 32

a stereoisomer of quinine, is used medicinally to treat atrial fibrillation (irregular heartbeat)

Question 33

semi-synthetic quinolines

Answer 33

alkaloids similar in structure to quinine, were first produced by biochemists in the late 1930s
-the most important is chloroquine, which shows higher activity and lower toxicity than quinine

Question 34

a related compound, hydroxchloroquine

Answer 34

is used to treat lupus erythematous (lupus), spurring the development of other synthetic anti-malarial quinolines such as quinacrine, primaquine, lumefantrine and mefloquine
-these are very effective but have unpleasant side effects, and are toxic to some patients