Anti-malarial drugs

Question 1

What was thought to be the cause of Malaria in the Dark ages ?

Answer 1

associations of the disease with swamps and marshes led the belief that malaria was caused by malignant vapors (miasmas)

Question 2

Paludisme

Answer 2

• french term
• “of the marshes”

Question 3

Charles Louis Alphonse Laveran

Answer 3

• french army surgeon
• was the first to notice parasites in the blood of a patient suffering from malaria
• won a nobel prize in 1907 for his discovery

Question 4

Cause of Malaria

Answer 4

• four species of protozoans from the genus Plasmodium cause different forms of disease
• Malaria is initiated by a bite of female Anopheles mosquito

Question 5

Symptoms of Malaria

Answer 5

• reoccuring bouts of fever and chills and anemia
• cerebral malaria results in death if left untreated

Question 6

Merozoites

Answer 6

• created by sporozoite form of parasite multiplied in the liver
• they invade red blood cells
• RBC cell rupture occurs 48-72 hours after invasion

Question 7

Discovery of Malaria ‘Cure’

Answer 7

• late 16th/early 17th century
• spanish invade the Incan empire in Peru
• observe that indigenous people used the bark of a mountain rain forest tree to treat fevers

Question 8

Introduction of bark to Europe

Answer 8

• 1650, brought to england
• 1680s, Peruvian bark was standard treatment

Question 9

Pelletier and Caventou

Answer 9

-1820
- two french chemists
- isolated the alkaloid quinine from the bark

Question 10

Cinchona officinalis

Answer 10

• first species to be described from the Genus Cinchona
• Andean highlands of Ecuador and Peru
• glossy leaves and pink or yellow flowers

Question 11

Quinine

Answer 11

• alkaloid
• compound found in the peruvian tree bark
• odorless white powder
• bitter taste

Question 12

how does quinine interfere with merozoite action?

Answer 12

• concentrated in parasite food vacuoles
• prevents polymerization of heme into hemozoin resulting in toxicity to the parasite

Question 13

Synthetic anti-malarial drugs

Answer 13

• chloroquine, malarone, mefloquine
• used to target difference Plasmodium life cycle and strains

Question 14

How does Quinine work?

Answer 14

words by preventing the formation of hemozoin, since it acts somehow to block biocrystalization

Question 15

Quinine Alternatives

Answer 15

• Artemisia annua
• Artemisia absinthium

Question 16

Artemisia annua

Answer 16

• wormwood
• chinese herbal medicine used in fever reduction
• contains a terpene compound called Artemisinin
• more effective synthetic versions have been created
• produced in trichomes

Question 17

How to address risk of resistance in Wormwood?

Answer 17

• approached by used combination therapies
• artemisinin based drugs combines with quinine derivatives and anti-metabolites

Question 18

Artemisia absinthium

Answer 18

• absinthe aka “Grand Wormwood”
• originated in the canton of Neichatel in switzerland in the late 18th century

Question 19

Dr. Pierre Ordinaire

Answer 19

• credited with the first production of absinthe in 1972
• developed originally as a cough medicine

Question 20

Absinthe is the “green fairy”

Answer 20

• drink of the Parisian abandon
• thought to infuse the drinker with creativity, intelligence and glamour

Question 21

Vincent Van Gogh

Answer 21

• cuts off his ear during an epileptic seizure
• unusual use of the color yellow
• both thought to be because of the consumption of absinthe

Question 22

Why backlash against absinthe

Answer 22

• is marketed for its extraordinary effects and becomes a target for prohibitionist lobby
• 1850: regular consumption of absinthe leads to ‘absinthism’
• scientific studies at that time show convulsions in mice due to synergism between alcohol and other components found in absinthe

Question 23

‘absinthism’

Answer 23

• scapegoat beverage for all social ills
• associated with epileptic seizures, orgy behavior, sexual diseases, corrupted artists, criminals
• mimics for absinthe sometimes contain grain alcohol and copper salts (for color) - probably toxic

Question 24

What does true absinthe mixture contain?

Answer 24

• true absinthe contains a variety of plant extracts including fennel, sweet balm, hyssop, angelica and anise
• the most important plant found in absinthe is a variety of wormwoods

Question 25

What terpene compounds does Wormwood contain

Answer 25

thujone and absinthin

Question 26

Thujone

Answer 26

• binds to and blocks GABAa receptors in brain neurons

Question 27

GABA

Answer 27

• inhibitory NT that modulated neuronal activity
• binds to different subtypes of receptors
• inhibition of normal GABA activity may lead to the seizures seen when under the influence of thujone