Anti-malarial drugs Flashcards
What was thought to be the cause of Malaria in the Dark ages ?
associations of the disease with swamps and marshes led the belief that malaria was caused by malignant vapors (miasmas)
Paludisme
- french term
- “of the marshes”
Charles Louis Alphonse Laveran
- 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
Cause of Malaria
- four species of protozoans from the genus Plasmodium cause different forms of disease
- Malaria is initiated by a bite of female Anopheles mosquito
Symptoms of Malaria
- reoccuring bouts of fever and chills and anemia
- cerebral malaria results in death if left untreated
Merozoites
- created by sporozoite form of parasite multiplied in the liver
- they invade red blood cells
- RBC cell rupture occurs 48-72 hours after invasion
Discovery of Malaria ‘Cure’
- 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
Introduction of bark to Europe
- 1650, brought to england
- 1680s, Peruvian bark was standard treatment
Pelletier and Caventou
-1820
- two french chemists
- isolated the alkaloid quinine from the bark
Cinchona officinalis
- first species to be described from the Genus Cinchona
- Andean highlands of Ecuador and Peru
- glossy leaves and pink or yellow flowers
Quinine
- alkaloid
- compound found in the peruvian tree bark
- odorless white powder
- bitter taste
how does quinine interfere with merozoite action?
- concentrated in parasite food vacuoles
- prevents polymerization of heme into hemozoin resulting in toxicity to the parasite
Synthetic anti-malarial drugs
- chloroquine, malarone, mefloquine
- used to target difference Plasmodium life cycle and strains
How does Quinine work?
words by preventing the formation of hemozoin, since it acts somehow to block biocrystalization
Quinine Alternatives
- Artemisia annua
- Artemisia absinthium
Artemisia annua
- wormwood
- chinese herbal medicine used in fever reduction
- contains a terpene compound called Artemisinin
- more effective synthetic versions have been created
- produced in trichomes
How to address risk of resistance in Wormwood?
- approached by used combination therapies
- artemisinin based drugs combines with quinine derivatives and anti-metabolites
Artemisia absinthium
- absinthe aka “Grand Wormwood”
- originated in the canton of Neichatel in switzerland in the late 18th century
Dr. Pierre Ordinaire
- credited with the first production of absinthe in 1972
- developed originally as a cough medicine
Absinthe is the “green fairy”
- drink of the Parisian abandon
- thought to infuse the drinker with creativity, intelligence and glamour
Vincent Van Gogh
- cuts off his ear during an epileptic seizure
- unusual use of the color yellow
- both thought to be because of the consumption of absinthe
Why backlash against absinthe
- 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
‘absinthism’
- 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
What does true absinthe mixture contain?
- 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
What terpene compounds does Wormwood contain
thujone and absinthin
Thujone
- binds to and blocks GABAa receptors in brain neurons
GABA
- 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
