Infections - Malaria
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Transcript of Infections - Malaria
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Plants used to treat infectious
disease - II
Antimalarials
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Malaria
Caused by unicellular parasites in genus
Plasmodium - 4 species ofPlasmodium: P. vivax,
P. ovale, P. malariae, P. falciparium - P.falciparum cause of most fatalities
Spread by bite of femaleAnopheles mosquito
Parasite multiplies in liver and released in blood
stream
Invade red blood cells - multiply and rupture RBC
Cycle repeats every few days -symptoms fever,
chills, anemia....death
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Fever bark tree
Genus Cinchona native to the slopes of the Andes
Mountains in South America
Small evergreen trees belong to the Rubiaceae, thecoffee family
Called quina-quina by the Incas
38 speciesC
inchona - several used to treat malaria
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Use of Quina-quina
Fever reducing powers of the tree were well
known to the Incas who shared knowledge with
Jesuit missionaries many variations on this story including the discovery of
the medicinal properties by the Jesuits themselves
Bark of tree used for many medicinal purposes
Analgesic, Anaesthetic, Antibacterial, Anti-
malarial, Anti-microbial, Anti-parasitic,
Antiseptic, Astringent, Febrifuge,Muscle-
relaxant
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Small specimen
ofCinchonapubescens in
the Rubiaceae
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Cinchonasp
.
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Jesuits bark Jesuits used bark to treat people with malaria
In 1638 - Countess of Cinchon, wife of the
Viceroy of Peru - miraculous recovery spreadreputation of the bark
Years later Linnaeus named the genus Cinchona
in honor of the countess
By the end of the 17th century the powdered bark
of the quina-quina tree was the standard treatment
for malaria
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Quinine In 1820 two French scientists isolated the
alkaloid quinine
Within a few years purified quinine was
available commercially
Demand for the bark increased even more
36 alkaloids in Cinchonabark - 4 have anti-
malarial properties
Quinine is the most effective
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Quinine
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Cinchona
Bark of wild Cinchona species may yield up
to 7% quinine - cultivated species as much
as 15%
British started plantations in India and
Dutch in Java in the 1860s to 1870s
Java soon became the leading producer ofquinine - accounting for 95% of the
commercial supply
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Physiological action Quinine kills parasite in blood stream
Effective as a prophylactic to prevent initial
infection of red blood cells in travelers
"gin and tonic one of the earliest prophylactics
Not 100% effective
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Quinine mode of action Parasite feeds on hemoglobin - Breaks down
globin proteins into a.a. in lysosomes - heme
converted to a non-toxic product by parasite
Quinine accumulates in lysosome of parasite in
RBC
Quinine binds to heme and inhibits conversion of
heme to non- toxic product Heme-quinine complex highly toxic to parasite
May function by disrupting lysosome membrane
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Side effects Ringing in the ears, possible hearing loss
Dizziness
Gastrointestinal upset: nausea, vomiting,
diarrhea, abdominal pain
Rashes
Visual disturbances - blurred vision
More serious side effects in rare cases
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Synthetics During World War II synthetics were developed
In 1944 Robert Woodward and William Doering
synthesized quinine from coal tar
Several synthetics have similar mode of
action to quinine
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Chloroquinine Today the most widely used drug for malaria is
chloroquine which is less toxic and more effective
than quinine - mefloquine another synthetic Widespread use of chloroquine has resulted in
chloroquine-resistant strains of the parasites
Parasites becoming resistant to other drugs as well
Quinine often used for these infections in
combination with other drugs - quinine also used
for complicated malaria
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Artemisinin
Artemesia annua
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Artemesia annua
Recently scientists have been investigating
anti-malarial properties of plantArtemesia
annua, wormwood, annual wormwood,
sweet wormwood, sweet Annie, qinghao
Herbaceous annual native to Asia -
probably China - often considered a weed Plant became naturalized in many countries
and now almost a worldwide distribution
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Artemesia annua
Sweet AnnieSweet wormwood
Annual wormwood
Qinghao
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Traditional uses of qinghao Used for treating malaria for over 2000 yrs
Mentioned in an early medical treatise that has
been dated at 168 BC
Mentioned in Chinese Handbook of Prescriptions
for Emergency Treatments of 340 AD for the
treatment of fevers
Modern scientific studies on this plant began in
the late 1960s and artemisinin isolated in 1972
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Artemesinin Sesquiterpene lactone
with an endoperoxide
bridge Artemisinin and
derivatives are being
called endoperoxides
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Distribution of artemisinin Essential oils ofArtemisia annua contain at
least 40 volatile oils and several nonvolatile
sesquiterpenese - artemisinin is one of these
The essential oils are found in glandular
trichomes on the leaves, stems, and flowers
Artemisinin content appears to be highest inthe trichomes of the flowers
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Current uses Artemisinin and derivatives are effective in
treating chloroquinine resistant strains of
Plasmodium
Artemisinin is being used in China,
Vietnam, Thailand, Myanmar (Burma)
where multi-drug resistance has occurred Clinical trials on-going in many areas
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