infections - malaria

8/6/2019 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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infections - malaria

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