Download Antimalerials - S. Vijaya lakshmi - Hindu college

Submitted by
Sirigiri Vijayalakshmi
M.Sc (Chemistry)
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Most important parasitic disease of humans,
causing hundreds of millions of illnesses and
probably over a million deaths each year
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Antimalarial drugs are used for the treatment
and prevention of malaria infection.
Most antimalarial drugs target the
erythrocytic stage of malaria infection, which
is the phase of infection that causes
symptomatic illness.
The extent of pre-erythrocytic (hepatic stage)
activity for most antimalarial drugs is not well
characterized.
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Treatment of the acute blood stage infection
is necessary for malaria caused by all malaria
species.
For infection due to Plasmodium ovale or P.
vivax, terminal prophylaxis is required with a
drug active against hypnozoites (which can
remain dormant in the liver for months -and occasionally years -- after the initial
infection).
Chloroquine: has activity against the blood
stages of Plasmodium ovale, P. malariae, and
susceptible strains of P. vivax and P.
falciparum.
Widespread resistance in most malariaendemic countries has led to decline in its
use for the treatment of P. falciparum,
although it remains effective for treatment of
P. ovale, P. malariae, and, in most regions, P.
vivax.
MECHANISM OF ACTION :
• Binds to and inhibits DNA and RNA polymerase;
interferes with metabolism and hemoglobin
utilization by parasites; inhibits prostaglandin
effects;
• chloroquine concentrates within parasite acid
vesicles and raises internal pH resulting in
inhibition of parasite growth;
• may involve aggregates of ferriprotoporphyrin IX
acting as chloroquine receptors causing
membrane damage; may also interfere with
nucleoprotein synthesis.
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Malaria, suppression or prophylaxis: Oral: 500
mg/week (300 mg base) on the same day each
week; begin 1-2 weeks prior to exposure;
continue for 4-6 weeks after leaving endemic
area; if suppressive therapy is not begun prior to
exposure, double the initial loading dose to 1 g
(600 mg base) and administer in 2 divided doses
6 hours apart, followed by the usual dosage
regimen.
Malaria, acute attack: Oral: 1 g (600 mg base) on
day 1, followed by 500 mg (300 mg base) 6
hours later, followed by 500 mg (300 mg base)
on days 2 and 3.
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Side effects of chloroquine include
headaches, dizziness, abdominal discomfort,
vomiting, and diarrhea.
Chloroquine may also produce pruritus in
some patients; this has been noted to occur
most frequently in African populations.
◦ The pruritus is transient, lasting 48 to 72 hours,
and is not responsive to antihistamines.
As clinical curative:
 Sulfadoxine 1500 mg + pyrimethamine 75
mg
(3 tab) single dose
Children
 9-14 yr 2 tab
 4-8 yr 1 tab
 1-4 yr ½ tab
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Antifolates include sulfonamides,
pyrimethamine, proguanil and dapsone.
These drugs act synergistically to target
enzymes involved in folate synthesis, a
pathway required for parasite DNA synthesis
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Tetracycline, doxycycline, and clindamycin target
prokaryotic protein synthesis.
In malaria parasites, these drugs appear to target
the apicoplast, an organelle derived from
prokaryotic ancestors.
They have relatively slow antimalarial activity
because they exert their toxic effects in the
subsequent cycle of cell division.
They are typically paired with fast-acting
antimalarials (usually quinine).
Doxycycline has a longer half life than
tetracycline so is used more commonly.
Resistance has not been detected to tetracycline,
doxycycline or clindamycin.
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The artemisinins are
derived from the leaves
of the Chinese sweet
wormwood plant,
Artemisia annua.
They have been used in
China for the treatment
of malaria for over
2000 years and came
to attention outside of
China in the 1970s and
1980s.
Uncomplicated P.falciparum malaria (oral):
 Mefloquine (Lariam)
 Proguanil/atovaquone (Malarone)
 Chloroquine (Aralen)
 Pyrimethamine/sulfadoxine (Fansidar)
 Quinine sulfate with antibiotics.