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7/30/2019 Anti Malaria - Copy
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ANTI MALARIA
Department of Pharmacology
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LEARNING OBJECTIVES
Student should be able to
Explain
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MALARIA
Malaria is caused by protozoanparasites of the genus Plasmodium,of which 4 species infect man: P. falciparum
P. vivax
P. malariae
P. ovale
The parasites are transmitted byfemale mosquitoes of the genusAnopheleswhile taking a bloodmeal.
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MALARIA CONTROL
STRATEGI
Current WHO Global Malaria
Control Strategy emphasises:
early diagnosis
treatment with effective
antimalarials
selective use of preventative
measures including vector controlwhere it can be sustained.
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MALARIA CONTROL
STRATEGI-cont
Potential targets for antimalarial
therapy must:
constitute essential features of the
parasite lifecycle
processes in the host to make
selectivity between host and
parasite possible.
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QUININE
Cinchona (Jesuits bark) first brought toSpain in 1639
Quinine, the main alkaloid in the bark ofthe Cinchonatree was isolated in 1820
Quinidine is also present, but is not usedbecause of its actions on the heart
Active against erythrocytic stages of theparasites
Its mode of action is not clearly defined but
may involve: Binding to DNA, stopping synthesis of nucleic
acids Inhibition of haem digestion
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Synthetic Antimalaria
One of the first synthetic
antimalarials was PAMAQUINEdeveloped during World War (WW)-1
Pamaquine was active againstavian malaria (the model) but not P.falciparum(the major human form)
In addition, it was toxic in humans.
However, it was found effective
against the vivax relapses.
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Synthetic Antimalaria
Chloroquine
Amodiaquine
Mefloquine Pyronaridine
Proguanil
Sulphonamides/SulphoneArtemisinin Derivatives
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Primaquine
Active against liver stages ofP.vivax
Mechanism of action may
involve oxidative stress in theparasite
Effective against other stages of
the life cycle, but it is too toxic Causes haemolysis and
methaemoglobinamia
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CHLOROQUINE
Synthesized during WW-II
Based on the quinine structure
Accumulates in the food vacuoleof the parasite
Interferes with haem digestion
Effective against blood stages
Relatively safe
Resistance is a problem
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Amodiaquine
Developed at the same time as
chloroquine
Effective against blood stages,even in some chloroquine-
resistant strains ofP. falciparum
Has an unacceptable risk of
toxicity towards granulocytesand the liver
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Mefloquine
Recommended formost risk areas.
Minor side effects(nausea,dizziness, difficulty sleeping) do not
last long and do not requirestopping the drug.
Not recommended for use if:
a known allergy to mefloquine
a history ofepilepsy, severe psychiatricdisorders orcardiac conductionabnormalities.
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Pyronaridine
Pyronaridine: potential
replacement for chloroquine
Too expensive
Requires new routes for
synthesis
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Proguanil
It is a prodrug that requiresmetabolic activation tocycloguanil
Effective against erythrocyticand liver stages ofP.falciparum
Inhibits dihydrofolate reductaseand hence DNA synthesis
Used as a prophylactic, but istoo slow for a cure
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Sulphonamides/Sulphone
Sulphones (e.g. Dapsone) andSulphonamides (e.g. Sulphadoxine) inhibitdihydropteroate synthase
involved in folate, and hence pyrimidine andDNA synthesis
They act too slowly on their own, but actsynergistically with proguanil andpyrimethamine because they act at
different parts of the same pathway Always used in combination therapy (Fansidar*)
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Artemisinin Derivatives
Artemisinin derivatives are:
Highly effective
Rapid
have limited toxicity
However, inappropriate use may
lead to the development ofresistance and untowardtoxicity.
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THE FREQUENT DRUG
USED
Quinine
Generic quinine ethylcarbonate tablet 100 mg
Chloroquine Chloroquine phosphate tablet 250
mg
Sulphonamides/Sulphone Sulfadoxin 500 mg-pyrimethamine
25 mg
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HOW TO USE DRUGS..
QUININE TAB 100 mg
Prevention
1-2 tab ante noctumonce/week(as long as out break situation)
Therapy
3 x 1-2 tab daily 1-2 weeks
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HOW TO USE DRUGS..
CHLOROQUINE TAB 250 mg Adult
Prevention 2 tab/week
Semi imun (in endemic area) 2 tab /1-2 weeks
Therapy Semi imun : single dosage 4 tab
Non imun : 4 tab2 tab (after 6-8 hours) 2 tab dailyfor 2 days
Child Prevention
5 mg/kgbb/week ( 1 week before until 4 week afterexposure
Therapy 10 mg/kgbb 5 mg/kgbb (after 6 hours) 5 mg/kgbb
daily for 2 days
Drug example Avloclor*, Malarex*, Mexaquin*, Riboquin*
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HOW TO USE DRUGS..
Sulfadoxyn 500-Pyrimethamine 25
Adult Prevention (1-2 DAYS before until 4 week after exposure)
Semi imun (in endemic area) 2-3 tab /4 weeks
NON Imun 2 tab /2 weeks
Therapy single dosage 2-3 tab
Child Prevention
Semi imune 9-14 th (2 tab), 4-8 th (1 tab),
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See USalam