Anti Malaria - Copy

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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