ANTI MALARIA

Department of Pharmacology
Medical School Unsoed
MALARIA
Malaria is caused by protozoan
parasites of the genus Plasmodium,
of which 4 species infect man:
P. falciparum
P. vivax
P. malariae
P. ovale
The parasites are transmitted by
female mosquitoes of the genus
Anopheles whilst taking a blood
meal.
MALARIA CONTROL
STRATEGI
Current WHO Global Malaria
Control Strategy emphasises:
early diagnosis
treatment with effective
antimalarials
selective use of preventative
measures including vector control
where it can be sustained.
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.
QUININE
Cinchona (Jesuits bark) first brought to
Spain in 1639
Quinine, the main alkaloid in the bark of the
Cinchona tree was isolated in 1820
Quinidine is also present, but is not used
because of its actions on the heart
Active against erythrocytic stages of the
parasites
Its mode of action is not clearly defined but
may involve:
Binding to DNA, stopping synthesis of nucleic
acids
Inhibition of haem digestion
Synthetic Antimalaria
One of the first synthetic
antimalarials was PAMAQUINE
developed during World War (WW)-1
Pamaquine was active against
avian 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.
Synthetic Antimalaria
Chloroquine
Amodiaquine
Mefloquine
Pyronaridine
Proguanil
Sulphonamides/Sulphone
Artemisinin Derivatives
Primaquine
Active against liver stages of P.
vivax
Mechanism of action may
involve oxidative stress in the
parasite
Effective against other stages
of the life cycle, but it is too toxic
Causes haemolysis and
methaemoglobinamia
CHLOROQUINE
Synthesized during WW-II
Based on the quinine structure
Accumulates in the food
vacuole of the parasite
Interferes with haem digestion
Effective against blood stages
Relatively safe
Resistance is a problem
Amodiaquine
Developed at the same time as
chloroquine
Effective against blood stages,
even in some chloroquine-
resistant strains of P. falciparum
Has an unacceptable risk of
toxicity towards granulocytes
and the liver
Mefloquine
Recommended for most risk areas.
Minor side effects (nausea,
dizziness, difficulty sleeping) do not
last long and do not require stopping
the drug.
Not recommended for use if:
a known allergy to mefloquine
a history of epilepsy, severe psychiatric
disorders or cardiac conduction
abnormalities.
Pyronaridine
Pyronaridine: potential
replacement for chloroquine
Too expensive
Requires new routes for
synthesis
Proguanil
It is a prodrug that requires
metabolic activation to
cycloguanil
Effective against erythrocytic
and liver stages of P. falciparum
Inhibits dihydrofolate reductase
and hence DNA synthesis
Used as a prophylactic, but is
too slow for a cure
Sulphonamides/Sulphone

Sulphones (e.g. Dapsone) and
Sulphonamides (e.g. Sulphadoxine) inhibit
dihydropteroate synthase
involved in folate, and hence pyrimidine and
DNA synthesis
They act too slowly on their own, but act
synergistically with proguanil and
pyrimethamine because they act at
different parts of the same pathway
Always used in combination therapy (Fansidar*)
Artemisinin Derivatives

Artemisinin derivatives are:
Highly effective
Rapid
have limited toxicity
However, inappropriate use may
lead to the development of
resistance and untoward
toxicity.
THE USE OF MALARIA
DRUG
Consider to life-cycle of
parasites (Plasmodium)
To have selective toxicity
between host and parasite
Good sensitivity in the various
stages
THE FREQUENT DRUG
USED
Quinine
Generic quinine ethyl
carbonate tablet 100 mg
Chloroquine
Chloroquine phosphate tablet 250
mg
Sulphonamides/Sulphone
Sulfadoxin 500 mg-pyrimethamine
25 mg
HOW TO USE DRUGS..
QUININE TAB 100 mg
Prevention
1-2 tab ante noctum once/week
(as long as out break situation)
Therapy
3 x 1-2 tab daily 1-2 weeks
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 daily
for 2 days
Child
Prevention
5 mg/kgbb/week ( 1 week before until 4 week after
exposure
Therapy
10 mg/kgbb 5 mg/kgbb (after 6 hours) 5 mg/kgbb
daily for 2 days
Drug example
Avloclor*, Malarex*, Mexaquin*, Riboquin*

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), <4 th (1/2 tab)
Non Imune 9-14 th (1 tab), 4-8 th (1 tab), <4 th (1/2 tab)
1-2 DAYS before until 4 week after exposure

Therapy
10-14 th (2 tab), 7-9 th (1 tab), 4-6 th (1 tab), <4 th (1/2 tab)
Drug example
Fansidarr*, Plasmodin*, Suldox*

See USalam