Antimalarial Agents 353dihydrofolate reductase. It is slow acting
erythrocytic schizontocide. It can eliminate
preerythrocytic phase of P. falciparum and the
secondary tissue phase of P. vivax.
Absorption of pyrimethamine from GIT is
slow but good. It is concentrated in liver,
spleen, kidney and lungs. It is metabolised
and excreted in urine. If it is employed alone
development of resistance occurs fast.
Pyrimethamine alone is used for prophylaxis
occasionally.
PYRIMETHAMINE-SULFONAMIDE
COMBINATION
Ultra long acting sulfonamides in
combination with pyrimethamine are used.
The effect is supraadditive due to sequential
block. It may be employed as a clinical
curative. Another advantage of the drug
combination is that the development of
resistance is retarded.
Its action is based on differential
requirement between host and parasite for
nucleic acid precursors involved in growth
as it selectively inhibits plasmodial
dihydrofolate reductase.
It is very well absorbed after oral use
and is metabolised in the liver.
Pyrimethamine is a safe drug and cause
only nausea, vomiting, skin reaction e.g. skin
rash, pruritus and higher dose can cause
megaloblastic anaemia and granulocytopenia.
The combination is indicated in chloro-
quine resistant malaria and prophylaxis. Py-
rimethamine-sulfadiazine combination is
used for treatment of toxoplasmosis.
ARTEMISININ DERIVATIVESArtemisinin is the active plant principle
isolated from plant Artemisia annua, active
against P. falciparum resistant strains.ARTESUNATE
It is a new, potent antimalarial drug
and is a water soluble synthetic analogue
of artemisinin.
It is concentrated in parasitized
erythrocytes, where it is activated by
parasite haem, generating free radicals.
Hence it causes increase in oxidant
stress on the infected red cells pro-
moting cytotoxicity and death of para-
sites. It rapidly clears parasitaemia,
faster than any other antimalarial drug.
After administration it is rapidly
absorbed and distributed in tissue e.g. liver,
intestine and kidneys. It is metabolised in
liver and converted to active metabolite
dihydroartemisinin.
Adverse effects include nausea, vom-
iting, dizziness, anorexia, gastrointestinal
disturbances and convulsions.
It is indicated in acute attack of multi-
drug resistant P. falciparum malaria where
quinine is not effective.ARTETHER
It is an ethyl ether derivative of
dihydroartemisinin in sterile arachis oil.
A racemic mixture of a, β-artether
(30:70 ratio) has greater solubility and
stability than artemisinin and is more
cost-effective.
It shows rapid schizonticidal action and
brings about quick clinical improvement in
falciparum malaria with low recrudescence
rate. It has some gametocidal action too.