Anti-Malaria drugs
| Class | Drug | Biological activity | |
| Blood schizontocide | Tissue schizontocide | ||
| 4-Aminoquinolines | chloroquine | ++ | 0 |
| Arylaminoalcohols | quinine | ++ | 0 |
| quinidine | ++ | 0 | |
| mefloquine | ++ | 0 | |
| Phenanthrene methanol | halofantrine | ++ | 0 |
| Artemisinine and derivatives |
artemisinine | ++ | 0 |
| artemether | ++ | 0 | |
| artesunate | ++ | 0 | |
| Antimetabolites | proguanil | + | + |
| pyrimethamine | + | 0 | |
| sufhadoxine | + | 0 | |
| sulfalene | + | 0 | |
| dapsone | + | 0 | |
| Antibiotics | tetracycline | + | + |
| doxycycline | + | + | |
| minocycline | + | + | |
| 8-Aminoquinoline | primaquine | 0 | + |
Anti-Malaria drugs
Blood schizontocides kill the erythocytic stages inside the red blood cells, while tissue schizontocides kill the liver stages of the parasite. In the case of falciparum malaria where there is no reinfection or relapse from the liver, a single blood schizontocidal drug is sufficient as treatment. In the case of infection by the other parasites, such treatment only suppresses the blood infection but does not lead to cure. Here a combination of both blood and tissue schizontocides has to be used.
Quinine is an effective anti-malarial originally isolated from the bark of the American cinchona tree. Indians from South America used to chew this bark as a treatment of fever probably resulting from malaria. Later these trees were imported by the Dutch into the East Indies where they were used for the large scale production of quinine. The Brittish in the colonies used quinine as a chemoprophylaxis by mixing it with water. The bitter taste of this tonicum was improved by the addition of some gin. This explains the popularity of the typical drink "gin and tonic" amongst the British. Quinine is a blood schizontocide. Though curative to falciparum malaria, it suppresses but fails to cure or provide prophylaxis against vivax malaria. It destroys the trophozoites present in the erythrocytes but has no effect on the exo-erythrocytic stages that develop in the liver. In the case of vivax and ovale malaria these stages have to be treated with the tissue schizontocide primaquine. The combined treatment with both a bood and tissue schizontocide is called radical cure of malaria.
Chloroquine a 4-amino-quinoline with a structure
related to quinine is also an effective anti-malarial for treatment and prophylaxis.
It was first used in the 1940s shortly after the Second World War and was effective
in curing all forms of malaria, with few side effects when taken in the dose prescribed
for malaria and it was low in cost. Unfortunately most strains of falciparum malaria
are now resistant to chloroquine and more recently
chloroquine resistant vivax malaria has also been reported.
Fansidar. This is a combination drug, each tablet
containing sulphadoxine 500mg. and pyrimethamine 25mg. Both drugs are antifolates
and interfere with the synthesis of thymidylate and DNA . It acts by interfering
with folate metabolism. Resistance to Fansidar is
now widespread and serious side effects have been reported. It is no longer recommended.
Mefloquine (Lariam). First introduced in 1971,
this quinoline methanol derivative is related structurally to quinine. The compound
was effective against malaria, resistant to other forms of treatment when first introduced
and because of its long half life was a good prophylactic, but widespread resistance
has now developed and this together with undesirable side effects have resulted in
a decline in its use.
Because of its relationship to quinine the two drugs must not be used together. There
have been reports of various undesirable side effects including several cases of
acute brain syndrome, which is estimated to occur in 1 in 10,000 to 1 in 20,000 of
the people taking this drug. It usually develops about two weeks after starting mefloquine
and generally resolves after a few days.
Artemisinine or Quinhoasu is a sesquiterpene lactone derived from the plantArtemisia annua. This effective anti-malarial is used as extracts in traditional medicine in China for the management of fever resulting from malaria. To improve its bioavailability the derivatives artemether and artesunate have been devoloped. When used on its own, a high rate of treatment failures has been reported and it is now being combined with mefloquine for the treatment of falciparum malaria. While widely used now in South-East Asia, the drug is not yet licensed for use in Australia, North America or Europe. Its main value at present is in the treatment of multi drug resistant falciparum malaria. If artemisinin is used to treat vivax malaria it should be accompanied by a course of primaquine. Unless used with a second antimalarial there is likely to be a high recrudescent rate. Side effects have been reported but these are comparatively rare and seldom severe. It is recommended only for treatment not for prophylaxis.