ATC Group: P01B Antimalarials

Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas.

Artemether/lumefantrine fixed-dose combination comprises a fixed ratio of 1:6 parts of artemether and lumefantrine, respectively. The site of antiparasitic action of both components is the food vacuole of the malarial parasite, where they are thought to interfere with the conversion of haem, a toxic intermediate produced during haemoglobin breakdown, to the nontoxic haemozoin, malaria pigment. Both artemether and lumefantrine have a secondary action involving inhibition of nucleic acid and protein synthesis within the malarial parasite.

Artemisinin is used in the treatment of malaria due to species Plasmodium.

Artemotil, also known as β-arteether, is a semi-synthetic derivative of artemisinin and a fast acting blood schizonticide specifically indicated for the treatment of chloroquine-resistant Plasmodium falciparum malaria and cerebral malaria cases.

Artenimol is an artemisinin derivative and antimalarial agent used in the treatment of uncomplicated Plasmodium falciparum infections. Artemisinin combination therapy is highly effective against malaria.

Artenimol is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems. The exact mechanism of action of piperaquine is unknown, but it likely mirrors that of chloroquine, a close structural analogue. Piperaquine is a bisquinoline, and this class has shown good antimalarial activity against chloroquineresistant Plasmodium strains in vitro.

Artesunate is a semi-synthetic artemisinin derivative, indicated for the initial treatment of severe malaria in adults and children. The antimalarial mechanism of action of artesunate is generally thought to depend upon activation involving iron-mediated cleavage of the endoperoxide bridge of DHA to generate an unstable organic free radical followed by alkylation, where the free radical binds to malarial proteins leading to destruction of parasite membranes.

Chloroquine binds to and alters the properties of DNA. Chloroquine also binds to ferriprotoporphyrin IX and this leads to lysis of the plasmodial membrane. In acute attacks of malaria, it interrupts erythrocytic schizogony of the parasite.

Hydroxychloroquine is a antimalarial agent with have several pharmacological actions which may be involved in their therapeutic effect in the treatment of rheumatic disease, but its role is not known.

Mefloquine acts on and destroys the asexual intraerythocytic forms of the human malaria parasites: Plasmodium falciparum, P. vivax. P. malariae and P. ovale. It is effective in the treatment and prophylaxis of malaria.

Primaquine is an 8-aminoquinoline compound which eliminates tissue (exoerythrocytic) infection. Thereby, it prevents the development of the blood (erythrocytic) forms of the parasite which are responsible for relapses in vivax malaria. Primaquine phosphate is also active against gametocytes of Plasmodium falciparum.

Proguanil is an antimalarial drug and dihydrofolate reductase inhibitor. It acts like the other antifolate antimalarials by interfering with the folic-folinic acid systems and thus exerts its effect mainly at the time the nucleus is dividing. Proguanil is effective against the exoerythrocytic forms of some strains of plasmodium falciparum but it has little or no activity against the exoerythrocytic forms of p. Vivax.

Atovaquone and proguanil interfere with two different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. The mechanism of action of atovaquone against P. falciparum is via inhibition of mitochondrial electron transport, and collapse of mitochondrial membrane potential. One mechanism of action of proguanil, via its metabolite cycloguanil, is inhibition of dihydrofolate reductase, which disrupts deoxythymidylate synthesis. Proguanil also has antimalarial and is able to potentiate the ability of atovaquone to collapse mitochondrial membrane potential in malaria parasites. This latter mechanism may explain the synergy seen when atovaquone and proguanil are used in combination.

Pyrimethamine is an antiparasitic agent. The antiparasitic action of pyrimethamine is due to its specific activity on folic acid metabolism in the Plasmodium and Toxoplasma parasites.

Quinine is a cinchona alkaloid and a 4-methanolquinoline antimalarial agent which is a rapidly acting blood schizontocide with activity against Plasmodium falciparum, P vivax, P ovale and P malariae. It is active against the gametocytes of P malariae and P vivax, but not against mature gametocytes of P falciparum.

Tafenoquine is an 8-aminoquinoline antimalarial drug. It is used for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged 16 years and older who are receiving chloroquine therapy for acute P. vivax infection.