Aminoquinolones

Aminoquinolones

Quinine, chloroquine, primaquine, hydrochloroquine and mefloquine(Lariam) are the well-known antimalarial drugs. The mechanism of action is not known, however, three hypotheses are postulated.

(1) Uptake of aminoquinolones by Plasmodium increases the pH in the lysosomes.

(2) Aminoquinolones interfere with the breakdown of erythrocyte haemoglobin and form a complex with a metabolite of haemoglobin, which

is toxic to the cell membrane of both parasite and erythrocyte.

(3) Aminoquinolones interact with the DNA and/or RNA synthesis of the parasite.

Chloroquine is highly effective against erythrocytic forms of P. vivax, P. ovale, P. malariae and chloroquine-sensitive strains of P. falciparum. It is first choice in malaria treatment and prophylaxis. When a malaria strain is resistant, mefoquine can be used as prophylaxis. For treatment, quinidine in combination with pyrimethamine or tetracycline or clindamycin can be applied.

If taken in proper doses, chloroquine is a safe drug. In high doses, adverse effects such as cardiovascular problems and CNS problems can occur.

Mefloquine is highly effective against malarial blood schizonts and trophozoites. This drug should be reserved for the prevention and treatment of resistant malaria strains.

1

Plasmodium falciparum is highly resistant to chloroquine.

2

Tetracyclines and certain antifolates are used in malaria therapy.

3

Pregnancy is a contra-indication for the use of chemoprophylaxis against malaria.