The development of resistance to conventional treatment has led WHO to recommend the use of combination therapies containing aemisinin derivative (aemisinin-based combination therapies also known as ACTs). All of the following combination therapies are recommended if such resistance is suspected, except:
Aemisinin-based combination therapy (ACT): Noting that use of antimalarial drugs singly has failed to cuail the prevalence of malaria globally, paicularly due to emergence of chloroquineresistant followed by multidrug-resistant P. Jalciparum, the WHO has recommended that acute uncomplicated resistant falciparum malaria should be treated only by combining one of the aemisinin compounds with another effective erythrocytic schizontocide. In choosing the companion drug, the most impoant consideration is its elimination tlh (governing stay in the body), because effective concentrations in blood must be maintained for at least 3 asexual cycles of the parasite, i.e. 6 days, to exhaust the parasite burden. Therefore, sho tlh drugs have to be given for 7 days, while longer acting drugs can be given for 1- 3 days. However, long tlh drugs allow subinhibitory concentrations to persist in the blood facilitating selection of resistant mutants. Combining a sho tlh drug with a long tlh drug in the conventional 3 day regimen runs the risk of de facto monotherapy after the sho tlh drug is eliminated. This risk is minimized by choosing a sho tlh drug that reduces the parasite load rapidly and drastically. Aemisinin compounds fillin this requirement, as they rapidly kill > 95% plasmodia. They leave only a small biomass of the parasites to be eliminated by the long tlh drug, reducing the chances of selecting resistant mutants. Advantages of ACT over other antimalarials are: * Rapid clinical and parasitological cure. * High cure rates (>95%) and low recrudescence rate * Absence of parasite resistance (the components prevent development of resistance to each other). * Good tolerability profile 1. Aesunate-sulfadoxine + pyrimethamine (AS/5/P) 2. Aesunate-mefloquine (AS/MQ) 3. Aemether-lumefantrine 4. Aesunate-pyronaridine 5. Aesunate-amodiaquine (AS/AQ) 6. Aesunate-chlorproguanil-dapsone ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:794,795,796
Aemether plus lumefantrine
Aesunate plus quinine
Aesunate plus pyrimethamine-sulfadoxine
Aesunate plus mefloquine
Chemotherapy