Anti-malaria drug

Antimalarial, Antiprotozoal, and Antihelmintic Agents

Protozoal Infections
Parasitic protozoa: live in or on humans malaria leishmaniasis amebiasis giardiasis trichomoniasis

Malaria

Caused by the plasmodium protozoa. Four different plasmodium species (P. vivax, P. ovale and P. Malariae,P.falciparum). Cause: the bite of an infected adult mosquito. Can also be transmitted by infected individuals via blood transfusion, or via infected needles by drug abusers.

Malarial Parasite (plasmodium)

Two Interdependent Life Cycles Sexual cycle: in the mosquito Asexual cycle: in the human Knowledge of the life cycles is essential in understanding antimalarial drug treatment. Drugs are only effective during the asexual cycle.

Plasmodium Life Cycle

Asexual cycle: two phasesExoerythrocytic phase:occurs “outside” the erythrocyteErythrocytic phase:occurs “inside” the erythrocyteErythrocytes = RBCs

Antimalarial Agents

Attack the parasite during the asexual phase, when it is vulnerable Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquine Exoerythrocytic phase drug: primaquine May be used together for synergistic or additive killing power.

Antimalarials: Mechanism of Action

4-aminoquinoline derivatives chloroquine and hydroxychloroquineBind to parasite nucleoproteins and interfere with protein synthesis.Prevent vital parasite-sustaining substances from being formed.Alter pH within the parasite.Interfere with parasite’s ability to metabolize anduse erythrocyte hemoglobin.Effective only during the erythrocytic phase

Antimalarials: Mechanism of Action

4-aminoquinoline derivatives quinine and mefloquineAlter pH within the parasite.Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin.Effective only during the erythrocytic phase.

Antimalarials: Mechanism of Action

diaminophyrimidines pyrimethamine and trimethoprim Inhibit dihydrofolate reductase in the parasite. This enzyme is needed by the parasite to make essential substances. Also blocks the synthesis of tetrahydrofolate. These agents may be used with sulfadoxine or dapsone for synergistic effects.

Antimalarials: Mechanism of Action

primaquine Only exoerythrocytic drug. Binds and alters DNA. sulfonamides, tetracyclines, clindamycin Used in combination with antimalarials to increase protozoacidal effects

Antimalarials: Drug Effects

Kill parasitic organisms. Chloroquine and hydroxychloroquine also have antiinflammatory effects.

Antimalarials: Therapeutic Uses

Used to kill plasmodium organisms, the parasites that cause malaria. The drugs have varying effectiveness on the different malaria organisms. Some agents are used for prophylaxis against malaria. Chloroquine is also used for rheumatoid arthritis and lupus.

Antimalarials: Side Effects

Many side effects for the various agents Primarily gastrointestinal: nausea, vomiting, diarrhea, anorexia, and abdominal pain Rare reactions include ;hemolysis in G6PD deficient persons, seizures , agranulocytosis and ECG changes with chloroquine

Contraindications: For Primaquine : this drug induced hemolytic Anemia in patients with genetically low levels of glucose 6 phosphate dehydrogenase,so Patients should be tested for G6PD deficiency before primaquine is prescripted.