AFSAR FATHIMA M.Pharm

DEFINITION: Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoan's.

Species of malaria Plasmodium vivax Plasmodium ovale Plasmodium falciparum Plasmodium malariae Plasmodium knowlesi

LIFE CYCLE OF MALARIA

DIAGNOSIS OF MALARIA

Classification of anti-malarial drugs

Therapeutic classification Chemical classification

Therapeutic classification Causal prophylaxis: (Primary tissue schizonticides) Destroy parasite in liver cells and prevent invasion of erythrocytes Primaquine, proguanil Supressives Prophylaxis: Supress the erythrocytic phase and thus attack of malarial fever can be used as prophylactics Chloroquine, proguanil, mefloquine, doxycycline Clinical cure: erythrocytic schizonticides used to terminate an episode of malarial fever

Fast acting high efficacy : Chloroquine, quinine, mefloquine, atovaquone, artemisinin Slow acting low efficacy drugs: Proguanil, pyrimethamine, sulfonamides, tetracyclines

Therapeutic classification Radical curatives: Eradicate all forms of P.vivax & P.ovale from the body. Suppressive drugs + hypnozoitocidal drugs For vivax: Primaquine 15 mg daily for 14 days Gametocidal: Destroy gametocytes and prevent transmission Primaquine, artemisinin – against all plasmodia Chloroquine, quinine – Pl Vivax Proguanil, pyrimethamine – prevent development of sporozoites

Chemical classification 4 aminoquinolines: Chloroquine, Hydroxychloroquine, Amodiaquine, Pyronaridine 8 aminoquinolines: Primaquine, Tafenoquine, Bulaquine Cinchona alkaloids: Quinine, Quinidine Quinoline methanol: Mefloquine Biguanides: Proguanil, Chlorproguanil

Sesquiterpene lactones: Diaminopyrimidines: Pyrimethamine Sulfonamides: Sulfadoxine, dapsone Tetracycline's: tetracycline, doxycycline Naphthoquinone: Atovaquone Sesquiterpene lactones: Artesunate, artemether, arteether

Chloroquine Hemoglobin Globin utilized by malarial parasite Heme (highly toxic for malaria parasite) Chloroquine , Quinine, mefloquine (-) Hemozoin (Not toxic to plasmodium)

Pharmacokinetics: Well absorbed, 60 % protein bound, Concentrated in liver , spleen, kidney, lungs , leucocytes .Selective accumulation in retina: ocular toxicity. Adverse drug reactions: Nausea, vomiting, anorexia, skin rashes, angioneurotic edema, photosensitivity, pigmentation, exfoliative dermatititis Therapeutic uses: Hepatic amoebiasis, Giardiasis, Clonorchis sinensis Rheumatoid arthritis, Discoid Lupus Erythematosus, Control manifestation of lepra reaction, Infectious mononucleosis. Hydroxy chloroquine: Less toxic, properties &uses similar Amodiaquine: As effective as chloroquine, Chloroquine resistant strains may be effective Adverse events: GIT, headache , photosensitivity, rarely agranulocytosis Pyronaridine: effective in resistant cases

Quinine: In 1820 Pelletier & caventou isolated quinine from cinchona bark. Erythrocytic forms of all malarial parasites including resistant falciparum strains Gametocidal for vivax & malariae. Adverse effects: Cinchonism, Tinnitus, nausea & vomiting. Headache mental confusion, vertigo, difficulty in hearing & visual disturbances Diarrhoea , flushing, respiratory depression , cyanosis. Primaquine: Primaquine Converted to electrophiles Generates reactive oxygen species

Adverse effects: epigastric distress, abdominal cramps, mild anemia, methaemoglobinemia, cyanosis, hemolytic anemia in G6PD deficiency . Tafenoquine: More active slowly metabolized analog of primaquine, has advantage that it can be given on weekly basis. Bulaquine: Partly metabolized to primaquine , Better tolerated in G6PD deficiency .