Anti-Malarial Agents The malarial parasite is a single cell protozoan called plasmodium. The main clinically important species of plasmodium are plasmodium falciparam, P.Vivax, P.ovale and P.malariae that cause malaria.

Classification: Based on Chemical structure : 1.4 Aminoquinolines: Chloroquine, Amodiaquine, Peperaquine, Pyronaridine 2. Chincona Alkaloids: Quinine 3. Quinoline methanol: Mefloquine. 4. Acridine: Mepacrine, Quinacrine Aminoquinolines: Primaquine, Bulaquine, Tafenoquine 6. Biguanides: Proguanil 7.Diaminopyrimidines: Pyrimethamine 8.Artemisinin Dervatives: Artesunate, Artemether 9.Phenanthrene methanol: Halofantrine, Lumefantrine. 10.Naphthoquinone: Atovaquone. 11.Antibiotics: Tetracycline, Doxycycline, Clindamycin 12.Sulfonamides and Sulfones: Sulfadoxine and Dapsone

Based on Affected Plasmodial State: Schizonticides : These kills schizoticides. 1.Tissue (Hepatic Schizonticides): These destroy the hepatic schizonts soon after infection. Primary tissue schizonticides acts on pre-erythrocytic state: Proguanil & Pymethamine. But active against only P.falciparum not P.Vivax & ovale. Secondary tissue Schizontcides acts on exo-erythrocytic state in liver. Eg. Primaquine. It is acts against pre & exorythrocytic stages of all plasmodial species. 2. Blood Schizonticides: These drugs destroy the blood schizonts (Merozoits→ Schizonts→Merozoites) and prevents erythrocytic schizogony to terminate the atteck of malarial fever. Chloroquine, Quinine, Mefloquine, Lumefantrine, Artemisinin & Atovaquone. Gametocides: These drugs destroy the gametocytes or make them ineffective in host blood so that mosquitoes cannot transmit the disease, such as Primaquine, Chliroquine & Quinine Sporontocides: These drugs make the gamocytes ineffective within the body of the mosquito. Pyrimethamine, Proguanil. However, the use of these drugs as gametocide provides no clinical advantage as their use in one infected person would not prevent widespread transmission of malaria in population.

Based on Clinical Use : Causal Prophylactics. No drug is available to destroy sporozoites prior to invasion into humans. Suppressive Prophylaxis: Drugs used for such purpose do not affect the hepatic phase of the malarial parasite but destroy the merozoites released from liver so that the very development of erythrocytic stage is prevented. Such drugs are mainly blood schizonticides. Suppressive prophylaxis is employed during the periods of exposure to infected mosquitos. Chloroquine 600 mg, Mefloquine 200 mg. Proguanil 200 mg. Radical cure: Eradication of both exoerythrocytic as well as erythrocytic states. Hence relapse doesn't occur. Primaquine & proguanil. Clinical Cure: The asexual erythrocytic schizogony state of malarial parasite is responsible clinical symptoms (Chills, Rigor, Fever) of malaria. Chloroquine, Quinine, Mefloquine, Artemisinin. Lamefantrine.

Chloroquine : This is most frequently used one. Malarial parasites digest haemoglobin in their lysosomes to utilise amino acids. The released heme is highly toxic but is converted by parasite polymerase to nontoxic hemozoin. Chliroquine is base drug, concentrates in the acidic lysosomes & binds to liberated heme. It accumulates in parasite’s food vacuoles, inhibits peptide formation and reduces the synthesis of aminoacides necessary for parasite viability. It also inhibits the parasite enzyme haeme polymerase and thus protects the host’s haem from being converted to haemozoin. The heme-quinoline complexes get incorporeted into the growing polymer chain interrupting the haeme polymerization. Free haem is toxic to the malarial parasite. Pharmacological Action: CVS: Depressant on myocardium & relaxant on vascular smooth muscle. Anti-inflammatory, Anti-histaminic and Local anesthetic actions. Anti-Malarial Actions: Chloroquine kills the erythrocytic forms of P.vivax, P.falcipam.

Adverse Effects : Nausea Vomiting(common). On larger doses on long term therapy serious effects are produced. Intolerance: Skin rashes, angioneurotic edema. Photosensitivity. Long term treatment lead to bleaching of hair, Eyebrows & Eyelashes. Eye: Temporary loss of accommodation with blurring of vision or diplopia. CNS : Insomnia & Transient depression, Psychotic episodes, seizures, Ototoxicity has been reported. CVS : Abnormality in ST Segment & T waves. Therapeutic Uses: Giardiasis, Clonorchis Sinensis (Chinese liver fluke) Rheumatoid arthritis. Discoid lupus Erythromatosis. QUININE: Pharmacological actions: Antimalarial: It is schizoticidal useful for suppressive. Gamatocides also effected. The MOA is just like chloroquine. No effect on sporozoites. Local Irritant Action: It is known as general protoplasmic poison. It depresses variety of enzymatic processes., reducess ciliary activity, inhibits phagocytosis. Causes pain, edema.

GIT: Bitter taste causes Nausea, Vomiting. CVS: Directly depresses myocardium, reduces its its excitability, conductibility & lengths refractory period. Hypotension due to direct depression. & dilation of Arterioles. Adverse Effects: Cinchonism : This occur when full dose is used for longer period. When mild, ringing in ears, nause, vomiting, headache, Visual disturbances. With larger doses, tinnitus, deafness, vertigo, blurred vision, disturbance in color vision, & Phtophobia. Toxic doses produce skin rashes, headach, fever, vomiting, confusion, delirium, As poisoning progressing, skin become cold, respiration depressed, BP falls, death occur due to failure of respiration. Black water fever: RBC gets burst and haemolysis occur in the blood vessels & into urine which causes kidney failure. Hypoglyceamia: Quinine causes the release of Insulin leads to hypoglycaemia.